Effect of Dangfei Liganning capsule on liver X receptor α/steroid regulatory element binding protein-1/fatty acid synthase signal pathway in rats with metabolic- associated fatty liver disease.

OBJECTIVE: To study the mechanism of Dangfei Liganning capsule in the treatment of rats with metabolic associated fatty liver disease (MAFLD). METHODS: Totally 48 specific pathogen free Sprague-Dawley male rats were randomly divided into normal Group, model group, Dangfei Liganning high, moderate, and low-dose groups and Essentiale group which were fed with high fat diet for 8 weeks, and gavage and molding were carried out simultaneously. Dangfei Liganning high, middle and low-dose group were given 0.27, 0.135 and 0.0675 g·kg·d respectively by gavage, Essentiale group was given 0.123 g·kg·d by gavage, the same amount of distilled water was given by gavage in the normal group and the model group. The rats were weighed at the 0th week, 2nd week, 4th week, 6th week and 8th weekend respectively. The rats were sacrificed at the end of the 8th week. Serum levels of alanine aminotransferase (ALT), alanine aminotransferase (AST), triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C), total protein (TP), albumin (Alb), globulin (GLB), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were measured. The levels of liver tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and liver pathology [hematoxylin and eosin (HE) staining, oil red O staining] were detected. The expression levels of liver X receptor α (LXRα), steroid regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS) were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction reverse transcription-polymerase chain reaction. RESULTS: From the beginning to the 8th week, the growth rate of body weight in the Dangfei Liganning high-dose group was slower than all other groups. There was no significant difference in ALB level in all groups ( 0.05). Compared with the model group, the levels of ALT, AST, LDL-C, TG, CHO, TP, GLB, TBIL, DBIL, IL-6, TNF-α were significantly decreased and HDL-C were significantly increased in Dangfei Liganning high-dose group (0.01, < 0.05). HE and oil red O staining showed that the fatty lesions in rat liver were alleviated, while the expressions of LXRα, SREBP-1, FAS mRNA and protein were significantly decreased (0.01). CONCLUSIONS: Dangfei Liganning capsule can slow down the increase of body weight of MAFLD rats, reduce the levels of transaminase, Lipid and inflammatory factors in MAFLD rats, promote the synthesis of liver protein and bile metabolism, and improve the liver fatty lesion of MAFLD rats, among which the Dangfei Liganning high-dose group is more effective. The mechanism of action may be through blocking LXR-SREBP-1-FAS signal pathway.

Lycium barbarum Polysaccharide Regulates the Lipid Metabolism and Alters Gut Microbiota in High-Fat Diet Induced Obese Mice.

Bioactive compounds provide new insights into the prevention and treatment of obesity. Lycium barbarum polysaccharide (LBP), a biological macromolecule extracted from Goji berry, has displayed potential for regulating lipid metabolism. However, the relationship between gut microbiota regulation and lipid metabolism is not entirely clear. In the present study, 50, 100, and 150 mg/kg LBP were intragastrically administered to C57BL/6J male mice fed with a high-fat diet simultaneously lasting for twelve weeks. The results showed that 150 mg/kg LBP showed significant results and all doses of LBP feeding (50, 100, 150 mg/kg) remarkably decreased both serum and liver total cholesterol (TC) and triglyceride (TG) levels. Treatment of 150 mg/kg LBP seems to be more effective in weight loss, lowering free fatty acid (FFA) levels in serum and liver tissues of mice. LBP feeding increased the gene expression of adiponectin and decreased the gene expression of peroxisome proliferator-activated receptor γ, Cluster of Differentiation 36, acetyl-coA carboxylase, and fatty acid synthase in a dose-dependent manner. In addition, the 16s rDNA Sequencing analysis showed that 150 mg/kg LBP feeding may significantly increase the richness of gut microbiota by up-regulation of the ACE and Chao1 index and altered ß-diversity among groups. Treatment of 150 mg/kg LBP feeding significantly regulated the microbial distribution by decreasing the relative abundance of Firmicutes and increasing the relative abundance of Bacteroidetes at the phylum level. Furthermore, the relative abundance of Faecalibaculum, Pantoea, and uncultured_bacterium_f_Muribaculaceae at the genus level was significantly affected by LBP feeding. A significant correlation was observed between body weight, TC, TG, FFA and bile acid and phyla at the genus level. The above results indicate that LBP plays a vital role in preventing obesity by co-regulating lipid metabolism and gut microbiota, but its effects vary with the dose.

Treatment of Obese Zebrafish with Saringosterol Acetate through AMP Activated Protein Kinase Pathway.

OBJECT: Edible Brown Seaweed Sargassum fusiforme (Harvey) Setchell, 1931 abbreviated as Sargassum fusiforme was used for folk medical therapy in East Asia countries over five hundred years. Saringosterol acetate (SA) was isolated from S. fusiforme in our previous study and indicated various effects. However, anti-obesity activity of SA and its mechanism still unknown. METHOD: The inhibitory effect of SA, isolated from S. fusiforme, on adipogenesis in 3T3-L1 adipocytes was investigated in vitro and in zebrafish model. Cell toxicity, differentiation, signaling pathway, and lipid accumulation of SA treated 3T3-L1 adipocytes were determined. The body weight and triglyceride content of diet-induced obese (DIO) adult male zebrafish were measured from 12 to 17 weeks after fertilization. RESULT: SA attenuated the differentiation of cells and reduced lipid accumulation, and triglyceride content in the 3T3-L1 adipocytes. During the differentiation of adipocytes, SA suppressed fat accumulation and decreased the expression of signal factors responsible for adipogenesis. In SA-treated adipocytes, while fatty acid synthetase was downregulated, AMP-activated protein kinase (AMPK) was upregulated. Furthermore, SA suppressed body weight and triglyceride content in DIO zebrafish. CONCLUSION: SA is a potential therapeutic agent in the management of metabolic disorders, such as obesity.

Evaluating anti-obesity potential, active components, and antioxidant mechanisms of Moringa peregrina seeds extract on high-fat diet-induced obesity.

There are no medical drugs that provide an acceptable weight loss with minimal adverse effects. This study evaluated the Moringa peregrina (MP) seed extract's anti-obesity effect. Twenty-four (6/each group) male Sprague Dawley rats were divided into group Ι (control), group ΙΙ (high-fat diet [HFD]), group ΙΙΙ (HFD+ MP [250 mg/kg b.wt]), and group ΙV (HFD+ MP [500 mg/kg b.wt]). MP administration significantly ameliorated body weight gains and HFD induced elevation in cholesterol, triglycerides, LDL, and reduced HDL. Moreover, MP seed oil showed high free radical-scavenging activity, delayed ß-carotene bleaching and inhibited lipoprotein and pancreatic lipase enzymes. High-performance liquid chromatography (HPLC) revealed three major active components: crypto-chlorogenic acid, isoquercetin, and astragalin. Both quantitative Real-time PCR (RT-PCR) and western blotting revealed that MP seeds oil significantly decreased the expression of lipogenesis-associated genes such as peroxisome proliferator-activated receptors gamma (PPARγ) and fatty acid synthase (FAS) and significantly elevated the expression of lipolysis-associated genes (acetyl-CoA carboxylase1, ACCl). The oil also enhanced phosphorylation of AMP-activated protein kinase alpha (AMPK-α) and suppressed CCAAT/enhancer-binding protein ß (C/EBPß). In conclusion, administration of M. peregrina seeds oil has anti-obesity potential in HFD-induced obesity in rats. PRACTICAL APPLICATIONS: M. peregrina seeds oil had a potential anti-obesity activity that may be attributed to different mechanisms. These included decreasing body weight, and body mass index and improving lipid levels by decreasing total cholesterol, triglycerides and LDL-C, and increasing HDL-C. Also, M. peregrina seeds oil regulated adipogenesis-associated genes, such as downregulating the expression of (PPARγ, C/EBPα, and FAS) and improving and upregulating the expression and phosphorylation of AMPKα and ACCl. Despite that M. peregrina extract has reported clear anti-obesity potential through animal and laboratory studies, the available evidence-based on human clinical trials are very limited. Therefore, further studies are needed that could focus on clinical trials investigating anti-obesity potential different mechanisms of M. peregrina extract in humans.