Cholinesterase Inhibiting Withanolides from Withania somnifera.

Choudhary, Muhammad Iqbal; Yousuf, Sammer; Nawaz, Syed Junaid; Ahmed, Shakil; Atta‐ur‐Rahman, Atta‐ur‐Rahman

doi:10.1002/chin.200515176

Cited by 15 publications

(19 citation statements)

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“…One of the most common variations in the withaferin A substitution pattern is the hydrolytic cleavage of the 5,6-epoxide according to the F€ urst-Plattner rule (16), to give the trans-diaxial 5a,6b-diol as in coagulin H (7) and coagulin S (8) isolated from W. coagulans (17,18). A less common cleavage is that occurring in a transdiequatorial manner, as found in 9 and 10 (14), later reported as new by Kuroyanagi et al (19), and in 4-deoxywithaperuvin (11) (20). Compound 12 represents an unusual variant of the above, with a 3a,6a-epoxy bridge (21), which could derive from the cyclization of 10 also present in the same extract.…”

Section: B6b-epoxywithanolides and Related Compoundsmentioning

confidence: 97%

“…Acetylcholinesterase (AChE) inhibitors activate central cholinergic function by increasing the acetylcholine levels in the brain. Bracteosins A (206), B (207), and C (208), isolated from Ajuga bracteosa (108), and withanolide A (504) and withaferin A (1) from W. somnifera, were moderate inhibitors of AChE and BChE (butyrylcholinesterase) (11). Molecular docking studies indicated that all compounds are imbedded in the aromatic gorge of AChE.…”

Section: Cholinesterase Inhibitionmentioning

confidence: 99%

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Withanolides and Related Steroids

Misico

Nicotra

Oberti

et al. 2011

Progress in the Chemistry of Organic Natural Products Vol. 94

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Section: B6b-epoxywithanolides and Related Compoundsmentioning

confidence: 97%

Section: Cholinesterase Inhibitionmentioning

confidence: 99%

Withanolides and Related Steroids

Misico

Nicotra

Oberti

et al. 2011

Progress in the Chemistry of Organic Natural Products Vol. 94

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“…We had expected a broader profile of cognitive benefits with WSE due to its diverse pharmacologic actions [22][23][24][25][26][30][31][32][33] ; however, narrower results were obtained in this study. Recent work has indicated that WSE reversed deficits in spatial learning and working memory tasks in mouse models of Alzheimer's disease 43 probably by promoting hepatic clearance of β-amyloid.…”

Section: Discussionmentioning

confidence: 71%

“…[31][32][33] Given these diverse pharmacologic actions, we postulated that adjunctive WSE treatment would improve cognitive functions broadly in subjects with bipolar disorder, eg, executive functions, working memory, attention, processing speed, and memory.…”

mentioning

confidence: 99%

Randomized Placebo-Controlled Adjunctive Study of an Extract ofWithania somniferafor Cognitive Dysfunction in Bipolar Disorder

Chengappa

Bowie²,

Schlicht³

et al. 2013

J. Clin. Psychiatry

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Objective:Cognitive impairments contribute significantly to inadequate functional recovery following illness episodes in bipolar disorder, yet data on treatment interventions are sparse. We assessed the cognitive effects of a standardized extract of the medicinal herb Withania somnifera (WSE) in bipolar disorder.Method: Sixty euthymic subjects with DSM-IV bipolar disorder were enrolled in an 8-week, double-blind, placebo-controlled, randomized study of WSE (500 mg/d) as a procognitive agent added adjunctively to the medications being used as maintenance treatment for bipolar disorder. Study enrollment and data analyses were completed between December 2008 and September 2012. Cognitive testing at baseline and 8 weeks assessed primary efficacy outcomes. Psychopathology and adverse events were monitored at scheduled visits.Results: Fifty-three patients completed the study (WSE, n = 24; placebo, n = 29), and the 2 groups were matched in terms of demographic, illness, and treatment characteristics. Compared to placebo, WSE provided significant benefits for 3 cognitive tasks: digit span backward (P = .035), Flanker neutral response time (P = .033), and the social cognition response rating of the Penn Emotional Acuity Test (P = .045). The size of the WSE treatment effect for digit span backward was in the medium range (Cohen d = 0.51; 95% CI, 0.25-0.77). None of the other cognitive tasks showed significant betweengroup differences. Mood and anxiety scale scores remained stable, and adverse events were minor. Conclusions:Although results are preliminary, WSE appears to improve auditory-verbal working memory (digit span backward), a measure of reaction time, and a measure of social cognition in bipolar disorder. Given the paucity of data for improving cognitive capacity in bipolar disorder, WSE offers promise, appears to have a benign side-effects profile, and merits further study.Trial Registration: ClinicalTrials.gov identifier: NCT00761761

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“…The main difference was the presence of an epoxy group linked at C-5/6, on the basis of NMR signals at : 3.16 (brs, H-6), 61.20 (C-6) and 64.51 (C-5) and confirmed by HMBC analysis. Compound 2 was established as 5b, 6b-epoxy-4b,17a,27-trihydroxy-1-oxowitha-2,24-dienolide, a withanolide previously isolated from W. somnifera and W. aristata (Choudhary et al, 2004;Llanos et al, 2012), but reported here for the first time in W. frutescens.…”

Section: Chemistrymentioning

confidence: 72%

Cytotoxic withanolides from the leaves of MoroccanWithania frutescens

Bouzidi

Mahiou-Leddet

Bun

et al. 2013

Pharmaceutical Biology

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Context: Withania species are a rich source of interesting phytochemical substances (withanolides) which have shown several biological properties. Objective: To investigate the cytotoxic potential of Withania frutescens (L.) Pauquy (Solanaceae) leaf extracts and isolated active compounds against cultured tumor cell lines. Materials and methods: The crude methanol extract of W. frutescens leaves was partitioned with dichloromethane, ethyl acetate and n-butanol. MeOH extract and its fractions were tested for their cytotoxic activity against cancer cell lines (HepG2 and HT29) using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Bioassay-guided fractionation was performed for the active CH 2 Cl 2 fraction employing column chromatography and preparative high-performance liquid chromatography. Structural elucidation of the isolated active compounds was carried out mainly by 1D and 2D NMR and mass spectrometry. The compounds were then tested for their cytotoxic activity. Results: The CH 2 Cl 2 fraction was the most active against HT29 cell line. The fractionation procedure resulted in the isolation of 4b,17a,27-trihydroxy-1-oxo-22-R-witha-2,5,24-trienolide (1), 5b,6b-epoxy-4b,17a,27-trihydroxy-1-oxowitha-2,24-dienolide (2) and 2,3-dihydroxywithaferin A-3b-O-sulfate (3). The latter exhibited the strongest cytotoxic activity against HT29 cancer cell lines (IC 50 of 1.78 AE 0.09 mM) which was comparable to that of 5-fluorouracil (5-FU) used as the positive antimitotic control. Discussion and conclusion: Compounds 2 and 3 were isolated from W. frutescens for the first time. Data obtained suggest that the sulfated steroidal lactone (3) can be considered as a compound with potential application in the new anticancer drugs development field.

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Cholinesterase Inhibiting Withanolides from Withania somnifera.

Cited by 15 publications

References 1 publication

Withanolides and Related Steroids

Withanolides and Related Steroids

Randomized Placebo-Controlled Adjunctive Study of an Extract ofWithania somniferafor Cognitive Dysfunction in Bipolar Disorder

Cytotoxic withanolides from the leaves of MoroccanWithania frutescens

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