Protective effect and mechanism of Qiwei Tiexie capsule on 3T3-L1 adipocytes cells and rats with nonalcoholic fatty liver disease by regulating LXRα, PPARγ, and NF-κB-iNOS-NO signaling pathways.

Qiwei Tiexie capsule (QWTX) is a representative prescription of Tibetan medicine, which is widely used for long-term treatment of chronic liver disease and nonalcoholic fatty liver disease (NAFLD). This study explored the effects and mechanism of QWTX on 3T3-L1 adipocytes and NAFLD. The 3T3-L1 preadipocytes and NAFLD rat model were used in the study. In 3T3-L1 cells, the cytotoxicity of QWTX was tested by CKK-8, and glucose uptake and fat acid oxidation were assessed by 2-deoxy-D-[3H] glucose and [1-14C] palmitic acid, respectively. The expression levels of carnitine palmitoyltransferase-1 (CPT-1), liver X receptor α (LXRα), peroxisome proliferator-activated receptor (PPAR) γ, inducible nitric oxide synthase (iNOS), ikappa B α (IκBα), and AKT were determined by PCR and western blot. NAFLD was established by the administration of fat emulsion and sucrose for 9 weeks. The effects of QWTX on lipid metabolism, liver function, and hepatic morphology were observed in NAFLD rats by HE and transmission electron microscope. Serum level of nitric oxide (NO) and fee fatty acid (FFA), superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver, as well as the expression levels of Cytochrome P450 2E1 (CYP2E1), NF-κB, monocyte chemoattractant protein 1 (MCP-1), CPT-1, LXRα, PPARα, PPARβ/δ, PPARγ, and iNOS were all detected. QWTX showed no cell cytotoxicity in 3T3-L1 preadipocyte cells, and increased the 14CO2 production rate to 4.15, which indicated the reducing the fatty accumulation. In NAFLD, QWTX attenuated liver steatosis, fat vacuoles and inflammation from the HE staining and electron micrograph tests. For the oxidative stress biomarkers, serum FFA level was reduced and serum NO level was enhanced after QWTX treatment. In liver tissue, SOD was decreased and MDA was significantly increased in NAFLD, and both of them were restored by QWTX. NF-κB and CYP2E1 were also upregulated in NAFLD, while downregulated by QWTX. Downregulation of LXRα, PPARγ and iNOS by QWTX were both observed in the 3T3-L1 adipocytes and NAFLD model. QWTX protected the liver injury in differentiated 3T3-L1 adipocytes and NAFLD by regulating the LXRα, PPARγ, and NF-κB-iNOS-NO signal pathways.

Suolang PC ，Liu BQ ，Chen J ，De J ，Nima ZB ，Dunzhu CR ... -  《-》

Li-Gan-Shi-Liu-Ba-Wei-San improves non-alcoholic fatty liver disease through enhancing lipid oxidation and alleviating oxidation stress.

Mongolian medicine is an important constituent of traditional Chinese medicine. Its representative prescription, Li-Gan-Shi-Liu-Ba-Wei-San (LGSLBWS), is widely used for long-term treatment of chronic liver disease and nonalcoholic fatty liver disease (NAFLD). This study explored the effects and mechanism of LGSLBWS on NAFLD. NAFLD rat model was established with high-fat diet. The effects of LGSLBWS on lipid metabolism, liver function, and hepatic morphology were observed in NAFLD rats. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver, as well as the expression levels of peroxisome proliferator-activated receptor (PPAR)α, PPARβ, inhibitor of nuclear factor κB α(IκBα), and inducible nitric oxide synthase (iNOS) were all detected. Finally, the effects of LGSLBWS on fatty acid oxidation, PPARα, PPARβ, IκBα, and iNOS were determined in HepG2 cells. LGSLBWS significantly reduced the fat deposition in the liver and the serum aspartate aminotransferase levels in NAFLD rats. Serum triglyceride and free fatty acid levels were reduced by LGSLBWS. Total cholesterol and triglyceride contents in the liver were also downregulated. SOD and MDA levels were increased and decreased by LGSLBWS, respectively. LGSLBWS can significantly promote fatty acid oxidation of HepG2 cells. Upregulation of PPARα, PPARβ, and IκBα and downregulation of iNOS by LGSLBWS were both observed in the NAFLD model and HepG2 cells. LGSLBWS can significantly improve NAFLD by enhancing fatty acid oxidation and alleviating oxidative stress.

Jiang Y ，Chen L ，Wang H ，Narisi B ，Chen B ... -  《-》

Sesamin ameliorates hepatic steatosis and inflammation in rats on a high-fat diet via LXRα and PPARα.

Nonalcoholic fatty liver disease (NAFLD) is defined by a nonalcohol relevant pathological accumulation of fat in the liver. Previous studies have shown that sesamin exerts antioxidant effects and improves lipid metabolism of the fatty liver. In this study, we hypothesized that sesamin improves lipid homeostasis of Sprague-Dawley rats fed a high-fat diet (HFD) by regulating the expression of genes related to de novo lipogenesis and β-oxidation. We induced NAFLD in rats with HFD and examined the effect of sesamin in vivo. The results showed that HFD rats accumulated total cholesterol and triacylglycerols in the liver and developed inflammation, as evidenced by the elevation of interleukin-6 and tumor necrosis factor-α in the liver and serum. Sesamin attenuated the disease progression by improving the blood lipid profile in a dose-dependent manner. Sesamin reduced the serum levels of total cholesterol, triacylglycerols, low-density lipoprotein cholesterol, and free fatty acid, whereas it increased the level of high-density lipoprotein cholesterol. Meanwhile, sesamin increased the activities of hepatic glutathione peroxidase and superoxide dismutase while reducing the level of malonaldehyde and cytochrome P450 2E1. Furthermore, higher doses of sesamin reduced the expression of liver X receptor α and its downstream target genes, whereas it upregulated the peroxisome proliferator-activated receptor α-mediated signaling. These findings suggest that sesamin attenuates diet-induced dyslipidemia and inflammation of NAFLD in rats via mechanisms regulated by liver X receptor α and peroxisome proliferator-activated receptor α.

Zhang R ，Yu Y ，Hu S ，Zhang J ，Yang H ，Han B ，Cheng Y ，Luo X ... -  《-》

Chinese herbal medicine mixture 919 syrup alleviates nonalcoholic fatty liver disease in rats by inhibiting the NF-κB pathway.

In many countries, nonalcoholic fatty liver disease (NAFLD) has risen to be the leading cause of liver disease, seriously threatening public health, while effective medical treatments are currently limited. 919 syrup (919 T J) is a Chinese herbal medicine, and both clinical and experimental studies have revealed that it can improve liver function. To study whether 919 T J shows a protective effect in a NAFLD rat model and explore its underlying mechanism, with a focus on the NF-κB pathway. Rats were randomly divided into three groups, including a control group, NAFLD group, and 919 T J group (n = 10 each). The control group received a standard diet, and the other two groups were fed a high-fat diet to establish the NAFLD model. From week 10, rats in the 919 T J group were intragastrically administered 919 T J for 4 weeks, and the NAFLD group was administered the same amount of saline. All rats were anesthetized at the beginning of week 14 to collect blood and liver specimens. Serum lipid levels, serum biochemical markers of liver function, and the gene expression levels of IL-1β, TNF-α, CXCL6, CXCR1, SREBP-1c, PPARγ, and NF-κB in the liver were measured. Oil Red O and hematoxylin and eosin staining of the liver was performed to observe pathological changes in the liver. Significant abnormalities in serum lipid levels and serum biochemical markers of liver function were found in the NAFLD group relative to those in the control group. In addition, serious abnormalities were noted in the expression levels of liver inflammatory factors and lipid metabolism-related genes. Treatment of NAFLD rats with 919 T J reduced body weight and food intake and ameliorated the abnormal blood lipid levels and liver function markers. By regulating the NF-κB pathway, 919 T J downregulated the NF-κB-related proinflammatory signals, ameliorating the expression of inflammatory (IL-1β, TNF-α, CXCL6, and CXCR1) and lipid metabolism-related (SREBP-1c) factors in the liver and improving the NAFLD-induced pathological changes in the liver. 919 T J reduces the liver injury, steatosis, and inflammation caused by NAFLD, thus reversing the disease process.

Chen M ，Xing J ，Pan D ，Peng X ，Gao P ... -  《-》

The anti-liver fibrosis effect of Tibetan medicine (Qiwei Tiexie capsule) is related to the inhibition of NLRP3 inflammasome activation in vivo and in vitro.

Qiwei Tiexie capsule (QWTX) is an improved form of a classical prescription of Tibetan medicine-Qiwei Tiexie pill. It has been employed in the treatment of a variety of chronic liver disorders, including liver fibrosis. Uncertainty still exists regarding the mechanism of QWTX action in liver fibrosis. Confirm the anti-liver fibrosis effect of QWTX and reveal its mechanism from the perspective of NOD-like receptor protein 3 (NLRP3) inflammasome activation. In vivo experiment: A rat model of carbon tetrachloride -induced liver fibrosis was constructed. All rats were randomly divided into six groups: a control group, a model group, a group receiving the positive drug (Biejia Ruangan tablet), and three groups receiving QWTX at high, medium, and low doses. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBil) were detected in serum. Hematoxylin and eosin staining and Masson's staining were used to assess the histomorphological alteration of the liver. The levels of glutathione peroxidase, hydroxyproline, tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) in the liver were determined using the corresponding detection kits. Real-time polymerase chain reaction, immunofluorescence, and western blotting were used to determine the expression levels of NLRP3, adaptor protein (ASC), caspase-1, and alpha-smooth muscle actin (α-SMA). In vitro experiment: Four groups of rat hepatic stellate cell line (HSC-T6) cells were created: the control group, the low-dose QWTX group (0.05 mg/mL), the medium-dose QWTX group (0.1 mg/mL), and the high-dose QWTX group (0.2 mg/mL). Cell viability was assessed using a cell counting kit, and the amounts of collagen type I (Col I) and IL-1β in the cell lysate were measured using an enzyme-linked immunosorbent assay kit. The mRNA and protein expression of NLRP3, ASC, caspase-1, and α-SMA were also estimated. QWTX had an inhibitory effect on liver fibrosis and a negative effect on HSC activation, while it improved liver histopathological injury and abnormal liver function and increased hydroxyproline content and glutathione peroxidase activity in vivo. QWTX decreased the expression of α-SMA, NLRP3, caspase-1, ASC, and IL-1β both in vitro and in vivo. Tibetan medicine QWTX had a significant anti-liver fibrosis effect that was related to the inhibition of NLRP3 inflammasome activation in vivo and in vitro.

Wang S ，Ye F ，Ren Q ，Sun S ，Xia W ，Wang Z ，Guo H ，Li H ，Zhang S ，Lowe S ，Chen M ，Du Q ，Weihong Li ... -  《-》