Inhibitory Effect of Cinobufagin on L-Type Ca2+Currents, Contractility, and Ca2+Homeostasis of Isol

Abstract

Cinobufagin (CBG), a major bioactive ingredient of the bufanolide steroid compounds of Chan Su, has been widely used to treat coronary heart disease. At present, the effect of CBG on the L-type Ca2+ current (I Ca-L) of ventricular myocytes remains undefined. The aim of the present study was to characterize the effect of CBG on intracellular Ca2+ ([Ca2+]i) handling and cell contractility in rat ventricular myocytes. CBG was investigated by determining its influence on I Ca-L, Ca2+ transient, and contractility in rat ventricular myocytes using the whole-cell patch-clamp technique and video-based edge-detection and dual-excitation fluorescence photomultiplier systems. The dose of CBG (10−8 M) decreased the maximal inhibition of CBG by 47.93%. CBG reduced I Ca-L in a concentration-dependent manner with an IC50 of 4 × 10−10 M, upshifted the current-voltage curve of I Ca-L, and shifted the activation and inactivation curves of I Ca-L leftward. Moreover, CBG diminished the amplitude of the cell shortening and Ca2+ transients with a decrease in the time to peak (Tp) and the time to 50% of the baseline (Tr). CBG inhibited L-type Ca2+ channels, and reduced [Ca2+]i and contractility in adult rat ventricular myocytes. These findings contribute to the understanding of the cardioprotective efficacy of CBG.

Cinobufagin Suppresses Melanoma Cell Growth by Inhibiting LEF1

“…Cinobufagin, which was approved by the Chinese State Food and Drug Administration as a chemotherapeutic drug for liver and prostate cancer treatment in China, is a major active ingredient isolated from the Traditional Chinese Medicine Venenum Bufonis [36]. Although cytotoxic side effects in cardiac myocytes by the administration of a high dose of cinobufagin contained in Chinese Medicine has been reported [37], emerging evidence has shown that cinobufagin effectively suppresses cancer growth and progression by inducing cell cycle arrest and apoptosis and inhibiting angiogenesis [38]. For example, cinobufagin was found to promote cell cycle arrest at the G2/M phase and apoptosis in hepatocellular carcinoma and esophageal squamous cell carcinoma by increasing the expression levels of pro-apoptotic p73 and BAX [39,40].…”

Bufalin, a bufanolide steroid from the parotoid glands of the Chinese toad, inhibits L‐type Ca2+ channels and contractility in rat ventricular myocytes

“…Chan Su, prepared from the auricular glands and skin glands of Chinese toads, is a traditional Chinese medicine which is used in diverse biological conditions such as inflammation, anesthesia and arrhythmia . As a traditional Chinese medicine, Chan Su has been listed in Pharmacopoeia of People's Republic of China (State Pharmacopoeia Committee, 2010) . The extracts of Chan Su play an important role in cardiac disease; they are described as dried toad venom in English, ‘toad cake’ in China, ‘Senso’ in Japan and ‘Somsa’ in Korea .…”

“…Bufalin (C 24 H 34 O 4 ) is one of the main active components of Chan Su . We recently showed that cinobufagin (another active ingredient in Chan Su) inhibits the L‐type calcium channels (LTCCs) .…”

Calcium homeostasis and endoplasmic reticulum stress are involved in Salvianolic acid B-offered protection against cardiac toxicity of arsenic trioxide

“…Calcium current is the primary inward current in cellular membrane repolarization, and Ca 2+ cycling regulates cardiac contraction. Increased [Ca 2+ ] I is also a critical sign of cell apoptosis, and has been associated with a number of abnormalities in cardiac tissues, such as ventricular arrhythmias and contractile dysfunction [ 8 ]. ATO can augment I Ca, L density, triggering intracellular calcium overload and disorder, and ultimately inducing arrhythmia and cell apoptosis [ 9 - 11 ].…”