Fermented Korean Red Ginseng Extract Enriched in Rd and Rg3 Protects against Non-Alcoholic Fatty Liver Disease through Regulation of mTORC1

Abstract

The fermentation of Korean red ginseng (RG) increases the bioavailability and efficacy of RG, which has a protective role in various diseases. However, the ginsenoside-specific molecular mechanism of the fermented RG with Cordyceps militaris (CRG) has not been elucidated in non-alcoholic fatty liver disease (NAFLD). A mouse model of NAFLD was induced by a fast-food diet (FFD) and treated with CRG (100 or 300 mg/kg) for the last 8 weeks. CRG-mediated signaling was assessed in the liver cells isolated from mice. CRG administration significantly reduced the FFD-induced steatosis, liver injury, and inflammation, indicating that CRG confers protective effects against NAFLD. Of note, an extract of CRG contains a significantly increased amount of ginsenosides (Rd and Rg3) after bioconversion compared with that of conventional RG. Moreover, in vitro treatment with Rd or Rg3 produced anti-steatotic effects in primary hepatocytes. Mechanistically, CRG protected palmitate-induced activation of mTORC1 and subsequent inhibition of mitophagy and PPARα signaling. Similar to that noted in hepatocytes, CRG exerted anti-inflammatory activity through mTORC1 inhibition-mediated M2 polarization. In conclusion, CRG inhibits lipid-mediated pathologic activation of mTORC1 in hepatocytes and macrophages, which in turn prevents NAFLD development. Thus, the administration of CRG may be an alternative for the prevention of NAFLD.

Diclofenac impairs autophagic flux via oxidative stress and lysosomal dysfunction: Implications for hepatotoxicity

“…Thus, mt-Keima enables differential imaging of mitochondria in the cytoplasm and those in acidic lysosomes [ 28 ]. To monitor the inhibition of mitophagy, we used Hep3B cells stably transfected with the mt-Keima construct where the basal level of mitophagy is relatively high [ 29 ]. High levels of acidic mitochondria were found in vehicle-treated control cells.…”

Ginseng Saponin Enriched in Rh1 and Rg2 Ameliorates Nonalcoholic Fatty Liver Disease by Inhibiting Inflammasome Activation

“…As shown in Table 3 and Figure 4 J, the saponin extract contained significantly increased amounts of several ginsenosides. Many of the upregulated ginsenosides, such as Rg1, Rg3, Rb1 [ 32 , 36 ], Rb2 [ 33 ], and Rd [ 35 ], were identified to be associated with NAFLD/NASH. In contrast, the role of Rh1 and Rg2 in hepatic pathophysiology remains unknown.…”

“…Additionally, saponin extract contained significantly increased amounts of several ginsenosides, such as Rh1 and Rg2. Although many studies have identified upregulated NAFLD/NASH-associated ginsenosides, such as Rg1, Rb1, Rg3 [ 32 , 36 ], Rd [ 35 ], and Rb2 [ 33 ], the effects of ginsenosides Rh1 and Rg2 on FFD-induced NAFLD and their potential mechanisms have not yet been explored. In the current study, the anti-inflammatory effects of saponin extract were investigated in vivo and in vitro.…”

“…Primary hepatocytes were isolated from the C57BL/6 mice, as previously described [ 35 ]. Hepatocytes were resuspended in complete M199 medium.…”

“…The medium was incubated for 24 h at 37 °C and then collected for the required assays. PA cytotoxicity towards primary hepatocytes was assessed, as previously described [ 35 ].…”