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

Kumar, Saneesh; Bouic, Patrick; Rosenkranz, Bernd

doi:10.1016/j.jep.2020.113766

Cited by 13 publications

(10 citation statements)

References 83 publications

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“…For Withania somnifera root extract it is not finally clarified as to whether there is an interaction with cytochrome P450 enzymes or choline esterases [ 116 , 117 , 118 , 119 ]. However, precaution regarding respective possible adverse effects or drug interactions with concomitant medication including modulation of drug efficacy is indicated.…”

Section: Discussionmentioning

confidence: 99%

Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

Witte

Sabat

Witte-Händel

et al. 2022

IJMS

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Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep-seated, inflamed nodules and pus-discharging abscesses and fistulas. Affecting about 1% of the population, this common disease has gained appropriate clinical attention in the last years. Associated with numerous comorbidities including metabolic syndrome, HS is considered a systemic disease that severely impairs the quality of life and shortens life expectancy. Therapeutic options for HS are limited, comprising long-term antibiotic treatment, the surgical removal of affected skin areas, and neutralization of TNF-α, the only approved systemic treatment. Novel treatment options are needed to close the therapeutic gap. HS pathogenesis is increasingly better understood. In fact, neutrophilic granulocytes (neutrophils) seem to be decisive for the development of the purulent destructive skin inflammation in HS. Recent findings suggest a key role of the immune mediators IL-1β, IL-17A and G-CSF in the migration into and activation of neutrophils in the skin. Although phytomedical drugs display potent immunoregulatory properties and have been suggested as complementary therapy in several chronic disorders, their application in HS has not been considered so far. In this review, we describe the IL-1/IL-17/G-CSF axis and evaluate it as potential target for an integrated phytomedical treatment of HS.

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Section: Discussionmentioning

confidence: 99%

Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

Witte

Sabat

Witte-Händel

et al. 2022

IJMS

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“…An aqueous extract of WS did not inhibit human recombinant CYP3A4 at doses as high as 1000 µg/mL [ 160 ]. Methanol and ethylacetate extracts of WS root had IC 50 values of 79 and 58 μg/mL, respectively, for CYP2B6 in HLM, whereas aqueous and ethanolic extracts were not inhibitory at up to 200 μg/mL [ 161 ]. None of the extracts inhibited β-esterase-dependent rifampicin metabolism in HLM or induced mRNA of CYP2B6 or CYP3A4 in HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia

Speers

Cabey

Soumyanath

et al. 2021

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Background: Withania somnifera (WS), also known as Ashwagandha, is commonly used in Ayurveda and other traditional medicine systems. WS has seen an increase in public use worldwide due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders. Objective: This review aims to provide a comprehensive summary of preclinical and clinical studies examining the neuropsychiatric effects of WS, specifically its application in stress, anxiety, depression, and insomnia. Methods: Reports of human trials and animal studies of WS were collected primarily from the PubMed, Scopus, and Google Scholar databases. Results: WS root and leaf extracts exhibited noteworthy anti-stress and anti-anxiety activity in animal and human studies. WS also improved symptoms of depression and insomnia, though fewer studies investigated these applications. WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through GABAergic and serotonergic pathways. While some studies link specific withanolide components to its neuropsychiatric benefits, there is evidence for the presence of additional yet unidentified active compounds in WS. Conclusion: While benefits were seen in the reviewed studies, significant variability in the WS extracts examined prevents a consensus on the optimum WS preparation or dosage from treating neuropsychiatric conditions. WS generally appears safe for human use; however, it will be important to investigate potential herb-drug interactions involving WS if used alongside pharmaceutical interventions. Further elucidation of active compounds of WS is also needed.

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“…However, several studies reported no significant inhibitory effects of W. somnifera extract on the CYP isoforms, which are associated with NAPQI generation from APAP (Savai et al, 2013;Varghese et al, 2014;Dey et al, 2015;Savai et al, 2015), indicating that it is less likely that WA exerts hepatoprotective effect towards APAP-induced liver injury by inhibiting CYP-mediated APAP metabolic activation. However, W. somnifera extract was found to exhibit inductive effects on CYP3A4 and CYP1A enzymes (Kumar et al, 2021). Thus, further study is warranted to determine the extent by which metabolic activation of APAP is involved in reducing APAP-induced hepatotoxicity after W. somnifera and WA treatment.…”

Section: Effects Of Wa In Thementioning

confidence: 97%

Withaferin A in the Treatment of Liver Diseases: Progress and Pharmacokinetic Insights

et al. 2021

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Withaferin A (WA) is a natural steroidal compound used in Ayurvedic medicine in India and elsewhere. While WA was used as an anti-cancer reagent for decades, its role in the treatment of liver diseases has only recently been experimentally explored. Here, the effects of WA in the treatment of liver injury, systematic inflammation, and liver cancer are reviewed, and the toxicity and metabolism of WA as well as pharmacological potentials of other extracts from W. somnifera discussed. The pharmacokinetic behaviors of WA are summarized and pharmacokinetic insights into current progress and future opportunities are highlighted. SIGNIFICANCE STATEMENTThis review outlines the current experimental progress of WA hepatoprotective activities and highlights gaps in the field. This work also discusses the pharmacokinetics of WA that can be used to guide future studies for the possible treatment of liver diseases with this compound.

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

Cited by 13 publications

References 83 publications

Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia

Withaferin A in the Treatment of Liver Diseases: Progress and Pharmacokinetic Insights

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