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.

Ethnopharmacological Relevance: 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).

Aim Of The Study: This study explored the effects and mechanism of QWTX on 3T3-L1 adipocytes and NAFLD.

Materials And Methods: 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-[H] glucose and [1-C] 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.

Results: QWTX showed no cell cytotoxicity in 3T3-L1 preadipocyte cells, and increased the CO 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.

Conclusions: QWTX protected the liver injury in differentiated 3T3-L1 adipocytes and NAFLD by regulating the LXRα, PPARγ, and NF-κB-iNOS-NO signal pathways.