Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment

In the paper

“C. paniculatus has not undergone clinical trials for safety and efficacy. Animal toxicology data is also lacking to date.”

In the paper

“E. alsionoides has not been studied systematically for clinical efficacy and toxicological effects.”

In the paper

“C. pluricaulis has not been studied for toxicity.”

In the paper

“Currently available therapies for AD management are based on this hypothesis [8].”

What the sources say

• Not checked yetcites [8] Anand, 2013, A review on cholinesterase inhibitors for Alzheimer’s disease, Arch. Pharmacal Res. source

In the paper

“The β-amyloid hypothesis, most cogent hypothesis [9,10,11,12] provides the basis for development of new therapeutic strategies for AD treatment [13].”

What the sources say

• Not checked yetcites [9] Beyreuther, 1991, Amyloid precursor protein (APP) and beta A4 amyloid in the etiology of Alzheimer’s disease, precursor-product relationships in the derangement of neuronal function, Brain Pathol. source
• Not checked yetcites [10] Hardy, 1991, Amyloid deposition as the central event in the aetiology of Alzheimer’s disease, Trends Pharmacol Sci. source
• Not checked yetcites [11] Hardy, 1992, Alzheimer’s disease, the amyloid cascade hypothesis, Science source
• Not checked yetcites [12] Selkoe, 1991, The molecular pathology of Alzheimer’s disease, Neuron source
• Not checked yetcites [13] Selkoe, 2016, The amyloid hypothesis of Alzheimer’s disease at 25 years, EMBO Mol. Med. source

In the paper

“The histopathological hallmarks of AD are neuritic plaque and neurofibrillary tangle (NFT) formation in the brain [14].”

What the sources say

• Not checked yetcites [14] Calabrese, 2008, Effects of a Standardized Bacopa monnieri Extract on Cognitive Performance, Anxiety, and Depression in the Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial, J. Altern. Complement. Med. source

In the paper

“This review is focused on the potential of herbal medicine in AD since it is responsible for more than two-thirds of all dementia cases [5,6].”

What the sources say

• Not checked yetcites [5] Kumar, A., Sidhu, J., Goyal, A., Goyal, A., and Tsao, J.W. (2020, November 25). Alzheimer Disease, StatPearls [Internet], Available online: https://www.ncbi.nlm.nih.gov/books/NBK499922/.
• Not checked yetcites [6] Nussbaum, 2003, Alzheimer’s disease and Parkinson’s disease, N. Engl. J. Med. source

In the paper

“Cholinergic hypothesis, which is the oldest theory, describes acetylcholine (ACh) deficiency as the causative factor [7].”

What the sources say

• Not checked yetcites [7] Davies, 1976, Selective Loss of Central Cholinergic Neurons in Alzheimer’s Disease, Lancet source

In the paper

“The leaf extract also had sedative, antidepressant and cholinomimetic activities [57] suggesting its suitability for treatment of AD associated cognitive dysfunction and depression and anxiety.”

What the sources say

• Not checked yetcites [57] Sakina, 1990, A psycho-neuropharmacological profile of Centella asiatica extract, Fitoterapia

In the paper

“Memantine showed promising anti-Alzheimer effects in preclinical experimental models, however, in clinical studies, it has not shown clear therapeutic efficacy in AD [33].”

What the sources say

• Not checked yetcites [33] Folch, 2018, Memantine for the Treatment of Dementia: A Review on its Current and Future Applications, J. Alzheimers Dis. source

In the paper

“Other adverse effects of AChE inhibitors such as extrapyramidal symptoms, sleep disorder and cardiorespiratory adverse effects, are associated with central cholinergic over-activity whereas muscle cramps, weakness and urinary incontinence, are associated with peripheral cholinergic over-activity [22].”

What the sources say

• Not checked yetcites [22] Inglis, 2002, The tolerability and safety of cholinesterase inhibitors in the treatment of dementia, Int. J. Clin. Pract. Suppl.

In the paper

“C. asiatica aqueous leaf extract showed improvement in learning and memory in rats, and modulated dopamine, 5-hydroxytryptamine (5-HT) and noradrenaline systems in the rat brain in-vivo [56].”

What the sources say

• Not checked yetcites [56] Nalini, 1995, Effects of Celastrus paniculatus on passive avoidance performance and biogenic amine turnover in albino rats, J. Ethnopharmacol. source

In the paper

“Though it performed better than tacrine [31], it is no longer recommended, as it may increase the risk of adverse cardiovascular events and breast cancer [32].”

What the sources say

• Not checked yetcites [32] Cummings, 2004, Alzheimer’s disease, N. Engl. J. Med. source

In the paper

“A study by Rao et al. [53] demonstrated that 15 days treatment with C. asiatica at a dose of 200 mg/kg from day 15 to 30 postpartum stimulated learning and memory in rats, which lasted for at least 6 months postpartum.”

What the sources say

• Not checked yetcites [53] Rao, 2005, Centella asiatica treatment during postnatal period enhances learning and memory in mice, Physiol. Behav. source

In the paper

“The leaf extract also had sedative, antidepressant and cholinomimetic activities [57] suggesting its suitability for treatment of AD associated cognitive dysfunction and depression and anxiety.”

What the sources say

• Not checked yetcites [57] Sakina, 1990, A psycho-neuropharmacological profile of Centella asiatica extract, Fitoterapia

In the paper

“Studies indicate that antioxidants (vitamins E and C) and non-steroidal anti-inflammatory drugs slow the progression of AD [25,26,27,28,29,30].”

What the sources say

• Not checked yetcites [25] Bagi, 2003, Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment, Am. J. Physiol. Circ. Physiol. source
• Not checked yetcites [26] Cole, 2004, NSAID and antioxidant prevention of Alzheimer’s disease, lessons from in vitro and animal models, Ann. N. Y. Acad. Sci. source
• Not checked yetcites [27] Engelhart, 2002, Dietary intake of antioxidants and risk of Alzheimer disease, JAMA source
• Not checked yetcites [28] Esposito, 2002, A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes, Neurobiol. Aging source
• Not checked yetcites [29] Moore, 2002, Neuroinflammation and anti-inflammatory therapy for Alzheimer’s disease, Adv. Drug Deliv. Rev. source
• Not checked yetcites [30] Pavlik, 2009, Vitamin E use is associated with improved survival in an Alzheimer’s disease cohort, Dement. Geriatr. Cogn. Disord. source

In the paper

“The combination was reported to be superior to donepezil monotherapy in terms of both safety and efficacy [49].”

What the sources say

• Not checked yetcites [49] Yancheva, 2009, GINDON Study Group. Ginkgo biloba extract EGb 761®, donepezil or both combined in the treatment of Alzheimer’s disease with neuropsychiatric features: A randomised, double-blind, exploratory trial, Aging Ment. Health source

In the paper

“They also observed an increase in dendritic arborization of hippocampal CA3 neurons, which may be one reason for improvement in brain function.”

What the sources say

• Not checked yetcites [53] Rao, 2005, Centella asiatica treatment during postnatal period enhances learning and memory in mice, Physiol. Behav. source

In the paper

“The effect of alcoholic extract of Bacopa has been evaluated at the dose of 20, 40 and 80 mg/kg on cognitive functions and neurodegeneration in the animal model of AD induced by bilateral intracerebroventricular administration of AF64A. They found that Bacopa improved the escape latency in the Morris water maze test and prevented the reduction in cholinergic neuron density [47,82].”

What the sources say

• Not checked yetcites [47] Uabundit, 2010, Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer’s disease model, J. Ethnopharmacol. source
• Not checked yetcites [82] Pandey, S.P., Singh, H.K., and Prasad, S.B. (2015). Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice. PLoS ONE, 10. source

In the paper

“Asiatic acid and its derivatives have shown a promising memory improving effect [65] by improving ACh synthesis [66,67].”

What the sources say

• Not checked yetcites [65] Lee, 2000, Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity, Res. Commun. Mol. Pathol. Pharmacol.
• Not checked yetcites [66] Kim, 2004, Asiatic acid derivatives enhance cognitive performance partly by improving acetylcholine synthesis, J. Pharm. Pharm. source
• Not checked yetcites [67] Orhan, 2012, Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential, Evid. Based Complement. Altern. Med. source

In the paper

“The leaf extract stimulated dendrites of neuronal cells in the rat brain [51] and induced neurite elongation in human SH-SY-5Y cells and accelerated axonal regenerate in rats [58].”

What the sources say

• Not checked yetcites [51] Rao, 2006, Centella asiatica (L.) Leaf Extract Treatment during the Growth Spurt Period Enhances Hippocampal CA3 Neuronal Dendritic Arborization in Rats, Evid. Based Complement. Altern. Med. source
• Not checked yetcites [58] Soumyanath, 2005, Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in vitro, J. Pharm. Pharmacol. source

In the paper

“Besides, bacosides has been proven for its antioxidant and anti-inflammatory effects [75] bacosides also attenuated the retrograde amnesia produced by immobilization induced stress, electroconvulsive shock and scopolamine [76].”

What the sources say

• Not checked yetcites [75] Singh, 2010, Modulation of Hydrogen Peroxide and Acrolein-Induced Oxidative Stress, Mitochondrial Dysfunctions and Redox Regulated Pathways by the Bacopa Monniera Extract: Potential Implication in Alzheimer’s Disease, J. Alzheimer’s Dis. source

In the paper

“Bacopa has been used for the treatment of various ailments for thousands of years by the practitioners of the traditional system of medicine of India [72].”

What the sources say

• Not checked yetcites [72] Aguiar, 2013, Neuropharmacological Review of the Nootropic Herb Bacopa monnieri, Rejuvenation Res. source

In the paper

“In acute toxicity study, C. asiatica extract up to 10 g/kg did not shown any sign of toxicity whereas in the subacute toxicity study, no toxicity was observed when the extract was administered at the doses of 10–1000 mg/kg. In the chronic toxicity study, doses up to 1200 mg/kg/day for six months did not result in significant toxicity in Wistar rats [70].”

What the sources say

• Not checked yetcites [70] Chivapat, 2004, Toxicity study of Centella asiatica (L) urban, J. Thai Trad Alt Med.

In the paper

“In children (age 6–8 years), Bacopa syrup (350 mg Bacopa powder), when administered three times a day for three months, resulted in significant improvement as compared to the placebo [92]. However, this study was not blinded.”

What the sources say

• Not checked yetcites [92] Sharma, 1987, Efficacy of Bacopa monnieri in revitalizing intellectual functions in children, J. Res. Educ. Indian Med.

In the paper

“The LD50 of orally administered Bacopa extracts in rats was 5 g/kg for aqueous extract and 17 g/kg of the alcoholic extract [77].”

What the sources say

• Not checked yetcites [77] Singh, 1997, Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monniera Linn. (Brahmi), Indian J. Pharmacol.

In the paper

“In a randomized, double-blind placebo-controlled, study, C. asiatica extract was administered to healthy volunteers as 250–750 mg once daily dose for 2 months. The high dose enhanced working memory and improved self-rated mood [68].”

What the sources say

• Not checked yetcites [68] Wattanathorn, 2008, Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica, J. Ethnopharmacol. source

In the paper

“Bacopa, at the dose of 50 mg/kg, demonstrated the neuroprotective effect in the colchicine model of dementia through its antioxidant effect and restored the activity of Na+K+ATPase and AChE [85].”

What the sources say

• Not checked yetcites [85] Saini, 2012, Neuroprotective Effects of Bacopa monnieri in Experimental Model of Dementia, Neurochem. Res. source

In the paper

“It also suppressed IL-1 and glial fibrillary acidic protein, reduced oxidative damage and plaque burden and decreased the amount of insoluble amyloid [26].”

What the sources say

• Not checked yetcites [26] Cole, 2004, NSAID and antioxidant prevention of Alzheimer’s disease, lessons from in vitro and animal models, Ann. N. Y. Acad. Sci. source

In the paper

“Curcumin has been shown to reduce both in-vivo and in-vitro Aβ plaque deposition [106,107].”

What the sources say

• Not checked yetcites [106] Lim, 2001, The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse, J. Neurosci. source
• Not checked yetcites [107] Yang, 2005, Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo, J. Biol. Chem. source

In the paper

“Additionally, curcumin treatment for 7 days caused reduction in plaques burden and reversed structural changes in dystrophic dendrites in APPswe/PS1dE9 mouse model of AD [112].”

What the sources say

• Not checked yetcites [112] Ramassamy, 2008, Faculty Opinions recommendation of Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model, Fac. Opin. Post-Publ. Peer Rev. Biomed. Lit.

In the paper

“It has been reported in various experimental studies to possess wide variety of biological and pharmacological activities including antioxidant, anti-inflammatory and cholesterol-lowering properties, all three of which are key processes involved in the pathogenesis of AD.”

In the paper

“Another experimental study showed that curcumin treatment restored learning and memory functions in the STZ model of AD by reducing the oxidative stress, enhancing ChAT activity and restoring insulin receptor protein [117,118].”

What the sources say

• Not checked yetcites [117] Agrawal, 2010, Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat, Pharm. Res. source
• Not checked yetcites [118] Ishrat, 2009, Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer’s type (SDAT), Eur. Neuropsychopharmacol. source

In the paper

“Curcumin can also reduce two other proamyloidogenic factors, oxidative damage [125,126] and raised cholesterol levels [127].”

What the sources say

• Not checked yetcites [125] Friedlich, 1994, Involvement of free oxygen radicals in beta-amyloidosis, an hypothesis, Neurobiol. Aging source
• Not checked yetcites [126] Hensley, 1994, A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: Relevance to Alzheimer disease, Proc. Natl. Acad. Sci. USA source
• Not checked yetcites [127] Soudamini, 1992, Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin, Indian J. Physiol. Pharmacol.

In the paper

“These nanoparticles were found to be able to destroy amyloid aggregation and exhibit antioxidative activity without a cytotoxic effect [99,100].”

What the sources say

• Not checked yetcites [99] Mathew, A., Fukuda, T., Nagaoka, Y., Hasumura, T., Morimoto, H., Yoshida, Y., Maekawa, T., Venugopal, K., and Kumar, D.S. (2012). Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS ONE, 7. source
• Not checked yetcites [100] Tiwari, 2013, Correction to Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer’s Disease Model via Canonical Wnt/β-Catenin Pathway, ACS Nano source

In the paper

“Nanoliposomes of curcumin have high affinity for Aβ1-42 fibrils and were found to inhibit the formation of fibrillar and oligomeric Aβ in-vitro [101,102].”

What the sources say

• Not checked yetcites [101] Mourtas, 2011, Curcumin-decorated nanoliposomes with very high affinity for amyloid-β1-42 peptide, Biomaterials source
• Not checked yetcites [102] Taylor, 2011, Effect of curcumin-associated and lipid ligand-functionalized nanoliposomes on aggregation of the Alzheimer’s Aβ peptide, Nanomedicine source

In the paper

“Curcumin can inhibit Aβ aggregation or promote its disaggregation at low concentrations (IC50 = 0.81–1 μM).”

In the paper

“A randomized, double-blind, placebo-controlled trial reported that Bacopa treatment (300 mg/kg, daily) for 12 weeks caused increased stool frequency, abdominal cramps and nausea, which may be due to either an upregulation of ACh level or saponin-mediated gastrointestinal tract irritation, or both [91].”

What the sources say

• Not checked yetcites [91] Morgan, 2010, Does Bacopa monnieri Improve Memory Performance in Older Persons? Results of a Randomized, Placebo-Controlled, Double-Blind Trial, J. Altern. Complement. Med. source

In the paper

“Curcumin also demonstrated a protective effect against Aβ neurotoxicity by decreasing Aβ production through downregulation of presenilin 1 (PS1) and GSK-3-β expression and accelerating Aβ fibril conversion [104,105].”

What the sources say

• Not checked yetcites [104] Caesar, I., Jonson, M., Nilsson, K.P.R., Thor, S., and Hammarström, P. (2012). Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila. PLoS ONE, 7. source
• Not checked yetcites [105] Xiong, 2011, Curcumin mediates presenilin-1 activity to reduce β-amyloid production in a model of Alzheimer’s disease, Pharm. Rep. source

In the paper

“Apolipoprotein E3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin (ApoE3-C-PBCA) provided photostability, enhanced the cellular uptake of curcumin and increased its efficacy against Aβ induced cytotoxicity [103].”

What the sources say

• Not checked yetcites [103] Mulik, 2010, ApoE3 Mediated Poly(butyl) Cyanoacrylate Nanoparticles Containing Curcumin: Study of Enhanced Activity of Curcumin against Beta Amyloid Induced Cytotoxicity Using In Vitro Cell Culture Model, Mol. Pharm. source

In the paper

“The intraperitoneal LD50 was 1000 mg/kg for aqueous extract and 15 g/kg for alcoholic extract [94].”

What the sources say

• Not checked yetcites [94] Martis, 1992, Neuropharmacological activity of Herpestis monniera, Fitoterapia

In the paper

“Low dose curcumin significantly lowered the soluble Aβ levels, insoluble amyloid and plaque burden by nearly 40% [106].”

What the sources say

• Not checked yetcites [106] Lim, 2001, The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse, J. Neurosci. source

In the paper

“Impaired insulin or insulin-like growth factor-1 (IGF-1) signaling is associated with AD. It leads to hyperphosphorylation of the tau protein, mitochondrial dysfunction, oxidative stress and necrosis, and contributes to cognitive impairment [113,114,115].”

What the sources say

• Not checked yetcites [113] Wands, 2005, Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system, relevance to Alzheimer’s disease, J. Alzheimers Dis. source
• Not checked yetcites [114] Schubert, 2003, Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation, J. Neurosci. source
• Not checked yetcites [115] Schubert, 2004, Role for neuronal insulin resistance in neurodegenerative diseases, Proc. Natl. Acad. Sci. USA source

In the paper

“W. somnifera exhibits a broad range of biological activities like anti-inflammatory, antioxidant, neuroprotective, antischemic, anti-Parkinson’s, antiepileptic, anxiolytic, antidepression, antiarthritic, cardioprotective, antidiabetic, anticancer, antistress, nephroprotective, heptoprotective, antihypoxic, immunomodulatory, hypolipidaemic and antimicrobial [152].”

What the sources say

• Not checked yetcites [152] Kumar, 2015, Chemistry and pharmacology of Withania somnifera: An update, Tang (Humanit. Med.)

In the paper

“Evidence also suggests that metals are concentrated in the AD brain and curcumin chelates iron and copper (but not zinc) bound to beta amyloid potentially contributing to amyloid reduction [134].”

What the sources say

• Not checked yetcites [134] Baum, 2004, Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models, J. Alzheimers Dis. source

In the paper

“Ethanolic extract of aerials parts and root of C. ternatea have been studied at 200–3000 mg/kg, p.o in mice. A cathartic effect of root extract was observed.”

What the sources say

• Not checked yetcites [140] Taranalli, 2000, Influence of Clitoria ternatea extracts on memory and central cholinergic activity in rats, Pharm Biol. source

In the paper

“The extract was not lethal orally but resulted in severe CNS depression and death when used intraperitoneally at dose of 2900 mg/kg and above [140].”

What the sources say

• Not checked yetcites [140] Taranalli, 2000, Influence of Clitoria ternatea extracts on memory and central cholinergic activity in rats, Pharm Biol. source

In the paper

“In an acute toxicity study, ethanolic extract of rhizome of C. longa at the doses of 0.5, 1.0 and 3.0 mg/kg did not cause any sign of toxicity in mice. Moreover, no toxicity was found at 100 mg/kg/day in the 90-day toxicity study in mice [137].”

What the sources say

• Not checked yetcites [137] Qadri, 2001, Acute toxicological evaluation of the aqueous extract of Eclipta alba Hassk, Pak. J. Sci. Ind. Res.

In the paper

“The extract improved retention in the passive avoidance task and spatial performance in the T-maze test.”

What the sources say

• Not checked yetcites [141] Rai, 2001, Clitoria ternatea (Linn) root extract treatment during growth spurt period enhances learning and memory in rats, Indian J. Physiol. Pharmacol.

In the paper

“Mice treated with a dose above 2000 mg/kg had ptosis and were lethargic.”

What the sources say

• Not checked yetcites [140] Taranalli, 2000, Influence of Clitoria ternatea extracts on memory and central cholinergic activity in rats, Pharm Biol. source

In the paper

“Sitoindosides VII-X and withaferin differentially (40 mg/kg for 7 days) but favorably altered the AChE activity and enhanced M1- and M2-muscarinic receptor-binding in various brain regions [157].”

What the sources say

• Not checked yetcites [157] Schliebs, 1997, Systemic administration of defined extracts from Withania somnifera (Indian ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain, Neurochem. Int. source

In the paper

“In the same study, β-amyloid fibril formation was prevented, possibly due to the presence of a serotonin moiety in both withanamide compounds.”

What the sources say

• Not checked yetcites [160] Jayaprakasam, 2010, Withanamides in Withania somnifera fruit protect PC-12 cells from beta-amyloid responsible for Alzheimer’s disease, Phytother Res. source

In the paper

“Treatment with Withania root extract (1 g/kg, p.o for 30 days) reversed the AD pathology by upregulating the low-density lipoprotein receptor-related protein, which enhanced the Aβ clearance and ameliorated the cognitive deficit in middle-aged and old APP/PS1 mice [161].”

What the sources say

• Not checked yetcites [161] Sehgal, 2012, Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver, Proc. Natl. Acad. Sci. USA source

In the paper

“In a systematic review, Ng and colleagues mentioned that W. somnifera extract ameliorated cognitive impairment and improved executive functions in adults with mild cognitive impairment [169].”

What the sources say

• Not checked yetcites [169] Ng, 2019, A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction, Phytother. Res. source

In the paper

“In-vitro, aqueous and hydroalcoholic extracts of E. alsinoides showed free radicals scavenging, anti-inflammatory and enzymes (cholinesterase, glycogen synthase kinase-3-β, Rho kinase (ROCKI I), prolyl endopeptidase, catechol-o-methyl transferase and monoglycerol lipase) inhibitory activity, all of which are involved in the pathophysiology of AD [15].”

What the sources say

• Not checked yetcites [15] Mehla, 2012, Amelioration of intracerebroventricular streptozotocin induced cognitive impairment by Evolvulus alsinoides in rats: In vitro and in vivo evidence, Neurochem. Int. source

In the paper

“The oil of C. paniculatus seeds when given for 14 days to Wistar rats at a dose of 400 mg/kg resulted in enhanced learning and memory in radial arm maze and decreased the AChE enzyme activity in hypothalamus, frontal cortex and hippocampus [178].”

What the sources say

• Not checked yetcites [178] Lekha, 2010, Cognitive enhancement and Neuroprotective effect of Celastrus paniculatus Willd. seed oil (Jyothismati oil) on male Wistar rats, J. Pharma. Sci. Tech.

In the paper

“W. somnifera (20 mg/mL) treatment mitigated the Aβ toxicity and mediated longevity in the AD model of Drosophila melanogaster [167].”

What the sources say

• Not checked yetcites [167] Halim, M.A., Rosli, I.M., Jaafar, S.S.M., Ooi, H., Leong, P., Shamsuddin, S., Najimudin, N., and Azzam, G. (2020). Withania somnifera showed neuroprotective effect and increase longevity in Drosophila Alzheimer’s disease model. bioRxiv. source

In the paper

“The methanol and water extract of E. alsinoides documented to exhibit acetylcholinesterase activity, supporting its potential in reverting neuronal dysfunctions and thus in management of AD [193].”

What the sources say

• Not checked yetcites [193] Patel, 2018, Medicinal plants with acetylcholinesterase inhibitory activity, Rev. Neurosci. source

In the paper

“The seed oil treatment for 14 days at the doses of 50, 200 and 400 mg/kg, p.o reversed scopolamine induced spatial memory impairment in the Morris water maze and increased locomotor activity without affecting AChE activity in rats [180].”

What the sources say

• Not checked yetcites [180] Gattu, 1997, Reversal of Scopolamine-Induced Deficits in Navigational Memory Performance by the Seed Oil of Celastrus paniculatus, Pharm. Biochem. Behav. source

In the paper

“Kim et al. [209] also reported that butanol fraction increased ACh content, decreased MAO-B activity and reduced oxidative stress in the rat brain.”

What the sources say

• Not checked yetcites [209] Kim, 2010, The butanol fraction of Eclipta prostrata (Linn) increases the formation of brain acetylcholine and decreases oxidative stress in the brain and serum of cesarean-derived rats, Nutr. Res. source

In the paper

“The root extract and their chemical constituents such as glycowithanolides also possess anxiolytic, antidepressant, anti-inflammatory and antioxidant activities, which may be relevant in AD treatment [164,165].”

What the sources say

• Not checked yetcites [164] Dhuley, 1998, Effect of ashwagandha on lipid peroxidation in stress-induced animals, J. Ethnopharmacol. source
• Not checked yetcites [165] Panda, 1997, Evidence for free radical scavenging activity of Ashwagandha root powder in mice, Indian J. Physiol. Pharmacol.

In the paper

“A prospective, randomized, double-blind, placebo-controlled study reported that treatment with ashwagandha-root extract (300 mg twice daily for eight weeks) improved immediate and general memory functions and enhanced executive function, attention and information processing speed in adults with a mild cognitive impairment [168].”

What the sources say

• Not checked yetcites [168] Choudhary, 2017, Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions, J. Diet. Suppl. source

In the paper

“The aqueous seed extract improved memory performance in elevated plus maze and in sodium nitrite induced amnesia by reducing the AChE activity [181].”

What the sources say

• Not checked yetcites [181] Bhanumathy, 2010, Nootropic activity of Celastrus paniculatus seed, Pharm. Biol. source

In the paper

“Furthermore, withanone, a chemical constituent from root extract of W. somnifera showed improvement in cognitive functions by inhibiting amyloid processing and reducing the elevated levels of proinflammatory cytokines and oxidative stress markers [166].”

What the sources say

• Not checked yetcites [166] Pandey, 2018, Multifunctional neuroprotective effect of Withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunction, Cytokine source

In the paper

“C. pluricaulis also possesses antioxidant and hypolipidemic effects, which may be partially responsible for improvement in cognitive function [190,241].”

What the sources say

• Not checked yetcites [190] Nahata, 2009, Anxiolytic activity of Evolvulus alsinoides and Convulvulus pluricaulis in rodents, Pharm Biol. source
• Not checked yetcites [241] Chaturvedi, 1997, Hypolipidaemic effect of Convolvulus microphyllus on cholesterol fed gerbils, J. Phytol. Res.

In the paper

“C. pluricaulis administration for 3 months at the dose of 150 mg/kg prevented aluminum chloride induced neurotoxicity by decreasing AChE activity, reducing oxidative stress and preserving the activity of ChAT and Nerve Growth Factor-Tyrosine kinase A receptor (NGF-TrkA) [242].”

What the sources say

• Not checked yetcites [242] Bihaqi, 2009, Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain, J. Ethnopharmacol. source

In the paper

“Administration for 20 days at a dose of 100 mg/kg/day significantly prolonged the shortened step-through latency induced by aluminum administration and also significantly improved retention of learning in aged rats [248].”

What the sources say

• Not checked yetcites [248] Handa, 1997, Effect of BR-16A (MentatR) on cognitive deficits in aluminium-treated and aged rats, Indian J. Pharmacol.

In the paper

“Sharma et al. [240] also reported that the ethanolic extract at 100 and 200 mg/kg oral dose significantly improved memory in young and aged mice but the retention was better in young mice.”

What the sources say

• Not checked yetcites [240] Sharma, 2010, Effect of Convolvulus pluricaulis Choisy and Asparagus racemosus Willd on learning and memory in young and old mice: A comparative evaluation, Indian J. Exp. Boil.

In the paper

“The LD50 was found to be 1.75 g/kg after intraperitoneal injection [254] and 2400 mg/kg after oral administration [250].”

What the sources say

• Not checked yetcites [254] Jagetia, 2003, Treatment of mice with a herbal preparation (Mentat) protects against radiation-induced mortality, Phytother. Res. source
• Not checked yetcites [250] Verma, 1991, Effect of a herbal psychotropic preparation, BR-16A (Mentat), on performance of mice on elevated plus-maze, Indian J. Exp. Boil.

In the paper

“BR-16A (Mentat) is a polyherbal formulation used as Medhya Rasayana in Ayurveda and is used to improve memory and cognitive deficits associated with chronic illness and aging [156].”

What the sources say

• Not checked yetcites [156] Bhattacharya, 1995, Effects of glycowithanolides from Withania somnifera on an animal model of Alzheimer’s disease and perturbed central cholinergic markers of cognition in rats, Phytother. Res. source

In the paper

“Convolvine, a chemical constituent of C. pluricaulis potentiated the effect of arecoline (memory enhancer) and improved cognitive dysfunction in AD [238,239].”

What the sources say

• Not checked yetcites [238] Asthana, 1996, Clinical pharmacokinetics of arecoline in subjects with Alzheimer’s disease, Clin. Pharm.
• Not checked yetcites [239] Mirzaev, 1998, Neuro- and psychopharmacological investigation of the alkaloids convolvine and atropine, Chem. Nat. Compd. source

In the paper

“It improved memory quotient of normal subjects in different age groups [252], increased memory span and attenuated fluctuations of attention in normal adults and improved learning ability in children with behavioral problems or minimal brain damage [253].”

What the sources say

• Not checked yetcites [252] Agarwal, 1991, Effect of Mentat on memory, anxiety scores and neuroticism index in normal subjectsin three age groups, Probe
• Not checked yetcites [253] Koti, 1991, Effect of Mentat on school students performance, Probe

In the paper

“E. alba also possesses antiviral, antinociceptive, anti-inflammatory, bronchodilator, antibacterial, antipyretic, tonic, expectorant and hepatoprotective activity [211,212].”

What the sources say

• Not checked yetcites [211] Kirtikar, K.R., and Basu, B.D. (1975). Indian Medicinal Plants, Jayyed Press. [2nd ed.].
• Not checked yetcites [212] Rajagopal, V. (2002). Standardization of Botanicals, Eastern Publishers.

In the paper

“Mentat has been shown to augment acquisition and retention of learning in rats and prevented cognitive deficits induced by variety of insults including prenatal undernutrition, postnatal environmental impoverishment, sodium nitrite hypoxia, aluminum, increasing age and electroconvulsive shock induced antero-grade and retro-grade amnesia [246,247,248].”

What the sources say

• Not checked yetcites [246] Bhattacharya, 1994, Nootropic effect of BR-16A (Mentat), a psychotropic herbal formulation, on cognitive deficits induced by prenatal undernutrition, postnatal environmental impoverishment and hypoxia in rats, Indian J. Exp. Boil.
• Not checked yetcites [247] Faruqi, 1995, Herbal pharmacotherapy for the attenuation of electroconvulsive shock-induced anterograde and retrograde amnestic deficits, Convuls. Ther.
• Not checked yetcites [248] Handa, 1997, Effect of BR-16A (MentatR) on cognitive deficits in aluminium-treated and aged rats, Indian J. Pharmacol.

In the paper

“The alcoholic extract did not show any toxicity in rats and mice and the minimum lethal dose was found to be greater than 2.0 g/kg when given orally and intraperitonially in mice [214].”

What the sources say

• Not checked yetcites [214] Singh, 1993, Hepatoprotective effect of ethanolic extract ofEclipta alba on experimental liver damage in rats and mice, Phytother. Res. source

In the paper

“Lipid lowering and antioxidant activities of Eclipta plants have also been reported [210].”

What the sources say

• Not checked yetcites [210] Kim, 2008, The butanol fraction of Eclipta prostrata (Linn) effectively reduces serum lipid levels and improves antioxidant activities in CD rats, Nutr. Res. source

In the paper

“The ethanolic leaf extract at a dose of 250 mg/kg, p.o for 14 days provided protection against cognitive impairment induced by ICV–colchicine. It restored colchicine induced changes in the brain norepinephrine, serotonin and dopamine levels [224].”

What the sources say

• Not checked yetcites [224] Ganguly, 2008, Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer’s disease & protection by Moringa oleifera, Indian J. Med Res.

In the paper

“Apart from these inherent risks of herbal medicines, several adverse effects associated with them may be due to improper labeling, unknown composition, a lack of standardization, inferior quality, contamination, adulteration, improper use and even quackery.”

In the paper

“However, much work remains to be done to translate this potential into actual medicine.”

In the paper

“The results of these studies indicate that Abana improves memory, which may be due to reduction in brain AChE activity.”

What the sources say

• Not checked yetcites [261] Parle, 2007, Memory Enhancing Activity of Abana®: An Indian Ayurvedic Poly-Herbal Formulation, J. Health Sci. source

In the paper

“Medicinal plants provide a fertile ground for new drug discovery because of the presence of various chemical constituents and their ability to act on different biological targets.”

In the paper

“The effect of memorin was evaluated by Andrade, 1998 in an age related memory disorder and reported beneficial effects in elderly persons who experienced age related memory decline [256].”

What the sources say

• Not checked yetcites [256] Andrade, 1998, Treatment of Age-Related Cognitive Decline with a Herbal Formulation: A Double-Blind Study, Indian J. Psychiatry