New diterpenoids from Callicarpa dichotoma and their anti-inflammatory activity

Callicarpa dichotoma is a distinctive herbal plant of the genus Callicarpa. However, research on the phytochemical and pharmacological properties of C. dichotoma is very limited. Presently, three new diterpenoids, named dichotomapene A - C(1-3), along with fourteen known analogues (4-17), were isolated from C. dichotoma. Their structures were elucidated by spectroscopy, quantum chemical electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 was an unusual abietane-type diterpenoid with a five-membered lactone ring formed between C-6 and C-18. The undescribed crystal structures of compounds 4, 6, and 13 were obtained for the first time. The anti-inflammatory activity of six diterpenoids on RAW 264.7 murine macrophages induced by LPS was further investigated by measuring the secretion of nitric oxide (NO). Cytotoxic experiments manifested that compound 14 had significant toxicity on RAW 264.7 cells. Griess assay results indicated that compound 7 displayed the best anti-inflammatory activity among five diterpenoids. Furthermore, molecular docking analysis was conducted to interpret the anti-inflammatory mechanism of 7 interacted with inducible nitric oxide synthase(iNOS). This study is the first investigation of diterpenoids within C. dichotoma.