Anti‐diabetic activities of cis‐ and trans‐2,3,5,4′‐tetrahydroxystilbene 2‐O‐β‐glucopyranoside from Polygonum multiflorum

Scope: Functional foods can be used alone or in combination with existing therapies in preventing and treating type 2 diabetes (T2D). Trans‐2,3,5,4′‐tetrahydroxystilbene 2‐O‐β‐glucopyranoside (trans‐THSG), a dominant bioactive compound from Polygonum multiflorum (PM)—a popular medicinal food in Asia, has attracted increasing research interests due to its strong antioxidant activity. The content of naturally occurring cis‐THSG (cis‐2,3,5,4′‐tetrahydroxystilbene 2‐O‐β‐glucopyranoside) was very low in PM root, but was prepared in this study by mimicking the traditional process of PM. The anti‐diabetic effects of trans‐ and cis‐THSG were evaluated in T2D to search for more efficacious food ingredient(s). Methods and results: Trans‐THSG was chromatographically purified from PM roots and cis‐THSG was prepared with our innovative process via exposure of trans‐THSG to UV‐light. The anti‐diabetic effects of both THSGs were tested with HFD‐induced male CF‐1 diabetic mice. Cis‐THSG was found more effective than trans‐THSG in hypoglycemic effect and in ameliorating glucose intolerance and insulin resistance. In HepG2 cells, cis‐THSG also demonstrated more potent activity than trans‐THSG in suppressing transcription of phosphoenopyruvate carboxykinase (PEPCK). Conclusion: Cis‐THSG can be an enriched bioactive ingredient in PM roots from post‐processing and is significantly more effective against hyperglycemia than trans‐THSG. One of the effective pathways was through inhibition of PEPCK. Trans‐2,3,5,4′‐tetrahydroxystilbene 2‐O‐β‐glucopyranoside (trans‐THSG) is the major active compound in a medicinal food in Asia, Polygonum multiflorum (PM), and it can be induced through UV light to cis‐THSG, which mimics the traditional process of PM. Cis‐THSG can be an enriched bioactive ingredient in PM roots from post‐processing after PM harvesting and is significantly more effective against hyperglycemia than trans‐THSG. One of the effective pathways was through inhibition of phosphoenopyruvate carboxykinase (PEPCK), an important enzyme in gluconeogenesis.