Ashwagandha extracts and liver drug enzymes in lab tests
What it found
In lab tests on human liver cells, a 70% ethanol ashwagandha root extract doubled the expression of the CYP3A4 enzyme, which handles about half of prescription drugs.
A high concentration of the 70% ethanol leaf extract reduced liver cell viability after 72 hours.
What they found
Animal and lab studies
CYP3A4 enzyme doubled
The 70% ethanol root extract (WSR-2) doubled the expression of the CYP3A4 enzyme compared with untreated cells. This was about 20% of the effect of the positive control rifampicin, and a follow-up activity test confirmed the increase.
Other enzymes unchanged
None of the ashwagandha extracts strongly increased CYP1A2 or CYP2B6 in the human liver cells. The 70% ethanol root extract did increase CYP2C8, but not CYP2C9 or CYP2C19.
Leaf extract and cell viability
A high concentration (0.57 mg/mL) of the 70% ethanol leaf extract (WSL-2) reduced liver cell viability after 72 hours. No changes were seen at 24 or 48 hours, and the other extracts kept cell viability above 90%.
Other findings
Precipitation in medium
Some extracts formed visible particles in the cell culture medium, and the withaferin A level dropped in the medium for most extracts. The 70% ethanol leaf extract was an exception, which the authors suggest may be due to chemical changes or release of bound withaferin A.
What the authors conclude
- They say the findings highlight the need for standardization of botanical dietary supplements and for evaluating their effects on drug metabolism pathways.
- They call for future research with diverse donor populations, including different genders and races, and for clinical studies to assess the safety of ashwagandha.
How it was done
Ashwagandha is one of the top 10 botanicals in the U.S. market, and its growing use raises concerns about interactions with prescription drugs. The authors wanted to see whether ashwagandha extracts can increase cytochrome P450 enzymes, which are important for how the body breaks down drugs.
They tested four ashwagandha extracts (water and 70% ethanol extracts of roots and leaves) on primary human liver cells from one 58-year-old male donor, using a sandwich-culture method. Cells were treated for 24 hours, and the researchers measured the expression of CYP3A4, CYP2B6, and CYP1A2, plus cell viability at 24, 48, and 72 hours.
What it can’t tell you
- This was a lab study using liver cells from a single donor, so it cannot show what happens in people who take ashwagandha.
- The results cannot prove that ashwagandha causes liver harm or that it changes drug levels in the body.
- The authors note that clinical studies are needed to determine the real-world relevance of these findings.
Who paid
- Funding
- Funded by NCCIH NIH HHS; NIH HHS; NCRR NIH HHS (from the PubMed record).
- Conflicts
- Disclosure statement. No potential conflict of interest was reported by the author(s).
- Authors work at
- Auburn University, USA; Oregon State University, USA; Oregon Health and Science University, USA
The paper
- Title
- Ashwagandha ( Withania somnifera ) Plant Extracts Affect the Cytochrome P450 System and Cytotoxicity of Primary Human Hepatocytes
- Type
- Study
- Evidence
- Animals and lab studies
- Summarised from
- Full text
- Cite
- McDonald KL, Raichura Z, Pondugula SR, et al (2025). Ashwagandha ( Withania somnifera ) Plant Extracts Affect the Cytochrome P450 System and Cytotoxicity of Primary Human Hepatocytes. Journal of dietary supplements. doi:10.1080/19390211.2025.2514458Free full textPubMed 40551718DOI
Summary written 29 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error