Research topic: lipid metabolism
Research topic: lipid metabolism
Guest Editor: Prof. WU Xu-Dong
Prof. WU Xu-Dong has been working in School of Life Sciences of Nanjing University as a full professor since 2018. Her current researches are focused on metabolic syndrome and inflammation. And she has published some representative achievements in many top journals, such as Gastroenterology, Hepatology, Nat Commun., Br J Pharmcol,, J Invest Dermatol., et al. Now she is the editorial board member of Chinese Journal of Natural Medicines and peer reviewer for Biochemical Pharmacology, International Journal of Biological Macromolecules, International Journal of Immunopharmacology, and so on.
Title: Fatty liver diseases, mechanisms, and potential therapeutic plant medicines
[Abstract] The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins (SIRTs), Forkhead box O (FoxO), Sterol-regulatory element-binding proteins (SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.
Cite this article as:ZHU Jia-Zhen, YI Hong-Wei, HUANG Wei, PANG Tao, ZHOU Hui-Ping, WU Xu-Dong. Fatty liver diseases, mechanisms, and potential therapeutic plant medicines [J]. Chin J Nat Med, 2020, 18(3): 161-168. doi: 10.1016/S1875-5364(20)30017-0
[Abstract] The objective of this study was to verify the protective effect of Bifidobacterium longum (BL) and the synergistical effect of Selenium and BL on alcohol plus high fat diet (HFD) induced hepatic injury in mice. We also want to explore the mechanism of Selenium-enriched Bifidobacterium longum (SeBL). C57BL/6 mice were treated with alcohol plus HFD with or without different dosage of BL or SeBL for 4 weeks. Serum levels of ALT, AST, TC, TG, LDL-C, HDL-C, FFAs, TNF-α, IL-6 and IL-1β, hepatic MDA level, SOD activity, the mRNA levels of AMPK, PPAR-α and SREBP1 were invested. SeBL inhibited lipid accumulation in hepatocytes; reduced serum AST and ALT levels; improved dyslipidemia; decreased serum FFAs, TC, TG and LDL-C levels. SeBL also inhibited alcohol plus HFD-induced hepatocyte oxidative stress through decrease in hepatic MDA levels and increase in SOD activity. SeBL also regulated lipid metabolism related genes such as AMPK, PPAR-α and SREBP1. Although BL had similar effect as SeBL, SeBL is more effective than BL. SeBL protected mice from alcohol plus HFD-induced hepatic injury in mice because of its inhibitory effect on hepatocellular oxidative stress, lipogenesis and inflammation. Selenium enhanced the protective effect of BL.
Cite this article as: YI Hong-Wei, ZHU Xiao-Xiao, HUANG Xiao-Li, LAI Yu-Zhu, TANG Yue. Selenium-enriched Bifidobacterium longum protected alcohol and high fat diet induced hepatic injury in mice [J]. Chin J Nat Med, 2020, 18(3): 169-177. doi: 10.1016/S1875-5364(20)30018-2
Title: MUC1 promotes glycolysis through inhibiting BRCA1 expression in pancreatic cancer
[Abstract] Enhanced glucose metabolism is one of the hallmarks of pancreatic cancer. MUC1, a transmembrane protein, is a global regulator of glucose metabolism and essential for progression of pancreatic cancer. To clarify the role of MUC1 in glucose metabolism, we knocked out MUC1 in Capan-1 and CFPAC-1 cells. MUC1 knockout (KO) cells uptook less glucose and secreted less lactate with a much lower proliferating rate. The mRNA level of key enzymes in glycolysis also decreased significantly in MUC1 KO cells. We also observed increased expression of breast cancer type 1 susceptibility protein (BRCA1) in MUC1 KO cells. Since BRCA1 has a strong inhibitory effect on glycolysis, we want to know whether the decreased glucose metabolism in MUC1 KO cells is due to increased BRCA1 expression. We treated wild type (WT) and MUC1 KO cells with BRCA1 inhibitor. BRCA1 inhibition significantly enhanced glucose uptake and lactate secretion in both WT and MUC1 KO cells. Expression of key enzymes in glycolysis also elevated after BRCA1 inhibition. Elevated glucose metabolism is known to facilitate cancer cells to gain chemoresistance. We treated MUC1 KO cells with gemcitabine and FOLFIRINOX in vitro and in vivo. The results showed that MUC1 KO sensitized pancreatic cancer cells to chemotherapy both in vitro and in vivo. In conclusion, we demonstrated that MUC1 promotes glycolysis through inhibiting BRCA1 expression. MUC1 may be a therapeutic target in pancreatic cancer treatment.
Cite this article as: FU Xiao, TANG Neng, XIE Wei-Qi, MAO Liang, QIU Yu-Dong. MUC1 promotes glycolysis through inhibiting BRCA1 expression in pancreatic cancer [J]. Chin J Nat Med, 2020, 18(3): 178-185. doi: 10.1016/S1875-5364(20)30019-4
Title: Berbamine ameliorates ethanol-induced liver injury by inhibition of hepatic inflammation in mice
[Abstract] Alcoholic liver disease (ALD) has become one of the leading causes of death in the world. Berbamine (BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medicine. However, the protective effect of BM on ALD remains unknown. In this study, we investigated the effect of BM on ethanol-induced hepatic injury in mice and its underlying mechanism. It was shown that BM at 0.3125−40 μmol·L−1 had no effect on macrophages and hepatocytes proliferation. BM at 5−20 μmol·L−1 significantly inhibited lipopolysaccharide (LPS) or acetate-induced IL-1β and IL-6 mRNA expression in RAW264.7 cells. Moreover, BM treatment significantly inhibited LPS-induced p65 and STAT3 phosphorylation in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kg−1 BM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels in ethanol-fed mice. Oil red O staining results showed that BM administration ameliorated hepatic lipid accumulation in ethanol-fed mice. Preventions of ethanol-induced hepatic injury by BM were reflected by markedly decreased serum and hepatic triglyceride (TG) and total cholesterol (TC) contents. Real-time PCR results showed that BM treatment significantly inhibited pro-inflammatory cytokines mRNA expression in ethanol-fed mouse liver. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 phosphorylation levels in liver. In addition, BM treatment significantly inhibited ERK phosphorylation but not JNK and p38 of MAPK pathway. Taken together, our results demonstrate a beneficial effect of BM on ethanol-induced liver injury via a mechanism associated with inactivation of NF-κB, STAT3 and ERK pathway, which gives insight into the further evaluation of the therapeutic potential of BM for ALD.
Cite this article as: LIU Xin-Yu, CHEN Guan-Nan, DU Guo-Ming, PAN Yue, SONG Wu-Qi, JIANG Ting-Wang, LIU Hai-Liang. Berbamine ameliorates ethanol-induced liver injury by inhibition of hepatic inflammation in mice [J]. Chin J Nat Med, 2020, 18(3): 186-195. doi: 10.1016/S1875-5364(20)30020-0
