RÉSUMÉ
Ginsenoside Rg1 (G-Rg1) has various pharmacological properties including antiobesity, immunomodulatory, and anti-inflammatory effects. This study aimed to explore the therapeutic effects and underlying mechanisms of G-Rg1 on colitis complicated by obesity. The results indicate that G-Rg1 effectively alleviates colitis in obese mice and improves serum lipid levels and liver function. Importantly, G-Rg1 improved the composition of gut microbiota in obese mice with colitis, with increases in alpha diversity indexes Sobs, Ace, and Chao, a significant down-regulation of the relative abundance of Romboutsia, and a significant up-regulation of Rikenellaceae_RC9_gut_group, Lachnospiraceae_NK4A136_group, Enterorhabdus, Desulfovibrio, and Alistipes. Meanwhile, G-Rg1 improved lipid metabolism in the colonic contents of obese mice with colitis. Additionally, G-Rg1 significantly reduced the percentages of helper T (Th)1, Th17, central memory T (TCM), and effector memory T (TEM) cells in obese mice with colitis while significantly increasing Naïve T and Th2 cells. In conclusion, G-Rg1 could be a promising therapeutic option for alleviating obesity complicated by colitis through regulation of the gut microbiota and lipid metabolism as well as Th1/Th2/Th17 cell differentiation.
Sujet(s)
Rectocolite hémorragique , Colite , Microbiome gastro-intestinal , Souris , Animaux , Rectocolite hémorragique/traitement médicamenteux , Rectocolite hémorragique/métabolisme , Souris obèse , Métabolisme lipidique , Cellules Th17 , Colite/traitement médicamenteux , Obésité/traitement médicamenteux , Obésité/métabolisme , Souris de lignée C57BL , Modèles animaux de maladie humaine , Sulfate dextran/métabolisme , Côlon/métabolismeRÉSUMÉ
Huxie Huaji (HXHJ) Ointment is a famous traditional Chinese medicinal prescription and is commonly used for the clinical treatment of hepatocellular carcinoma by boosting immunity and detoxification. However, the scientific evidence for the effect of HXHJ Ointment on hepatocellular carcinoma and the underlying molecular mechanism are lacking. The present study aimed to identify the effects of HXHJ Ointment on hepatocellular carcinoma in vitro and in vivo as well as investigating the mechanistic basis for the anticancer effect of HXHJ ointment. First, liquid chromatography-mass spectrometry was used to verify the composition of HXHJ Ointment and quality control. Second, in vitro, Cell Counting Kit (CCK8) cell viability assay and Hoechst 33342 staining assay were performed to explain the cell apoptosis. The protein levels of tumor suppressor protein (p53), B-cell lymphoma 2 gene (Bcl-2), cytochrome C (Cyt-C), and aspartate proteolytic enzyme-3 (caspase-3) were examined by immunofluorescence. Finally, in vivo, hematoxylin and eosin (H&E) staining was used to observe the pathological changes in hepatocellular carcinoma samples. Western blots and immunohistochemistry were used to detect the anticancer properties of HXHJ ointment. The results in vitro showed that 20% HXHJ Ointment serum could significantly inhibit HepG2 cell proliferation, increased tumor suppressor gene p53, downregulated antiapoptotic protein Bcl-2, promoted the release of mitochondrial Cyt-C, activated caspase-3, and induced HepG2 cell apoptosis. Furthermore, in vivo experiments showed that HXHJ Ointment could effectively inhibit tumor growth in nude mice xenotransplanted with HepG2 cells, changed the morphology of tumor cells, and regulated the expression of apoptosis-related protein pathway p53/Bcl-2/Cyt-C/caspase-3. HXHJ Ointment can significantly inhibit the development of hepatocellular carcinoma, and its mechanism may be related to the regulation of p53/Bcl-2/Cyt-C/caspase-3 signaling pathway to induce cell mitochondrial apoptosis.
RÉSUMÉ
Erzhi Pill (EZP) is one of the basic prescriptions for treating liver diseases in traditional Chinese medicine. However, its mechanism of action is still undefined. The PI3K/AKT/Raptor/Rictor signaling pathway is closely related to apoptosis and plays a significant role in the pathogenesis of liver disease. To define the mechanism of the hepatoprotective effect of EZP in the treatment of liver disease, hepatic injury induced by 2-acetylaminofluorene/partial hepatectomy was treated by EZP for 14 days. The therapeutic effect of EZP was confirmed by the decreased production of aspartate aminotransferase and alanine aminotransferase, recovery of pathological liver injury, followed by inhibition of pro-inflammatory cytokines and transforming growth factor-ß1. Bromodeoxyuridine assay and TUNEL staining indicated that apoptosis was suppressed and the numbers of cells in S phase and G0/G1phase were decreased. The crucial proteins in the PI3K/AKT/Raptor/Rictor signaling pathway were deactivated in rats with experimental liver injury treated by EZP. These results indicated that the hepatoprotective effect of EZP via inhibition of hepatocyte apoptosis was closely related to repression of the PI3K/Akt/Raptor/Rictor signaling pathway.