urn:uuid:9658baa1-d0d8-35f4-d304-5a5bef440130 RUcore Syndication System, v1.0 Copyright 2018, Rutgers, The State University of New Jersey https://doi.org/doi:10.7282/T3BG2R0W Tang, Wenping 2018-05-07T20:15:00-04:00

Diabetes is one of the leading causes of death in the U. S. The number of people with diabetes has been increasing dramatically, and is expected to reach 366 million worldwide by 2030. Type 2 diabetes, affecting more than 90% of diabetes patients, is strongly associated with oxidative stress and is characterized by insulin resistance. There has been a strong need for safe and effective hypoglycemic agents due to side effects from anti-diabetic drugs. Polygonum multiflorum (PM) has long been used as a tonic in traditional Chinese medicine. The medicinal effects of PM are believed to be mediated through its strong antioxidant activity. Our objective is to test if PM extract has anti-diabetic effect, and to identify its active compounds. We gave 0.075% PM extract to KK CgAy/J type 2 diabetic mice in drinking water and after 7 weeks, PM-treated mice had significantly lower glucose level than control mice (p<0.003). We explored possible mechanisms with Elisa and Western Blotting and suggested that the effect was through maintaining β cell function. The major peak in the extract, also the major active compound in PM, trans-2,3,5,4’-tetrahydroxystilbene 2-O-β-glucopyranoside (trans-SG) was evaluated using the same animal model, however, no hypoglycemic effect was found. In exploring efficacious compounds, we identified cis-SG in PM extract and induced isomerization from trans- to cis- SG with UV light. In a high fat-induced type 2 diabetic mice model, crude extract containing cis- and trans- SG with the ratio of 2:3 exhibited significant hypoglycemic capacity, while pure trans-SG and crude extract with the ratio of 1:20 did not. The mechanism of differential anti-diabetic activities of trans- and cis- SG are investigated using PEPCK assay with HepG2 liver cell culture, and both isomers could effectively suppress Dex/cAMP induced PEPCK transcription, with cis-SG offering slightly better results. We also utilized high fat-induced CF-1 male mice to study the anti-diabetic effect of these two isomers. Both SGs were effective in lowering blood glucose in this model, and cis-SG improved glucose intolerance while trans-SG did not. And from the HOMA model the effect in the animal study was found to be through ameliorating insulin resistance.