Structurally Diverse Labdane Diterpenoids from Leonurus japonicus and Their Anti-inflammatory Properties in
Xing-Jie Zhang1, Wei-Mao Zhong2, Rui-Xue Liu1
1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Research & Development Center for Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, People's Republic of China.
Abstract:
A phytochemical study on the aerial parts of Leonurus japonicus led to the isolation and identification of 38 labdane diterpenoids, including 18 new (1, 2, 11, 12, 16-21, 24, 30-34, 37, 38) and 20 known (3-10, 13-15, 22, 23, 25-29, 35, 36) analogues. Their structures were elucidated based on physical data analysis, including 1D and 2D NMR, HRMS, UV, IR, and X-ray diffraction. The structure of the known compound 4 was confirmed by single-crystal X-ray diffraction data. These compounds can be divided into furanolabdane (1-10), tetrahydrofuranolabdane (11-15), lactonelabdane (16-23), labdane (24-29), and seco-labdane (30-38) type diterpenoids. All compounds were screened by lipopolysaccharide (LPS)-induced nitric acid (NO) production in RAW264.7 cells to evaluate anti-inflammatory effects. Compounds 1, 5, 10-13, 16-19, 31-33, and 38 inhibited NO production with IC50 values lower than 50 μM, with compound 30 being the most active, with an IC50 value of 3.9 ± 1.7 μM. Further studies show that compound 30 inhibits pro-inflammatory cytokine production and IKK α/β phosphorylation and restores the IκB expression levels in the NF-κB signaling pathway.
