Cassane diterpenoids with hepatic gluconeogenesis inhibitory activity from the seeds of Caesalpinia decapetala (Roth) Alston

A chemical investigation of the seeds of Caesalpinia decapetala (Roth) Alston led to the isolation of fifteen cassane diterpenoids, including ten previously undescribed compounds (1–10) and five known analogues (11–15). The structures of 1–10 were determined using ¹H, ¹³C, and 2D NMR, HRESIMS, and IR data. Their absolute configurations were confirmed by comparing experimental electronic circular dichroism data with calculated values, coupled with single-crystal X-ray diffraction analysis. Structurally, compounds 1 and 2 are rare cassane diterpenoids featuring a ketone carbonyl group at C-3. Excessive hepatic gluconeogenesis plays an important role in the occurrence and development of type 2 diabetes mellitus. In the present study, compounds 1, 3, 4, 6, 11, and 12 exhibited potent inhibitory effects on gluconeogenesis at a concentration of 20 μM in primary mouse hepatocytes, with inhibitory capacities of 68.2 ± 6.8 %, 78.4 ± 3.5 %, 53.8 ± 6.1 %, 94.8 ± 5.5 %, 85.1 ± 4.1 %, and 106.9 ± 2.9 %, respectively. Further studies indicated that these compounds inhibited gluconeogenesis in a dose-dependent manner across a concentration range from 1 to 50 μM. Notably, compounds 6 and 12 exhibited potent inhibitory effects on gluconeogenesis at a concentration of 2 μM, comparable to the effects of 500 μM metformin, suggesting their potential for ameliorating hyperglycemia.