Mangiferin relieves CCl4-induced liver fibrosis in mice.

Hepatic fibrosis is a late stage process of many chronic liver diseases. Blocking the fibrosis process will be beneficial to the treatment and recovery of the diseases. Mangiferin has many pharmacological activities. Recently, it has been reported that mangiferin may relieve tissue fibrosis, including renal, myocardial, pulmonary fibrosis via anti-inflammatory and anti-oxidative effects in animal models. Here, we investigate the effects of mangiferin on CCl4-induced liver fibrosis and the underlying mechanism in mice. Thirty-two male C57BL/6 mice were randomly divided into 4 groups (n = 8 in each group), injected with carbon tetrachloride (10% CCl4) for 8 weeks, and oral administrated with mangiferin (50 mg/kg or 100 mg/kg) from the fifth week. The serum levels of ALT, AST were analyzed to evaluate liver function. H&E, Masson's trichrome and Sirius red staining were used to assess liver morphology and the degree of liver fibrosis. Quantitative RT-PCR and Western blot were used to assay the gene expression and protein levels. The results showed that mangiferin alleviated the serum levels of AST, ALT, ALP, TBA and TBIL, reduced liver lesions, prevented hepatic parenchymal necrosis, and ameliorated collagen accumulation in the liver of CCl4-treated mice. Meanwhile, mangiferin inhibited the expression of inflammatory genes IL-6 and IL-1ß, fibrogenic genes α-SMA, TGF-ß and MMP-2 and bile acid metabolism genes ABCB4, ABCB11, SULT2A1 in the liver of CCl4-treated mice. Furthermore, mangiferin reduced collagen accumulation and HSCs activation, inhibited the p-IκB and p-p65 protein levels. Our results suggest that mangiferin could alleviate liver fibrosis in CCl4-treated mice through inhibiting NF-κB signaling, and mango consuming may have beneficial effects to hepatic fibrosis.

Berbamine reduces body weight via suppression of small GTPase Rab8a activity and activation of paraventricular hypothalamic neurons in obese mice.

Small GTPase Rab8a is involved in fat-specific protein 27 (Fsp27) mediated lipid droplet accumulation in adipocytes. By screening inhibitors of Rab8a GTPase from a natural compound library, berbamine (BBM), a marketing drug for treatment of leukopenia in China, was identified to inhibit the activity of Rab8a GTPase and block the differentiation of 3T3-L1 adipocytes. Animal study showed that BBM could reduce body weight, improved glucose and lipid metabolic homeostasis in high-fat diet-induced obesity (DIO) C57BL/6 mice and db/db mice. Additional, BBM increased energy expenditure and inhibited food intake in mice but not in lean mice. Moreover, intracerebroventricular injection (i.c.v.) of BBM inhibited feeding behavior and increased c-Fos expression in paraventricular nucleus of the hypothalamus (PVH) of mice. Our data suggest that BBM may improve obesity through the inhibition of Rab8a GTPase activity and the activation of anorexigenic energy-sensing neuron in PVH.

Tangeretin promotes lifespan associated with insulin/insulin-like growth factor-1 signaling pathway and heat resistance in Caenorhabditis elegans.

Tangeretin is a polymethoxylated flavonoid naturally occurred in citrus fruits with many pharmacological activities, such as anti-inflammatory, antiproliferative, and neuroprotective properties. A previous study reported that tangeretin-enriched orange extract could prolong the lifespan in Caenorhabditis elegans. However, the antiaging effect of tangeretin remains uncertain. In this study, we used the model organism C. elegans to conduct a lifespan test, observed the aging-related functional changes of nematodes, the fluorescence changes of stress-related proteins (DAF-16 and HSP-16.2) and its response to stress assay, and monitored the effect of tangeretin on the mRNA expression levels. The results showed that tangeretin supplementation (30 and 100 µM) extended the mean lifespan, slowed aging-related functional declines, and increased the resistance against heat-shock stress. Furthermore, tangeretin upregulated the mRNA expression of daf-16, hsp-16.2, and hsp-16.49, promoted the nuclear localization of DAF-16, and enhanced the fluorescence intensity of HSP-16.2, while it had no effect on the lifespan of daf-2, age-1, and daf-16 mutants. The current findings suggest that tangeretin can significantly extend the lifespan and enhance heat stress tolerance in an insulin/insulin-like growth factor signaling dependent manner.

Notoginsenoside Fe suppresses diet induced obesity and activates paraventricular hypothalamic neurons.

Obesity has become a major public health challenge worldwide. Energy imbalance between calorie acquisition and consumption is the fundamental cause of obesity. Notoginsenoside Fe is a naturally occurring compound in Panax notoginseng, a herb used in the treatment of cardiovascular diseases in traditional Chinese medicine. Here, we evaluated the effect of notoginsenoside Fe on obesity development induced by high-fat diet in C57BL/6 mice. Our results demonstrated that notoginsenoside Fe decreased food intake and body weight, as well as protected liver structure integrity and normal function. Metabolic cage analysis showed that notoginsenoside Fe also promoted resting metabolic rate. In addition, intracerebroventricular (i.c.v) injection of notoginsenoside Fe induced C-Fos expression in the paraventricular nucleus (PVH) but not the arcuate nucleus (ARC) of the hypothalamus. These results suggest that Fe may reduce body weight through the activation of energy-sensing neurons in the hypothalamus.