Type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by b-cell dysfunction and insulin resistance, and its prevalence has reached epidemic proportions worldwide.1-3) Protein-tyrosine phosphatase 1B (PTP1B) is a major non-transmembrane phosphotyrosine phosphatase expressing ubiquitously in the classical insulin-targeted tissues 4,5) and functions as a negative regulator of the insulinsignaling pathway.6,7) Inhibition of PTP1B has been demonstrated to be an effective therapeutic approach to treatment of T2DM and much attention has been paid to PTP1B inhibitors for antidiabetic drug design. 8,9) Sambucus adnata (Caprifoliaceae) is a perennial herbaceous plant distributed in Southwest of China, and has long been used in Traditional Chinese Medicine (TCM) to treat bastard measles and acute nephritis.10) The chemical constituents of S. adnata and their bioactive activities are still not well understood, but has been reported to contain triterpenes, lignans, flavonols and sterols, and the isolated flavonols shows angiotensin-converting enzyme inhibitory activity.
11,12)During our PTP1B inhibitor screening program from TCM, 13) the MeOH extract of S. adnata showed significant inhibitory activity against PTP1B with an IC 50 value of 0.96Ϯ0.09 mg/ml. Further bioassay-guided fractionation of this extract resulted in the isolation of a novel acylated triterpene (1), together with other twelve known compounds (2-13). Herein, we report the isolation, structural determination, and evaluation of the PTP1B inhibitory activities of these compounds. The MeOH extract from the whole plants of Sambucus adnata has shown significant protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity. Chemical study on the extract resulted in the isolation of thirteen compounds, including a novel triterpene (1). The structure of 1 was determined to be 1a a,3b b-dihydroxy-urs-12-en-11-one-3-yl palmitate on the basis of extensive spectroscopic analyses. Among the isolated compounds, ursolic acid, oleanolic acid and (؎)-boehmenan showed the most potent PTP1B inhibitory activity in vitro with the IC 50 values of 4.1, 14.4 and 43.5 m mm, respectively. The kinetic analysis indicated that (؎)-boehmenan inhibits PTP1B activity in a competitive manner.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.