Study on the Chemical Components and Protein Tyrosine Phosphatase 1B Inhibition Activity of the Roots of Kashiwagi
Dysoxylum densiflorum is native to Xishuangbanna, Yunnan Province, China (Mengla, Jinghong). It grows in the rainforests of wet tropical seasonal valleys and riverbank slopes at elevations of 520-800m. Modern research has shown that the honey plant Kashiwagi contains abundant chemical components such as sesquiterpenes, triterpenes, diterpenes, and limonoids. Some compounds have good pharmacological activities such as antibacterial, anti-tumor, and analgesic effects. Protein tyrosine phosphatases (PTPs) are a group of enzymes that catalyze the dephosphorylation of protein tyrosine. Protein tyrosine phosphatase 1B (PTP-1B) plays a crucial role in regulating insulin action by activating insulin receptors and downstream substrate proteins through dephosphorylation. Therefore, PIP-1B is a key negative regulatory protein in insulin signal transduction pathway, and PTP-1B inhibitor is an important choice for developing anti diabetes drugs. The research team found in the early stage that the diterpenoid components in the multi vein Kashiwagi tree of the Meliaceae family exhibited inhibitory effects on PTP-1B, but this activity has not been reported in other plants of the same genus. Therefore, in order to further explore the active ingredients of Kashiwagi, this experiment used silica gel column chromatography, semi preparative chromatography, and preparative chromatography combined with nuclear magnetic resonance spectroscopy to study the ethyl acetate extraction site of Kashiwagi root extract, in order to provide a basis for inhibiting the discovery of PTP-1B active ingredients.

 

In this study, a total of 23 components were isolated from the ethyl acetate extract of Kashiwagi root and screened for PTP-1B inhibitory activity. Based on this, the structure-activity relationship was preliminarily explored. Compounds 3, 16, and 21 are all of the cleanane type, while compound 12 is of the prenyluledemane type and has the best inhibitory effect, indicating that prenyluledemane type diterpenes have stronger inhibitory activity than cleanane type diterpenes; Compounds 3 and 21 are both in the E configuration, while compound 16 is in the Z configuration. Compound 16 exhibits strong inhibitory activity, second only to compound 12, indicating that Z-type diterpenoid compounds have stronger inhibitory activity; Compounds 3 and 16 contain acetyl groups in their structures and exhibit good inhibitory activity. Further investigation is needed to determine whether acetyl groups are related to inhibitory activity.
Diterpenoids have played a good role in the development of small molecule natural PTP-1B inhibitors. Jaya is a rich source of diterpenoids, and it is worth further exploring the natural source of anti diabetes candidate drugs from this genus.