Structurally diverse clerodane diterpenoids with anti-inflammatory and anti-diabetic effects from Tinospora crispa (L.) Hook.f. & Thomson.

Eight previously unreported clerodane diterpenoids (1-8), named tinocrispines A-H, and fifteen related known compounds (9-23), were isolated from Tinospora crispa (L.) Hook.f. & Thomson. Spectral data combined with quantum chemical calculations were applied to investigate the structural characteristics and absolute configurations. All of the isolated clerodanes contain 6/5/6/6, 6/5/6, 6/6/5, 6/6/6, and 6/6 fused ring systems with different heterocyclics. The effects of isolated clerodane diterpenoids on inflammation were assessed using a cell-based assay that measures nitric oxide (NO) release in LPS-treated RAW264.7 macrophages. Tinosporol C (IC50 = 5.4 μM) and rumphioside F (IC50 = 8.7 μM) demonstrated strong inhibitory effects on NO release. Molecular docking studies reveal that tinosporol C and rumphioside F can engage with the active sites of iNOS/COX-2 proteins via hydrogen bonds and hydrophobic interactions. Notably, borapetoside E displayed significant α-glucosidase inhibitory activity (IC50 = 2.3 μM), which was 14 times lower than that of quercetin (IC50 = 32.3 μM). Molecular docking and molecular dynamics simulation indicate that borapetoside E can effectively interact with the amino acid residues near the active sites of α-glucosidase through hydrogen bonds and hydrophobic interactions. Such observations contribute to science-based applications of T. crispa in diabetes and inflammatory diseases.