School of Life Sciences, Jilin University, Changchun 130012, China.
Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China.
Nutrients. 2022 Jul 24;14(15):3031. doi: 10.3390/nu14153031.
The aim of this study was to provide a practical experimental basis for the development of Neocryptotanshinone (NCTS) as an effective hypoglycemic drug and a theoretical method for the rapid screening of natural compounds with hypoglycemic effects. Molecular docking was used to screen the most suitable ligand. Hematoxylin and eosin, immunohistochemical staining, enzyme-linked immunosorbent assay and Western Blotting approved the hypoglycemic effect of NCTS. According to the free energy of binding, among 180 active compounds from the Traditional Chinese Medicine Integrated Database, NCTS was finally chose for investigation its hypoglycemic effects. In db/db mice, NCTS significantly reduced body weight and plasma glucose, improved glucose tolerance and levels of fasting plasma glucose and glycated hemoglobin A1c, and decreased insulin resistance after six-week administration. NCTS restored the pathological state in the liver of db/db mice and significantly decreased protein tyrosine phosphatase 1B (PTP1B) expression in the liver and muscle of db/db mice, which is related to the regulatory effect of NCTS on insulin receptor substrate 1. In conclusion, we successfully explored the hypoglycemic effect of NCTS in db/db mice via regulating the expression of PTP1B.
本研究旨在为开发新型隐丹参酮（NCTS）作为有效降糖药物提供实用的实验基础，并为快速筛选具有降糖作用的天然化合物提供理论方法。采用分子对接筛选最适合的配体。苏木精-伊红、免疫组织化学染色、酶联免疫吸附试验和 Western Blotting 证实了 NCTS 的降糖作用。根据结合自由能，从中药整合数据库的 180 种活性化合物中，最终选择 NCTS 来研究其降糖作用。在 db/db 小鼠中，NCTS 显著降低体重和血浆葡萄糖，改善葡萄糖耐量和空腹血糖及糖化血红蛋白 A1c 水平，并降低胰岛素抵抗。NCTS 恢复了 db/db 小鼠肝脏的病理状态，显著降低了 db/db 小鼠肝脏和肌肉中蛋白酪氨酸磷酸酶 1B（PTP1B）的表达，这与 NCTS 对胰岛素受体底物 1 的调节作用有关。总之，我们成功地通过调节 PTP1B 的表达，探索了 NCTS 在 db/db 小鼠中的降糖作用。
