Stilbenes: Source plants, chemistry, biosynthesis, pharmacology, application and problems related to their clinical Application-A comprehensive review

Stilbenes are some of the important phenolic compounds originating from plant families like Vitaceae, Leguminaceae, Gnetaceae, and Dipterocarpaceae. Structurally, they have a C6-C2-C6 skeleton, usually with two isomeric forms. Stilbenes are biosynthesized due to biotic and abiotic stresses such as microbial infections, high temperatures, and oxidation. This review aims to provide a comprehensive overview of stilbenes' botanical sources, chemistry, biosynthetic pathways, pharmacology, and clinical applications and challenges based on up-to-date data. All included studies were collected from PubMed, ScienceDirect, Google Scholar, and CNKI, and the presented data from these indexed studies were analyzed and summarized. A total of 459 natural stilbene compounds from 45 plant families and 196 plant species were identified. Pharmacological studies also show that stilbenes have various activities such as anticancer, antimicrobial, antioxidant, anti-inflammatory, anti-degenerative diseases, anti-diabetic, neuroprotective, anti-aging, and cardioprotective effects. Stilbene synthase (STS) is the key enzyme involved in stilbene biosynthetic pathways. Studies on the therapeutic application of stilbenes pinpoint that challenges such as low bioavailability and isomerization are the major bottlenecks for their development as therapeutic drugs. Although the medicinal uses of several stilbenes have been demonstrated in vivo and in vitro, studies on the development of stilbenes deserve more attention in the future.