BackgroundNon-alcoholic fatty liver disease (NAFLD) is a common, chronic liver disease worldwide. Recent studies have shown that T helper (Th) 17 and regulatory T (Treg) cells play critical roles in various disorders of liver inflammation. Here, we explored the value of polyene phosphatidylcholine capsules (PPC) for regulating the imbalance of Th17/Treg cells in the pathogenesis of mice with NAFLD.MethodsC57BL/6 mice were randomly divided into three groups as follows:normal diet (ND), high-fat diet (HF),and HF plus PPC(HF + PPC). The frequencies of splenic Th17 and Treg cells were measured by flow cytometry, and their related cytokines were analyzed by CBA and real-time PCR.ResultsAt the end of 24 weeks, mice in the HF group had a higher frequency of intrahepatic Th17 cells,and a lower proportion of Treg cells compared with the ND group. The levels of Th17 cell-related cytokines (IL-6, IL-17 and IL-23) in serum and in liver tisse were increased,and the hepatic mRNA levels of RORγt, STAT3 and IL-6 were also increased. By contrast,the FoxP3 mRNA level was decreased in the HF group. Moreover, significant pathological and biochemical changes in the liver, as well as serum biochemical changes, were found in mice with NAFLD. Interestingly, following treatment with PPC, the levels of liver inflammation,frequencies of Th17/Treg cells and associated cytokines,and biochemical data were significantly altered.ConclusionThese findings demonstrate a critical role for PPC in partially attenuating liver inflammatory responses in mice with NAFLD that involves the imbalance of Treg/Th17 cells and associated cytokines.

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Background and Purpose Mas oncogene‐related gene (Mrg) receptors are exclusively distributed in small‐sized neurons in trigeminal and dorsal root ganglia (DRG). We investigated the effects of MrgC receptor activation on inflammatory hyperalgesia and its mechanisms. Experimental Approach A selective MrgC receptor agonist, bovine adrenal medulla peptide 8‐22 (BAM8‐22) or melanocyte‐stimulating hormone (MSH) or the μ‐opioid receptor (MOR) antagonist CTAP was administered intrathecally (i.t.) in rats injected with complete Freund's adjuvant (CFA) in one hindpaw. Thermal and mechanical nociceptive responses were assessed. Neurochemicals were measured by immunocytochemistry, Western blot, ELISA and RT‐PCR. Key Results CFA injection increased mRNA for MrgC receptors in lumbar DRG. BAM8‐22 or MSH, given i.t., generated instant short and delayed long‐lasting attenuations of CFA‐induced thermal hyperalgesia, but not mechanical allodynia. These effects were associated with decreased up‐regulation of neuronal NOS (nNOS), CGRP and c‐Fos expression in the spinal dorsal horn and/or DRG. However, i.t. administration of CTAP blocked the induction by BAM8‐22 of delayed anti‐hyperalgesia and inhibition of nNOS and CGRP expression in DRG. BAM8‐22 also increased mRNA for MORs and pro‐opiomelanocortin, along with β‐endorphin content in the lumbar spinal cord and/or DRG. MrgC receptors and nNOS were co‐localized in DRG neurons. Conclusions and Implications Activation of MrgC receptors suppressed up‐regulation of pronociceptive mediators and consequently inhibited inflammatory pain, because of the activation of up‐regulated MrgC receptors and subsequent endogenous activity at MORs. The uniquely distributed MrgC receptors could be a novel target for relieving inflammatory pain.

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Pure total flavonoids from Citrus (PTFC) effectively reduce the symptoms of non-alcoholic fatty liver disease (NAFLD). Our previous microarray analysis uncovered the alterations of important signaling pathways in the treatment of NAFLD with PTFC. However, the underlying core genes that might be targeted by PTFC, which play important roles in the progression of NALFD are yet to be identified. In this study, we predicted the vascular endothelial growth factor-C (VEGF-C) as potential key molecular target of PTFC against NAFLD via network pharmacology analysis. The network pharmacology approach presented here provided important clues for understanding the mechanisms of PTFC treatment in the development of NAFLD.

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