Flavonoids from Sophora alopecuroides L. improve palmitate-induced insulin resistance by inhibiting PTP1B activity in vitro

• Published in: Bioorganic & medicinal chemistry letters Vol. 35; p. 127775
• Main Authors: Zhang, Ming, Zhang, Yuwei, Huang, Qiqi, Duan, Hui, Zhao, Guodong, Liu, Lei, Li, Yuxin
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.03.2021; Elsevier
• Subjects: Chemistry; Chemistry, Medicinal; Chemistry, Organic; Flavonoids; Insulin resistance; Leguminosae; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; PTP1B; Science & Technology; Sophora alopecuroides L; Sophora alopecuroides L; Insulin resistance; Flavonoids; PTP1B; Leguminosae
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.127775

Two new compounds (1 and 2), along with fifteen known compounds (3–17) were isolated from Sophora alopecuroides L. All compounds were screened by in vitro insulin resistance cell model. Among them, compounds 1, 2, 7, 13, 14, 15, 16, and 17 were proven to improve the insulin resistance of C2C12 myotubes and significantly increase glucose consumption levels. These compounds were then combined with PTP1B for molecular docking and enzyme activity test. It’s exciting that compounds 1, 2, 13, 14, 16, and 17 can improve insulin resistance and inhibit PTP1B activity, and are expected to become new PTP1B inhibitors. [Display omitted] Seventeen flavonoids (1–17) were isolated from Sophora alopecuroides L.. Compounds 1 and 2 were new compounds, and compounds 5, 8, 11, 12, and 17 were isolated from S. alopecuroides for the first time. The sources of compounds 1 and 2 were determined from the seeds of S. alopecuroides by UPLC-QE-Orbitrap-MS, and compounds 1, 2, 7, 13, 14, 15, 16, and 17 were proven to improve the insulin resistance of C2C12 myotubes and significantly increase glucose consumption levels. Among them, compounds 1, 2, 13, 14, 16, and 17 could bind to protein tyrosine phosphatase 1B (PTP1B), thereby significantly inhibiting the enzyme activity of PTP1B. Compound 2 had the strongest inhibitory effect, with an inhibition rate of 95.22% at 0.1 μg mL−1.