In vitro Effect of Withania somnifera, Mucuna pruriens and Pausinystalia johimbe on Hepatic Cytochrome P450 in Rat

Sultana, Rajia; Sultan, Zakir

doi:10.3329/bpj.v21i2.37922

Cited by 4 publications

(2 citation statements)

References 13 publications

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“…Proposed mechanisms underlying those events involve: 1) interactions between adaptogen and cytochrome 450 isoenzymes responsible for antidepressant metabolism and 2) the addition of side effects of both substances. The first mechanism is related to the suggested inhibitory effect of Withania somnifera extracts on CYP3A4 and CYP2D6 ( Brinker, 2010 ; Sultana and Sultan, 2018 ). This results in an increase in the concentration and side effects of antidepressants metabolized by those cytochromes, particularly escitalopram (myalgia of intensity >5 according to the numeric rating scale (NRS), epigastric pain, nausea, vomiting, restless legs syndrome, and severe non-productive cough), paroxetine (generalized myalgia (NRS = 4–5), ophthalmalgia, and ocular hypertension), and reboxetine (testicle pain, ejaculatory dysfunctions, and pain during ejaculation).…”

Section: Discussionmentioning

confidence: 99%

“…However, there are conflicting results concerning the nature of those interactions. In vitro studies reported that Withania somnifera extracts may inhibit ( Sultana and Sultan, 2018 ), induce ( Kumar et al, 2021a ), or reveal no significant impact on CYP3A4 ( Savai et al, 2013 , Savai et al, 2015 ). Further studies are required to understand the associations between CYP isoenzymes and Withania somnifera extracts, as well as the clinical relevance of these findings.…”

Section: Discussionmentioning

confidence: 99%

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Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs

Siwek,

Woroń,

Wrzosek

et al. 2023

Front. Pharmacol.

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Aim: We aimed to systematically evaluate the prevalence and clinical characteristics of adverse events associated with the adaptogens and antidepressant drug interactions in a retrospective chart review.Methodology: A total of 1,816 reports of adverse events were evaluated. Cases were included in the analysis if the pharmacoepidemiological analysis showed the presence of a high probability of a causal relationship between an adaptogen and antidepressant interaction and the occurrence of adverse events. The following data were extracted from the reports: age, sex, antidepressant, plant products containing adaptogens, other concomitant medications, and clinical consequences of the interactions and their possible mechanisms.Results: Adaptogens were involved in 9% of adverse events associated with the concomitant use of antidepressants and other preparations. We identified 30 reports in which side effects presented a causal relationship with the use of antidepressants and adaptogens. Here, we present the list of adaptogens with the corresponding antidepressants and the side effects caused by their interactions: Withania somnifera: reboxetine (testicle pain and ejaculatory dysfunctions), sertraline (severe diarrhea), escitalopram (myalgia, epigastric pain, nausea, vomiting, restless legs syndrome, and severe cough), and paroxetine (generalized myalgia, ophthalmalgia, and ocular hypertension); Eleutherococcus senticosus: duloxetine (upper gastrointestinal bleeding), paroxetine (epistaxis), sertraline (vaginal hemorrhage), and agomelatine (irritability, agitation, headache, and dizziness); Schisandra chinensis: bupropion (arthralgia and thrombocytopenia), amitriptyline (delirium), and fluoxetine (dysuria); Tribulus terrestris: citalopram (generalized pruritus), escitalopram (galactorrhea), and trazodone (psoriasis relapse); Coptis chinensis: mianserin (arrhythmias), mirtazapine (edema of lower limbs and myalgia), and fluoxetine (gynecomastia); Cimicifuga racemosa: mianserin (restless legs syndrome), paroxetine (gynecomastia and mastalgia), and venlafaxine (hyponatremia); Bacopa monnieri: agomelatine (back pain and hyperhidrosis) and moclobemide (myocardial infarction); Gynostemma pentaphyllum: duloxetine (back pain); Cordyceps sinensis: sertraline (upper gastrointestinal bleeding); Lepidium meyenii: mianserin (restless legs syndrome); and Scutellaria baicalensis: bupropion (seizures).Conclusion: Clinicians should monitor the adverse events associated with the concomitant use of adaptogens and antidepressant drugs in patients with mental disorders. Aggregation of side effects and pharmacokinetic interactions (inhibition of CYP and p-glycoprotein) between those medicines may result in clinically significant adverse events.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs

Siwek,

Woroń,

Wrzosek

et al. 2023

Front. Pharmacol.

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Investigation of CYP2B6, 3A4 and β-esterase interactions of Withania somnifera (L.) dunal in human liver microsomes and HepG2 cells

Kumar

Bouic

Rosenkranz

2021

Journal of Ethnopharmacology

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Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats

Wangikar,

Chaudhari,

Sharma

et al. 2024

Drug Metabolism and Personalized Therapy

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Objectives Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. The existing study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90 days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. Methods In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90 days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90 days were also observed. Results In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90 days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. Conclusions The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

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In vitro Effect of Withania somnifera, Mucuna pruriens and Pausinystalia johimbe on Hepatic Cytochrome P450 in Rat

Cited by 4 publications

References 13 publications

Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs

Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs

Investigation of CYP2B6, 3A4 and β-esterase interactions of Withania somnifera (L.) dunal in human liver microsomes and HepG2 cells

Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats

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