Unveiling the therapeutic promise of natural products in alleviating drug‐induced liver injury: Present advancements and future prospects

Abstract

Drug‐induced liver injury (DILI) refers to adverse reactions to small chemical compounds, biological agents, and medical products. These reactions can manifest as acute or chronic damage to the liver. From 1997 to 2016, eight drugs, including troglitazone, nefazodone, and lumiracoxib, were removed from the market due to their liver‐damaging effects, which can cause diseases. We aimed to review the recent research on natural products and their bioactive components as hepatoprotective agents in mitigating DILI. Recent articles were fetched via searching the PubMed, PMC, Google Scholar, and Web of Science electronic databases from 2010 to January 2023 using relevant keywords such as “natural products,” “acetaminophen,” “antibiotics,” “paracetamol,” “DILI,” “hepatoprotective,” “drug‐induced liver injury,” “liver failure,” and “mitigation.” The studies reveal that the antituberculosis drug (acetaminophen) is the most frequent cause of DILI, and natural products have been largely explored in alleviating acetaminophen‐induced liver injury. They exert significant hepatoprotective effects by preventing mitochondrial dysfunction and inflammation, inhibiting oxidative/nitrative stress, and macromolecular damage. Due to the bioavailability and dietary nature, using natural products alone or as an adjuvant with existing drugs is promising. To advance DILI management, it is crucial to conduct well‐designed randomized clinical trials to evaluate natural products' efficacy and develop new molecules clinically. However, natural products are a promising solution for remedying drug‐induced hepatotoxicity and lowering the risk of DILI.

Ameliorative Effect of Polyherbal Formulation for Restoring Liver Health: A Systematic Review

“…India, a country well-known for its biodiversity, is home to some 40,000 plant species, 15,000 of which are thought to offer therapeutic benefits. In India, communities use 7,000-7,500 plants to treat a range of illnesses Kotmire et al (2024), Ali & Datusalia (2024), Singh et al (2024). Numerous plant species are used in the many native medical systems, including Ayurveda, Siddha, and Unani, to cure various illnesses Sane (2002), Farnsworth et al (1985), Abraham & Paridhavi (2013), Kunwar et al (2010).…”

Comments on: Unveiling the therapeutic promise of natural products in alleviating drug‐induced liver injury: Present advancements and future prospects

“…To the Editor, We read with great interest a recent review by Singh et al (2023) in Phytotherapy Research summarizing a literature search on the use of natural products in drug-induced liver injury (DILI). As acetaminophen (APAP) overdose is the clinically most relevant drug hepatotoxicity and the mechanisms of cell death and organ injury are by far better understood than any other form of DILI (Jaeschke & Ramachandran, 2024;Ramachandran et al, 2018), the focus of the review was not unexpectedly mainly on APAP.…”

“…As acetaminophen (APAP) overdose is the clinically most relevant drug hepatotoxicity and the mechanisms of cell death and organ injury are by far better understood than any other form of DILI (Jaeschke & Ramachandran, 2024;Ramachandran et al, 2018), the focus of the review was not unexpectedly mainly on APAP. The authors concluded based on the list of papers from their search that natural products "prevent mitochondrial dysfunction and inflammation, inhibiting oxidative/nitrative stress, and macromolecular damage," and so on and then suggest randomized clinical trials to test their clinical efficacy (Singh et al, 2023). However, the problem is that Singh et al (2023) took most of the mechanistic conclusions of these natural product papers at face value.…”

“…The authors concluded based on the list of papers from their search that natural products "prevent mitochondrial dysfunction and inflammation, inhibiting oxidative/nitrative stress, and macromolecular damage," and so on and then suggest randomized clinical trials to test their clinical efficacy (Singh et al, 2023). However, the problem is that Singh et al (2023) took most of the mechanistic conclusions of these natural product papers at face value. There was no critical evaluation of any of these papers.…”

“…Without taking this into consideration, natural product studies continue to be of limited value and certainly these compounds have limited prospects of being advanced to the clinic. The review of Singh et al (2023) missed a critical opportunity to point out these problems, which could have helped improve future studies.…”