The role of ginseng total saponin in transient receptor potential melastatin type 7 channels

Abstract

Although ginsenosides have a variety of physiologic or pharmacologic functions in various regions, there are only a few reports on the effects of transient receptor potential melastatin 7 (TRPM7) channels. Here, we showed evidence suggesting that TRPM7 channels play an important role in ginseng total saponin (GTS)-mediated cellular injury. The combination techniques of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) method and cell death assays were used. GTS depolarized the resting membrane potentials and decreased the amplitude of pacemaker potentials in cultured interstitial cells of Cajal (ICCs) in gastrointestinal (GI) tract. The TRPM7-like currents in single ICCs and the overexpressing TRPM7 in HEK293 cells were inhibited by GTS. However, GTS had no effect on Ca 2 ' -activated Cl ( conductance. GTS inhibited the survival of human gastric (AGS) and breast (MCF-7) adenocarcinoma cells. Also, GTS inhibited the TRPM7-like currents in AGS and MCF-7 cells. The GTSmediated cytotoxicity was inhibited by TRPM7-specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells was inhibited by GTS. Thus, TRPM7 channels are involved in GTS-mediated cell death in AGS and MCF-7 cells, and these channels may represent a novel target for physiological disorders where GTS plays an important role.

Ginsenoside Re inhibits pacemaker potentials via adenosine triphosphate-sensitive potassium channels and the cyclic guanosine monophosphate/nitric oxide-dependent pathway in cultured interstitial cells of Cajal from mouse small intestine

“…The pacemaker activity of ICCs in the murine small intestine occurs primarily because of periodic activations of TRPM7 [16] or ANO1 channels [20] . Ginsenoside Rf has no effects on TRPM7 or ANO1 channels [3] , but GTS and ginsenoside Rg3 block TRPM7 channels [40] , [41] . However, the specific details of ion channel involvement during the upstroke and plateau phases of pacemaker potentials in the presence of GRe have not been elucidated.…”

Role of transient receptor potential melastatin type 7 channel in gastric cancer

“…Meyer and a well-known folk medicine and tonic), ginseng total saponin (GTS) 61 and ginsenosides Rg3 62 and Rd 63 were found to induce AGS cell death by blockading TRPM7 channel activity. Thus, these results suggested that TRPM7 channels are involved in GTS, ginsenoside Rg3, and Rd-induced gastric cancer cell apoptosis.…”

Inhibiting the ERK pathway and the TRPM7 ion channel in gastric and bladder cancer cells

“…Ginseng is one of the most popular herbal remedies and contains ginsenosides, also known as steroid-like saponins known for activating antioxidant enzymes. A study has suggested that ginsenosides cause cellular injury by damaging the DNA and causing endoplasmic reticulum (ER) stress (18). More specifically, ginsenoside Rd has the ability to inhibit TRPM7 channels that were overexpressed in kidney cells and human gastric adenocarcinoma cells as well as inhibit the phosphorylation of the MAPK pathway (18).…”

“…A study has suggested that ginsenosides cause cellular injury by damaging the DNA and causing endoplasmic reticulum (ER) stress (18). More specifically, ginsenoside Rd has the ability to inhibit TRPM7 channels that were overexpressed in kidney cells and human gastric adenocarcinoma cells as well as inhibit the phosphorylation of the MAPK pathway (18). Because of its role as a magnesium transporter, TRPM7 is essential for magnesium-dependent cell survival of gastric cancer cells and is also involved in apoptosis caused by ginsenosides, steroid-like saponins in ginseng, like ginsenoside Rd (9).…”