The objective of this study was to investigate the effects of ethanol extract of Ganoderma lucidum (GL95) on hyperlipidaemia and gut microbiota, and its regulation mechanism in Wistar rats fed on a high-fat diet (HFD). UPLC-QTOF MS indicated that GL95 was enriched with triterpenoids, especially ganoderic acids. The results of the animal experiment showed that oral administration of GL95 markedly alleviated the dyslipidemia through decreasing the levels of serum total triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and inhibiting hepatic lipid accumulation and steatosis. Furthermore, GL95 supplementation altered the composition of gut microbiota, in particular modulating the relative abundance of functionally relevant enterotypes compared with the HFD group. The Spearman's correlation analysis revealed that Alistipes, Defluviitalea, Peptococcaceae and Alloprevotella were negatively correlated with serum and hepatic lipid profiles. Meanwhile, the GL95 treatment regulated the mRNA expression levels of the genes involved in lipid and cholesterol metabolism. The findings above illustrate that Ganoderma triterpenoids have the potential to ameliorate lipid metabolic disorders, in part through modulating specific gut microbiota and regulating the genes involved in lipid and cholesterol metabolism, suggesting Ganoderma triterpenoids as a potential novel functional food for the treatment or prevention of hyperlipidaemia.

Ethanol extract of Ganoderma lucidum ameliorates lipid metabolic disorders and modulates the gut microbiota composition in high-fat diet fed rats.

Traditionally, Andrographis paniculata has been used as an herbal remedy for lung infection treatments. Its leaves contain a diterpenoid labdane called andrographolide responsible for a wide range of biological activities such as antioxidant, anti-inflammatory, and anti-cancer properties. This manuscript is a brief review of the antioxidant mechanisms and the regulation of the Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling pathway by andrographolide.

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Andrographolide, a Natural Antioxidant: An Update.

Chlorogenic acid and caffeic acid from Sonchus oleraceus Linn synergistically attenuate insulin resistance and modulate glucose uptake in HepG2 cells.

A review for the neuroprotective effects of andrographolide in the central nervous system.

Introduction: Recent advances in diagnostic modalities and therapeutic agents have raised the importance of prognostic factors in predicting overall survival, as well as predictive factors for surg...

Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies

BACKGROUND The purpose of the present study was to investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). METHODS Rats received vehicle or CA (20, 50, or 100 mg/kg per day) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR and western blot. RESULTS After BDL, plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology. Hepatic uptake transporters (Ntcp, Oatp 1a4, and Oatp 1b2) were downregulated, while efflux transporters (Bsep and Mrp 2/3/4) were upregulated. BDL inhibited the expressions of Cyp7a1, Cyp8b1, and Cyp27a1 and induced Ugt1a1. CA treatment decreased ALT, AST, TBIL, and TBA (P < 0.05) and alleviated the liver pathological changes. The degree of expression changes in the transporters and enzymes was extended by CA (P < 0.05). SIRT1 protein was induced after CA treatment in BDL rats. CONCLUSIONS Chlorogenic acid attenuated hepatotoxicity and cholestasis by decreasing the uptake and synthesis of bilirubin and bile acids and accelerating the metabolism and efflux of bilirubin and bile acids.

Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxicity and cholestasis in bile duct ligation rats: involvement of SIRT1-mediated deacetylation of FXR and PGC-1α.

To investigate if andrographolide impairs cholestatic liver injury. All rats were randomly divided into six groups—(1) control (n = 6), (2) control + 200 mg/kg andrographolide (n = 6), (3) alpha-naphthylisothiocyanate (ANIT)-control (n = 6), (4) ANIT + 50 mg/kg andrographolide (n = 6), (5) ANIT + 100 mg/kg andrographolide (n = 6), and (6) ANIT + 200 mg/kg andrographolide (n = 6). We gavaged 50 mg/kg ANIT to mimic cholestatic liver injury in rats. Seven days after treatment, all the rats were killed. Serum biochemistry and hepatic histopathological assays were performed to evaluate liver injury. We observed that 200 mg/kg andrographolide significantly decreased the level of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, total bilirubin, and total bile acid in the blood. It also markedly decreased hepatic interleukin-6 and tumor necrosis factor α. Furthermore, 200 mg/kg andrographolide significantly decreased malondialdehyde but increased superoxide dismutase, glutathione, and erythrocyte glutathione peroxidase. Moreover, 200 mg/kg andrographolide effectively increased the accumulation of sirtuin 1 and nuclear erythroid 2-related factor-2. It also attenuated the level of nuclear factor kappa-light-chain-enhancer of activated B and cyclooxygenase-2. These data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.

Andrographolide impairs alpha-naphthylisothiocyanate-induced cholestatic liver injury in vivo

// Peng Liu 1, * , Xianbin Zhang 1, 2, * , Yuru Shang 1 , Lili Lu 3 , Fei Cao 1 , Min Sun 4 , Zhaohui Tang 5 , Brigitte Vollmar 2 and Peng Gong 1, 6 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China 2 Institute of Experimental Surgery, University of Rostock, Schillingallee 69a, Rostock, 18059, Germany 3 Department of Epidemiology, Dalian Medical University, Dalian, 116044, China 4 Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, 430071, China 5 Department of General Surgery, Xinhua Hospital Shanghai Jiaotong University, Shanghai, 200092, China 6 Dalian Key Laboratory of Hepatobiliary Pancreatic Diseases Prevention and Treatment and Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, 116011, China * These authors contributed equally to this work Correspondence to: Xianbin Zhang, email: zhangxianbin@hotmail.com Peng Gong, email: gongpengdalian@163.com Keywords: pancreatic neuroendocrine neoplasms, lymph node ratio, examined lymph nodes, lymph node metastasis, overall survival Received: January 18, 2017      Accepted: June 28, 2017      Published: July 12, 2017 ABSTRACT Aim: To evaluate the prognostic significance of lymph node metastasis, extent of examined lymph nodes (ELNs) and lymph node ratio (LNR) for resected pancreatic neuroendocrine neoplasms (pNENs). Materials and Methods: Surgically resected pNENs were assimilated from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier and Cox proportional hazard models were used to examine the prognostic effect of clinicopathological characteristics on overall survival; Harrell’s concordance index was performed to assess the prognostic accuracy of all independent prognostic factors; and the Spearman’s rank correlation was used to assess the correlation between LNR and other clinicopathological characteristics. Results: Totally, 1,273 pathologically confirmed pNENs were included in our study. The extent of ELNs failed to show any survival benefit in entire cohort (ELNs ≤ 12 vs. ELNs > 12, P = 0.072) or pNENs without lymph node metastasis (ELNs ≤ 28 vs. ELNs > 28, P = 0.108). Lymph node metastasis and LNR > 0.40 were significantly (both P 0.40 was the independent predictor of survival after adjusted for other clinicopathological characteristics. Besides LNR, the age, gender, primary tumor site, grade and stage also were the independent predictors of overall survival; and this survival model had an acceptable predictive power (Harrell’s concordance index, 0.731). Conclusions: The current study suggested that the LNR, not the total number of ELNs and the lymph node metastasis, is an independent prognostic indicator of overall survival for pNENs after surgical resection.

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Lymph node ratio, but not the total number of examined lymph nodes or lymph node metastasis, is a predictor of overall survival for pancreatic neuroendocrine neoplasms after surgical resection.

ObjectivesWe aim to examine the predictive effect of the total number of examined lymph nodes on N stage and survival in pancreatic neuroendocrine neoplasms (pNENs) and to determine the optimal threshold.MethodsA pNENs data set from 2004 to 2013 was extracted from the Surveillance, Epidemiology, and

Fei Cao

Papers

Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxicity and cholestasis in bile duct ligation rats: involvement of SIRT1-mediated deacetylation of FXR and PGC-1α.

Andrographolide impairs alpha-naphthylisothiocyanate-induced cholestatic liver injury in vivo

Lymph node ratio, but not the total number of examined lymph nodes or lymph node metastasis, is a predictor of overall survival for pancreatic neuroendocrine neoplasms after surgical resection.

Predictive Effect of the Total Number of Examined Lymph Nodes on N Staging and Survival in Pancreatic Neuroendocrine Neoplasms.