chrysin and Non-alcoholic-Fatty-Liver-Disease

Uganda was affected by two major waves of coronavirus disease 2019 (COVID-19). The first wave during late 2020 and the second wave in late April 2021. This study compared epidemiologic characteristics of hospitalized (HP) and non-hospitalized patients (NHP) with COVID-19 during the two waves of COVID-19 in Uganda.. Wave 1 was defined as November-December 2020, and Wave 2 was defined as April-June 2021. In total, 800 patients were included in this study. Medical record data were collected for HP (200 for each wave). Contact information was retrieved for NHP who had polymerase-chain-reaction-confirmed COVID-19 (200 for each wave) from laboratory records; these patients were interviewed by telephone.. Demographic and epidemiologic characteristics of HP and NHP differed between and within Waves 1 and 2 of COVID-19 in Uganda.

Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Cyprinidae; DNA Damage; Flavonoids; Fresh Water; Fructose; Gills; Insecticides; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Peptide Fragments; Peptidyl-Dipeptidase A; Pyridines; Rats; Receptors, G-Protein-Coupled; Renin-Angiotensin System; Water; Water Pollutants, Chemical

Obesity is a complex multifactorial disease characterized by excessive adiposity, and is linked to an increased risk of nonalcoholic fatty liver disease (NAFLD). Flavonoids are natural polyphenolic compounds that exert interesting pharmacological effects as antioxidant, anti-inflammatory, and lipid-lowering agents. In the present study, we investigated the possible therapeutic effects of the flavonoid chrysin on obesity and NAFLD in rats, and the role of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways in mediating these effects.. Thirty-two Wistar male rats were divided into two groups: the control group and the obese group. Obesity was induced by feeding with an obesogenic diet for 3 months. The obese rats were subdivided into four subgroups, comprising an untreated group, and three groups treated orally with different doses of chrysin (25, 50, and 75 mg/kg/day for one month). Results revealed that chrysin treatment markedly ameliorated the histological changes and significantly and dose-dependently reduced the weight gain, hyperglycemia, and insulin resistance in the obese rats. Chrysin, besides its antioxidant boosting effects (increased GSH and decreased malondialdehyde), activated the AMPK pathway and suppressed the mTOR and lipogenic pathways, and stimulated expression of the genes controlling mitochondrial biogenesis in the hepatic tissues in a dose-dependent manner. In conclusion, chrysin could be a promising candidate for the treatment of obesity and associated NAFLD, aiding in attenuating weight gain and ameliorating glucose and lipid homeostasis and adipokines, boosting the hepatic mitochondrial biogenesis, and modulating AMPK/mTOR/SREBP-1c signaling pathways.

Topics: AMP-Activated Protein Kinases; Animals; Antioxidants; Diet, High-Fat; Flavonoids; Lipids; Lipogenesis; Liver; Male; Non-alcoholic Fatty Liver Disease; Obesity; Rats; Rats, Wistar; TOR Serine-Threonine Kinases; Weight Gain

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease histologically characterized by liver steatosis, hepatocellular injury, inflammation and fibrosis, resulting in cirrhosis and hepatocellular carcinoma, but effective measures and obvious pathogenesis for NASH remain elusive. Chrysin (CH) has been reported to have anti-inflammatory effects but shows lower bioavailability.. In this study, a chrysin nanoliposome (CH-NL) was first prepared and characterized. Then, we used the methionine-choline-deficient (MCD) diet to induce a mouse model of NASH. Finally, the effects of CH and CH-NL on NASH were evaluated in the liver of NASH mice.. The results showed that CH or CH-NL significantly reduced the accumulation of lipids in hepatocytes, alleviated liver injury, decreased the generation of radical oxygen species, and attenuated the accumulation of collagen fibre in the liver of NASH mice. In addition, CH and its nano-liposomes markedly inhibited the production of inflammatory cytokines and inflammatory cell infiltration in the liver of NASH mice. Further studies found that CH-NL and CH-NL downregulated the MCD diet-induced activation of Toll-like receptor 4 (TLR4) signalling pathway in the liver of mice.. CH and its nanoliposome alleviated MCD diet-induced NASH in mice, which might be through inhibiting TLR4 signalling pathway.

Topics: Animals; Choline; Diet; Disease Models, Animal; Flavonoids; Liver; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Toll-Like Receptor 4

We aimed to elucidate the therapeutic potential of Chrysin (CN) against the high-fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) and its mechanism.. To assess the hypothesis, NAFLD was induced in C57BL/6 mice by feeding a high-fat diet for up to two months, followed by CN administration (for three months). Liver injury/toxicity, lipid deposition, inflammation and fibrosis were detected via molecular and biochemical analysis, including blood chemistry, immunoimaging and immunoblotting. Moreover, we performed proteomic analysis to illuminate Chrysin's therapeutic effects further.. CN treatment significantly reduced liver-fat accumulation and inflammation, ultimately improving obesity and liver injury in NAFLD mice. Proteomic analysis showed that CN modified the protein expression profiles in the liver, particularly improving the expression of proteins related to energy, metabolism and inflammation. Mechanistically, CN treatment increased AMP-activated protein and phosphorylated CoA (P-ACC). Concurrently, it reduced inflammation and inflammation activation by inhibiting NLRP3 expression.. In summary, CN treatment reduced lipid metabolism by AMPK and inflammasome activation by NLRP3 inhibition, ultimately improving NAFLD progression. These findings suggest that CN could be a potential treatment candidate for the NFLAD condition.

Topics: AMP-Activated Protein Kinases; Animals; Diet, High-Fat; Inflammation; Lipid Metabolism; Liver; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Proteomics

The incidence of nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has significantly increased in recent years and has become an important public health issue. However, no U.S. Food and Drug Administration (FDA)-approved first-line drug is currently available for the treatment of NAFLD and NASH; therefore, research on new drugs is currently a hot topic. Oroxylum indicum (Linn.) Kurz is extensively distributed in South China and South Asia and has many biological activities. However, its effects on NAFLD or even NASH and the corresponding mechanisms are still not clear.. To investigate the effect and mechanism of O. indicum seed extract (OISE) on preventing anti-inflammatory action in the progression from simple nonalcoholic fatty liver (NAFL) to NASH.. A network pharmacology method to construct ingredient-target networks and the protein-protein interaction (PPI) network of OISE in NASH were constructed for topological analyses and hub-target screening. Enrichment analyses were performed to identify the critical biological processes and signaling pathways. Simultaneously, in vitro and in vivo experiments investigated the effect and mechanism of OISE, baicalein, and chrysin on inflammation by biochemical indicator detection, luciferase reporters, pathological staining, and immunoblotting in oleic acid-stimulated HepG2 cells or in high-fat diet-fed rats.. The network pharmacology showed that OISE prevented the development and progression of NAFL into NASH through various pathways and targets and that the nuclear factor NF-κB (NF-κB) pathway regulated by baicalein and chrysin played an important role in the treatment of NASH. In in vitro experiments, we further showed that OISE and its ingredients, namely, baicalein and chrysin, all improved the inflammatory status in oleic acid-stimulated HepG2 cells, inhibited the nuclear transcriptional activities of NF-κB, increased the IκB level, and decreased the phosphorylation level of NF-κB. Furthermore, in a high-fat diet-induced NASH model in rats, we also showed that OISE prevented the development and progression of NASH by inhibiting the nuclear transcriptional activity of NF-κB.. OISE suppressed inflammatory responses and prevented the development and progression of NAFL into NASH through inhibition of the nuclear transcriptional activity of NF-κB. OISE may be used to treat NAFLD through many functions, including an increase in insulin sensitivity, a decrease in lipid accumulation in the liver, suppression of inflammation, and clearance of free radicals.

Topics: Animals; Bignoniaceae; Diet, High-Fat; Flavanones; Flavonoids; Hep G2 Cells; Humans; Lipid Metabolism; Liver Cirrhosis; Male; NF-kappa B; Non-alcoholic Fatty Liver Disease; Oleic Acid; Plant Extracts; Protein Interaction Maps; Rats, Sprague-Dawley; Seeds; Signal Transduction

We investigated the effects of chrysin (CHR) on nonalcoholic fatty liver disease (NAFLD) in mice. The NAFLD mouse model was established using a diet deficient in methionine and choline (MCD). CHR was shown to attenuate MCD-induced hepatic fat accumulation, increase very low-density lipoprotein (VLDL) secretion, and decrease hepatic oxidative stress in NAFLD mice. Inhibition of oxidative stress or direct suppression of protein kinase C (PKC) by CHR significantly reduced PKC activity in the liver, leading to a decrease in inhibitory phosphorylation of hepatocyte nuclear factor 4α (HNF4α). The resulting activation of HNF4α led to induced transcription of apolipoprotein B and VLDL secretion. Together, these results show that CHR effectively ameliorates MCD-induced fatty liver in NAFLD mice by targeting the hepatic oxidative stress/PKC/HNF4α signaling pathway.

Topics: Animals; Choline Deficiency; Diet; Disease Models, Animal; Flavonoids; Hep G2 Cells; Hepatocyte Nuclear Factor 4; Hepatocytes; Humans; Lipoproteins, VLDL; Male; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Protein Kinase C; Secretory Pathway; Signal Transduction; Treatment Outcome

Topics: Animals; Bees; Diet, High-Fat; Disease Models, Animal; Flavanones; Flavonoids; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Pollen; Rutin; Schisandra

Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of the metabolic syndrome. It begins with the accumulation of fat in the liver (simple steatosis), which if untreated can progress to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Chrysin is a flavonoid present in bee propolis and many other plants. The objective of this study was to determine if chrysin can ameliorate NAFLD induced by feeding a high fructose diet (HFD) in rats. The rats were divided into five groups: normal control, HFD control, chrysin (25, 50, and 100 mg/kg p.o. body weight). Biochemical estimations were carried out in the serum and liver of rats. The gene expressions of SREBP-1c and PPAR α were determined in the liver. The histopathology of the liver was also studied. Chrysin caused a significant decrease in the serum fasting glucose and improved the insulin resistance, dyslipidemia, and liver enzymes. It caused a significant decrease in the liver weight and hepatic free fatty acids, triglyceride, and cholesterol content. Chrysin exerted antioxidant effects, reduced carbonyl content, advanced glycation end products, collagen, TNF-α, and IL-6 concentrations in the liver. Chrysin significantly reduced the hepatic gene expression of SREBP-1c and increased that of PPAR-α. The histopathology of liver of rats treated with chrysin showed significant decrease in the steatosis, ballooning, and lobular inflammation when compared to the HFD control group. Thus, chrysin demonstrated anti-steatotic, antiglycating, antioxidant, anti-inflammatory, and antifibrotic effects and seems to be a promising molecule for the management of NAFLD.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Collagen; Dietary Sugars; Flavonoids; Fructose; Glycation End Products, Advanced; Interleukin-6; Liver; Male; Non-alcoholic Fatty Liver Disease; PPAR alpha; Rats, Wistar; Sterol Regulatory Element Binding Protein 1; Tumor Necrosis Factor-alpha

Chrysin (5,7-di-OH-flavone), a widely distributed natural flavonoid, has been well documented for involving in various biological activities, especially in regulation of peroxisome proliferator activated receptor γ (PPARγ) activity as a modest modulator. However, the exact molecular mechanism is still unrevealed. In the current study, for the first time, we discovered that, chrysin not only significantly attenuated inflammation in high-fat feeding mice, but also alleviated high fat diet-induced hepatic, muscular steatosis in obese mice without altering the body weight. Chrysin decreases the infiltration of macrophages into adipose tissue in obese mice. In addition, chrysin was also found to induce an anti-inflammatory M2 phenotype and decreases M1 phenotype, both in peritoneal macrophages of obese mice and cultured macrophages in vitro, and thereby, chrysin changed the M1/M2 status. Our data further showed that chrysin regulated the phenotype of macrophages through enhancing the transcriptional activation of PPARγ and the expression of its target genes. Taken together, we conclude that chrysin may serve as an effective modulator of PPARγ during the pathogenesis of inflammation, thereby our findings shed light on the potential therapeutic feature of chrysin in recovering inflammatory diseases via regulating M1/M2 status.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Division; Cell Line, Transformed; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Fatty Liver; Flavonoids; Humans; Liver; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Myositis; Non-alcoholic Fatty Liver Disease; Obesity; PPAR gamma; Random Allocation; Specific Pathogen-Free Organisms; Transcription, Genetic