CN: 32-1845/R
ISSN: 2095-6975
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ZHANG Xiang-Yu, LI Wei, WANG Jian, LI Ning, CHENG Mao-Sheng, KOIKE Kazuo. Protein tyrosine phosphatase 1B inhibitory activities of ursane-type triterpenes from Chinese raspberry, fruits of Rubus chingii[J]. Chinese Journal of Natural Medicines, 2019, 17(1): 15-21

Protein tyrosine phosphatase 1B inhibitory activities of ursane-type triterpenes from Chinese raspberry, fruits of Rubus chingii

ZHANG Xiang-Yu1,3, LI Wei1,2, WANG Jian1,3, LI Ning1, CHENG Mao-Sheng1,3, KOIKE Kazuo2
1 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;
2 Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan;
3 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
Abstract:
Protein tyrosine phosphatase 1B (PTP1B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii (Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1B inhibitory ursane-type triterpenes:ursolic acid (1), 2-oxopomolic acid (2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Kinetics analyses revealed that 1 was a non-competitive PTP1B inhibitor, and 2 and 3 were mixed type PTP1B inhibitors. Compounds 1-3 and structurally related triterpenes (4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases (TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxy-urs-12-ene-28-oic acid (5), and pomolic acid-3β-acetate (6) bound at the allosteric site including α3, α6, and α7 helix of PTP1B.
Key words:    Protein tyrosine phosphatase 1B    Raspberry    Rubus chingii    Triterpene    Ursane   
Received: 2018-08-20   Revised:
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Articles by ZHANG Xiang-Yu
Articles by LI Wei
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