International Immunopharmacology, Год журнала: 2022, Номер 106, С. 108583 - 108583
Опубликована: Фев. 9, 2022
Язык: Английский
Biomolecules, Год журнала: 2022, Номер 12(6), С. 824 - 824
Опубликована: Июнь 13, 2022
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated (MAFLD), is one of the most common causes diseases worldwide. NAFLD growing in parallel with obesity epidemic. No pharmacological treatment available to treat NAFLD, specifically. The reason might be that a multi-factorial an incomplete understanding mechanisms involved, absence accurate and inexpensive imaging tools, lack adequate non-invasive biomarkers. consists accumulation excess lipids liver, causing lipotoxicity progress steatohepatitis (NASH), fibrosis, hepatocellular carcinoma. for pathogenesis current interventions management disease, role sirtuins as potential targets are discussed here. In addition, diagnostic non-coding RNAs emerging biomarkers summarized. availability biomarkers, diagnosis tools crucial detection early signs progression NAFLD. This will expedite clinical trials validation therapeutic treatments.
Язык: Английский
Процитировано
244
Drug Discovery Today, Год журнала: 2024, Номер 29(3), С. 103910 - 103910
Опубликована: Фев. 1, 2024
Язык: Английский
Процитировано
48
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 774 - 774
Опубликована: Янв. 17, 2025
Over-accumulation of reactive oxygen species (ROS) causes hepatocyte dysfunction and apoptosis that might lead to the progression liver damage. Sirtuin-3 (SIRT3), main NAD+-dependent deacetylase located in mitochondria, has a critical role regulation mitochondrial function ROS production as well antioxidant mechanism. This study explores roles astragaloside IV (AST-IV) formononetin (FMR) connection with SIRT3 for potential antioxidative effects. It was shown condition combined pre- post-treatment AST-IV or FMR at all concentrations statistically increased rescued cell proliferation. levels were not affected by pre-or individually pre-treatment FMR; however, resulted significant increases groups. Significant decreases seen when 5 10 μM, 20 μM. In μM AST-IV, there increase SOD activity, transcriptional Sod2, Cat, GPX1 treatment groups, which is indicative detoxification. Furthermore, activated PGC-1α AMPK expression AML12 hepatocytes exposed t-BHP-induced oxidative stress, especially high FMR. presents novel mechanism whereby yield an effect through induction protein activation biogenesis content potential. The findings suggest these agents can be used modulators treating oxidative-injury hepatocytes.
Язык: Английский
Процитировано
2
Scientific Reports, Год журнала: 2021, Номер 11(1)
Опубликована: Март 5, 2021
Abstract Considering high prevalence of non-alcoholic fatty liver diseases (NAFLD) in patients with inflammatory bowel disease (IBD), this study aimed to elucidate molecular mechanisms for how intestinal conditions are causally linked hepatic steatosis and dyslipidemia. Both younger older mice treated acute or chronic dextran sodium sulfate (DSS) developed colitis, which was evidenced by weight loss, colon length shortening, elevated activity index inflammation score. They also showed decreased expression barrier function-related proteins plasma lipopolysaccharide level, indicating DSS-induced dysfunction thereby increased permeability. Interestingly, they displayed phenotypes fat accumulation abnormal blood lipid profiles. This colitis-associated metabolic due overall disruption processes including acid oxidation, lipogenesis, lipolysis, reverse cholesterol transport, bile synthesis, white adipose tissue browning brown thermogenesis, most mediated key regulators energy homeostasis such as FGF21, adiponectin, irisin, via SIRT1/PGC-1α- LXRα-dependent pathways. Our suggests a potential mechanism underlying the comorbidity NAFLD IBD, could provide understanding two pathogenically discovering critical therapeutic targets their treatment.
Язык: Английский
Процитировано
78
Oxidative Medicine and Cellular Longevity, Год журнала: 2021, Номер 2021(1)
Опубликована: Янв. 1, 2021
The overproduction of reactive oxygen species (ROS) and consequent oxidative stress contribute to the pathogenesis acute chronic liver diseases. It is now acknowledged that nonalcoholic fatty disease (NAFLD) characterized as a redox‐centered due role ROS in hepatic metabolism. However, underlying mechanisms accounting for these alternations are not completely understood. Several nuclear receptors (NRs) dysregulated NAFLD, have direct influence on expression set genes relating progress lipid homeostasis generation. Meanwhile, NRs act redox sensors response metabolic stress. Therefore, targeting may represent promising strategy improving oxidation damage treating NAFLD. This review summarizes link between impaired metabolism highlights some involved regulating oxidant/antioxidant turnover context shedding light potential therapies based NR‐mediated modulation generation accumulation.
Язык: Английский
Процитировано
67
World Journal of Clinical Cases, Год журнала: 2022, Номер 10(30), С. 10840 - 10851
Опубликована: Окт. 19, 2022
The growing worldwide burden of insulin resistance (IR) emphasizes the importance early identification for improved management. Obesity, particularly visceral obesity, has been a key contributing factor in development IR. obesity-associated chronic inflammatory state contributes to obesity-related comorbidities, including Adipocytokines, which are released by adipose tissue, have investigated as possible indicators Visfatin was one adipocytokines that attracted attention due its insulin-mimetic activity. It is from variety sources, fat and macrophages, it influences glucose metabolism increases inflammation. relationship between visfatin IR obesity debatable. As result, purpose this review better understand role homeostasis literature on association levels IR, cardiovascular diseases, renal diseases obesity.
Язык: Английский
Процитировано
50
Antioxidants, Год журнала: 2022, Номер 11(11), С. 2152 - 2152
Опубликована: Окт. 30, 2022
Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair protect the liver until now. We intended to discover empagliflozin's (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) TAA (100 mg/kg, IP) thrice weekly for weeks. both doses retracted serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, increased albumin. At same time, replenished hepatic content of GSH, ATP, AMP, AMPK, SIRT-1 mitigated MDA, TNF-α, IL-6, NF-κB, HIF-1α a dose-dependent manner. Likewise, photomicrograph stained hematoxylin eosin Masson trichrome stain revealed marked regression hepatotoxic effect minimal injury. Similarly, rats given mg/kg), immunohistochemically either α-SMA caspase-3 compared group. Therefore, we concluded that possessed an antifibrotic inhibiting The present study provided new insight into novel fibrosis.
Язык: Английский
Процитировано
47
Ageing Research Reviews, Год журнала: 2022, Номер 84, С. 101833 - 101833
Опубликована: Дек. 22, 2022
Язык: Английский
Процитировано
45
Livers, Год журнала: 2022, Номер 2(1), С. 30 - 76
Опубликована: Фев. 1, 2022
Non-alcoholic fatty liver disease (NAFLD) is a challenging caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in gastrointestinal tract, contribute to lipotoxic hepatic (and extrahepatic) damage acids great variety their biologically active metabolites “multiple parallel-hit model”. leads inflammation fibrogenesis contributes NAFLD progression. The alterations oxidant/antioxidant balance affect also metabolism-related organelles, leading peroxidation, mitochondrial dysfunction, endoplasmic reticulum stress. OS-induced at least partially counteracted physiological antioxidant response. Therefore, modulation this defense system emerges as interesting target prevent development For instance, probiotics, prebiotics, diet, fecal microbiota transplantation represent new therapeutic approaches targeting gut dysbiosis. OS its counter-regulation are under influence individual genetic epigenetic factors well. In near future, precision medicine taking into consideration or environmental risk coupled with biomarkers, will likely assist noninvasive diagnosis monitoring progression further personalizing treatments.
Язык: Английский
Процитировано
44
Biomedicines, Год журнала: 2023, Номер 11(1), С. 143 - 143
Опубликована: Янв. 6, 2023
The isolation of phlorizin from the bark an apple tree in 1835 led to a flurry research on its inhibitory effect glucose transporters intestine and kidney. Using as prototype drug, antidiabetic agents with more selective activity towards transport at kidney have subsequently been developed. In contrast, hydrolysis product body, phloretin, which is also found plant, has weak properties. Phloretin, however, displays range pharmacological effects including antibacterial, anticancer, cellular organ protective properties both vitro vivo. this communication, molecular basis anti-inflammatory mechanisms that attribute scrutinised. These include inhibiting signalling pathways inflammatory mediators' expression support suppressive immune cells overactivation, obesity-induced inflammation, arthritis, endothelial, myocardial, hepatic, renal lung injury, inflammation gut, skin, nervous system, among others.
Язык: Английский
Процитировано
38