Alkyl-benzofuran dimers from Eupatorium chinense with insulin-sensitizing and anti-inflammatory activities

Five new racemic alkyl-benzofuran dimers, (+/-)-dieupachinins I-M (1-5), were isolated from the root tubers of Eupatorium chinense, a well-known traditional Chinese medicine for the treatment of diphtheria in Guangdong province. The structures of these compounds, especially the first examples of 12,10 '-epoxy dimer dieupachinin I (1), 12-nor-dimer dieupachinin J (2), and 12,12 '-dinor-dimer dieupachinin K (3), were elucidated by spectroscopic data analysis. Chiral resolution were further carried out on a cellulose column by HPLC, and compounds 2-5 were successfully separated into two enantiomers, respectively. The absolute configurations of (+)-(2-5) and (- )-(2-5) were established by theoretical ECD calculation. All the compounds were evaluated for insulinstimulated glucose uptake in C2C12 myotubes and (+/-)-dieupachinin I (1) exhibited the best activity. Compound 1 enhanced insulin-stimulated glucose uptake via activating the insulin receptor substrate 1/protein kinase B/glycogen synthase kinase-3 beta signaling pathway. Moreover, all the isolates were tested for their nitric oxygen (NO) inhibitory effects in lipopolysaccharide-treated RAW264.7 macrophages, and compounds (+/-)-1, (+/-)-2, and (+/-)-4 showed promising inhibitory effects with IC50 values of 6.42 +/- 1.85, 6.29 +/- 1.94, and 16.03 +/- 2.07 mu M, respectively. (+/-)-Dieupachinin I (1) again dose-dependently suppressed LPS-induced expression of inducible NO synthase and nuclear translocation of p65.

Automated summary

Five new racemic alkyl-benzofuran dimers were isolated from the root tubers of Eupatorium chinense, with compound 1 exhibiting the best activity in enhancing insulin-stimulated glucose uptake. Some isolates showed promising inhibitory effects on nitric oxide (NO) in macrophages, with compound 1 also suppressing LPS-induced expression of inducible NO synthase and nuclear translocation of p65.