Unlocking the hidden health benefits of Guggulsterone isolated from ancient spices: A comprehensive review

Guggulsterone is a bioactive substance predominantly derived from the oleo-gum resin of plants belonging to the Commiphora and Boswellia genus. Modern pharmacological studies have confirmed that guggulsterone has a broad range of pharmacological activities, with significant therapeutic effects on a variety of diseases including inflammatory diseases, neurodegenerative diseases, diabetes mellitus, and cancers. In this study, we retrieved relevant literature up to 2024 from the CNKI, Web of Science, ScienceDirect, and PubMed database, and conducted a systematic review to comprehensively summarize the pharmacological activity, toxicity, and pharmacokinetic characteristics of guggulsterone. The results showed that guggulsterone exhibits potent antioxidant, anti-inflammatory, anticancer, antiviral, antidepressant, lipid-lowering, and cardiovascular protective activities mainly via regulating various signaling pathways, such as the JAK/STAT3, Nrf2/HO-1, Nrf2/Keap, NF-κB, AMPK, PI3K/Akt, MAPK/AP-1, among others. Furthermore, guggulsterone can compensate for the limitations of chemotherapy in cancer treatment by regulating the tolerance phenomenon through p-glycoprotein. Following hepatic P450 oxidative metabolism, it does not exhibit significant adverse reactions. In summary, this study provides a comprehensive review of the sources, pharmacological activities, toxicity, pharmacokinetic properties, and relevant applications of guggulsterone. Future attention should be paid to the modification of the chemical structure of guggulsterone, the development of new formulations, and its combination with other drugs to expand its applications.