Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 167, С. 115464 - 115464

Опубликована: Сен. 15, 2023

Luteolin is a flavonoid widely present in various traditional Chinese medicines. In recent years, luteolin has received more attention due to its impressive liver protective effect, such as metabolic associated fatty disease, hepatic fibrosis and hepatoma. This article summarizes the pharmacological effects, pharmacokinetic characteristics, toxicity of against diseases, provides prospect. The results indicate that improves lesions through mechanisms, including inhibiting inflammatory factors, reducing oxidative stress, regulating lipid balance, slowing down excessive aggregation extracellular matrix, inducing apoptosis autophagy cancer cells. Pharmacokinetics research manifested bioavailability relatively low. It worth noting appropriate modification, new delivery systems, derivatives can enhance bioavailability. Although many studies have shown minimal, strict experiments are still needed evaluate safety promote reasonable development. addition, this study also discussed clinical applications related luteolin, indicating it key component commonly used drugs practice. view excellent expected become potential drug for treatment diseases.

Язык: Английский

---

Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis

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

---

Regulation and targeting of SREBP-1 in hepatocellular carcinoma

Cancer and Metastasis Reviews, Год журнала: 2023, Номер 43(2), С. 673 - 708

Опубликована: Дек. 1, 2023

Abstract Hepatocellular carcinoma (HCC) is an increasing burden on global public health and associated with enhanced lipogenesis, fatty acid uptake, lipid metabolic reprogramming. De novo lipogenesis under the control of transcription factor sterol regulatory element-binding protein 1 (SREBP-1) essentially contributes to HCC progression. Here, we summarize current knowledge regulation SREBP-1 isoforms in based cellular, animal, clinical data. Specifically, (i) address overarching mechanisms for regulating transcription, proteolytic processing, nuclear stability, transactivation (ii) critically discuss their impact HCC, taking into account (iii) insights from pharmacological approaches. Emphasis placed cross-talk phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt)-mechanistic target rapamycin (mTOR) axis, AMP-activated (AMPK), A (PKA), other kinases that directly phosphorylate SREBP-1; factors, such as liver X receptor (LXR), peroxisome proliferator-activated receptors (PPARs), γ co-activator (PGC-1), signal transducers activators (STATs), Myc; epigenetic mechanisms; post-translational modifications SREBP-1-regulatory metabolites oxysterols polyunsaturated acids. By carefully scrutinizing role development, progression, metastasis, therapy resistance, shed light potential SREBP-1-targeting strategies prevention treatment.

Язык: Английский

---

What are the common downstream molecular events between alcoholic and nonalcoholic fatty liver?

Lipids in Health and Disease, Год журнала: 2024, Номер 23(1)

Опубликована: Фев. 8, 2024

Liver fat storage, also called hepatic steatosis, is increasingly common and represents a very frequent diagnosis in the medical field. Excess not without consequences. In fact, steatosis contributes to progression toward liver fibrosis. There are two main types of fatty disease, alcoholic disease (AFLD) nonalcoholic (NAFLD). Although AFLD NAFLD similar their initial morphological features, both conditions involve same evolutive forms. Moreover, there various mechanisms underlying diseases, including NAFLD, which commonalities. this Review, authors explore downstream signaling events involved onset entities but completely different entities, predominantly focusing on gut microbiome. Downstream molecular events, such as roles sirtuins, cytokeratins, adipokines others, should be considered. Finally, complete feature, some new tendencies therapeutic approach presented.

Язык: Английский

---

Aging exaggerates acute‐on‐chronic alcohol‐induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1‐C/EBPα‐miRNA‐223 axis

Hepatology, Год журнала: 2021, Номер 75(3), С. 646 - 660

Опубликована: Сен. 12, 2021

Abstract Background and Aims Aging exacerbates liver neutrophil infiltration alcohol‐associated disease (ALD) in mice humans, but the underlying mechanisms remain obscure. This study aimed to examine effect of aging alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) microRNA‐223 (miR‐223), their contribution ALD pathogeneses. Approach Results Young aged myeloid‐specific Sirt1 knockout were subjected chronic‐plus‐binge ethanol feeding. Blood samples from healthy controls patients with chronic drinking who presented acute intoxication analyzed. Neutrophilic miR‐223 expression down‐regulated compared young mice. Deletion gene myeloid cells including neutrophils exacerbated ethanol‐induced injury inflammation expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting C/EBPα, a key transcription factor biogenesis, subsequently elevated neutrophils. Importantly, down‐regulation was also observed circulating middle‐aged elderly subjects those individuals. Chronic users had reduction patients, greater latter group. The correlated serum alanine transaminase levels patients. Conclusions increases susceptibility alcohol‐induced humans through SIRT1‐C/EBPα‐miR‐223 axis, which could be therapeutic target for prevention and/or treatment ALD.

Язык: Английский

---

Genes and Longevity of Lifespan

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1499 - 1499

Опубликована: Янв. 28, 2022

Aging is a complex process indicated by low energy levels, declined physiological activity, stress induced loss of homeostasis leading to the risk diseases and mortality. Recent developments in medical sciences an increased availability nutritional requirements has significantly average human lifespan worldwide. Several environmental factors contribute aging process. However, about 40% life expectancy inherited among generations, many associated genes, genetic mechanisms pathways have been demonstrated during last decades. In present review, we evaluated genes their non-human orthologs established for role regulation lifespan. The study included more than fifty reported literature contributions longevity life. Intact genomic DNA essential activities at level cell, tissue, organ. Nucleic acids are vulnerable oxidative stress, chemotherapies, exposure radiations. Efficient repair maintenance integrity, damaged not replicated transferred next generations rather presence deleterious initiates signaling cascades cell cycle arrest or apoptosis. modifications, methylation, histone acetylation damage can eventually lead towards importance calorie restriction therapy extension also discussed. involved such as DAF-16/FOXO (forkhead box protein O1), TOR JNK particularized. provides updated account with extended interactive contributory cellular pathways.

Язык: Английский

---

Auricularia polytricha and Flammulina velutipes reduce liver injury in DSS-induced Inflammatory Bowel Disease by improving inflammation, oxidative stress, and apoptosis through the regulation of TLR4/NF-κB signaling pathways

The Journal of Nutritional Biochemistry, Год журнала: 2022, Номер 111, С. 109190 - 109190

Опубликована: Окт. 19, 2022

Язык: Английский

---

Post-Translational Modifications and Diabetes

Biomolecules, Год журнала: 2024, Номер 14(3), С. 310 - 310

Опубликована: Март 6, 2024

Diabetes and its associated complications have increasingly become major challenges for global healthcare. The current therapeutic strategies involve insulin replacement therapy type 1 diabetes (T1D) small-molecule drugs 2 (T2D). Despite these advances, the complex nature of necessitates innovative clinical interventions effective treatment complication prevention. Accumulative evidence suggests that protein post-translational modifications (PTMs), including glycosylation, phosphorylation, acetylation, SUMOylation, play important roles in pathological consequences. Therefore, investigation PTMs not only sheds light on mechanistic regulation but also opens new avenues targeted therapies. Here, we offer a comprehensive overview role several diabetes, focusing most recent advances understanding their functions regulatory mechanisms. Additionally, summarize pharmacological targeting advanced into trials diabetes. Current future perspectives are provided.

Язык: Английский

---

Alcohol‐induced liver injury is mediated via α4‐containing nicotinic acetylcholine receptors expressed in hepatocytes

Alcohol Clinical and Experimental Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Our previous study demonstrated that alcohol induced the expression of α4 subunit nicotinic acetylcholine receptors (nAChRs) in livers wild type mice (WT), and whole-body nAChR knockout (α4KO) showed protection against alcohol-induced steatosis, inflammation, injury. Based on these findings, we hypothesized hepatocyte-specific nAChRs may directly contribute to detrimental effects liver. Hepatocyte-specific (α4HepKO) were generated, absence was confirmed through PCR genomic DNA. Female WT α4HepKO exposed NIAAA chronic + binge model. After 10 days Lieber-DeCarli liquid diet containing 5% (vol/vol) or isocaloric maltose-dextrin, gavaged with a single dose maltose-dextrin. The euthanized 9 h later their organs harvested. Additionally, hepatocytes isolated from WT, α4HepKO, α4floxed, α4KO 80 mM vitro for 24 h. Steatosis, cell injury assessed both liver hepatocytes. In mice, exposure resulted hepatic as evidenced by increased triglycerides, neutrophil infiltration, serum concentrations enzymes. All responses markedly lower mice. mRNA genes involved lipogenesis (Srebf1, Fasn, Dgat2) inflammation (TNFα, Cxcl5, Cxcl1, Serpine1) vivo vitro. These changes not observed lacking nAChRs. expressed mediate alcohol-associated hepatoxicity. Therefore, development therapeutic strategies targeting hepatocyte α4-containing could help reduce burden ALD.

Язык: Английский

---

Screening of Gehua Jiejiu Dizhi Decoction Active Components for the Treatment of Alcoholic Fatty Liver Disease and Their Effects of Taxifolin and Genistein on Sirtuin 1/Sirtuin 3-Forkhead Boxo1 Signaling

Опубликована: Янв. 1, 2025

Язык: Английский

---