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Cited by 69Medicinal Plants and NeuroprotectionCholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatments

Alpha-terpinyl acetate: A natural monoterpenoid from Elettaria cardamomum as multi-target directed ligand in Alzheimer’s disease

Open access
Chowdhury, Suman, Kumar, Suresh·2020·Journal of Functional Foods
DOI 10.1016/j.jff.2020.103892
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Abstract

Alzheimer's disease (AD), is a multifactorial neurodegenerative disorder characterized by memory loss and cognitive deficit. Various drug targets implicated in AD are β-amyloid (Aβ) peptides, cholinesterase enzymes, and free radicals. Plants derived phytoconstituents provides a vast pool of diverse compounds as a source of novel drugs. In view of this, the Elettaria cardamomum L. Maton. extract and its active phytoconstituents alpha-terpinyl acetate were used to study the disease-modifying effects in AD. The present study successfully demonstrated for the first time the therapeutic potential of alpha-terpinyl acetate as it binds to multiple drug targets, resulting in inhibition of acetylcholinesterase (AChE) enzyme, butyrylcholinesterase (BuChE) enzyme, reduced Aβ induced neurotoxicity, reduced hydrogen peroxide induced oxidative stress, antioxidant capacity, and anti-amyloidogenic property. In conclusion, alpha-terpinyl acetate can be used as a suitable lead to develop a molecule that might have multi-targeted directed ligand (MTDL) potential and disease amelioration effects in AD.

AI snapshot

Written from the paper’s full text.

TL;DR

Alpha-terpinyl acetate, the major phytoconstituent of *Elettaria cardamomum* seed ethanolic extract, was tested in vitro and in silico and showed multi-target activity against cholinesterases, Aβ₁₋₄₂-induced toxicity, H₂O₂-induced oxidative stress, and HEWL fibril formation. The authors propose it as a lead for multi-target-directed ligand development in Alzheimer’s disease.

Key findings

  • GC-MS identified 88 peaks in the ethanolic seed extract; alpha-terpinyl acetate was the most abundant constituent at 46.12% area (retention time 14.499), followed by arachidic alcohol at 9.71%.
  • Alpha-terpinyl acetate inhibited AChE with IC₅₀ 54.72 ± 10.03 μM and BuChE with IC₅₀ 47.46 ± 2.03 μM; the crude extract was stronger (AChE IC₅₀ 27.07 ± 1.33 μg/ml; BuChE IC₅₀ 86.44 ± 4.59 μg/ml), while donepezil showed IC₅₀ 0.148 ± 0.01 μM and 5.77 ± 0.02 μM, respectively.
  • In PC12 cells, alpha-terpinyl acetate at 1 μM gave 97.07 ± 13.09% viability against H₂O₂-induced oxidative stress and up to 75% viability against Aβ₁₋₄₂-induced toxicity.
  • Alpha-terpinyl acetate at 50 μM inhibited HEWL fibril formation by 51.08 ± 1.18% in the ThT assay (tannic acid: 68 ± 3.21%); docking scores were −5.15 for AChE and −2.83 for BuChE versus donepezil −10.88 and −6.81, and ADMET analysis showed no Lipinski violations, 100% human oral absorption, CNS activity, and BBB penetration.

Methods

  • In vitro: ethanolic extract of *E. cardamomum* seeds was analyzed by GC-MS; Ellman’s assay measured AChE/BuChE inhibition and kinetics; FRAP and DPPH assays measured antioxidant capacity; PC12 cells were used for MTT viability assays against H₂O₂ and Aβ₁₋₄₂; HEWL fibril formation was assessed by ThT fluorescence, Congo red binding, intrinsic fluorescence, and TEM.
  • In silico: molecular docking was performed against AChE (PDB 4EY6), BuChE (PDB 1P0M), and HEWL (PDB 6LYZ); ADMET/pharmacokinetic properties were predicted using QikProp and Lazar.
  • Statistics: experiments were performed in triplicates; data are mean ± SD; student t-test was used with p < 0.05 considered significant.

Limitations

  • The paper does not state a dedicated limitations section.
  • Evident from the text: all experimental evidence is in vitro or in silico, with no in vivo Alzheimer’s disease animal model or human data; neuroprotection was tested in PC12 rat pheochromocytoma cells, and amyloid inhibition used HEWL as a generic model rather than Aβ or tau.
  • Evident from the text: alpha-terpinyl acetate showed low antioxidant activity, weaker cholinesterase binding than donepezil, and the crude extract’s stronger cholinesterase inhibition may reflect other phytoconstituents; in vivo bioavailability, safety, and disease-modifying effects remain untested.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jff.2020.103892

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 18 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Alpha-terpinyl acetate reduces Aβ-induced neurotoxicity.

    “reduced Aβ induced neurotoxicity”
    Quote in the paperSubstantial claim
  • Findingown data

    Alpha-terpinyl acetate has anti-amyloidogenic property.

    “anti-amyloidogenic property”
    Quote in the paperSubstantial claim
  • Findingown data

    Alpha-terpinyl acetate reduces hydrogen peroxide-induced oxidative stress in PC12 cells, with 97.07 ± 13.09% viability at 1 μM compared to H2O2-only control.

    “MTT assay showed alpha-terpinyl acetate significantly protected PC12 cells against H 2 O 2 induced oxidative stress, at 1 µM final concentration, the percentage of viability observed was 97.07 ± 13.09% as compared to the negative control (H 2 O 2 only) (Fig. 3A).”
    • Also stated in: § Abstract · plain
      “reduced hydrogen peroxide induced oxidative stress”
    Quote in the paperSubstantial claim
  • Findingown data

    Alpha-terpinyl acetate binds to multiple drug targets implicated in Alzheimer's disease.

    “The present study successfully demonstrated for the first time the therapeutic potential of alpha-terpinyl acetate as it binds to multiple drug targets, resulting in inhibition of acetylcholinesterase (AChE) enzyme, butyrylcholinesterase (BuChE) enzyme, reduced Aβ induced neurotoxicity, reduced hydrogen peroxide induced oxidative stress, antioxidant capacity, and anti-amyloidogenic property.”
    Quote in the paperSubstantial claim
  • Findingown data

    Alpha-terpinyl acetate showed low antioxidant potential in FRAP and DPPH assays.

    “Both the extract and alpha-terpinyl acetate showed low antioxidant potential due to low Fe 3+ reducing ability and DPPH percentage scavenging activity (Table 2).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Findingown data

    Alpha-terpinyl acetate inhibits acetylcholinesterase (AChE), with 69% inhibition at 127 μM and IC50 54.72 ± 10.03 μM.

    “Alpha-terpinyl acetate at 127 μM final concentration showed inhibition of 69% with an IC 50 value of 54.72 ± 10.03 μM for AChE as compared to control (p < 0.05).”
    • Also stated in: § Abstract · plain
      “inhibition of acetylcholinesterase (AChE) enzyme”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Alpha-terpinyl acetate inhibits butyrylcholinesterase (BuChE), with 68% inhibition at 127 μM and IC50 47.46 ± 2.03 μM.

    “Alpha-terpinyl acetate at 127 μM final concentration showed inhibition of 68% inhibition with an IC 50 value of 47.46 ± 2.03 μM as compared to control (p < 0.05) for BuChE.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The ethanolic extract of E. cardamomum at 200 μg/ml showed 86% inhibition of AChE with IC50 27.07 ± 1.33 μg/ml.

    “The ethanolic extract of E. cardamomum at 200 μg/ml final concentration showed significant inhibition of 86% with an IC 50 value of 27.07 ± 1.33 μg/ml for AChE as compared to control (p < 0.05).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the Congo red binding assay, HEWL at 50 μM shows increased absorbance and a redshift compared to Congo red alone.

    “HEWL solution spectrum at 50 μM concentration showed an increase in the absorbance as well as a redshift as compared to the CR alone spectrum.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The ethanolic extract of E. cardamomum at 200 μg/ml showed 88% inhibition of BuChE with IC50 86.44 ± 4.59 μg/ml.

    “For the BuChE enzyme, the ethanolic extract of E. cardamomum seed at 200 μg/ml final concentration showed 88% inhibition with an IC 50 value of 86.44 ± 4.59 μg/ml as compared to control (p < 0.05).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both E. cardamomum extract and alpha-terpinyl acetate showed low antioxidant potential in FRAP and DPPH assays.

    “Both the extract and alpha-terpinyl acetate showed low antioxidant potential due to low Fe 3+ reducing ability and DPPH percentage scavenging activity (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In TEM, HEWL control incubated for 24 h exhibits predominant fibrillary structures, whereas alpha-terpinyl acetate (50 μM) shows shorter aggregates.

    “The control sample of HEWL fibrils, incubated for 24 h exhibited predominant fibrillary structures, whereas in the presence of alpha-terpinyl acetate (50 μM) showed shorter aggregates suggesting inhibition of HEWL fibril formation (Fig. 4D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Alpha-terpinyl acetate shows mixed inhibition for BuChE; Vmax decreases and Km increases with increasing concentration.

    “For BuChE, mixed inhibition was observed.Vmax decreases and Km increases with increasing concentration of alpha-terpinyl acetate (Fig. 2B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Alpha-terpinyl acetate does not violate any Lipinski's rule of five and is predicted non-carcinogenic and non-mutagenic.

    “The ADMET analysis revealed that alpha-terpinyl acetate did not violate any Lipinski's rule of five, and is non-carcinogenic and nonmutagenic.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Alpha-terpinyl acetate has docking scores of -5.15 for AChE and -2.83 for BuChE, compared to donepezil -10.88 and -6.81, respectively.

    “The alpha-terpinyl acetate showed a docking score of -5.15 and -2.83 as compared to donepezil -10.88 and -6.81 for AChE and BuChE enzymes, respectively (Table 3a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Alpha-terpinyl acetate hydrophobically interacts with AChE residues including catalytic site residues, Gly120/Gly121 of the oxyanion hole, Trp86 at the quaternary ammonium binding locus, and Tyr124 of the PAS region.

    “The alpha-terpinyl acetate was seen hydrophobically interacting with the above-mentioned residues.Alpha-terpinyl acetate also interacted with Gly120 and Gly121, the residues of oxyanion hole, Trp86 residue at quaternary ammonium binding locus and Tyr124 residues of PAS region (Fig. 5A and B) (Johnson & Moore, 2006).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Alpha-terpinyl acetate shows hydrogen bonding with Asn59 and Try63 of HEWL, where Try63 is in the amyloidogenic region.

    “The alpha-terpinyl acetate showed hydrogen bonding with Asn59 and Try63, where the Try63 is the residue of the amyloidogenic region.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ADMET analysis predicted 100% human intestinal absorption, active CNS activity, and blood-brain barrier penetration for alpha-terpinyl acetate.

    “With 100% human intestinal absorption, active CNS activity, and blood-brain barrier (BBB) penetration, alpha-terpinyl acetate will be able to reach molecular targets in the AD patient's brain.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Alpha-terpinyl acetate has potential as a multi-targeted directed ligand and disease amelioration effects in AD.

    “In conclusion, alpha-terpinyl acetate can be used as a suitable lead to develop a molecule that might have multi-targeted directed ligand (MTDL) potential and disease amelioration effects in AD.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: In vitro and in silico results are predictive of in vivo therapeutic effects in AD.

  • May combine two claims.

    Premisecitation

    AD involves multiple pathological factors including Aβ fibril formation, oxidative stress, tau protein aggregation, and reduced acetylcholine levels.

    “The leading cause of AD has not yet fully understood, it involves multiple pathological factors such as β-amyloid (Aβ) fibril formation, oxidative stress, tau protein aggregation, and reduced levels of acetylcholine (Jellinger, 2003).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jellinger, 2003

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Aβ-induced toxicity is caused by abnormal mitochondrial activity, synaptic transmission, and axonal transport, as Aβ disrupts membranes and generates oxidative stress.

    “Aβ induced toxicity is caused due to abnormal mitochondrial activity, synaptic transmission, and axonal transport as Aβ causes disruption of membranes and the generation of oxidative stress (Rauk, 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rauk, 2008 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The plant material was identified by a botanist and a voucher specimen (USBT/SK/SC1) was stored.

    “A Botanist identified the plant material.A voucher specimen (USBT/SK/SC1) was stored at GGSIP University, Dwarka.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Previous studies have reported alpha-terpinyl acetate as the active and most abundant phytoconstituent of cardamom.

    “Previous studies have also reported alpha-terpinyl acetate as the active and most abundant phytoconstituents of cardamom (Husain & Ali, 2014;Okugawa et al., 1988).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Husain & Ali, 2014

      Not checked in the free run.

    • cites Okugawa et al., 1988

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Spices have an important role in traditional medicine like Ayurveda and Unani medicine.

    “Spices have shown to be an important role in traditional medicine like Ayurveda and Unani medicine (Ahire & Kashikar, 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ahire & Kashikar, 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The theory of Shad Rasa in Ayurveda emphasizes the importance of phytoconstituents from spices in ameliorating neurological disease.

    “The theory of Shad Rasa in Ayurveda has emphasized the importance of phytoconstituents from spices in ameliorating neurological disease (Aggarwal & Kunnumakkara, 2009;Mirmosayyeb et al., 2017).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Aggarwal & Kunnumakkara, 2009

      Not checked in the free run.

    • cites Mirmosayyeb et al., 2017 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    All experiments were performed in triplicates, and data are mean ± SD; statistical significance was assessed by student t-test with p<0.05 considered significant.

    “All the experiments were performed in triplicates, and the data represent mean ± SD.For the comparison between the two groups, student t-test was applied using GraphPad software, p < 0.05 was considered significant, and p < 0.01 was considered very significant, and p < 0.001 was extremely significant.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A previous review has discussed the role of monoterpenes in mechanisms related to Aβ formation, aggregation, and clearance, τ-protein phosphorylation, and aggregation.

    “A previous review on monoterpenes has already discussed the role of monoterpenes in mechanisms related to Aβ formation, aggregation, and clearance, τ-protein phosphorylation, and aggregation (Habtemariam, 2018).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Habtemariam, 2018 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The docking protocol was validated by re-docking the cocrystallized ligands to the binding site of the target enzyme, as described in a previous study.

    “Validation of docking protocol was done as described in the previous study, by re-docking the cocrystallized ligands to the binding site of the target enzyme (Kumar et al., 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kumar et al., 2017 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    E. cardamomum possesses many pharmacological activities such as antioxidant, anti-inflammatory, antibacterial, anticancer, anti-fungal and insecticidal activity.

    “The E. cardamomum possesses many pharmacological activities such as antioxidant, anti-inflammatory antibacterial, anticancer, anti-fungal and insecticidal activity (Ashokkumar, Murugan, Dhanya, & Warkentin, 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ashokkumar, Murugan, Dhanya, & Warkentin, 2019

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Donepezil, used as positive control, showed IC50 0.148 ± 0.01 μM for AChE and 5.77 ± 0.02 μM for BuChE, and inhibited AChE 64% at 0.6 μM and BuChE 66% at 20 μM.

    “Donepezil was used as a positive control, a known inhibitor of AChE and BuChE enzymes, which showed a significant IC 50 value of 0.148 ± 0.01 μM and 5.77 ± 0.02 μM, respectively.At 0.6 μM final concentration, donepezil showed 64% inhibition of AChE and at 20 μM final concentration, it showed 66% inhibition for BuChE.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The higher inhibition by the crude extract might be due to the presence of other phytoconstituents.

    “The ethanolic extract of E. cardamomum showed high percentage inhibition for AChE/BuChE enzyme as compared to alpha-terpinyl acetate, which might be due to the presence of other phytoconstituents in the crude extract of E. cardamomum.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    E. cardamomum improves glucose intolerance and memory in amnesic mice.

    “It also improves glucose intolerance, and memory in amnesic mice (Gomaa et al., 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gomaa et al., 2019 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    The anti-amyloidogenic activity of alpha-terpinyl acetate could be due to its cyclohexane ring structure with a methyl group, as it is a p-menthane monoterpene.

    “As alpha terpinyl acetate is a pmenthane monoterpene, the anti-amyloidogenic activity could be due to its cyclohexane ring structure with a methyl group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Only PC12 cell cultures with more than 95% viability were used for experimentation.

    “flask with more than 95% of cell viability were further used for experimentation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The occurrence of neurodegenerative disease is higher in western countries as compared to Asian countries like India, possibly due to food habits including spice use.

    “According to previously reported studies, the occurrence of neurodegenerative disease is higher in western countries as compared to Asian countries like India.The reason might be due to food habits, specifically the use of a variety of spices, as they are an integral part of culinary and delicacies (Kannappan, Gupta, Kim, Reuter, & Aggarwal, 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kannappan, Gupta, Kim, Reuter, & Aggarwal, 2011

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The protective effect of alpha-terpinyl acetate against H2O2-induced oxidative stress is in correlation with previous research.

    “Hence, the protective effect of alpha-terpinyl acetate against H 2 O 2 induced oxidative stress is in correlation with the previous research.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Alpha-terpinyl acetate shows low binding affinity for AChE and BuChE, which might allow it to bind several targets simultaneously due to the flexibility provided by weak binding.

    “Here, the alpha terpinyl acetate shows a low binding affinity for AChE and BuChE enzymes, which might be responsible for binding of alpha terpinyl acetate with several targets simultaneously due to the flexibility provided by weak binding.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Previous drug discovery studies showed that natural products with weak binding affinity can have high therapeutic efficiency, and high therapeutic efficiency is not necessarily associated with high binding affinity.
    • Rests on an assumption: Molecules tightly binding to a target have less probability of interacting with other targets.

  • May combine two claims.

    Premisecitation

    The human AChE active binding site for ligands is 20 Å deep, with Ser203, His447, and Glu334 as catalytic site residues and Phe295 and Phe297 in the acyl-binding pocket at the base of the gorge.

    “The human AChE active binding site for ligands is 20 Å deep.Ser203, His447, and Glu334 are the catalytic site residues, Phe295 and Phe297 residues of acyl-binding pocket present at the base of the gorge.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Johnson & Moore, 2006

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Alpha-terpinyl acetate demonstrated anti-cholinesterase, anti-oxidative, anti-amyloidogenic, and neuroprotective potential.

    “Alpha-terpinyl acetate demonstrated anti-cholinesterase, anti-oxidative, anti-amyloidogenic and neuroprotective potential and can be used as a lead to develop a novel, safe and effective therapy for AD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The active binding site of human BuChE has an active site of 20 Å, same as AChE, with Ser198, His438, Glu325 as catalytic site residues.

    “The active binding site of human BuChE also has an active site of 20 Å the same as AChE.Ser198, His438, Glu325 are the three residues of the catalytic site.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cokugras, 2003

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    E. cardamomum and its major phytoconstituent alpha-terpinyl acetate bind to multiple drug targets implicated in AD.

    “With this aim, the present study investigated and demonstrated that E. cardamomum and its major phytoconstituent alpha-terpinyl acetate binds to multiple drug target implicated in AD.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The multi-target drug ligand strategy of a single drug interacting with and inhibiting multiple targets is currently suggested for therapeutic intervention in AD.

  • May combine two claims.

    Premisecitation

    A high docking score corresponds to more stable ligand-enzyme interactions and a low docking score suggests low binding affinity.

    “As the docking score is the estimation of binding energy, the high docking score corresponds to more stable interactions between the ligand and the enzyme and low docking score suggests low binding affinity (Friesner et al., 2004).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Friesner et al., 2004 source

      Not checked in the free run.

37 of 37

  • The authors state this as an assumption.

    The data for substrate kinetics follow Michaelis-Menten kinetics.

    “The data for substrate kinetics were assumed to follow Michaelis-Menten kinetics analyzed using Lineweaver Burk method for the determination of Km (Michaelis constant or the dissociation constant) and Vmax (maximum velocity).”

  • The paper relies on this without support.

    No drug has been proven to have a disease-modifying effect against AD.

    “At present, no drug has been proven to have a disease-modifying effect against AD, due to the pathological complexity of the disease.”

  • The paper relies on this without support.

    The leading cause of AD is not fully understood.

    “The leading cause of AD has not yet fully understood, it involves multiple pathological factors such as β-amyloid (Aβ) fibril formation, oxidative stress, tau protein aggregation, and reduced levels of acetylcholine (Jellinger, 2003).”

  • The paper relies on this without support.

    PC12 cells are a suitable model for AD-related neurotoxicity.

    “Protective effect of alpha-terpinyl acetate against H 2 O 2 induced oxidative stress in PC12 cells assessed by incubating the cells with different concentrations of alpha-terpinyl acetate using MTT assay as described in Section 2.9.”

  • The paper relies on this without support.

    In vitro and in silico results are predictive of in vivo therapeutic effects in AD.

    “In conclusion, alpha-terpinyl acetate can be used as a suitable lead to develop a molecule that might have multi-targeted directed ligand (MTDL) potential and disease amelioration effects in AD.”

  • The paper relies on this without support.

    Previous drug discovery studies showed that natural products with weak binding affinity can have high therapeutic efficiency, and high therapeutic efficiency is not necessarily associated with high binding affinity.

    “However, previous drug discovery studies showed that natural products with weak binding affinity showed high therapeutic efficiency, emphasising that high therapeutic efficiency of natural products is not necessarily associated with a high binding affinity.”

  • The paper relies on this without support.

    Molecules tightly binding to a target have less probability of interacting with other targets.

    “For molecules tightly binding to target will result in less probability of interaction with other targets.”

  • The paper relies on this without support.

    In silico ADMET predictions of human intestinal absorption, CNS activity, and BBB penetration imply that alpha-terpinyl acetate will reach molecular targets in the AD patient's brain.

    “With 100% human intestinal absorption, active CNS activity, and blood-brain barrier (BBB) penetration, alpha-terpinyl acetate will be able to reach molecular targets in the AD patient's brain.”

  • The paper relies on this without support.

    The multi-target drug ligand strategy of a single drug interacting with and inhibiting multiple targets is currently suggested for therapeutic intervention in AD.

    “For the complex disease AD, the strategy of a single drug interacting and inhibiting multiple targets is currently suggested for therapeutic intervention.”

  • The paper relies on this without support.

    In silico docking and ADMET predictions are predictive of in vivo therapeutic efficacy.

    “Therefore, alpha-terpinyl acetate is very likely drug candidate.”

  • The paper relies on this without support.

    The protective effect of alpha-terpinyl acetate against Aβ1-42 induced cytotoxicity is being demonstrated for the first time.

    “The protective effect of alpha-terpinyl acetate against Aβ 1-42 induced cytotoxicity is being demonstrated for the first time.”
11 of 11

Claims other papers make about this one

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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.

  • Arachidic alcohol peak area differs from Table 1

    Minor

    The results state that arachidic alcohol has a percentage area of 9.71, whereas Table 1 lists 9.17 for that compound.

  • Penicillin and streptomycin concentrations are swapped

    Minor

    The materials section assigns 100 U/ml to penicillin and 100 μg/ml to streptomycin; the cell-culture section assigns those units and concentrations to the opposite antibiotics.

  • Aβ exposure duration differs between methods and results

    Minor

    The methods specify 15 hours of incubation with Aβ 1-42 fibrils, but the results describe the same treatment as lasting 24 hours.

3 of 3

Cites

Flagged first, then by citations

11 of the 45 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. Ahire, 2014, Dietetics and diet therapy: An Ayurvedic review, Ayurlog, 2, 47
  2. Cokugras, 2003, Butyrylcholinesterase: Structure and physiological importance, Turkish Journal of Biochemistry, 28, 54
  3. Husain, 2014, Analysis of volatile oil of the fruits of Elettaria cardamomum (L.) Maton and its antimicrobial activity, World Journal of Pharmacy and Pharmaceutical Sciences, 3, 1798
  4. Korikanthimathm, 2000, Medicinal properties of cardamom Elettaria cardamomum, Journal of Medicinal and Aromatic Plant Sciences, 22, 683
  5. Padmakumari Amma, 2010, Chemical composition, flavonoid-phenolic contents and radical scavenging activity of four major varieties of cardamom, International Journal of Biological & Medical Research, 3, 20
  6. Zarrad, 2017, Anticholinesterase Potential of monoterpenoids on the whitefly Bemisia tabaci and their kinetic studies, Journal of Agricultural Sciences and Technology, 19, 643

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Authors
Chowdhury, S., & Kumar, S.
Affiliations
Guru Gobind Singh Indraprastha University (IN)
Corresponding author
Kumar, Suresh
ORCID
Venue
Journal of Functional Foods
Publisher
Elsevier BV
Published
2020-05
Volume
68
Pages
103892
ISSN
1756-4646 (ISSN-L)
DOI
10.1016/j.jff.2020.103892
OpenAlex
W3012319191
Semantic Scholar
567a18d202d176fa8204122acd2435a4555b134b
Cited by
69
References
45
Citations by year
2026: 4 · 2025: 7 · 2024: 14 · 2023: 18 · 2022: 12 · 2021: 11 · 2020: 3
FWCI
12.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Functional Foods (publishedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Indian Council of Medical Research
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
α-terpinyl acetate, cardamom, Alzheimer's disease, multi-target-directed ligands, acetylcholinesterase inhibition, butyrylcholinesterase inhibition, amyloid-beta, neurotoxicity, oxidative stress, antioxidant activity, anti-amyloidogenic activity, phytochemical constituents, disease-modifying therapy

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

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.

What counts as a claim ›How we measure confidence ›How we check this ›

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