Chemical constituents from aerial parts of Caryopteris incana and cytoprotective effects in human HepG2 cells.

An ethyl acetate fraction of the aerial parts of Caryopteris incana (Verbenaceae) showed potent cytoprotective effects against damage to HepG2 cells induced by tert-butylhydroperoxide (t-BHP). To search for hepatoprotective components of C. incana, various chromatographic separations of the ethyl acetate soluble fraction of C. incana led to isolation of three phenylpropanoid glycosides, 6‴-O-feruloylincanoside D, 6‴-O-sinapoylincanoside D and caryopteroside, and two iridoid glycosides, incanides A and B, together with 17 known compounds. Structures of these compounds were determined by spectroscopic analyses. The absolute stereochemistry of the caryopteroside was established with the help of circular dichroism data and in comparison with literature data. All isolated substances were determined for their cytoprotective effects against t-BHP-induced toxicity in HepG2 cells. Among the tested compounds, 6'-O-caffeoylacteoside exhibited the most potent cytoprotective activity with an IC50 value of 0.8±0.1 µM against t-BHP-induced toxicity. Structure-activity relationships of the assay results indicated an important role of the catechol moiety in phenylpropanoid, iridoid and flavonoid derivatives in eliciting cytoprotective effects.

Chrysosplenol C increases contraction in rat ventricular myocytes.

Chrysosplenol C (4',5,6-trihydroxy-3,3',7-trimethoxyflavone) is a flavone contained in several medicinal plants including Miliusa balansae and Pterocaulon sphacelatum. This compound is known to have an antiviral effect and show cytotoxic activity in several cell lines. In the present study, we explored the effect of chrysosplenol C on contractility in isolated adult rat ventricular myocytes. Chrysosplenol C was isolated from M. balansae, and cell shortenings were measured in field-stimulated single myocytes using a video edge detection method at room temperature. Chrysosplenol C was found to increase cell shortenings in a dose-dependent manner with a half-maximal effective concentration of 45 ± 7.8 µM. Maximal effect of chrysosplenol C, approximately 185% of control, was observed at ≥80 µM. The positive inotropic effect caused by chrysosplenol C was reversible. Time-to-peak contraction and time-to-relengthening were significantly increased by chrysosplenol C. The velocity of cell shortening was slightly accelerated, whereas that of relaxation was not altered by chrysosplenol C. The chrysosplenol C­induced positive inotropic effect was not inhibited by propranolol posttreatment or H-89 pretreatment, suggesting that chrysosplenol C increased contraction independently of ß-adrenergic receptor stimulation and protein kinase A. Our findings are the first to demonstrate that chrysosplenol C is a positive inotropic agent in cardiac myocytes.