Probing herb induced liver injury (HILI) using population data and computational phyto-analysis
Year: 2014
Type: dissertation
Abstract: Despite the ‘natural’ origin of herbal medicines, they can cause adverse effects such as hepatotoxicity, which has led to regulatory action including market withdrawal. This study aimed to explore herb-hepatotoxicity associations and to identify a common pharmacophore among the phytoconstituents of implicated herbs. Data from the United States adverse event reporting system (AERS) (2004-2011) were analysed retrospectively for herb-hepatotoxicity associations using disproportionality analysis. Chemical constituents in identified hepatotoxic herbs were examined for a common pharmacophore and validated against a set of known hepatotoxic and non-hepatotoxic compounds. Significant herb-liver injury associations (p<0.05) were found for 15 herbs including kava, valerian and black cohosh. Analysis of specific adverse reaction groupings revealed new information: HILI with immune features was significantly associated with seven herbs including kava, evening primrose and valerian. Pharmacophore analysis revealed a 3-point hypothesis with 1 hydrogen bond acceptor, 1 hydrogen bond donor and 1 hydrophobic group that gained a high survival score, high selectivity and high specificity relative to other hypotheses. This hypothesis may be a clue to a common toxicity pathway shared by these herbs. Further research is required to investigate whether a causal relationship exists between the implicated herbs and liver injury and to identify the toxicity mechanisms.
Author: Woroud Maan Ibrahim Alzaher
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W189933031