20(S)-Ginsenoside Rg3

20(S)-Ginsenoside Rg3 is the main component of Panax ginseng C. A. Meyer. Ginsenoside Rg3 inhibits Na⁺ and hKv1.4 channel with IC₅₀s of 32.2±4.5 and 32.6±2.2 μM, respectively. 20(S)-Ginsenoside Rg3 also inhibits Aβ levels, NF-κB activity, and COX-2 expression. IC50 & Target:IC50: 32.2±4.5 μM (Na⁺ channel)^[1]
IC50: 32.6±2.2 μM (hKv1.4 channel)^[2]
NF-κB p65^[3]
COX-2^[3]
Aβ40 and Aβ42^[4] In Vitro: Ginsenoside Rg3 plays an important role in its effect on the Na⁺ channel. Treatment with Ginsenoside Rg3 reversibly inhibits the inward Na+ peak current (INa) with an IC₅₀ of 32.2±4.5 μM, and the inhibition is voltage-dependent^[1]. Ginsenoside Rg3 at 100 μM inhibits the hKv1.4 channel currents by an average of 65%.The Ginsenoside Rg3 effect is concentration-dependent and reversible. The IC₅₀ value and Hill coefficient are 32.6±2.2 μM and 1.59±0.13, respectively^[2]. Ginsenoside Rg3 shows the significant inhibition of NF-κB activity thereby reduced COX-2 expression. To examine the cytotoxicity of Ginsenoside Rg3 on IL-1β-induced inflamed A549 cells, the cells are firstly treated with IL-1β (10?ng/mL) for 4?h and treated with 100 to 900?ng/mL concentration of Ginsenoside Rg3 for 12?h. Cell viability is analyzed using an MTT assay. There is no observed cytotoxicity of Ginsenoside Rg3 in IL-1β-induced inflamed A549 cells compared to only PBS-treated cells (Con).To obtain the anti-inflammatory effects of Ginsenoside Rg3 on inflammation induced human lung epithelial cells, A549 cells inflammation is induced by IL-1β (10?ng/mL) and then treated by 5?μM of Dexamethasone (Dex) or 900?nM of Rg3. The NF-κB activation is analyzed by a western blot analysis to evaluate the effect of Ginsenoside Rg3 treatment on A549 cells. Phospho-NF-κB p65/total NF-κB p65 densitometry in the cells treated with Rg3 shows the significant decrease compared to IL-1β-induced inflamed A549 cells. The meaning of reducing the ratio of p-p65/p65 by Rg3 treatment is associated with NF-κB activation. Ginsenoside Rg3 also downregulates the expression of COX-2 effectively^[3]. In Vivo: Ginsenoside Rg3 ((20S)-Rg3) is an Aβ-lowering Natural Compound. APP/PS1 mice are treated with Ginsenoside Rg3 once a day for 4 weeks by intraperitoneal injection (10 mg/kg/day). Aβ ELISA analysis of brain tissues reveal that Ginsenoside Rg3 treatment results in a significant reduction of Aβ40 and Aβ42 in the brain^[4].