Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice.

BACKGROUND: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). OBJECTIVE: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. METHODS: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group's liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. RESULTS: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). CONCLUSIONS: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.

Anti-Obesity Effect of Lactobacillus plantarum LB818 Is Associated with Regulation of Gut Microbiota in High-Fat Diet-Fed Obese Mice.

Worldwide, obesity has become a major risk factor associated with health risks such as diabetes, hypertension, hypercholesterolemia, cardiovascular disease, stroke, and certain forms of cancer. In this study, we estimated the anti-obesity effect of the bacterial strain Lactobacillus plantarum LB818 (designated as LB818) using male C57BL/6J mice, which were treated with high-fat diet (HFD) to induce obesity. Next, LB818 (109 colony-forming units [CFU]/mL) was orally administered for 8 weeks. The results showed that feeding HFD+LB818 (109 CFU/mL) ameliorated body weight gain and decreased total body fat by regulating fasting glucose levels in HFD-fed mice. LB818 treatment significantly lowered aspartate aminotransferase, alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), and elevated high-density lipoprotein levels in serum and decreased deposition of fat droplets in liver. LB818 treatment increased the respective abundances of essential bacteria, including Bacteroidetes, Akkermansia, Bifidobacterium, Lactobacillus, and increased the Bacteroidetes:Firmicutes ratio; however, it significantly decreased the levels of Firmicutes. Taken together, this study demonstrates that LB818 is effective in attenuating obesity and hepatic steatosis and regulated gut microbiota in HFD-fed obese mice.

Gastroprotective Effects of Plants Extracts on Gastric Mucosal Injury in Experimental Sprague-Dawley Rats.

Rubus crataegifolius (black raspberry, RF), Ulmus macrocarpa (elm, UL), and Gardenia jasminoides (cape jasmine, GJ) are well known for hundreds of years as folk medicines in China and Korea to treat various gastrointestinal disturbance. The present study evaluated the gastroprotective effects of these plants either single or in combination against HCl/EtOH-induced gastritis and indomethacin-induced ulcer in rat model. Stomach ulcer was induced by oral ingestions of HCl/EtOH or indomethacin. Treatment with RF, UL, and GJ separately or in combination was done 1 h before ulcer induction. On HCl/EtOH-induced gastritis RF, UL, and GJ at a dose of 150 mg/kg showed comparable antigastritis effect (less than 50% inhibition) with lesion index of 94.97±8.05, 108.48±11.51, and 79.10±9.77 mm compared to cimetidine (45.33±23.73 mm). However, the combination of RF, UL, and GJ at a dose of 150 mg/kg with a ratio of 50:50:50 showed remarkable antigastritis effect with 77% inhibition. The observed lesion index at a ratio of 50:50:50 was 23.34±9.11 mm similar to cimetidine (18.88±19.88 mm). On indomethacin-induced ulcer, RF and GJ showed 38.28% and 51.8% inhibition whereas UL showed around 17.73% inhibition at 150 mg/kg. Combination of RF, UL, and GJ at 150 mg/kg showed strong antigastritis effect with 83.71% inhibition. These findings suggest strong gastroprotective effect of combined extract. In addition, these plants showed significant antioxidant activity in DPPH scavenging assay and antilipid peroxidation activity. Combination of black raspberry, elm, and cape jasmine might be a significant systemic gastroprotective agent that could be utilized for the treatment and/or protection of gastritis and gastric ulcer.

Peroxynitrite: cellular pathology and implications in autoimmunity.

In inflamed tissues, the reaction of nitric oxide and superoxide leads to the formation of an extremely reactive peroxynitrite (ONOO-), which is a well known oxidizing and nitrating agent that exhibits high reactivity at physiological pH. The peroxynitrite formed can attack a wide range of biomolecules via direct oxidative reactions or indirect radical-mediated mechanisms thus triggering cellular responses leading to cell signaling, oxidative injury, committing cells to necrosis or apoptosis. Cellular DNA is an important target for ONOO- attack, and can react with deoxyribose, nucleobases or induces single strand breaks. The free radical-mediated damage to proteins results in the modification of amino acid residues, cross-linking of side chains and fragmentation. Free/protein-bound tyrosines are attacked by various reactive nitrogen species (RNS), including peroxynitrite, to form free/protein-bound nitrotyrosine (NT). The formation of NT represents a specific peroxynitrite-mediated protein modification, and the detection of NT in proteins is considered as a biomarker for endogenous peroxynitrite activity. The peroxynitrite-driven oxidation and nitration of biomolecules may lead to autoimmunity and age-related neurodegenerative diseases. Hence, peroxynitrite modified DNA and nitrated proteins can act as neoantigens and lead to the generation of autoantibodies against self-components in autoimmune disorders.

Standardized Combined Plant Extract, RUG-com, Reduces Bacterial Levels and Suppresses Acute and Chronic Inflammation in Balb/c Mice Infected with CagA+ Helicobacter pylori.

Helicobacter pylori are etiological agents in the development of gastritis, gastroduodenal ulcers, gastric cancer, and mucosa-associated lymphoid tumors. Our previous investigations demonstrated that standardized combined plants extracts (Rubus crataegifolius and Ulmus macrocarpa) inhibit the growth of H. pylori in in vitro experiments. Also, we demonstrated that Gardenia jasminoides is effective in preventing gastritis and gastric ulcers in animal experiments. In the present work, we tested the standardized combined three plant extract (RUG-com) on the mouse model of H. pylori infectious disease to examine the effects of RUG-com on both the prevention and curing on the stomachs of infected mice. After the final administrations, biopsy samples of gastric mucus were assayed for bacterial numbers, biochemical analysis, inflammatory scores, and histology. Treatment with standardized plants extracts, single or combined, reduced the H. pylori load compared with the control. Treatment also significantly (P<0.05) reduced both acute and chronic mucosal and subacute inflammation, and epithelial cell degeneration and erosion induced by H. pylori infection. Further investigations demonstrated that H. pylori-induced inflammation was decreased by RUG-com extracts via down regulating cyclooxygenase-2 and inducible nitric oxide synthase pro-inflammatory gene expression. Our results suggest that RUG-com is useful to prevent H. pylori infection, H. pylori-induced inflammation and associated gastric damage.

Daesiho-Tang Is an Effective Herbal Formulation in Attenuation of Obesity in Mice through Alteration of Gene Expression and Modulation of Intestinal Microbiota.

BACKGROUND: Obesity has become a major global health challenge due to its increasing prevalence, and the associated health risk. It is the main cause of various metabolic diseases including diabetes, hypertension, cardiovascular disease, stroke and certain forms of cancer. METHODS AND RESULTS: In the present study we evaluated the anti-obesity property of Daesiho-tang (DSHT), an herbal medicine, using high fat diet (HFD)-induced obese mice as a model. Our results showed that DSHT ameliorated body weight gain, decreased total body fat, regulated expression of leptin and adiponectin genes of adipose tissue and exerted an anti-diabetic effect by attenuating fasting glucose level and serum insulin level in HFD-fed animals. In addition, DSHT-treatment significantly reduced total cholesterol (TC), triglycerides (TG) and increased high density lipoprotein-cholesterol (HDL), glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) levels in serum and reduced deposition of fat droplets in liver. DSHT treatment resulted in significantly increased relative abundance of bacteria including Bacteroidetes, Bacteroidetes/Firmicutes ratio, Akkermansia Bifidobacterium., Lactobacillus, and decreased the level of Firmicutes. Using RT2 profiler PCR array, 39 (46%) genes were found to be differentially expressed in HFD-fed mice compared to normal control. However, normal gene expressions were restored in 36 (92%) genes of HFD-fed mice, when co-exposed to DSHT. CONCLUSION/MAJOR FINDINGS: The results of this study demonstrated that DSHT is an effective herbal formulation in attenuation of obesity in HFD-fed mice through alteration of gene expressions and modulation of intestinal microbiota.