Evidence map›Paper›PMID 40023576›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2025

Evaluation of reversible cytochrome P450 inhibition by Withania somnifera leaf and root extracts.

Zarna Raichura, Kabre Heck, Jaewoo Choi, Liping Yang, Mikah Brandes, Luke Marney, Armando Alcázar Mangaña, Cody Neff, Claudia S Maier, Amala Soumyanath and 3 more

Abstract read
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Ashwagandha (Journal of dietary supplements · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Zarna RaichuraDepartment of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, Alabama.
Kabre HeckDepartment of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, Alabama.
Jaewoo ChoiLinus Pauling Institute, Oregon State University, Corvallis, Oregon; Botanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA), Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, Oregon.
Liping YangDepartment of Chemistry, Oregon State University, Corvallis, Oregon; Botanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA), Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, Oregon.
Mikah BrandesBotanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA), Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, Oregon; Department of Neurology, Oregon Health & Science University, Portland, Oregon.
Luke MarneyDepartment of Chemistry, Oregon State University, Corvallis, Oregon; Botanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA), Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, Oregon.
Armando Alcázar MangañaDepartment of Chemistry, Oregon State University, Corvallis, Oregon; Botanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA), Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, Oregon.
Cody NeffBotanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA), Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, Oregon; Department of Neurology, Oregon Health & Science University, Portland, Oregon.
Claudia S MaierDepartment of Chemistry, Oregon State University, Corvallis, Oregon; Linus Pauling Institute, Oregon State University, Corvallis, Oregon; Botanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA), Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, Oregon.
Amala SoumyanathBotanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA), Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, Oregon; Department of Neurology, Oregon Health & Science University, Portland, Oregon.
Richard B van BreemenLinus Pauling Institute, Oregon State University, Corvallis, Oregon.
Robert D ArnoldDepartment of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, Alabama.
Angela I CalderónDepartment of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, Alabama. Electronic address: aic0001@auburn.edu.

Funding

Evaluation of the potential of Ashwagandha extracts to produce CYP-mediated drug interactions.R03AT011501 · NCCIH · AUBURN UNIVERSITY AT AUBURN · PI ARNOLD, ROBERT D · 2021 to 2022
$149k
NCCIH NIH HHS R03 AT011501
6 · The paper itself

Abstract

It is important to understand the potential of botanical-drug interactions to ensure the safe use of botanical dietary supplements (BDS). Cytochrome P450 (P450) is one of the most abundant phase 1 drug-metabolizing enzymes and is accountable for a great deal of pharmacokinetic botanical-drug interactions. This problem is particularly acute for older adults who often consume BDS with multiple prescription medicines. The consequences of botanical-drug interactions can lead to lack of prodrug efficacy or drug toxicity from reduced drug clearance through inhibition of P450 metabolizing enzymes. In this study, a 7-in-1 cocktail P450 inhibition assay with 7 Food and Drug Administration-recommended P450s (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, and CYP3A4/5) including CYP2B6 recombinant enzyme was performed, minimizing substrate interactions with respect to specificity while maximizing assay sensitivity. High-performance liquid chromatography-mass spectrometry was used for quantitative determination of probe substrate metabolism. Withania somnifera L. Dunal (ashwagandha), a popular BDS in the United States with sales of ∼$16 million in 2021, is used to promote sleep and relieve stress and anxiety, especially in older adults. However, comprehensive studies of pharmacokinetic drug interactions with ashwagandha, especially with leaf extracts, have not been reported. Four extracts from ashwagandha root or leaf were evaluated for P450 inhibition, and no reversible inhibition was detected at IC

Indexed as

Cytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemHerb-Drug InteractionsPlant ExtractsPlant RootsWithaniaDrug InteractionsHumansPlant LeavesCytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemPlant ExtractsAshwagandhaBotanical-drug interactionsCytochrome P450Enzyme inhibitionLiquid chromatography-mass spectrometry

Identifiers

PMID40023576
PMCPMC13095409

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.