Ashwagandha (<i>Withania somnifera</i>) Plant Extracts Affect the Cytochrome P450 System and Cytotoxicity of Primary Human Hepatocytes
McDonald KL, Raichura Z, Pondugula SR, Marney L, Yang L, Choi J, Salamat JM, Brandes MS, Neff C, Adams K, Farmer G, Dennis C, Maier CS, Soumyanath A, Arnold RD, Calderón AI
Journal of dietary supplements · 6 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Institutes of Health
- Government
- National Center for Research Resources
- Government
- National Center for Complementary and Integrative Health
- Government
- National Institutes of Health Office of the Director
- Government
- National Institutes of Health National Center for Complementary and Integrative Health
- Government
- NCCIH NIH HHS
- Government
- National Institutes of Health National Center for Research Resources
- Government
- NIH HHS
- Government
- NCRR NIH HHS
- Grants
- National Center for Complementary and Integrative Health (U19 AT010829); National Center for Research Resources (S10 RR027878); National Center for Complementary and Integrative Health (R03 AT011501); National Institutes of Health (1s10od026922-01)
Based on 9 listed funder(s).
Publication
- Published
- 2025-06-24 · J Diet Suppl · vol. 22 · issue 4 · pp. 613–639
- Publisher
- Taylor & Francis
- Cited
- 7 citations · more than 97% of similar papers · 7.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 48 works
- Access
- Open access (repository copy)
- Research areas
- Phytochemicals and Medicinal Plants · Medicinal Plants and Neuroprotection
- Keywords
- Withania somnifera, Cytotoxicity, Viability assay, Pharmacology, Traditional medicine, Cytochrome P450, Nutraceutical, Biology, Chemistry, Biochemistry, Enzyme, In vitro, Medicine
- MeSH
- cells, cultured, hepatocytes, humans, withania, plant leaves, plant roots, cytochrome p-450 enzyme system, cytochrome p-450 cyp1a2, plant extracts, cell survival, herb-drug interactions, cytochrome p-450 cyp3a, hep g2 cells, cytochrome p-450 cyp2b6
16 authors
From US
- Kelli L. McDonaldAuburn University
- Zarna RaichuraAuburn University
- Satyanarayana R. PondugulaAuburn University
- Luke C. MarneyOregon State University; Oregon Health & Science University
- Liping YangOregon State University; Oregon Health & Science University
- Jae‐Woo ChoiOregon State University; Oregon Health & Science University
Abstract
Ashwagandha (Withania somnifera [L] Dunal) is emerging as one of the top 10 botanicals in the market due to its claimed health benefits as an adaptogen. Alongside its popularity, the lack of standardization in botanical dietary supplements and potential interactions with prescription drugs raise safety concerns. This study aimed to investigate the potential of ashwagandha extracts to induce cytochrome P450 (P450) enzymes, which are critical for drug metabolism and implicated in botanical-drug interactions. A sandwich-cultured in vitro assay using primary human hepatocytes was utilized to evaluate the induction potential of aqueous and 70% ethanolic extracts of ashwagandha roots and leaves on CYP3A4, CYP2B6, and CYP1A2-enzymes commonly involved in drug metabolism. Unlike prior studies that focused on root extracts or used HepG2 cell lines, this research included both root and leaf plant extracts, with the latter being assessed for the first time. Our approach using primary hepatocytes enhances clinical relevance compared to other in vitro models (such as HepG2 cell lines). Additionally, cytotoxicity was examined using CellTitre-Glo Luminescent Assay, measuring cell viability at three different incubation times (24, 48, and 72 hours) to assess the potential cytotoxic effect of the ashwagandha plant extracts. Our findings revealed that 70% ethanol ashwagandha root extracts (WSR-2) modulated CYP3A4 enzyme expression and activity. Preliminary studies on cytotoxicity indicated dose- and time-dependent impact on hepatocyte viability with a high concentration of 70% ethanol ashwagandha leaf extracts (WSL-2). The study highlights the importance of understanding ashwagandha's impact on P450-based drug metabolism and its safe co-administration with prescribed drugs.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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