Hepatorenal Toxicity of Alcohol-Based and Alcohol-Free Polyherbal Formulations (PHFs): A Mini Review of the Mechanistic Insights and Toxicological Perspectives

Abstract

Background: Combining extracts from different therapeutic plants to improve therapeutic efficacy has become a common traditional practice. Combinations of these plant extracts, with or without alcohol as a base, are termed alcohol-free or alcohol-based polyherbal formulations, respectively. Several polyherbal formulations, especially alcoholic bitters, have been reported to be used to treat or manage ailments such as erectile dysfunction, hyperglycaemia, cardiovascular diseases, irregular menstruation, infertility, pain, overweight, gastrointestinal disorders, and organ detoxification, amongst others. However, toxic effects of these formulations, particularly nephrotoxicity and hepatotoxicity, have also been reported. Methodology: This review aimed to gather recent literature on the toxicity of polyherbal formulation drinks, identify the types of toxicity causing the greatest concern, and collect evidence on potentially non-toxic herbal formulations. Eligible studies were conducted in experimental animals or humans, were original research articles published in peer-reviewed journals, had full text available in the English language, and were published between 2010 and 2026. Studies were retrieved from Google Scholar, PubMed, ScienceDirect, the Cochrane Library, and BIOSIS. Search terms such as “polyherbal formulation toxicity”, “toxicity of polyherbal alcoholic drinks”, “alcohol-free polyherbal formulations”, and “herbal bitters” were used. However, meta-analysis was not performed because of substantial heterogeneity in study designs, preparation matrices, analytical methods, and reporting formats. Instead, a narrative synthesis was conducted, organising findings by reported toxicity, preparation matrix, health risk, and geographic sub-region. Results: A total of 76 studies published between 2010 and 2026 were included after screening, of which 34 papers addressed polyherbal-induced toxicity, while 42 studies addressed the protective effects of polyherbal formulations. The included studies were conducted globally: 61 studies were from West Africa, 11 were from India and Bangladesh, and four were from Europe. Conclusion: The reviewed studies indicated that alcohol may negatively counteract the phytocontents of plant extracts, rendering them less useful, while alcohol itself may act as a toxicant and source of oxidative stress. However, alcohol-free polyherbal formulations were shown to have nephroprotective and hepatoprotective properties. These protective attributes were associated with antioxidative, antifibrotic, anti-inflammatory, immunomodulatory, and enhanced detoxification mechanisms. Therefore, to prevent polyherbal-induced kidney or liver toxicity and associated diseases, alcohol-based polyherbal formulations or mixtures should be avoided.