Ginsenosides, one of the active ingredients of Panax ginseng, show various pharmacological and physiological effects, and they are converted into compound K (CK) or protopanaxatriol (M4) by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. The gamma-aminobutyric acid receptorC (GABAC) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on GABAC receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant GABAC receptor (rho1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing GABAC receptor cRNA, we found that CK or M4 alone had no effect in oocytes. However, co-application of either CK or M4 with GABA inhibited the GABA-induced inward peak current (IGABA). Interestingly, pre-application of M4 inhibited IGABA more potently than CK in a dose-dependent and reversible manner. The half-inhibitory concentration (IC50) values of CK and M4 were 52.1+/-2.3 and 45.7+/-3.9 microM, respectively. Inhibition of IGABA by CK and M4 was voltage-independent and non-competitive. This study implies that ginsenoside metabolites may regulate GABAC receptor channel activity in the brain, including in the eyes.
Brain ; Eye ; gamma-Aminobutyric Acid ; Ginsenosides ; Humans ; Oocytes ; Panax ; Retinal Bipolar Cells ; RNA, Complementary ; Sapogenins ; Xenopus

The aim of the present study was to investigate the effects of prenatal alcohol exposure (PAE) on the development and cell differentiation of retina in offspring. The mouse model of PAE was made. HE staining and immunofluorescent labeling were carried out to visualize the structure, development and cell differentiation of the retina from postnatal day 0 (P0)-P30 offspring. The results showed that PAE can lead to the retardation of retinal development, the reduction of number of bipolar cells and horizontal cells, the disorder of horizontal cells' polarity, as well as the retinal thickening in a dose-dependent manner. The data suggest that alcohol exposure during pregnancy can lead to the developmental retardation of retina and decreased number of bipolar cells and horizontal cells in the retina of offspring.
Animals ; Cell Differentiation ; drug effects ; Disease Models, Animal ; Ethanol ; adverse effects ; Female ; Male ; Mice ; Pregnancy ; Prenatal Exposure Delayed Effects ; chemically induced ; Retina ; cytology ; drug effects ; Retinal Bipolar Cells ; drug effects ; Retinal Horizontal Cells ; drug effects

Resveratrol is a phytoalexin found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-inflammatory, and life-prolonging effects. However, relatively little is known about the effects of resveratrol on the regulation of ligand-gated ion channels. We have previously reported that resveratrol regulates subsets of homomeric ligand-gated ion channels such as those of 5-HT3A receptors. The gamma-aminobutyric acidC (GABAC) receptor is mainly expressed in retinal bipolar cells and plays an important role in visual processing. In the present study, we examined the effects of resveratrol on the channel activity of homomeric GABAC receptor expressed in Xenopus oocytes injected with cRNA encoding human GABAC rho subunits. Our data show that the application of GABA elicits an inward peak current (IGABA) in oocytes that express the GABAC receptor. Resveratrol treatment had no effect on oocytes injected with H2O or with GABAC receptor cRNA. Co-treatment with resveratrol and GABA inhibited IGABA in oocytes with GABAC receptors. The inhibition of IGABA by resveratrol was in a reversible and concentration-dependent manner. The IC50 of resveratrol was 28.9+/-2.8 microM in oocytes expressing GABAC receptor. The inhibition of IGABA by resveratrol was in voltage-independent and non-competitive manner. These results indicate that resveratrol might regulate GABAC receptor expression and that this regulation might be one of the pharmacological actions of resveratrol on the nervous system.
Fruit ; gamma-Aminobutyric Acid ; Humans ; Inhibitory Concentration 50 ; Ligand-Gated Ion Channels ; Nervous System ; Oocytes ; Receptors, GABA ; Retinal Bipolar Cells ; RNA, Complementary ; Sesquiterpenes ; Stilbenes ; Vitis ; Wine ; Xenopus