Dammarane-Type Triterpenoids from the Roots of Rhus chinensis and Their Preventive Effects on Zebrafish Heart Failure and Thrombosis

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2020-02, Vol.83 (2), p.362-373
• Main Authors: Ye, Miao, Xu, Wen, He, Da-Qing, Wu, Xian, Lai, Wen-Fang, Zhang, Xiao-Qin, Lin, Yu, Xu, Wei, Li, Xu-Wen
• Format: Article
• Language: English
• Subjects: Animals; Dammaranes; Heart Failure - drug therapy; Molecular Structure; Plant Roots - chemistry; Rhus - chemistry; Thrombosis - drug therapy; Triterpenes - chemistry; Triterpenes - isolation & purification; Triterpenes - pharmacology; Zebrafish - physiology
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.9b00857

Eight new dammarane-type triterpenoids (1–8), together with a related known analogue (9), were isolated from the roots of Rhus chinensis, a traditional Chinese medicine for treating coronary artery heart disease, guided by LC-MS analysis. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Notably, compounds 1–7 and 9 possess an unusual 17α-side chain, and 1–4, 6, and 9 contain an uncommon 3-methyl-5,6-dihydro-2H-pyran-2-one moiety in the side chain. Compounds 1–5 and 9 have a 3,19-hemiketal bridge in the A ring. In an in vivo bioassay, 1, 2, and 4–6 exhibited significant preventive effects on zebrafish heart failure at 0.5 μg/mL, improving heart dilatation, venous congestion, cardiac output, blood flow velocity, and heart rate. Compound 5, displaying the most promising heart failure preventive activities, showed even better effects on increasing cardiac output (72%) and blood flow velocity (83%) than six first-line heart failure therapeutic drugs. Moreover, 1, 2, and 6 prevented the formation of thrombosis in zebrafish at 0.5 μg/mL. The present investigation suggests that the new dammarane triterpenoids might be partially responsible for the utility of R. chinensis in treating coronary artery heart disease.