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

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.

The laxative effect of emodin is attributable to increased aquaporin 3 expression in the colon of mice and HT-29 cells.

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a stimulant laxative and used to treat constipation. Aquaporin 3 (AQP3) plays an important role in regulating water transfer in the colon. In the study, we investigated whether the laxative effect of emodin is associated with the regulation of AQP3 in the colon. Our results showed that treatment with emodin increased the fecal water content in the colon of mice and evaluation index of defecation in a dose-dependent manner. More interestingly, emodin significantly increased the AQP3 protein and mRNA expression both in the colon of mice and in human intestinal epithelial cells (HT-29). Mechanistically, emodin obviously up-regulated the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A catalytic subunits α (PKA C-α) and phosphorylated cAMP response element-binding protein (p-CREB Ser133) expression in HT-29 cells. These results suggest that the laxative effect of emodin is associated with the increased expression of AQP3 by up-regulating PKA/p-CREB signal pathway.