The DOI matches its Crossref record; 164 of the 167 references it cites were found in a registry or an index; 3 of the 141 sources its claims cite were checked for support.
Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy
Open accessAbstract
Alzheimer’s disease (AD) is a gradually growing irreversible illness of the brain that almost affects every fifth person (aged > 80 years) in the world. World Health Organization (WHO) also revealed that the prevalence of this disease will enhance (upto double) significantly upto 2030. The poor cholinergic transmission at the synapse is considered to be one of the main reasons behind the progression and occurrence of this disorder. Natural inhibitors of acetylcholine (ACh) such as galanthamine and rivastigmine are used commercially in the treatmentof AD. The biomolecules such assesquiterpenes, possess a great structural diversity and are responsible for a plethora of pharmacological properties. The potential of various sesquiterpenes as anticholinesterase has been reviewed in this article. For this purpose, the various databases, mainly PubMed, Scopus, and Web of Science were investigatedwith different keywords such as “sesquiterpenes+acetylcholinesterase” and “sesquiterpenes+cholinesterase+inhibitors” in the surveyed time frame (2010–2020). A vast literature was evident in the last decade, which affirms the potential of various sesquiterpenes in the improvement of cholinergic transmission by inhibiting the AChE. After data analysis, it was found that 12 compounds out of a total of 58 sesquiterpenes were reported to possess IC50 < 9 μM and can be considered as potential candidates for the improvement of learning and memory. Sesquiterpene is an important category of terpenoids, found to possess a large spectrum of biological activities. The outcome of the review clearly states that sesquiterpenes (such as amberboin, lipidiol, etc.) from herbs could offer fresh, functional compounds for possible prevention and treatment of AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This narrative review surveys sesquiterpenes and sesquiterpene-containing extracts as acetylcholinesterase (AChE) inhibitors for Alzheimer’s disease, drawing on literature from 2010–2020. It reports that 12 of 58 sesquiterpenes had AChE IC50 <9 µM and highlights amberboin and lipidiol as promising leads, while noting assay and safety caveats.
Key findings
- Across 58 sesquiterpenes reviewed, 12 had AChE IC50 <9 µM and were considered potential candidates for improving learning and memory.
- Amberboin and lipidiol from *Volutaria abyssinica* inhibited AChE with IC50 = 0.8 ± 0.03 µM and 0.5 ± 0.01 µM, respectively; amberboin also inhibited BChE (IC50 = 0.6 ± 0.13 µM), compared with galanthamine (AChE IC50 = 3 ± 0.2 µM; BChE IC50 = 47 ± 1 µM).
- Volvalerenic acid K had in vitro AChE IC50 = 0.16 µM and improved learning/memory in APPswe/PS1E9 mice; Huperzine-A showed reversible AChE inhibition (IC50 = 22 µM) and is described as the only sesquiterpene alkaloid clinically established and USFDA-approved for AD.
- Sesquiterpenes were also linked to alternate AD targets: Stigmene A and B reduced Aβ aggregation by 82.9 ± 2.52% and 70.1 ± 3.01% vs 69.8 ± 1.55% for positive control; bilobalide antagonized GABA_A receptors (IC50 = 4.6 ± 0.5 µM); nootkatone and ambrosin reduced NF-κβp65 expression.
Methods
- Narrative review; PubMed, Scopus, and Web of Science were searched with keywords “sesquiterpenes+acetylcholinesterase” and “sesquiterpenes+cholinesterase+inhibitors” for 2010–2020.
- Synthesized studies on sesquiterpenoids, sesquiterpene lactones, coumarins, agarofuran, and alkaloids; AChE inhibition was commonly assessed by Ellman’s method, with some docking and in vivo mouse studies.
- Qualitative synthesis; the paper reports counting 58 sesquiterpenes and identifying 12 with IC50 <9 µM.
Limitations
- Stated: IC50 alone should not determine anti-Alzheimer potential; Ellman assays with carbonyl-containing compounds can produce false positives; most plant actives were not evaluated for unwanted side effects; animal-model and clinical confirmation are needed; galliardin has cytotoxic properties.
- Evident: as a narrative review, it lacks a formal systematic protocol, explicit inclusion/exclusion criteria, risk-of-bias assessment, or meta-analysis; evidence is heterogeneous (in vitro IC50 values, essential-oil mixtures, docking, and mouse models) and IC50 units vary (µM, µg/mL, mg/mL).
- Evident: many compounds are discussed without blood-brain barrier permeability, bioavailability, or toxicity data, though the paper notes lipophilicity may aid bioavailability and calls for toxicological profiling.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
102 Not checked yet · 18 Own interpretation · 13 No basis given · 2 Partly supported · 1 Own result · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Hence ambrosin and nootkatone, as novel sesquiterpenes, could significantly reduce the expression of this transcription factor (NF-κβp65) in experimental groups.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [143] Wanga, 2018, Nootkatone, a neuroprotective agent from AlpiniaeOxyphyllae Fructus, improves cognitive impairment in lipopolysaccharide-induced mouse model of Alzheimer’s disease, Int. Immunopharmacol. source
- Partly supportedcites [144] Khalil, M.N., Choucry, M.A., El Senousy, A.S., Hassan, A., El-Marasy, S.A., El Awdan, S.A., and Omar, F.A. (2019). Ambrosin, a potent NF-κβ inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin. PLoS ONE, 14. sourceExperimental — accuracy not yet measured
The Results (‘Curcumin and ambrosin reduced NF-κβp65 transcript and protein levels’; page unavailable) report that ambrosin significantly reduced NF-κβp65 expression in the LPS-treated experimental model. The paper compares ambrosin with curcumin; it does not report a nootkatone experimental group or establish the claimed effect for nootkatone. (LLM, conf=0.90)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Both the oils showed significant AChE and BChE inhibitory activity (p < 0.05) in a dose-dependent manner at the concentration of 416 µg/mL.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [96] Olawuni, 2018, In vitro anti-cholinesterase and cognitive enhancing properties of essential oils from Piper nigrum L. and Monodora myristica (Gaertn) dunal, Int.J. Pharmacol. Toxicol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In contrast, the extract exhibited 63 ± 0.8% activity only against BChE at the concentration of 500 μg/mL.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [94] Tel, 2010, Chemical composition of the essential oil and hexane extract of Salvia chionantha and their antioxidant and anticholinesterase activities, Food Chem. Toxicol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Further, amberboin also inhibited the BChE at IC50 of 0.6 ± 0.13 µM.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.2. Sesquiterpene Lactones (SLs)
What the sources say
- Not checked yetcites [121] Elsebaia, 2018, Amberboin and lipidiol: X-ray crystalographic data, absolute configuration and inhibition of cholinesterase, Phytochem. Lett. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Petroleum ether fraction was found to be loaded with SLs (about 80%), accounting for its anti-AChE activity.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.2. Sesquiterpene Lactones (SLs)
What the sources say
- Not checked yetcites [125] Patel, M.B., and Amin, D. (2012). Sphaeranthus indicus flower derived constituents exhibits synergistic effect against acetylcholinesterase and possess potential antiamnestic activity. J. Complement. Integr. Med., 9. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The oil was observed to exhibit AChE inhibitory activity with an IC50 = 8 ± 0.6 mg/mL, which can be helpful in the treatment of AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [92] Christianah, 2018, Acetylcholinesterase inhibitory effect and characterization of the essential oil of Plectranthusa egyptiacus (Forssk.) C. Chr. growing in Nigeria, Med. Aromat. Plants
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: In vitro AChE inhibition by a sesquiterpene is sufficient to indicate potential for treating AD or improving learning and memory.
In the paper
“It was concluded that essential oil from flower buds of Hertia cheirifolia are rich in the anti-AChE activity of 1.86 mg Eq donepezil/g of essential oil due to the presence of Germacrene d.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [93] Rahali, 2017, Antioxidant, α-amylase, and acetylcholinesterase inhibitory activities of Hertiacheiri folia essential oils: Influence of plant organs and seasonal variation, Int. J. Food Prop.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: In vitro AChE inhibition by a sesquiterpene is sufficient to indicate potential for treating AD or improving learning and memory.
In the paper
“Furthermore, the bisabolane-type sesquiterpenoid derivatives from plants, such as (+)-(7S,9S)-ar-turmerol, (+)-(7S,9R)-ar-turmerol, (+)-(7S,9S)-dihydro-ar-turmerol, (+)-(7S,9R)-dihydro-ar-turmerol, (+)-(S)-ar-curcumene, and (+)-(S)-dihydro-ar-curcumene, were synthesized which were found to exhibit the acetylcholinesterase inhibitory activity in the order hydrocarbons <alcohols < ketones.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [90] Fujiwara, 2010, Acetylcholinesterase inhibitory activity of volatile oil from Peltophorum dasyrachis Kurz ex Bakar (yellow batai) and bisabolane-type sesquiterpenoids, J. Agric. Food Chem. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The β-asarone showed the maximum inhibition against AChE [95].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [95] Mukherjee, 2007, In vitro acetylcholinesterase inhibitory activity of the essential oil from Acorus calamus and its main constituents, Planta Medica source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The maximum activity was observed through the oxidation of the functional group at C9 position and C10–C11 structure of single-bond moiety, (+)-(S)-dihydro-ar-turmerone.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [90] Fujiwara, 2010, Acetylcholinesterase inhibitory activity of volatile oil from Peltophorum dasyrachis Kurz ex Bakar (yellow batai) and bisabolane-type sesquiterpenoids, J. Agric. Food Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 22
- It may state two separate claims as one. 62
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, it has been established that for the proper functioning of neurons, there should be a critical balance between the excitatory and inhibitory neurotransmitters [155,156,157,158].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Partly supportedcites [155] Kehrer, C., Maziashvili, N., Dugladze, T., and Gloveli, T. (2008). Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia. Front. Mol. Neurosci., 1. sourceExperimental — accuracy not yet measured
The Abstract describes a functional imbalance between excitatory and inhibitory transmission at the network level in schizophrenia. The NMDA-Hypofunction Theory section says loss of inhibition is likely to compromise network activity, but it does not establish a critical balance required for the proper functioning of individual neurons generally. Page numbers were not available in our copy. (LLM, conf=0.78)
- Not checked yetcites [156] Cummings, 2009, Alterations in cortical excitation and inhibition in genetic mouse models of Huntington’s disease, J. Neurosci. source
- Supportedcites [157] Sun, 2009, Imbalance between GABAergic and glutamatergic transmission impairs adult neurogenesis in an animal model of Alzheimer’s disease, Cell Stem Cell source
The Introduction says adult hippocampal neurogenesis is tightly regulated by the balance between GABAergic and glutamatergic inputs. It also links neurological deficits to aberrant excitatory and inhibitory activity, supporting the citing sentence’s broad point about neuronal function. (LLM, conf=0.86)
- Not checked yetcites [158] Gueli, 2013, Alzheimer’s disease: Amino acid levels and brain metabolic status, Neurol. Sci. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After data analysis, it was found that 12 compounds out of a total of 58 sesquiterpenes were reported to possess IC50 < 9 μM and can be considered as potential candidates for the improvement of learning and memory.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: An IC50 below 9 μM is an appropriate threshold for considering a sesquiterpene a potential candidate for improving learning and memory.
- Rests on an assumption: In vitro AChE inhibition by a sesquiterpene is sufficient to indicate potential for treating AD or improving learning and memory.
In the paper
“The leaf oil inhibited the AChE with IC50 = 85 µg/mL), On the other hand, stem oil showed the same inhibition with IC50 = 92 μg/mL. It indicated the leaf oil as a stronger inhibitor of AChE activity than the stem oil.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [91] Miyazawa, 2016, Chemical composition, aroma evaluation, and inhibitory activity towards acetylcholinesterase of essential oils from Gynura bicolor DC, J. Nat. Med. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The results clearly stated that the two isolated sesquiterpene lactones are the better inhibitors of AChE and BChEas compared to the reference, galanthamine (IC50 = 3 ± 0.2 μM and 47 ± 1 μM for AChE and BChE, respectively).”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.2. Sesquiterpene Lactones (SLs)
What the sources say
- Not checked yetcites [121] Elsebaia, 2018, Amberboin and lipidiol: X-ray crystalographic data, absolute configuration and inhibition of cholinesterase, Phytochem. Lett. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The IC50 values for alcoholic extract, essential oil, and two chief constituents of oil, i.e., β-asarone (11) and α-asarone (12) were reported as 182 ± 17 μg/mL, 11 ± 0.8 μg/mL, 3 ± 0.02 μM, and 46 ± 3 μM, respectively.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [95] Mukherjee, 2007, In vitro acetylcholinesterase inhibitory activity of the essential oil from Acorus calamus and its main constituents, Planta Medica source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Their IC50 (μM) for AChE inhibition was reported as 17 ± 0.01, 9 ± 0.2, 0.9 ± 0.02 and 1 ± 0.08 for sesquiterpene lactones Amberin (37), Amberbin-A (38), Amberbin-B (39), and Amberbin-C (40), respectively”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.2. Sesquiterpene Lactones (SLs)
What the sources say
- Not checked yetcites [124] Ibrahim, 2013, Acetyl and butyryl cholinesterase inhibitory sesquiterpene lactones from Amberboaramosa, Chem. Cent. J. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Di hydro derivative of turmerone is most potent with IC50 at 82 ± 0.2 μM, followed by volatile oil (IC50 = 83 ± 3 μg/mL).”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [90] Fujiwara, 2010, Acetylcholinesterase inhibitory activity of volatile oil from Peltophorum dasyrachis Kurz ex Bakar (yellow batai) and bisabolane-type sesquiterpenoids, J. Agric. Food Chem. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The crude extract with artemisinin and chrysosplenetin showed the inhibition of AChE activity by 72% and 80% at 0.1 mg/mL with IC50 of 104 µM and 73 µM.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [51] Duan, 2001, Immunosuppressive sesquiterpene alkaloids from Tripterygium wilfordii, J. Nat. Prod. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“M. myristica elicited stronger inhibition for AChE and BChE with IC50 of 205 ± 0.06 µg/mL and 178 ± 0.02 µg/mL with 79% and 89% inhibition”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [96] Olawuni, 2018, In vitro anti-cholinesterase and cognitive enhancing properties of essential oils from Piper nigrum L. and Monodora myristica (Gaertn) dunal, Int.J. Pharmacol. Toxicol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Long term exposure to chloroform extract improved the cognitive abilities while performing the behavioral tasks, increased the glutathione peroxidase (GSH-px) activities, decreased the acetylcholinesterase (AChE), malondialdehyde level (MDA), and β-amyloid (Aβ), and ultimately overturned the microglia activation, neuronal acidophilia degeneration, and cortex and hippocampus nuclear condensation.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [89] Shi, S.H., Zhao, X., Liu, B., Li, H., Liu, A.J., Wu, B., Bi, K.S., and Jia, Y. (2014). The effects of sesquiterpenes-rich extract of Alpinia oxyphylla Miq. on amyloid-𝛽-induced cognitive impairment and neuronal abnormalities in the cortex and hippocampus of mice. Oxidative Med. Cell. Longev. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It was observed that petroleum ether fraction was the only portion with AChE inhibitory potential with an IC50 of 37 mg/mL and the extract at a dose of 10 mg/kg, per orally. in mice considerably inverted the cognitive damages caused through the passive avoidance test (p < 0.05).”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.2. Sesquiterpene Lactones (SLs)
What the sources say
- Not checked yetcites [125] Patel, M.B., and Amin, D. (2012). Sphaeranthus indicus flower derived constituents exhibits synergistic effect against acetylcholinesterase and possess potential antiamnestic activity. J. Complement. Integr. Med., 9. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, the greenish-yellow color essential oil from the Salvia chionantha moderate AChE and BChE activity, i.e., 57 ± 2% and 41 ± 9%, respectively.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [94] Tel, 2010, Chemical composition of the essential oil and hexane extract of Salvia chionantha and their antioxidant and anticholinesterase activities, Food Chem. Toxicol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“whereas the P. nigrum oil inhibited the AChE (75%) and BChE (85%) with IC50 = 0.3 ± 0.02 µg/mL and 223 ± 0.002 µg/mL, respectively.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [96] Olawuni, 2018, In vitro anti-cholinesterase and cognitive enhancing properties of essential oils from Piper nigrum L. and Monodora myristica (Gaertn) dunal, Int.J. Pharmacol. Toxicol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, the Turmerone was analyzed to be a competitive inhibitor of AChE, whereas the dihydro derivative is the non-competitive inhibitor of this enzyme.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [90] Fujiwara, 2010, Acetylcholinesterase inhibitory activity of volatile oil from Peltophorum dasyrachis Kurz ex Bakar (yellow batai) and bisabolane-type sesquiterpenoids, J. Agric. Food Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Docking study of both compounds confirms the affinity of them towards the active sites of AChE, which indicated inhibitory activity against AChE at IC50 = 0.8 ± 0.03 µM and 0.5 ± 0.01 µM, respectively.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.2. Sesquiterpene Lactones (SLs)
What the sources say
- Not checked yetcites [121] Elsebaia, 2018, Amberboin and lipidiol: X-ray crystalographic data, absolute configuration and inhibition of cholinesterase, Phytochem. Lett. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Molecular docking scores predict binding affinity and AChE inhibitory activity.
In the paper
“Isolated compounds were found out to be 7-β-H-9-(10)-ene-11,12-epoxy-8-oxoeremophilane (5) (48 ± 2% inhibition at 50 mg/mL with IC50 = 275 ± 5 µM); 7α-H-9(10)-ene-11,12-epoxy-8-oxoeremophilane (6) with 31 ± 1% inhibition at 50 mg/mL with IC50 = 491 ± 4 µM); neopetasane (7) (62 ± 1% inhibition at 50 mg/mL with IC50 = 158 ± 4 µM).”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [87] Yang, 2014, Fragrant agarofuran and eremophilane sesquiterpenes in agarwood ‘Qi-Nan’ from Aquilaria sinensis, Phytochem. Lett. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The oil exhibited the AChE inhibitory potential with IC50 = 0.08 μg/mL, and this activity is attributed to the higher binding affinity of δ-cadinene and γ-cadinene (oil constituents) toward AChE as predicted by the docking score of –7.35 and –6.77, respectively [97].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [97] Holanda, 2020, Chemical composition and acetylcholinesterase inhibitory potential, in silico, of Myrciaria floribunda (H. West ex Willd.) O. Berg fruit peel essential oil, Ind. Crops Prod. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Molecular docking scores predict binding affinity and AChE inhibitory activity.
In the paper
“The compounds showed potential inhibitory activity against AChE (IC50 = 6 ± 0.03 μM and 1 ± 0.01 μM, respectively) and BChE (IC50 = 10 ± 0.24μM and 1 ± 0.19 μM, respectively) and established the plant as an emerging source in AD treatment.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.3. Miscellaneous Sesquiterpenes
What the sources say
- Not checked yetcites [129] Guvenalp, 2017, Cholinesterase inhibition and molecular docking studies of sesquiterpene coumarin ethers from Heptapteracilicica, Rec. Nat. Prod. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This compound exhibited significant butyrylcholinesterase activity with the IC50 = 68 μM when compared to the positive control, berberine (IC50 = 19 μM)”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [86] Jung, 2017, Sesquiterpenoids from the heartwood of Juniperus chinensis, Nat. Prod. Sci. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The results of the study showed that, in mice (APPswe/PS1E9 double-transgenic mouse) from middle and high dose groups, the AChT (acetylcholine transferase) activity had been improved in the brain tissues, while the AChE activity was significantly decreased causing an increase in the learning memory.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [88] Chen, 2016, Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo, Fitoterapia source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It was observed that the Volvalerenic acid K (8) improved the learning and memory abilities of mice, with IC50 = 0.16 µM in vitro.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [88] Chen, 2016, Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo, Fitoterapia source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: In vitro AChE inhibition by a sesquiterpene is sufficient to indicate potential for treating AD or improving learning and memory.
In the paper
“GC–MS analysis confirmed the presence of (E)-β-caryophyllene (31%) and bicycle germacrene (8%) as the major sesquiterpenoids from the Gynura bicolor DC leaves oil.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [91] Miyazawa, 2016, Chemical composition, aroma evaluation, and inhibitory activity towards acetylcholinesterase of essential oils from Gynura bicolor DC, J. Nat. Med. source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Pterosinone was reported to have mild inhibitory activity against acetyl and butyl cholinesterase enzymes with IC50 = 88 μM and 73 μM, respectively.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [85] Choi, 2018, (−)-Pteroside N and pterosinone, new BACE1 and cholinesterase inhibitors from Pteridium aquilinum, Phytochem. Lett. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AChE inhibition can help in maintaining the normal neurotransmission mediated by ACh in a healthy brain and could prevent the occurrence or slow down the progression of AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The poor cholinergic transmission at the synapse is considered to be one of the main reasons behind the progression and occurrence of this disorder.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the reduction in substrate concentration (AChE) by these inhibitors may affect the Aβ plaque formation and thus justify the use of ChEi as multi-target therapy for AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the light of the above-cited examples, various SLs (Figure 3) seem to be promising acetylcholinesterase inhibitors and helpful in improving the equilibrium between the excitatory and inhibitory potential of neurons and thus can be used in the possible management of AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.2. Sesquiterpene Lactones (SLs)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: In vitro AChE inhibition by a sesquiterpene is sufficient to indicate potential for treating AD or improving learning and memory.
None of the sources cited for this claim have been checked yet.
In the paper
“One of the chemotypes contained prenylated 4-hydroxycoumarins, which are toxic while the second one demonstrated therapeutic activity because of the presence of the SC ethers [127,128].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.3. Miscellaneous Sesquiterpenes
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It was concluded that the Alpinia oxyphylla ameliorates the learning and memory deficits by attenuating the oxidative stress, regulating the activation of the microglia, and degeneration of the neuronal acidophilia to reinforce the cholinergic functions.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
What the sources say
- Not checked yetcites [89] Shi, S.H., Zhao, X., Liu, B., Li, H., Liu, A.J., Wu, B., Bi, K.S., and Jia, Y. (2014). The effects of sesquiterpenes-rich extract of Alpinia oxyphylla Miq. on amyloid-𝛽-induced cognitive impairment and neuronal abnormalities in the cortex and hippocampus of mice. Oxidative Med. Cell. Longev. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: In vitro AChE inhibition by a sesquiterpene is sufficient to indicate potential for treating AD or improving learning and memory.
In the paper
“However, during the late stages of AD, the concentration of AChE decreases significantly (upto 45%) and BuChE is enhanced (upto 40–90%).”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
What the sources say
- Not checked yetcites [34] Arendt, 1992, Changes in acetylcholinesterase and butyrylcholinesterase in Alzheimer’s disease resemble embryonic development—A study of molecular forms, Neurochem. Int. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The essential oils containing sesquiterpenoids in comparison to the oils containing monoterpenoids were found to be more effective inhibitors of AChE activity, and the same is the case of mixtures where it ruled by monoterpenoids showed weaker inhibition than the mixture dominated by sesquiterpenoids.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.1. Sesquiterpenoids
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The ACh temporarily sequesters to the PAS through π-cation interaction between tryptophan on enzyme surface and quaternary amine of ACh.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Qi et al. [138] investigated the waste produced of Stigma maydis (maize) industry and isolated macrocarpene type sesquiterpenes compounds, namely Stigmene A and Stigmene B”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [138] Qi, 2018, Sesquiterpenes from stigma maydis (Zea mays) as a crop by-product & their potential neuroprotection and inhibitory activities of Aβ aggregation, Ind. Crops Prod. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The compounds and their AChE inhibitory potential of (IC50 in mg/mL) were found to be, 1-α,2-α,6,8α-tetraacetoxy-9-benzoyloxy-15-hydroxy agarofuran (52) (0.1 ± 0.01)”
- Also stated in: § 2.3. Miscellaneous Sesquiterpenes · plain
“1-α-acetoxy-6-β, 9-β-difuroyloxy-4-β-hydroxy- β-agarofuran (56) (0.4 ± 0.04), and 6-β,8-α-diacetoxy-9-β-furoyloxy-1-α-hydroxy-β-agarofuran(57) (0.3 ± 0.02).”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.3. Miscellaneous Sesquiterpenes
What the sources say
- Not checked yetcites [132] Astudillo, 2008, Inhibition of acetylcholinesterase activity by dihydro-β-agarofuran sesquiterpenes isolated from Chilean Celastraceae, Zeitschriftfür Naturforschung
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Also stated in: § 2.3. Miscellaneous Sesquiterpenes · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Later, a tetrahedral intermediate forms at CAS (at the deeper gorge of enzyme) by a reaction between the oxygen atom of the acetyl group of ACh and serine–histidine–glutamate residue of the enzyme through a covalent bond (Figure 1) [27,28].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Moreover, the active constituents of different essential oils such as farnesol, caryophyllene, and α-humulene significantly alter the various intracellular signaling parameters of inflammation [64].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
What the sources say
- Not checked yetcites [64] Andrade, 2015, Sesquiterpenes from essential oils and anti-inflammatory activity, Nat. Prod. Commun.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Halting the expression of this factor could reduce the production of β-amyloid (Aβ), which results in enhancement of cholinergic transmission at the synapse.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [144] Khalil, M.N., Choucry, M.A., El Senousy, A.S., Hassan, A., El-Marasy, S.A., El Awdan, S.A., and Omar, F.A. (2019). Ambrosin, a potent NF-κβ inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin. PLoS ONE, 14. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The enzyme mainly has two active sites, peripheral anionic site (PAS) and catalytic active site (CAS), for the binding of substrate, i.e., acetylcholine.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“and can enhance cognitive abilities and task switching functions rapidly in people suffering from AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.3. Miscellaneous Sesquiterpenes
What the sources say
- Not checked yetcites [133] Gul, 2019, Huperzine: A response to cognitive impairment and task switching deficits in patients with Alzheimer’s disease, J. Chin. Med. Assoc. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The potency level of bilobalide decreased with increasing GABA concentrations indicating a module of competitive antagonism.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [139] Huanga, 2003, Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant α1β2Ƴ2L GABAA receptors, Eur. J. Pharmacol. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This study indicated that the compound, nootkatone, might play a role as a potent therapeutic agent in treating AD and neuroinflammation via improvement in cholinergic transmission, clearing amyloid-β-peptide, and reducing oxidative stress.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [143] Wanga, 2018, Nootkatone, a neuroprotective agent from AlpiniaeOxyphyllae Fructus, improves cognitive impairment in lipopolysaccharide-induced mouse model of Alzheimer’s disease, Int. Immunopharmacol. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Findings from animal models of AD translate to humans.
In the paper
“It was observed that (%) decrease in Aβ aggregation was found more in the case of Stigmene A (82.9 ± 2.52%) and Stigmene B (70.1 ± 3.01%) when compared against a positive control, (69.8 ± 1.55%).”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [138] Qi, 2018, Sesquiterpenes from stigma maydis (Zea mays) as a crop by-product & their potential neuroprotection and inhibitory activities of Aβ aggregation, Ind. Crops Prod. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“PAS of AChE also reported to have an affinity toward the peptide of Aβ and the binding of this protein to enzyme promotes the amyloid fibrogenesis and converts the non-amyloidogenic form of Aβ to amyloidogenic form [29].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
What the sources say
- Not checked yetcites [29] Valenzuela, 2006, Dual binding site acetylcholinesterase inhibitors: Potential new disease-modifying agents for AD, J Mol. Neurosci. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The bilobalide IC50 (4.6 ± 0.5 μM) was reported as comparable to conventional antagonists of GABA receptors, picrotoxinin (2.4 ± 0.5 μM) and bicuculline (2.0 ± 0.1 μM) at α1β2γ2LGABAA receptors against GABA neurotransmitter.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [139] Huanga, 2003, Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant α1β2Ƴ2L GABAA receptors, Eur. J. Pharmacol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Sesquiterpene such as nerolidol was reported to reduce the damage to biomolecules (DNA, protein, lipids) due to elevated levels of reactive oxygen species in cells [62].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
What the sources say
- Not checked yetcites [62] Chan, W.K., Tan, L.T.H., Chan, K.G., Lee, L.H., and Goh, B.H. (2016). Nerolidol: A sesquiterpene alcohol with multi-faceted pharmacological and biological activities. Molecules, 21. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This natural compound showed reversible AChE inhibitory activity (IC50 = 22 μM)”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.3. Miscellaneous Sesquiterpenes
What the sources say
- Not checked yetcites [133] Gul, 2019, Huperzine: A response to cognitive impairment and task switching deficits in patients with Alzheimer’s disease, J. Chin. Med. Assoc. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This factor upregulates the expression of inflammatory cytokines and genes related to oxidative stress and BACE-1 (B-site APP Cleaving Enzyme), responsible for the production of β-amyloid [141,142].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [141] Shi, 2016, Upstream regulators and downstream effectors of NF-κB in Alzheimer’s disease, J. Neurol. Sci. source
- Not checked yetcites [142] Srinivasan, 2015, Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer’s disease and multiple sclerosis, Expert Opin. Ther. Targets source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Bilobalide amplified the levels of GABA in the cerebral cortex and hippocampus of mice; in addition, bilobalide also enhanced the neuronal excitability in hippocampus sites through the blockade of GABAergic neurotransmission, which is directly correlated with the learning and memory motions.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [139] Huanga, 2003, Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant α1β2Ƴ2L GABAA receptors, Eur. J. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Cholinesterase inhibitors (ChEi) such as galantamine and rivastigmine mainly bind to the peripheral site in a competitive and reversible manner and spare the ACh at the synapse and thus help in the improvement of cholinergic transmission [31,32].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
What the sources say
- Not checked yetcites [31] Heinrich, 2010, Galanthamine from galanthus and other amaryllidaceae—Chemistry and biology based on traditional use, Alkaloids Chem. Biol. source
- Not checked yetcites [32] Thomsen, 1990, Selective inhibition of human acetylcholinesterase by galanthamine in vitro and in vivo, Life Sci. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Huang et al. [3] investigation about the compound provided a marked base for the establishment of this compound as a reversible, selective, potent, and finely tolerated inhibitor of acetylcholinesterase which can considerably improve the memory and learning deficit in the persons suffering from Alzheimer’s disease.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 2. Review Methodology and Current Developments > 2.3. Miscellaneous Sesquiterpenes
What the sources say
- Not checked yetcites [3] Huang, 2013, Natural products as sources of new lead compounds for the treatment of Alzheimer’s disease, Curr. Top. Med. Chem. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The above-stated SLs compounds showed a considerable effect on oxidative stress and enhanced the memory power in animals that received Aβ-42 infusion.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [140] Amoah, 2015, Inhibitory effect of sesquiterpene lactones and these squiterpene alcohol aromadendrane-4β, 10α-diol on memory impairment in a mouse model of Alzheimer, Eur. J. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This study confirmed that ARD, HDS, and PDA, the constituents of H. brasiliense, are efficient in inhibiting the cognitive deficits of animals and may be used in treating AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [140] Amoah, 2015, Inhibitory effect of sesquiterpene lactones and these squiterpene alcohol aromadendrane-4β, 10α-diol on memory impairment in a mouse model of Alzheimer, Eur. J. Pharmacol. source
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Findings from animal models of AD translate to humans.
In the paper
“Hence, this could be the possible rationale for the inclusion of these herbs as food supplements for AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 4. Market Formulations to Alleviate AD Symptoms
What the sources say
- Not checked yetcites [41] Mancuso, 2012, Natural substances and Alzheimer’s disease: From preclinical studies to evidence based medicine, Biochimica Biophysica Acta (BBA) Mol. Basis Dis. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
None of the sources cited for this claim have been checked yet.
In the paper
“In recent years, the treatment paradigm for AD is moving toward alleviating the inflammation associated with the development of this disease [163,164].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [163] Karunaweera, 2015, Plant polyphenols as inhibitors of NF-κB induced cytokine production—A potential anti-inflammatory treatment for Alzheimer’s disease?, Front. Mol. Neurosci. source
- Not checked yetcites [164] Carrillo, 2016, The roles of inflammation and immune mechanisms in Alzheimer’s disease, Alzheimers Dement. Transl. Res. Clin. Interv. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The above-cited compounds may potentially be used as moieties in the building of a better multi-target anti-AD drug for possible prevention and treatment of AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: In vitro AChE inhibitory activity of sesquiterpenes predicts clinical efficacy in Alzheimer's disease.
- Rests on an assumption: Findings from animal models of AD translate to humans.
In the paper
“However, mere possession of significant IC50 (for AChE) should not be the criteria for the selection of a compound for anti-Alzheimer potential. Because the evaluation of cholinesterase inhibition potential of compounds, with carbonyl group, by in vitro methods such as Ellman reagent could produce the false positive [149].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [149] Rhee, 2003, Qualitative determination of false-positive effects in the acetylcholinesterase assay using thin layer chromatography, Phytochem. Anal. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The extracts of these herbs are reported to contain sesquiterpenes such asBilabolide and Jatanolides/Jatamansone as main ingredients.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 4. Market Formulations to Alleviate AD Symptoms
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Nowadays, the paradigm for AD management has shifted toward the management of neuroinflammation by novel compounds.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 6. Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Critically analyzing the literature, it has been found that 12 compounds out of total 58 sesquiterpenes were reported to possess IC50 < 9 µM and can be considered as potential candidates for the improvement of learning and memory.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It was concluded that memory enhancement could be a result of the facilitation of cholinergic transmission in the brain becausethe extract showed potential against scopolamine-induced impairment.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [146] Joshi, 2006, Nardostachysjatamansi improves learning and memory in mice, J. Med. Food source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recent clinical studies have shown that the AChE inhibitors significantly alleviate Alzheimer’s symptoms and also lessen the rates of related mortality [154].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [154] Castells, 2017, Discontinuation, efficacy, and safety of cholinesterase inhibitors for Alzheimer’s disease: A meta-analysis and metaregression of 43 randomized clinical trials enrolling 16 106 patients, Int. J. Neuropsychopharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Preclinical studies prove the neuroprotective role of these herbs due to reduction in neuronal damage by free radicals and restoration of calcium homeostasis [41].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 4. Market Formulations to Alleviate AD Symptoms
What the sources say
- Not checked yetcites [41] Mancuso, 2012, Natural substances and Alzheimer’s disease: From preclinical studies to evidence based medicine, Biochimica Biophysica Acta (BBA) Mol. Basis Dis. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Hence, the exploration of novel sesquiterpenes for the expression of NF-κβp65 could be a target for scientists for the management of neurodegenerative disorderssuch asAD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [163] Karunaweera, 2015, Plant polyphenols as inhibitors of NF-κB induced cytokine production—A potential anti-inflammatory treatment for Alzheimer’s disease?, Front. Mol. Neurosci. source
- Not checked yetcites [164] Carrillo, 2016, The roles of inflammation and immune mechanisms in Alzheimer’s disease, Alzheimers Dement. Transl. Res. Clin. Interv. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The Jatanolides, Jatamansone, and Jatamansic acid are the main sesquiterpene alkaloids isolated from the Nardostachys jatamansi, which are helpful in cognitive disorders as they improve the learning and memory supremacy of a person [145,146].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, the extract also reversed the aging-related amnesia proving it as a beneficial memory restorative constituent in elderly individuals with dementia.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [146] Joshi, 2006, Nardostachysjatamansi improves learning and memory in mice, J. Med. Food source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Findings from animal models of AD translate to humans.
None of the sources cited for this claim have been checked yet.
In the paper
“It is evident that β-amyloid (Aβ) could also enhance the translation of GABAA receptor (at α6 subunit) by the phosphorylation of mTOR and ERK in the cerebellum of experimental mice [28,159,160], and hence an increase in inhibitory transmission at synapse affects the learning and memory process [161].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [28] Li, 2016, Implications of GABAergic neurotransmission in Alzheimer’s disease, Front. Aging Neurosci. source
- Not checked yetcites [159] Zhan, 2014, A β40 modulates GABAA receptor α6 subunit expression and rat cerebellar granule neuron maturation through the ERK/mTOR pathway, J. Neurochem. source
- Not checked yetcites [160] Schweizer, 2003, The γ2 subunit of GABAA receptors is required for maintenance of receptors at mature synapses, Mol. Cell. Neurosci. source
- Not checked yetcites [161] Palop, 2007, Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease, Neuron source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, it can also be concluded that the use of suggested herbs as nutraceuticals/dietary supplements could significantly alleviate the symptoms of AD and prove highly beneficial for mankind.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 6. Conclusions
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds. It may state two separate claims as one.
- Rests on an assumption: In vitro AChE inhibitory activity of sesquiterpenes predicts clinical efficacy in Alzheimer's disease.
- Rests on an assumption: Findings from animal models of AD translate to humans.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, the pathophysiology of Alzheimer’s disease includes the degeneration of neurons at vulnerable spots in the brain such as thehippocampus and cortex region [150,151,152].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [150] Selkoe, 1998, The cell biology of β-amyloid precursor protein and presenilin in Alzheimer’s disease, Trends Cell Biol. source
- Not checked yetcites [151] Hu, J., Liu, C.C., Chen, X.F., Zhang, Y.W., Xu, H., and Bu, G. (2015). Opposing effects of viral mediated brain expression of apolipoprotein E2 (apoE2) and apoE4 on apoElipidation and Aβ metabolism in apoE4- targeted replacement mice. Mol. Neurodegener., 10. source
- Not checked yetcites [152] Stancu, I.C., Vasconcelos, B., Terwel, D., and Dewachter, I. (2014). Models of β-amyloid induced Tau-pathology: The long and “folded” road to understand the mechanism. Mol. Neurodegener., 9. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Moreover, the Aβ application also increases the concentration of AChE in cultures and the simultaneous feeding of experimental animals with farnesene (a sesquiterpene) significantly reduces the enzyme concentration [162].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [162] Mehmet, E.A., Hasan, T., and Adil, M. (2020). In vitro neuroprotective effects of farnesene sesquiterpene on Alzheimer’s disease model of differentiated neuroblastoma cell line. Int. J. Neurosci., 1–10.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The described sesquiterpenes are supposed to act as novel compounds for the researchers willing to find some other alternatives than the existing ones for the possible treatment of neurodegenerative diseases, i.e., Alzheimer’s disease.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: In vitro AChE inhibitory activity of sesquiterpenes predicts clinical efficacy in Alzheimer's disease.
- Rests on an assumption: Findings from animal models of AD translate to humans.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the sesquiterpenes such as Farnesene, Bilabolide, and Jatamansone were found to exert a significant effect on different AD targets such as Aβ plaque, neuron excitability, and oxidative stress.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 6. Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Joshi and Parle [146] studied the ethanolic extract of Nardostachys jatmansi in mice to evaluate its memory enhancing property and found it capable of significantly improving the learning and memory at a dose of 200 mg/kg and also reversed the scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) induced amnesia.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 3. Sesquiterpenes for Alternate AD Targets
What the sources say
- Not checked yetcites [146] Joshi, 2006, Nardostachysjatamansi improves learning and memory in mice, J. Med. Food source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition, the large number of formulations having extracts of Ginkgo biloba and Nardostachys jatamansi are mentioned in Table 2 and mainly prescribed as a nutraceutical for delaying symptoms (such as amnesia) of AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 4. Market Formulations to Alleviate AD Symptoms
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Furthermore, the Galliardin, a guainolide-type sesquiterpene, possesses good AChE inhibitory potential, but it also has significant cytotoxic properties [123].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [123] Hajimehdipoor, 2014, Natural sesquiterpene lactones as acetylcholinesterase inhibitors, Anais da Academia Brasileira de Ciências source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In spite of the availability of bulk knowledge related to this progressive disorder, we have access only to symptomatic treatment, not to a complete cure.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 6. Conclusions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, to be a potential candidate for Alzheimer’s therapy, a compound must pass the blood-brain barrier (BBB) and should be sufficiently bioavailable in the affected area of the brain.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Sesquiterpenes such asBilabolide could help in achieving the equilibrium of excitatory and inhibitory transmission because it was reported as an antagonist to α1β2γ21 subunits of GABAA receptors that enhanced the excitability of neurons in hippocampal slices [139].”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 5. Final Remarks and Future Prospects
What the sources say
- Not checked yetcites [139] Huanga, 2003, Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant α1β2Ƴ2L GABAA receptors, Eur. J. Pharmacol. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Moreover, Huperzine A is the only sesquiterpene alkaloid that is clinically established as an AChE inhibitor and receivedthe approval of USFDA to manage AD.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 4. Market Formulations to Alleviate AD Symptoms
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper relies on this without support.
An IC50 below 9 μM is an appropriate threshold for considering a sesquiterpene a potential candidate for improving learning and memory.
“After data analysis, it was found that 12 compounds out of a total of 58 sesquiterpenes were reported to possess IC50 < 9 μM and can be considered as potential candidates for the improvement of learning and memory.”
The paper relies on this without support.
In vitro AChE inhibition by a sesquiterpene is sufficient to indicate potential for treating AD or improving learning and memory.
“The outcome of the review clearly states that sesquiterpenes (such as amberboin, lipidiol, etc.) from herbs could offer fresh, functional compounds for possible prevention and treatment of AD.”
The paper relies on this without support.
Molecular docking scores predict binding affinity and AChE inhibitory activity.
“Docking study of both compounds confirms the affinity of them towards the active sites of AChE, which indicated inhibitory activity against AChE at IC50 = 0.8 ± 0.03 µM and 0.5 ± 0.01 µM, respectively.”
The authors state this as an assumption.
AChE lyses acetylcholine at a very fast rate, up to 10,000 molecules per second.
“AChE is assumed to lyse the acetylcholine at a very fast rate (up to 10,000 molecules per second).”
The paper relies on this without support.
Structural features such as double bonds at C1–10, C3–4, and C11–12 with a ketone group at C2 increase AChE inhibitory activity.
“this property might be attributed to its structural configuration where two double bonds at C1–10 and C3–4 and C11–12with a ketone group at C2 are supposed to increase the inhibitory activity.”
The paper relies on this without support.
In vitro AChE inhibitory activity of sesquiterpenes predicts clinical efficacy in Alzheimer's disease.
“Therefore, it was observed that the agarofuran compounds isolated from the aerial parts of Maytenus disticha and seeds of Maytenus boaria have good signs for their further use in the treatment of AD or as acetylcholinesterase inhibitors.”
The paper relies on this without support.
Agarofuran compounds have low toxicity.
“It was concluded from the above-cited examples that the selective inhibitory potential of agarofuran compounds for AChE and low toxicity might lead to the development of novel therapeutic agents for possible AD management.”
The paper relies on this without support.
Findings from animal models of AD translate to humans.
“This study confirmed that ARD, HDS, and PDA, the constituents of H. brasiliense, are efficient in inhibiting the cognitive deficits of animals and may be used in treating AD.”
The paper relies on this without support.
AChE inhibition is a valid therapeutic strategy that delays AD progression and relieves AD-associated symptoms.
“Improvement in cholinergic transmission by inhibiting the AChE was considered to delay the AD progression and relieve the AD-associated symptoms.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Arya et al. [168] carried out an analysis of lipidiol and amberboin sesquiterpenes belonging to an important category of terpenoids found mainly in herbaceous plants and capable of causing inhibition in cholinesterases with an IC50 < 9 M, being potential candidates for learning and memory improvement in patients with AD, and possible preventive treatment for this neurodegenerative pathology.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [168]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > Abstract
“World Health Organization (WHO) also revealed that the prevalence of this disease will enhance (upto double) significantly upto 2030.”
§ Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy > 1. Introduction
“The World Health Organization (WHO) has estimated that there will be more than 100% growth of this number by the end of the year 2030.”
Citations
Cites
A new and rapid colorimetric determination of acetylcholinesterase activity
Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961) · Biochemical Pharmacology · doi:10.1016/0006-2952(61)90145-9 · Cited by 27,221
Molecular properties that influence the oral bioavailability of drug candidates
Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020017n · Cited by 8,420
The cholinergic hypothesis of geriatric memory dysfunction
Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982) · Science · doi:10.1126/science.7046051 · Cited by 5,545 · cited 1×
“It has also been observed that cholinergic neurons are highly damaged in the forebrain during the progression of AD [16,17].”
BackgroundThe role of acetylcholine in learning and memory
Hasselmo, M. E. (2006) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.09.002 · Cited by 1,693
Palop, J. J., Chin, J., Roberson, E. D., Wang, J., Thwin, M. T., Bien-Ly, N., Yoo, J., Ho, K. O., Yu, G.-Q., Kreitzer, A., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.025 · Cited by 1,653
Anti-infective potential of natural products: How to develop a stronger in vitro ‘proof-of-concept’
Cos, P., Vlietinck, A. J., Berghe, D. V., & Maes, L. J. R. M. (2006) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2006.04.003 · Cited by 1,615 · cited 1×
“penes+cholinesterase+inhibitors” in the surveyed time frame (2010–2020) [75].”
BackgroundMolecular and cellular biology of cholinesterases
Massoulié, J., Pezzementi, L., Bon, S., Krejci, E., & Vallette, F.-M. (1993) · Progress in Neurobiology · doi:10.1016/0301-0082(93)90040-y · Cited by 1,214
Acetylcholinesterase: Enzyme structure, reaction dynamics, and virtual transition states
Quinn, D. M. (1987) · Chemical Reviews · doi:10.1021/cr00081a005 · Cited by 1,072
Biosynthesis and Biological Functions of Terpenoids in Plants
Tholl, D. (2015) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2014_295 · Cited by 991
The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease
Selkoe, D. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01363-4 · Cited by 862
Cited by
Sorted by citations
Items 101–109 of 109
A Possible Treatment for Memory Loss and Associated Disorders
Marsh, R. W. (2026) · Journal of Neurology Research Review & Reports · doi:10.47363/jnrrr/2026(8)248
Targeting oxidative stress and neurodegeneration: the role of Putranjiva roxburghii in Alzheimer’s
Bhardwaj, V., Goel, F., & Rajput, M. S. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02200-x
Neggaz, S., Kořínek, M., El-Shazly, M., et al. (2026) · Journal of Food Measurement & Characterization · doi:10.1007/s11694-026-04237-6
“Previous studies, such as that by Arya et al. (2012) [86], have demonstrated that sesqui-terpenes like spathulenol and globulol exhibit significant permeability in microbial cells.”
Zhang, J., Jiang, W., Xu, Z., et al. (2026) · The Analyst · doi:10.1039/d6an00156d
Calva, J., & Ramírez, J. (2026) · Plants · doi:10.3390/plants15101447 · Cited by 1
“…in AChE inhibition through non-covalent interaction with the peripheral anionic site (PAS) and the catalytic active site (CAS) of the enzyme [28,29], trans -muurola-4(14),5-diene (27.85%), a bicyclic sesquiterpene of the muurolane skeleton, has not been directly studied for AChE inhibition;…”
InfluentialJadhav, M. M., Kulkarni, A., Mane, S. M., et al. (2026) · BioNanoScience · doi:10.1007/s12668-026-02605-6
Chemical profiling and antimicrobial activity of essential oils from Blumea mollis (D. Don) Merr.
Bisht, B. S., Vishwakarma, M. C., & Arya, D. (2026) · Journal of Essential Oil Bearing Plants · doi:10.1080/0972060x.2026.2680691
Aouidene, M., Bouabidi, N., Jebri, D., Znati, M., Jalouli, M., Othman, M., & Jannet, H. B. (2026) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2026.146848
Liang, H., Wang, J.-Q., Zhou, H., et al. (2026) · Talanta · doi:10.1016/j.talanta.2026.130527
Metadata
- Authors
- Arya, A., Chahal, R., Rao, R., Rahman, M. H., Kaushik, D., Akhtar, M. F., Saleem, A., Khalifa, S. M. A., El-Seedi, H. R., Kamel, M., Albadrani, G. M., Abdel-Daim, M. M., & Mittal, V.
- Affiliations
- Maharshi Dayanand University (IN)
- Guru Jambheshwar University of Science and Technology (IN)
- Yonsei University (KR)
- Riphah International University (PK)
- Government College University, Faisalabad (PK)
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden
- Jiangsu University (CN)
- Cairo University (EG)
- Princess Nourah bint Abdulrahman University (SA)
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
- Corresponding author
- Mittal, Vineet
- ORCID
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2021-02-25
- Volume
- 11
- Issue
- 3
- Pages
- 350
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC7996600
- OpenAlex
- W3133291488
- Semantic Scholar
- c774a72404128cca19bd1f2f1d48e529250d165d
- Cited by
- 111
- References
- 167
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 18 · 2023: 25 · 2022: 26 · 2021: 9
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deanship of Scientific Research at Princess Nourah bint Abdulrahman University (Fast-track Research Funding Program.)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- sesquiterpenes, acetylcholinesterase inhibitors, Alzheimer's disease, cholinergic neurotransmission, anticholinesterase activity, terpenoids, learning and memory, natural product drug candidates
- MeSH terms
- Rivastigmine, Acetylcholinesterase, Alzheimer Disease, Animals, Cholinesterase Inhibitors, Galantamine, Humans, Sesquiterpenes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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