Flavonoids from Dracocephalum Tanguticum and Their Cardioprotective Effects Against Doxorubicin-induced Toxicity in H9c2 Cells

Two new flavonoids, ladanetin-6-O-β-(6″-O-acetyl)glucoside (1) and pedalitin-3'-O-β-glucoside (2), together with 15 known compounds (3-17), were isolated from the whole plants of Dracocephalum tanguticum. Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by the comparison with spectroscopic data reported in the literature. Antioxidant capacities of the isolated substances were determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferrous ions, and ABTS(·)(+) radical in vitro assay, and their cytoprotective activities were also tested on doxorubicin (DOX)-induced toxicity in H9c2 cardiomyocytes. Among all the tested compounds, luteolin-7-O-β-D-glucopyranoside (7) exhibited both strong antioxidative effect and high protective activity against DOX-induced toxicity. Further investigation found 7 could decrease DOX-induced death of H9c2 cell, reduce LDH and CK level, and inhibit the elevated intracellular concentration of ROS and [Ca(2+)](i). The preliminary structure-activity relationships (SAR) of these compounds revealed the Δ(2,3) double bond on C-ring and 3',4'-di-OHs on B-ring with a flavone skeleton such as luteolin and its derivatives, were necessary for their cardioprotective effects.