Effect of Eucommia ulmoides leaves on hyperuricemia and kidney injury induced by a high-fat/high-fructose diet in rats

Eucommia ulmoides leaves have unique advantages in the treatment of metabolic diseases. In this study, network pharmacology and molecular-docking methods were used to predict the effects and action mechanisms of the major components of E. ulmoides leaves on hyperuricemia. Combining literature collection, we used SciFinder and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to collect E. ulmoides leaf flavonoid and iridoid components. Swiss Target Prediction, SEA, GeneCards, and the OMIM database were used to obtain core targets, and the STRING protein database was performed as core targets for gene ontology enrichment Set and KEGG analyses. Molecular docking was applied to predict the pathways regulating the metabolism of uric acid. The selected targets and targeting efficacy were validated using a rat model of hyperuricemia and renal injury induced by a high-fat and high-fructose diet. A total of 32 chemical components with effective targets, which regulated the PI3K-AKT pathway and endocrine resistance, were collected. Isoquercetin, kaempferol, and quercetin were predicted via network pharmacology to have potential bioactivities and strong docking binding forces. Molecular docking results showed that iridoids and flavonoids are bound to proteins related to inflammation and uric acid metabolism. In addition, it was verified via animal experiments that an E. ulmoides leaf extract ameliorated hyperuricemia, renal injury, and inflammation, which are closely related to the targets IL-6, TNF-α, TLR4, and GLUT9. In conclusion, E. ulmoides leaf flavonoids and iridoids ameliorate hyperuricemia and uric-acid–induced inflammation through a multi-component, multi-target, and multi-pathway mechanism, which provides a theoretical basis for the development of therapeutics from E. ulmoides leaf components.

Cynanchum atratum Alleviates Non-Alcoholic Fatty Liver by Balancing Lipogenesis and Fatty Acid Oxidation in a High-Fat, High-Fructose Diet Mice Model

Cynanchum atratum, a medicinal herb, is traditionally used as an antidote, diuretic, and antipyretic in eastern Asia. The current study aimed to investigate the anti-fatty liver capacity of the ethanol extract of Cynanchum atratum (CAE) using a 10-week high-fat, high-fructose diet mouse model. A six-week treatment of CAE (from the fifth week) significantly attenuated the weights of the body, liver, and mesenteric fat without a change in diet intake. CAE also considerably restored the alterations of serum aminotransferases and free fatty acid, fasting blood glucose, serum and hepatic triglyceride, and total cholesterol, as well as platelet and leukocyte counts. Meanwhile, CAE ameliorated hepatic injury and lipid accumulation, as evidenced by histopathological and immunofluorescence observations. Additionally, CAE significantly lowered the elevation of hepatic TNF-α, the TNF-α/IL-10 ratio, fecal endotoxins, and the abundance of Gram-negative bacteria. Hepatic lipogenesis and β-oxidation-related proteins and gene expression, including PPAR-α, SREBP-1, SIRT1, FAS, CTP1, etc., were normalized markedly by CAE. In particular, the AMPK, a central regulator of energy metabolism, was phosphorylated by CAE at an even higher rate than metformin. Overall, CAE exerts anti-hepatic steatosis effects by reducing lipogenesis and enhancing fatty acid oxidation. Consequently, Cynanchum atratum is expected to be a promising candidate for treating chronic metabolic diseases.

CHRONIC AEROBIC EXERCISE PREVENTS HIGH-FRUCTOSE DIET-INDUCED IMPAIRMENT IN BLOOD PRESSURE IN HEALTHY YOUNG ADULTS: A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

The purpose of the study was to verify the effect of 4 weeks of a high-fructose diet associated with aerobic training on the risk factors for cardiometabolic diseases. Twenty-one young adults were randomized into three groups: high-fructose diet (HFD: 1 g/kg body weight of fructose/day), high-glucose diet (HGD: 1 g/kg body weight of glucose/day), and high-fructose diet and exercise (HFDE: 1 g/kg body weight of fructose/day + 3 weekly 60-minute sessions of aerobic exercise). Before and after the 4 weeks of the intervention, blood samples were taken and flow-mediated dilatation, insulin resistance index, pancreatic beta cell functional capacity index, insulin sensitivity index, and 24-hour blood pressure were evaluated. HFD showed an increase in uric acid concentrations (p = 0.040), and HGD and HFDE groups showed no changes in this outcome between pre- and post-intervention; however, the HFDE group showed increased uric acid concentrations from the middle to the end of the intervention (p = 0.013). In addition, the HFD group showed increases in nocturnal systolic blood pressure (SBP) (p = 0.022) and nocturnal diastolic blood pressure (DBP) (p = 0.009). The HGD group exhibited decreases in nocturnal SBP (p = 0.028) and nocturnal DBP (p = 0.031), and the HFDE group showed a decrease in 24-hour SBP (p = 0.018). The consumption of 1 g/kg of fructose per day can increase uric acid concentrations and blood pressure in adults. Additionally, aerobic exercises along with fructose consumption attenuate changes in uric acid concentrations and prevent impairment in nocturnal blood pressure.

Analysis of N6-Methyladenosine Methylation Modification in Fructose-Induced Non-Alcoholic Fatty Liver Disease

Improvements in living standards have led to non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases worldwide. Recent studies have shown that N6-methyladenosine (m6A), a type of RNA modification, is strongly associated with many important biological processes. However, the relationship between m6A methylation modifications and NAFLD remains poorly understood. In the present study, through methylated RNA immunoprecipitation sequencing and RNA transcriptome sequencing in high fructose diet-induced NAFLD mice, we found that hypermethylation-encoding genes were mainly enriched in lipid metabolism processes. We identified 266 overlapping and differentially expressed genes (DEGs) that changed at both the mRNA expression level and m6A modification level. Among them, 193 genes displayed increased expression and m6A modification, indicating that m6A RNA modifications tend to be positively correlated with NAFLD. We further compared the high fructose diet-induced NAFLD mouse model with leptin receptor-deficient mice and found that DEGs enriched in the lipid metabolism pathway were up-regulated in both groups. In contrast, DEGs associated with the immune inflammatory response were up-regulated in the high fructose diet group, but down-regulated in leptin receptor-deficient mice. Taken together, our results demonstrate that m6A methylation modifications may play an important role in the development of NAFLD.

Efek Pemberian High Fat High Fructose Diet (HFHFD) dan Carbon tetrachloride (CCL4) Terhadap Kadar Cystatin C Serum

<p>Tingkat konsumsi lemak dan fruktosa tinggi dapat mengakibatkan gangguan fungsi ginjal. High Fat High Fructose Diet (HFHFD) / Diet tinggi lemak tinggi fruktosa merupakan pemberian diet tinggi lemak dan diberikan fruktosa dalam air minum atau dalam makanan. Pemberian Karbon tetraklorida pada tikus menyebabkan kerusakan pada ginjal. Cystatin C merupakan pemeriksaan untuk mengetahui gangguan dini pada fungsi ginjal. Tujuan penelitian adalah untuk mengetahui pengaruh pemberian HFHFD dan injeksi CCl4 terhadap kadar cystatin C serum pada tikus. Penelitian ini terdiri dari 4 kelompok yang terdiri dari: 1) kelompok tikus diberi pakan standar; 2) kelompok tikus HFHFD; 3) kelompok tikus HFHFD yang diinjeksi CCl4 intraperitoneal (IP) dua kali seminggu; dan 4) kelompok tikus yang diberikan pakan standar dan diinjeksi CCl4 IP dua kali seminggu, dengan 24 ekor tikus. Perlakuan diberikan selama 8 minggu. Parameter yang diuji yakni kadar Cystatin C serum pada tikus yang diberikan pakan standar dibandingkan dengan tikus yang diberikan diet tinggi lemak dan tambahan fruktosa pada air minumnya (HFHFD), tikus yang diberi HFHFD dan suntikan CCl4 dua kali seminggu, dan tikus dengan pakan standar dan diinjeksi CCl4 dua kali seminggu. Hasil penelitian menunjukkan bahwa tikus yang diberikan HFHFD dan CCl4 mengalami peningkatan Cystatin C serum paling tinggi dibandingkan dengan tikus yang diberikan HFHFD saja, suntikan CCl4 saja dengan pakan standar, dan yang hanya diberikan pakan standar. Pemberian kombinasi HFHFD + CCl4 menunjukkan perbedaan Cystatin C yang bermakna secara statistik dibandingkan dengan kelompok kontrol (p=0.004). Simpulan diperoleh bahwa pemberian HFHFD dan CCl4 meningkatkan kadar Cystatin C serum pada tikus.</p>

High-Fructose Diet Alters Intestinal Microbial Profile and Correlates with Early Tumorigenesis in a Mouse Model of Barrett’s Esophagus

Esophageal adenocarcinoma (EAC) is mostly prevalent in industrialized countries and has been associated with obesity, commonly linked with a diet rich in fat and refined sugars containing high fructose concentrations. In meta-organisms, dietary components are digested and metabolized by the host and its gut microbiota. Fructose has been shown to induce proliferation and cell growth in pancreas and colon cancer cell lines and also alter the gut microbiota. In a previous study with the L2-IL-1B mouse model, we showed that a high-fat diet (HFD) accelerated EAC progression from its precursor lesion Barrett’s esophagus (BE) through changes in the gut microbiota. Aiming to investigate whether a high-fructose diet (HFrD) also alters the gut microbiota and favors EAC carcinogenesis, we assessed the effects of HFrD on the phenotype and intestinal microbial communities of L2-IL1B mice. Results showed a moderate acceleration in histologic disease progression, a mild effect on the systemic inflammatory response, metabolic changes in the host, and a shift in the composition, metabolism, and functionality of intestinal microbial communities. We conclude that HFrD alters the overall balance of the gut microbiota and induces an acceleration in EAC progression in a less pronounced manner than HFD.

Ficus thonningii Stem Bark Extracts Prevent High Fructose Diet Induced Increased Plasma Triglyceride Concentration, Hepatic Steatosis and Inflammation in Growing Sprague-Dawley Rats

BACKGROUND: Ficus thonningii extracts exhibit hypoglycaemic, hypolipidaemic and antioxidant activities. We investigated the potential of methanolic F. thonningii stem-bark extracts (MEFT) to protect growing Sprague-Dawley (SD) against high-fructose diet-induced metabolic derangements (MD) in a model mimicking children fed obesogenic diets. METHODS: Eighty (40 males; 40 females) 21-days old SD rat pups were randomly allocat-ed to and administered, for 8 weeks, five treatment regimens: 1 - standard rat chow (SC) + water (PW), 2 - SC + 20% (w/v) fructose solution (FS), 3 - SC + FS + fenofibrate at 100 mg/kg bwt/day, 4 - SC + FS + low dose MEFT (LD; 50 mg/kg bwt/day) and 5 - SC + FS + high dose MEFT (HD; 500 mg/kg bwt/day). Body weight, glucose load tolerance, fasting blood glucose and triglyceride, plasma insulin concentration, sensitivity to insulin, liver mass and fat content, steatosis and inflammation were determined. RESULTS: Fructose had no effect on the rats&rsquo; growth, glucose and insulin concentration, glucose tolerance and insulin sensitivity (P&gt;0.05) but increased triglycerides in females; in-duced hepatic microsteatosis and inflammation in both sexes but macrosteatosis in females (P&lt;0.05). In females, MEFT prevented fructose-induced plasma triglyceride increase. Low dose MEFT increased liver lipid content in females (P&lt;0.05). The MEFT protected the rats against hepatic steatosis and inflammation but fenofibrate protected against hepatic mi-crosteatosis. CONCLUSION: MEFT can be used as prophylaxis against dietary fructose-induced ele-ments of MD but caution must be taken as low dose MEFT increases hepatic lipid accretion in females predisposing to fatty liver disease.