Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway.

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3ß pathway.

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic ß-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3ß proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3ß signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.

Enhanced Anti-Inflammatory Effects of Silibinin and Capsaicin Combination in Lipopolysaccharide-Induced RAW264.7 Cells by Inhibiting NF-κB and MAPK Activation.

Silibinin and capsaicin both are natural product molecules with diverse biological activities. In this article, we investigated the anti-inflammatory effects of silibinin combined with capsaicin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The results showed that silibinin combined with capsaicin strongly inhibited LPS-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and COX-2. Moreover, silibinin combined with capsaicin potently inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results of the present study indicate that silibinin combined with capsaicin effectively inhibits inflammation.

Inclusion Complex of Isoliquiritigenin With Sulfobutyl Ether-ß-Cyclodextrin: Preparation, Characterization, Inclusion Mode, Solubilization, and Stability.

Isoliquiritigenin (ISL) possesses a wide variety of pharmacological properties, however, its poor solubility and oral bioavailability pose a significant barrier to its application. In present studies, the ISL inclusion complex was prepared with sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD). The physicochemical characterizations of ISL-SBE-ß-CD were performed with Fourier transform infrared (FT-IR) spectroscopy and X-ray powder diffraction (XRD). Phase solubility study suggested a 1:1 formation of ISL-SBE-ß-CD complexes. The water solubility of ISL rose from 13.6 µM to 4.05 mM by the inclusion of SBE-ß-CD. The antioxidant activities (IC50) of ISL-SBE-ß-CD reached 42.2 µg/ml, which was significantly lower than that of ISL (60.5 µg/ml). Its stability in biological environments was also enhanced.