Triterpenoids with diverse skeletons from the roots of Rhus chinensis and their protective effects on isoproterenol-induced heart failure in zebrafish

In the ongoing quest to discover previously unreported lead compounds that provide protection against heart failure (HF), ten formerly undescribed ( 1 – 10 ) and nine known ( 11 – 19 ) triterpenoids were obtained from the roots of Rhus chinensis Mill. The isolated triterpenoids exhibited distinct skeletal types, including rare 17- epi -dammarane ( 1 , 6 , 7 , 11 , and 12 ), conventional dammarane ( 2 – 5 , 8 , and 9 ), oleanane ( 10 and 13 – 17 ) and lupane ( 18 and 19 ). Their structures were elucidated via a comprehensive analysis of the HRESIMS, NMR , and ECD data, as well as quantum chemical calculations of NMR parameters. Notably, compounds 1 – 5 , 10 – 15 , and 19 possessed an unusual 3,19 (or 25)-hemiketal structure bridging over ring A, while the remaining compounds were classified as 3-oxotriterpenoids. The skeletal diversity observed in these compounds was further elaborated from a biosynthetic perspective . Subsequently, the protective effects of fourteen compounds ( 1 , 3 , 4 , 6 – 9 , 11 – 14 , and 16 – 18 ) against HF were evaluated using zebrafish models of isoproterenol-induced HF at a concentration of 1 μg/mL. Remarkably, all fourteen compounds significantly ameliorated pericardial edema, with five compounds ( 3 , 6 , 11 , 14 , and 16 ) also attenuating impaired cardiac output (CO), and eight compounds ( 1 , 3 , 4 , 7 – 9 , 14 , and 16 ) inhibiting cardiomyocyte apoptosis. Notably, certain compounds even restored the impaired pericardium and CO to near-normal levels. These findings highlight the therapeutic potential of triterpenoids derived from R. chinensis as promising agents for the treatment of HF.