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Cited by 45Medicinal Plants and NeuroprotectionAlzheimer's disease research and treatmentsGinkgo biloba and Cashew Applications

Multi-target neuroprotective effects of herbal medicines for Alzheimer's disease

Open access
Fernandes, Filipe, Barroso, M. Fátima, De Simone, Angela, Emriková, Eliška, Dias-Teixeira, Mónica, Pereira, José Paulo, Chlebek, Jakub, Fernandes, Virgínia Cruz +4 more·2022·Journal of Ethnopharmacology
DOI 10.1016/j.jep.2022.115107
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Abstract

ETHNOPHARMACOLOGICAL RELEVANCE Alzheimer's disease is the most common form of dementia, but its treatment options remain few and ineffective. To find new therapeutic strategies, natural products have gained interest due to their neuroprotective potential, being able to target different pathological hallmarks associated with this disorder. Several plant species are traditionally used due to their empirical neuroprotective effects and it is worth to explore their mechanism of action. AIM OF THE STUDY This study intended to explore the neuroprotective potential and the safety in regard to pesticide residues of seven traditional medicinal plants, namely Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, Curcuma longa, Lavandula angustifolia, Trigonella foenum-graecum and Rosmarinus officinalis. The safety assessment with reference to pesticides residues was also aimed. MATERIALS AND METHODS Decoctions prepared from these species were chemically characterized by HPLC-DAD and screened for their ability to scavenge four different free radicals (DPPH●, ABTS●+, O2●‒ and ●NO) and to inhibit enzymes related to neurodegeneration (cholinesterases and glycogen synthase kinase-3β). Cell viability through MTT assay was also evaluated in two different brain cell lines, namely non-tumorigenic D3 human brain endothelial cells (hCMEC/D3) and NSC-34 motor neurons. Furthermore, and using GC, 20 pesticides residues were screened. RESULTS Regarding chemical composition, chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions. All extracts were able to scavenge free radicals and were moderate glycogen synthase kinase-3β inhibitors; however, they displayed weak to moderate acetylcholinesterase and butyrylcholinesterase inhibition. G. biloba and L. angustifolia decoctions were the less cytotoxic to hCMEC/D3 and NSC-34 cell lines. No pesticides residues were detected. CONCLUSIONS The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.

AI snapshot

Written from the paper’s full text.

TL;DR

Seven traditional medicinal plant decoctions were chemically profiled and screened in vitro for antioxidant, cholinesterase, GSK-3β, cytotoxicity, and pesticide-residue effects relevant to Alzheimer’s disease. All extracts scavenged free radicals and inhibited GSK-3β by more than 60% at 4.2 μg/mL, but cholinesterase inhibition was weak to moderate and no pesticide residues were detected.

Key findings

  • HPLC-DAD identified flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, trigonelline, and hypericin across the seven decoctions. Total phenolic content ranged from 29.00 ± 3.49 mg GAE/g extract dw for *T. foenum-graecum* to 327.31 ± 26.88 mg GAE/g extract dw for *R. officinalis*.
  • *H. perforatum* and *R. officinalis* were the most potent DPPH• scavengers (100.01 ± 7.43 and 91.57 ± 9.16 mg GAE/g extract dw, respectively) and ABTS•+ scavengers (350.45 ± 10.55 and 282.94 ± 12.30 mg TE/g extract dw, respectively), while *C. longa* was weakest (22.54 ± 3.34 and 30.38 ± 1.96 TE/g extract dw). For O2•− and •NO, *R. officinalis* (IC50 = 53.65 and 121.33 μg/mL) and *H. perforatum* (IC50 = 59.34 and 151.25 μg/mL) were most active.
  • AChE inhibition reached 50% only for *S. baicalensis* (IC50 = 796.55 μg/mL), *G. biloba* (IC50 = 2076.07 μg/mL), and *R. officinalis* (IC50 = 1068.44 μg/mL); BuChE inhibition was considerable only for *L. angustifolia* (IC50 = 2145.94 μg/mL) and *R. officinalis* (IC50 = 858.75 μg/mL). *R. officinalis* inhibited both cholinesterases non-competitively. All extracts showed >60% GSK-3β inhibition at 4.2 μg/mL, with *S. baicalensis* most potent (83.42 ± 2.99%).
  • *G. biloba* and *L. angustifolia* were least cytotoxic to hCMEC/D3 and NSC-34 cells (IC50 > 1000 μg/mL). *T. foenum-graecum* was most toxic to NSC-34 (IC50 < 250 μg/mL), and *T. foenum-graecum*, *R. officinalis*, and *C. longa* markedly decreased hCMEC/D3 viability (IC50 < 250 μg/mL). No organochlorine or organophosphorus pesticide residues were detected among the 21 screened.

Methods

  • Decoctions (n = 4) were prepared by boiling 0.5 g of ground commercial plant material in 125 mL water for 10 min, then filtering and lyophilizing; extraction yields ranged from 18.25 ± 0.63% (*C. longa*) to 47.17 ± 1.82% (*S. baicalensis*).
  • Chemical characterization used Folin-Ciocalteu total phenolic content and HPLC-DAD with external calibration curves. Pesticide screening used SPE cleanup followed by GC for 21 organochlorine and organophosphorus pesticides.
  • Bioassays measured DPPH•, ABTS•+, O2•−, and •NO scavenging; AChE, BuChE, and GSK-3β inhibition; and MTT cell viability in hCMEC/D3 and NSC-34 cells. Statistical analysis used one-way ANOVA with Tukey’s test, Pearson correlations, and GraphPad Prism 8.0.1.

Limitations

  • The paper does not state a limitations section. Evident from the text: all bioactivity data are in vitro, with no in vivo Alzheimer’s disease models, clinical outcomes, or bioavailability/BBB permeability assessment.
  • Evident from the text: only decoctions from commercial samples were tested, so findings may not generalize to other extraction methods, plant sources, or preparations. Cholinesterase inhibition was weak to moderate for most extracts, and GSK-3β inhibition was tested at a single concentration (4.2 μg/mL) rather than as IC50 values.
  • Evident from the text: pesticide safety was limited to 21 organochlorine and organophosphorus pesticides in liquid extracts, leaving other contaminant classes and plant materials unassessed.

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

Integrity signals

Registry

Crossref · 10.1016/j.jep.2022.115107

Cites

87 of 87 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 56 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions.

    “chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions.”
    Quote in the paperNot a substantial claim
  • Findingown data

    S. baicalensis decoction showed better DPPH than ABTS radical scavenging activity.

    “S. baicalensis decoction showed better DPPH • than ABTS •+ RSA”
    Quote in the paperNot a substantial claim
  • Findingown data

    O2•- and •NO scavenging activities were positively correlated (r = 0.600).

    “Both O 2 •-and • NO scavenging activities were positively correlated, although with a r far from 1 (r = 0.600)”
    Quote in the paperNot a substantial claim
  • Findingown data

    In terms of IC50 values, the most active extracts against DPPH and ABTS radicals were H. perforatum, L. angustifolia, and R. officinalis.

    “In terms of IC 50 values, results also demonstrated that the most active extracts against these two radicals were those of H. perforatum, L. angustifolia and R. officinalis.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Other phenolic acids and flavonoids previously reported for R. officinalis and L. angustifolia were not found in the current samples.

    “Other phenolic acids and flavonoids previously reported for these two species were not found in the current samples (Cesur Turgut et al., 2017;Mena et al., 2016).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 31
  • Classified as probably not a substantial claim. 26
  • The quote only partly states this claim. 6

  • May combine two claims.

    Findingown data

    For R. officinalis non-competitive BuChE inhibition, Vmax was 1.62 × 10−5 M/min, Km was 18.98 × 10−2 mM, and Ki was 747.50 μg/mL.

    “while for BuChE inhibition values of V max = 1.62 × 10 -5 M/min, K m = 18.98 × 10 -2 mM and K i = 747.50μg/mL were obtained.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    No pesticides residues were detected.

    “No pesticides residues were detected.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For hCMEC/D3 cells, S. baicalensis (IC50 = 633.52 μg/mL) and H. perforatum (IC50 = 731.87 μg/mL) moderately affected viability, while T. foenum-graecum, R. officinalis, and C. longa induced a marked decrease (IC50 < 250 μg/mL).

    “hCMEC/D3 cells viability was moderately affected by S. baicalensis (IC 50 = 633.52μg/mL) and Hypericum perforatum (IC 50 = 731.87μg/mL) while T. foenum graecum, R. officinalis and C. longa induced a marked decreased in cells viability (IC 50 < 250 μg/mL).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C. longa decoction contained p-coumaric acid, ferulic acid, and three curcuminoids: bisdemethoxycurcumin, demethoxycurcumin, and curcumin.

    “Besides p-coumaric (11) and ferulic (13) acids, three curcuminoids were identified in C. longa decoction, namely, bisdemethoxycurcumin (39), demethoxycurcumin (41) and curcumin (42) (Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For NSC-34 cells, G. biloba, H. perforatum, C. longa, and L. angustifolia were the least cytotoxic (IC50 > 1000 μg/mL), followed by S. baicalensis (IC50 = 722.11 μg/mL) and R. officinalis (IC50 = 634.66 μg/mL), and T. foenum-graecum was the most toxic (IC50 < 250 μg/mL).

    “Concerning NSC-34, G. biloba, H. perforatum, C. longa and L. angustifolia were the less cytotoxic (IC 50 > 1000 μg/mL), followed by S. baicalensis (IC 50 = 722.11μg/mL) and R. officinalis (IC 50 = 634.66μg/mL) and the most toxic one was T. foenum graecum (IC 50 < 250 μg/mL).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Only S. baicalensis, G. biloba, and R. officinalis decoctions achieved 50% AChE inhibition, with IC50 values of 796.55, 2076.07, and 1068.44 μg/mL, respectively.

    “Concerning ChEs inhibition, it was only possible to achieve 50% of AChE inhibition for decoctions prepared with S. baicalensis (IC 50 = 796.55μg/mL) (Delerue et al., 2021), G. biloba (IC 50 = 2076.07μg/mL) (Delerue et al., 2021), and R. officinalis (IC 50 = 1068.44μg/mL)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For R. officinalis non-competitive AChE inhibition, Vmax was 2.22 × 10−5 M/min, Km was 15.28 × 10−2 mM, and Ki was 501.60 μg/mL.

    “The parameters V max , K m , and K i were determined with this model and were found to be 2.22 × 10 -5 M/min, 15.28 × 10 -2 mM and 501.60 μg/mL for AChE inhibition, respectively”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    H. perforatum and R. officinalis decoctions were the most potent samples for DPPH and ABTS scavenging, while C. longa was the weakest.

    “From all samples, H. perforatum and R. officinalis decoctions were the most potent ones for DPPH • (100.01 ± 7.43 and 91.57± 9.16 mg GAE/g extract dw, respectively) and ABTS •+ (350.45 ± 10.55 and 282.94 ± 12.30 mg TE/g extract dw, respectively) assays, while C. longa was the weakest one (22.54± 3.34 and 30.38 ± 1.96 TE/g extract dw).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Rosmarinic acid was present in both R. officinalis and L. angustifolia decoctions, in higher amount in R. officinalis than in L. angustifolia (21.06 ± 1.97 vs 13.28 ± 1.68 mg/g extract dw).

    “Rosmarinic acid (21) was present in both species from Lamiaceae family, in higher amounts in R. officinalis than in L. angustifolia (21.06 ± 1.97 vs 13.28 ± 1.68 mg/g extract dw).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For R. officinalis decoction, a non-competitive inhibition model fitted the experimental results best for both AChE and BuChE, with highest R2 and lowest sum of squared errors.

    “Different models (uncompetitive, competitive, non-competitive) were fitted to the experimental results and, for both enzymes, non-competitive inhibition model resulted in the highest R 2 (0.8530 for AChE and 0.9275 for BuChE) and AdjR 2 (0.8412 for AChE and 0.9214 for BuChE) values and the lowest sum of the squared errors (1.11 × 10 -10 for AChE and 2.15 × 10 -11 for BuChE).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    R. officinalis decoction contained protocatechuic acid, caffeic acid, an apigenin derivative, carnosol, and carnosic acid.

    “Other two hydroxycinnamic acids (4 and 8) were also identified in L. angustifolia, while protocatechuic acid (3), caffeic acid (9), an apigenin derivative (33), carnosol (38) and carnosic acid (43) were also found in R. officinalis decoction (Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    H. perforatum decoction contained small amounts of hypericin (0.18 ± 0.08 mg/g extract dw), with quercetin-3-O-galactoside (27.00 ± 7.74 mg/g extract dw) and quercetin-3-O-glucoside (11.74 ± 1.99 mg/g extract dw) as major constituents, followed by catechin derivatives, quercetin-3-O-rhamnoside, and protocatechuic acid.

    “H. perforatum contained small amounts of the naphthodianthrone hypericin (44; 0.18 ± 0.08 mg/g extract dw), and the major constituents were quercetin-3-O-galactoside (22; 27.00 ± 7.74 mg/g extract dw) and quercetin-3-O-glucoside (24; 11.74 ± 1.99 mg/g extract dw), followed by catechin derivatives (7, 10 and 12), quercetin-3-Orhamnoside (27) and protocatechuic acid (3) (Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Only L. angustifolia and R. officinalis decoctions displayed considerable BuChE inhibition, with IC50 values of 2145.94 and 858.75 μg/mL, respectively.

    “while only L. angustifolia and R. officinalis displayed considerable BuChE inhibition (IC 50 = 2145.94and 858.75 μg/mL, respectively) (Fig. 3A-E).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The HPLC-DAD analysis of the five decoctions other than S. baicalensis and G. biloba showed very distinct chemical compositions.

    “The HPLC-DAD analysis of the other five decoctions showed very distinct chemical compositions (Fig. 1, Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    T. foenum-graecum decoction contained trigonelline as its major compound (16.41 ± 0.24 mg/g extract dw), followed by four C-glycosyl flavones and one apigenin derivative.

    “T. foenum-graecum contained an alkaloid, trigonelline (1), as its major compound (16.41 ± 0.24 mg/g extract dw), followed by four C-glycosyl flavones (luteolin-8-C-glucoside (14), apigenin-8-C-glucoside (15), luteolin-6-C-glucoside (17) and apigenin-6-C-glucoside (19)) and one apigenin derivative (26) (Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    O2•- and •NO scavenging activities were negatively correlated with total phenolic content (r = -0.813 and r = -0.631, respectively).

    “and were negatively correlated with TPC (r = -0.813and r = -0.631,respectively).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Except G. biloba and L. angustifolia, which were not cytotoxic at the tested concentrations, all other samples induced a concentration-dependent decrease in cell viability in both hCMEC/D3 and NSC-34 cell lines.

    “Except for G. biloba (IC 50 > 1000 μg/mL) and L. angustifolia (IC 50 > 1000 μg/mL), which were not cytotoxic at the tested concentrations, all the other samples induced a concentration-dependent decrease in cell viability in both cell lines.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Ginkgo biloba leaf extract has become one of the most widely used herbal remedies for dementia.

    “The extract from G. biloba leaves has become one of the most widely used herbal remedies for dementia (Yuan et al., 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Yuan et al., 2017 source

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    Premisecitation

    Mixtures of drugs or plant extracts might have advantages over single drugs by impacting different targets simultaneously, potentially being a more effective treatment option for Alzheimer's disease.

    “Mixtures of drugs or plant extracts might have advantages over single drugs as they can impact different targets simultaneously, which could be a novel and more effective treatment option for AD (Chen et al., 2021).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Chen et al., 2021 source

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    Premisecitation

    There are five drugs in clinic for Alzheimer's disease, including three cholinesterase inhibitors, that only provide palliative and supporting treatment.

    “There are five drugs in clinic, including three cholinesterase inhibitors, that only provide palliative and supporting treatment (Butterfield and Boyd-Kimball, 2020;Zagórska and Jaromin, 2020;Gul et al., 2021).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Butterfield and Boyd-Kimball, 2020 source

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    • cites Zagórska and Jaromin, 2020 source

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    • cites Gul et al., 2021 source

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    Premisecitation

    BACE-1 and GSK-3β inhibition are being studied as possible targets for Alzheimer's disease.

    “Nowadays, other possible targets are being studied, such as beta-secretase 1 (BACE-1) and glycogen synthase kinase-3β (GSK-3β) inhibition (De Simone et al., 2021;Prati et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites De Simone et al., 2021 source

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    • cites Prati et al., 2015 source

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

    Premisecitation

    Reactive oxygen species and reactive nitrogen species can damage macromolecules and compromise normal cell functions.

    “ROS and reactive nitrogen species (RNS) are capable of damaging and modifying several types of macromolecules, such as DNA, RNA, lipids, and proteins, compromising the normal functions of the cells (Butterfield and Boyd-Kimball, 2020; Persson et al., 2014).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Butterfield and Boyd-Kimball, 2020 source

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    • cites Persson et al., 2014

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    Premisecitation

    Several natural products, mainly plant extracts, have been reported to be used in traditional medicine for neuroprotective, memory enhancing, and antiageing functions.

    “Several natural products, mainly plants extracts, have been reported to be used in traditional medicine for neuroprotective, memory enhancing, and antiageing functions”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Chen and Chang, 2015

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    • cites Long et al., 2014 source

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    • cites Doležal et al., 2019 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Study design and conductown data

    The extracts were analysed in triplicate (n = 3) by HPLC-DAD.

    “The extracts were analysed (n = 3) on an analytical HPLC unit”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Statistical analysis used one-way ANOVA followed by Tukey's test with p values less than 0.05 considered statistically significant.

    “Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by the Tuckey's test and p values less than 0.05 were considered to be statistically significant.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    GSK-3β inhibition assays were tested in duplicate and the experiments repeated three times.

    “All decoctions were tested in duplicate, and the experiments were repeated three times.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    This study demonstrated the importance of plant extracts as multitarget agents, showing benefits of seven medicinal plants against different Alzheimer's hallmarks, including oxidative and nitrosative stresses and cholinesterases and GSK-3β inhibition.

    “This study demonstrated the importance of plant extracts as multitarget agents, showing the benefits of seven different medicinal plants against different Alzheimer's hallmarks, including oxidative and nitrosative stresses and cholinesterases and GSK-3β inhibition.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    WHO guidelines for assessing quality of herbal medicines describe potentially hazardous contaminants and residues and report national and regional limits.

    “The WHO guidelides for assessing quality of herbal medicines describes the potentially hazardous contaminants and residues that may occur in herbal medicines and reports the national and regional limits set for the various types contaminants (World Health Organization, 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites World Health Organization, 2007

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    Premisecitation

    The purity of plants may be compromised by dirt, weeds, bacteria, moulds, and multiple contaminants such as pesticides, toxic metals, and polychlorinated biphenyls.

    “The purity of the plants may be compromised due to several factors, namely, by the presence of dirt, weeds, bacteria, moulds, and multiple contaminants (e.g., pesticides, toxic metals, polychlorinated biphenyls (PCB), etc) (Jordan et al., 2010;Luo et al., 2021).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Jordan et al., 2010 source

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    • cites Luo et al., 2021 source

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

    Study design and conductown data

    The total phenolic content experiment was performed in triplicate (n = 3).

    “The experiment was performed in triplicate (n = 3).”
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Study design and conductnone given

    NSC-34 cells at passages 4-6 were used with n = 5.

    “Passages 4-6 were used (n = 5).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Pearson correlation analyses were carried out to determine possible relations between the contents of phenolic compounds and the observed bioactivities.

    “Pearson correlation analyses were carried out to determine the possible relations between the contents of phenolic compounds and the observed bioactivities.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The quality of herbal medicine products is a particular challenge in safety data.

    “A particular challenge in safety data on herbal medicines is the quality of the products.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Jordan et al., 2010 source

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    • cites Luo et al., 2021 source

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    Study design and conductnone given

    For all radical scavenging assays, triplicate measurements were made for each extract.

    “For all the assays, triplicate measurements were made for each extract.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Decoctions from Ginkgo biloba leaves and Scutellaria baicalensis roots displayed moderate acetylcholinesterase and butyrylcholinesterase inhibition and strong scavenging activity against hydrogen peroxide.

    “Therefore, in a previous study, we have demonstrated that the decoctions prepared from the leaves of G. biloba and from the roots of S. baicalensis displayed moderate acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition as well as a strong scavenging activity against hydrogen peroxide, a ROS (Delerue et al., 2021).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Delerue et al., 2021 source

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  • May combine two claims.

    Interpretationown data

    The decoctions from S. baicalensis, G. biloba, L. angustifolia, and R. officinalis are moderate to weak cholinesterase inhibitors, while C. longa and T. foenum-graecum decoctions are not active against these enzymes.

    “These results demonstrated that the decoctions prepared from these four species are moderate to weak cholinesterases inhibitors, while those prepared from C. longa and T. foenum graecum (Fig. 3B and D) are not active against these enzymes.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    All experiments were repeated at least three times.

    “All the experiments were repeated at least three times.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Study design and conductnone given

    hCMEC/D3 cells at passages 50-54 were employed with n = 5.

    “Passages 50-54 were employed (n = 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Rosmarinus officinalis and Lavandula angustifolia contain rosmarinic acid, which is active against amyloid fibrillation.

    “Both species contain rosmarinic acid that is active against amyloid fibrillation (Adsersen et al., 2006;Lobbens et al., 2017).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Adsersen et al., 2006 source

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    • cites Lobbens et al., 2017 source

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  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Study design and conductnone given

    Acetylcholinesterase and butyrylcholinesterase inhibition assays were tested in triplicate and the experiments repeated three times.

    “Results are expressed as IC 50 values and decoctions were tested in triplicate and the experiments repeated three times.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.

    “The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The in vitro bioassays used (radical scavenging, enzyme inhibition, cell viability) are predictive of neuroprotective effects in Alzheimer's disease.

  • May combine two claims.

    Interpretationreasoning

    Taking all results together, T. foenum-graecum and C. longa were the weakest antioxidant samples, while R. officinalis and H. perforatum are among the most active, showing potential to counteract ROS and RNS.

    “Taking all the results together, T. foenum graecum and C. longa were the weakest antioxidant samples, while R. officinalis and H. perforatum are among the most active ones, showing their potential to counteract ROS and RNS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The antioxidant activity of H. perforatum can be attributed to flavonoids and phenolic acids, while phloroglucinols and naphthodianthrones have no significant activity.

    “According to Orčić et al. (2011), the antioxidant activity of H. perforatum can be attributed to flavonoids and phenolic acids, while phloroglucinols and naphthodianthrones have no significant activity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Orčić et al. (2011)

      Not checked in the free run.

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

    Premisecitation

    The presence of organochlorine and organophosphorus pesticides in medicinal plants is commonly reported in the literature.

    “Although the presence of organochlorine and organophosphorus pesticides in medicinal plants is commonly reported in the literature (Fu et al., 2019;Luo et al., 2021;Xu et al., 2011), in this work it has not been verified.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Fu et al., 2019

      Not checked in the free run.

    • cites Luo et al., 2021 source

      Not checked in the free run.

    • cites Xu et al., 2011

      Not checked in the free run.

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

    Premisecitation

    Trigonelline is an important chemotaxonomic marker of Trigonella species.

    “Trigonelline is an important chemotaxonomic marker of Trigonella species (Mohammadi et al., 2020;Shailajan et al., 2011;Zameer et al., 2018) and was found to be the major compound in the sample analysed herein.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Mohammadi et al., 2020 source

      Not checked in the free run.

    • cites Shailajan et al., 2011 source

      Not checked in the free run.

    • cites Zameer et al., 2018 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    An imbalance between protective •NO and highly cytotoxic ONOO− may be crucial in the initial step of development of several vascular and neuronal diseases, including AD.

    “An imbalance between protective • NO and highly cytotoxic ONOO -may be crucial in the initial step of the development of several vascular and neuronal diseases, including AD (Malinski, 2007).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Malinski, 2007 source

      Not checked in the free run.

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

    Premisecitation

    Rosmarinic acid is the most important chemotaxonomic marker of species from the Lamiaceae family.

    “Concerning R. officinalis and L. angustifolia, it is also worth to mention that rosmarinic acid is also the most important chemotaxonomic marker of species from Lamiaceae family (Janicsák et al., 1999)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Janicsák et al., 1999 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Leaf maturation (green vs yellow) and plant sex (male vs female) influence the amount of phenolics in G. biloba, being responsible for the wide range of TPC values reported in literature.

    “Indeed, for G. biloba, it was found that leaf maturation (green vs yellow) and plant sex (male vs female) have influence on the amount of phenolics, being these factors responsible for the wide range of TPC values reported in literature (Kobus-Cisowska et al., 2020;Koczka et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kobus-Cisowska et al., 2020 source

      Not checked in the free run.

    • cites Koczka et al., 2015 source

      Not checked in the free run.

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

    Premisecitation

    For R. officinalis, the phenolic diterpenes carnosic acid and carnosol are considered important chemotaxonomic markers.

    “and, for R. officinalis, the phenolic diterpenes carnosic acid and carnosol are also considered important (Mena et al., 2016;Troncoso et al., 2005;Yeddes et al., 2019;Yilmaz et al., 2018;Zhang et al., 2012).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Mena et al., 2016 source

      Not checked in the free run.

    • cites Troncoso et al., 2005 source

      Not checked in the free run.

    • cites Yeddes et al., 2019 source

      Not checked in the free run.

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

    Premisecitation

    It is difficult to guarantee total safety of herbal medicines as it involves different areas, such as environmental and agricultural practices.

    “However, it is a difficult task to guarantee total safety as it involves different areas, such as environmental and agricultural practices (World Health Organization, 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites World Health Organization, 2007

      Not checked in the free run.

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

    Premisecitation

    Some pesticides showed a significant decrease in transfer rate from plant to infusion.

    “Recently, Florea et al. (2020) reported the degree of pesticides transfer in three types of preparations (infusion, decoction and maceration), and demonstrated that some pesticides showed a significant decrease in transfer rate from plant to infusion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Florea et al. (2020) source

      Not checked in the free run.

51 of 51

  • The paper relies on this without support.

    The in vitro bioassays used (radical scavenging, enzyme inhibition, cell viability) are predictive of neuroprotective effects in Alzheimer's disease.

    “The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.”

  • The paper relies on this without support.

    This is the first study on GSK-3β inhibition of these plant species.

    “To the best of our knowledge, this is the first study on the GSK-3β inhibition of these plant species.”

  • The paper relies on this without support.

    The cholinergic hypothesis holds that the main cause of AD is the reduction in acetylcholine synthesis.

    “According to the cholinergic hypothesis, the main cause of AD is the reduction in acetylcholine synthesis.”

  • The paper relies on this without support.

    hCMEC/D3 is a stable, easily grown blood brain barrier model cell line.

    “hCMEC/D3 represents a stable, easily grown blood brain barrier (BBB) model cell line and NSC-34 is a hybrid cell line produced by fusion of neuroblastoma with mouse motoneuron-enriched primary spinal cord cells.”

  • The paper relies on this without support.

    There are no previous studies about the effect of these decoctions on the viability of hCMEC/D3 and NSC-34 cell lines.

    “To the best of our knowledge, there are no previous studies about the effect of these decoctions on the viability of these cell lines.”

  • The paper relies on this without support.

    Absence of the 21 screened organochlorine and organophosphorus pesticides in the decoctions implies they are safe for possible nutraceutical application.

    “We can say that looking at the 21 pesticides under study, the 7 decoctions are safe for their possible nutraceutical application.”
6 of 6

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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.

  • DPPH activity uses conflicting equivalent units

    Minor

    The methods say DPPH activity was expressed in Trolox equivalents (mg TE/g dw), but the results report the DPPH values in gallic acid equivalents (mg GAE/g extract dw).

1 of 1

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Authors
Fernandes, F., Barroso, M. F., De Simone, A., Emriková, E., Dias-Teixeira, M., Pereira, J. P., Chlebek, J., Fernandes, V. C., Rodrigues, F., Andrisano, V., Delerue-Matos, C., & Grosso, C.
Affiliations
  • Rede de Química e Tecnologia (PT)
  • University of Bologna (IT)
  • Escola Superior de Saúde Ribeiro Sanches (PT)
  • Charles University (CZ)
  • Universidade Técnica do Porto (PT)
Corresponding author
Grosso, Clara
ORCID
Venue
Journal of Ethnopharmacology
Publisher
Elsevier BV
Published
2022-05
Volume
290
Pages
115107
ISSN
0378-8741 (ISSN-L)
DOI
10.1016/j.jep.2022.115107
OpenAlex
W4213306104
Semantic Scholar
5dd4df9076f986497bf818aa3c9b3d12680b0810
Cited by
45
References
88
Citations by year
2026: 6 · 2025: 9 · 2024: 16 · 2023: 10 · 2022: 4
FWCI
10.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Ethnopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc-nd)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
Funders
  • Ministério da Ciência, Tecnologia e Ensino Superior (UIDB 50006/2020, UIDP/50006/2020, CEECIND/03436/2020)
  • Fundação para a Ciência e a Tecnologia (CEECIND/03436/2020, UIDP/50006/2020, MTS/SAS/0077/2020, CEECIND/03107/2020, SFRH/BPD/109153/2015, CEECIND/01886/2020, UIDB/50006/2020)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Complementary and alternative medicine › Ginkgo biloba and Cashew Applications
Keywords
Alzheimer's disease, neuroprotection, traditional medicinal plants, herbal decoction, Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, turmeric, Lavandula angustifolia, fenugreek, Rosmarinus officinalis, cholinesterase inhibition, glycogen synthase kinase-3β inhibition, antioxidant activity, flavonoids, phenolic acids, curcuminoids, pesticide residues, cytotoxicity, brain endothelial cells, motor neurons
MeSH terms
Alzheimer Disease, Cell Line, Cell Survival, Cholinesterases, Dose-Response Relationship, Drug, Glycogen Synthase, Humans, Medicine, Chinese Traditional, Pesticide Residues, Plant Extracts, Plants, Medicinal, Free Radical Scavengers, Neuroprotective Agents

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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.

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