From traditional medicinal use to functional food: The pharmacological activity, hepatotoxicity mechanism and detoxification strategies of gardenia fructus

Gardenia fructus (GF), a medicinal and edible herb with over 2,000 years of use, possesses diverse bioactive compounds including iridoids, crocins, and organic acids. Herein, we summarize the ethnomedicinal applications, phytochemistry, pharmacological activities, and safety concerns. GF exhibits a wide range of pharmacological activities, notably hepatoprotective, renoprotective, and neuroprotective effects. However, dose-dependent hepatotoxicity and nephrotoxicity - primarily linked to genipin, a metabolite of geniposide - pose significant safety challenges. Mechanisms involve oxidative stress, mitochondrial dysfunction, bile acid dysregulation, and inflammatory cascade activation. The field lacks sufficient clinical translation, comprehensive bioactivity analysis, and stringent quality control. Future research should prioritize elucidating molecular toxicity pathways, developing quality control benchmarks include geniposide, and advancing clinical trials to balance efficacy with safety. This positions GF as a sustainable resource for nutraceuticals and functional foods, necessitating rigorous safety assessments for rational utilization. • Gardenia fructus is used as a functional food, for medicinal purposes, and as a dye, with a long history of application. • Geniposide and crocin are the active component groups that exert pharmacological effects in Gardenia fructus. • The excessive accumulation of geniposide and genipin is the main cause of hepatotoxicity and nephrotoxicity. • Compatibility, processing are effective measures to reduce the risk of hepatotoxicity and nephrotoxicity.