Research for natural products including alkaloids that inhibit TRP channels

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Hoshi University
• Principal Investigator: Kaneda Toshio 星薬科大学, 薬学部, 准教授 (70339521)
• Co-Investigator(Renkei-kenkyūsha): MORITA Hiroshi 星薬科大学, 生薬学教室, 教授 (70220069)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: alkaloid / decipic acid / TRP channel / vasodilation

Outline of Final Research Achievements

In this study, we aimed to isolate natural compounds that inhibit TRP channel, which possibly act as vasorelaxant. Isolated natural products and various plant extracts were evaluated using TRPC6/3/adrenergic alpha1 receptor expressing cells. However, we could not find the active compounds that directly inhibit TRPC6/3.
(2R, 3S, 15R)-Decipic acid (DA) isolated from Calophyllum scriblitifolium bark showed vasodilation activity.
Thus, we examined the mechanism by which DA induces vasorelaxation on rat vascular smooth muscle cells (VSMCs). The phosphorylation levels of MLC and MYPT1 were modulated by DA treatment. DA increased the phosphorylation of MYPT1 Ser695 and MYPT1 Ser668, which is reportedly phosphorylated by PKA. DA increases PKA substrates phosphorylation in concentration-dependent manner. Furthermore, DA decreased AKT phosphorylation at Thr308 and Ser473. Taken together, this study indicates that DA induces vasorelaxation through AKT-PKA-MYPT1-MLC pathway.

Free Research Field

生薬・天然物化学