Schwarzinicine A inhibits transient receptor potential canonical channels and exhibits overt vasorelaxation effects.

Abstract

This study investigated the vasorelaxant effects of schwarzinicine A, an alkaloid recently reported from Ficus schwarzii Koord. Regulation of calcium homeostasis in vascular smooth muscle cells (VSMC) is viewed as one of the main mechanisms for controlling blood pressure. L-type voltage-gated calcium channel (VGCC) blockers are commonly used for controlling hypertension. Recently, the transient receptor potential canonical (TRPC) channels were found in blood vessels of different animal species with evidence of their roles in the regulation of vascular contractility. In this study, we studied the mechanism of actions of schwarzinicine A focusing on its regulation of L-type VGCC and TRPC channels. Schwarzinicine A exhibited the highest vasorelaxant effect (123.1%) compared to other calcium channel blockers. It also overtly attenuated calcium-induced contractions of the rat isolated aortae in a calcium-free environment showing its mechanism to inhibit calcium influx. Fluorometric intracellular calcium recordings confirmed its inhibition of hTRPC3-, hTRPC4-, hTRPC5- and hTRPC6-mediated calcium influx into HEK cells with IC50 values of 3, 17, 19 and 7 μM, respectively. The evidence gathered in this study suggests that schwarzinicine A blocks multiple TRPC channels and L-type VGCC to exert a significant vascular relaxation response.

• Authors: Yin-Ying Mak, Bi-Juin Loong, Paul Millns, Claudia C Bauer, Robin S Bon, Yvonne Mbaki, Fong-Kai Lee, Kuan-Hon Lim, Cin Kong, Sue-Mian Then, Kang-Nee Ting
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 36 Issue 7 Pg. 2952-2963 (Jul 2022) ISSN: 1099-1573 [Electronic] England
• PMID: 35537691 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.

Chemical References

• Calcium Channel Blockers
• Calcium Channels, L-Type
• Transient Receptor Potential Channels
• Vasodilator Agents
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels, L-Type (pharmacology)
• Rats
• Transient Receptor Potential Channels (pharmacology)
• Vasodilation
• Vasodilator Agents (pharmacology)