ArticleFree radical biology & medicine2016
Withaferin A induces Nrf2-dependent protection against liver injury: Role of Keap1-independent mechanisms.
Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Effects of Withania somnifera (Ashwagandha) on Hematological and Biochemical Markers, Hormonal Behavior, and Oxidant Response in Healthy Adults: A Systematic Review.Current nutrition reports · 2023Pooled it
- Evaluation of 2-Thiothiazolidine-4-Carboxylic Acid, a Common Metabolite of Isothiocyanates, as a Potential Biomarker of Cruciferous Vegetable Intake.Molecular nutrition & food research · 2019Trial
- New Vistas for Withania somnifera in Signal Transduction of Inflammation and Aging.Pharmaceutical research · 2026Review
- Ashwagandha (Withania Somnifera): a comprehensive narrative review of its role in enhancing physical performance and health.Nutrition & metabolism · 2026Review
- The effect of a multi-herbal product,Research in pharmaceutical sciences · 2026Article
- Modulatory effects of Withania somnifera supplementation on p38 MAPK/NF-κB/COX-2 and TRPC1/CHOP signaling pathways in methotrexate-induced parotid and submandibular salivary gland toxicity in rats.Journal of molecular histology · 2026Article
- Natural Nrf2 activators modulate antioxidant gene expression and apoptosis in leukemic K-562 cells.Medical oncology (Northwood, London, England) · 2025Article
- Preclinical Evidence ofInternational journal of molecular sciences · 2025Review
- Activation of Nrf2 and FXR via Natural Compounds in Liver Inflammatory Disease.International journal of molecular sciences · 2024Review
- Withaferin A as a Potential Therapeutic Target for the Treatment of Angiotensin II-Induced Cardiac Cachexia.Cells · 2024Article
- On the Question of CO's Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources.ACS chemical biology · 2024Article
- Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal PlantPharmaceuticals (Basel, Switzerland) · 2023Review
- An updated review on phytochemistry and molecular targets ofFrontiers in pharmacology · 2023Review
- Ashwagandha-loaded nanocapsules improved the behavioral alterations, and blocked MAPK and induced Nrf2 signaling pathways in a hepatic encephalopathy rat model.Drug delivery and translational research · 2023Article
- Hepatoprotective Effects of Radish (Nutrients · 2022Article
- Hepatoprotective Activity of Ethanol Extract of Rice Solid-State Fermentation ofMolecules (Basel, Switzerland) · 2022Article
- Withaferin A in the Treatment of Liver Diseases: Progress and Pharmacokinetic Insights.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- An Injectable Dual-Function Hydrogel Protects Against Myocardial Ischemia/Reperfusion Injury by Modulating ROS/NO Disequilibrium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Review
- Withaferin A alleviates ethanol-induced liver injury by inhibiting hepatic lipogenesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Small molecules of plant origin offer presumptively safe opportunities to prevent carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the mechanisms of action of such plant-based agents remain largely unknown. In recent years the stress responsive transcription factor Nrf2 has been validated as a target for disease chemoprevention. Withania somnifera (WS) is a herb used in Ayurveda (an ancient form of medicine in South Asia). In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models. The goals of this study are to evaluate withanolides such as WA as well as Withania somnifera root extract as inducers of Nrf2 signaling, to probe the underlying signaling mechanism of WA and to determine whether prevention of acetaminophen (APAP)-induced hepatic toxicity in mice by WA occurs in an Nrf2-dependent manner. We observed that WA profoundly protects wild-type mice but not Nrf2-disrupted mice against APAP hepatotoxicity. WA is a potent inducer of Nrf2-dependent cytoprotective enzyme expression both in vivo and in vitro. Unexpectedly, WA induces Nrf2 signaling at least in part, in a Keap1-independent, Pten/Pi3k/Akt-dependent manner in comparison to prototypical Nrf2 inducers, sulforaphane and CDDO-Im. The identification of WA as an Nrf2 inducer that can signal through a non-canonical, Keap1-independent pathway provides an opportunity to evaluate the role of other regulatory partners of Nrf2 in the dietary and pharmacological induction of Nrf2-mediated cytoprotection.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.