Metabolic-Associated Fatty Liver Disease: The Influence of Oxidative Stress, Inflammation, Mitochondrial Dysfunctions, and the Role of Polyphenols

Pharmaceuticals, Год журнала: 2024, Номер 17(10), С. 1354 - 1354

Опубликована: Окт. 10, 2024

Metabolic-Associated Fatty Liver Disease (MAFLD) is a clinical-pathological scenario that occurs due to the accumulation of triglycerides in hepatocytes which considered significant cause liver conditions and contributes an increased risk death worldwide. Even though possible causes MAFLD can involve interaction genetics, hormones, nutrition, lifestyle (diet sedentary lifestyle) most influential factor developing this condition. Polyphenols comprise many natural chemical compounds be helpful managing metabolic diseases. Therefore, aim review was investigate impact oxidative stress, inflammation, mitochondrial dysfunction, role polyphenols MAFLD. Some reverse part damage related or among them are anthocyanin, baicalin, catechin, curcumin, chlorogenic acid, didymin, epigallocatechin-3-gallate, luteolin, mangiferin, puerarin, punicalagin, resveratrol, silymarin. These have actions reducing plasma enzymes, body mass index, waist circumference, adipose visceral indices, lipids, glycated hemoglobin, insulin resistance, HOMA index. They also reduce nuclear factor-KB (NF-KB), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), blood pressure, fat content, steatosis fibrosis. On other hand, they improve HDL-c, adiponectin levels, fibrogenesis markers. results show promising prevention treatment

Язык: Английский

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FucoVital® inhibits fatty acid accumulation in liver cells in vitro and reduces triglycerides levels in patients with NAFLD

PharmaNutrition, Год журнала: 2025, Номер 31, С. 100429 - 100429

Опубликована: Янв. 9, 2025

Язык: Английский

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Blockade of the STAT3/BCL-xL Axis Leads to the Cytotoxic and Cisplatin-Sensitizing Effects of Fucoxanthin, a Marine-Derived Carotenoid, on Human Bladder Urothelial Carcinoma Cells

Marine Drugs, Год журнала: 2025, Номер 23(2), С. 54 - 54

Опубликована: Янв. 22, 2025

Bladder cancer is a globally prevalent urological malignancy, with transitional carcinoma (TCC) representing the majority of cases. Cisplatin primary drug for metastatic bladder chemotherapy; however, its application limited by nephrotoxicity and resistance. Signal Transducer Activator Transcription 3 (STAT3) an oncogenic transcription factor often overactivated in various cancers, making it appealing target. Fucoxanthin, marine carotenoid, has significant anticancer properties. This study explored Fucoxanthin’s cytotoxic effects potential to potentiate efficacy Cisplatin, along mechanisms underlying these effects, on human TCC cells. We demonstrated that Fucoxanthin cells inducing apoptosis, evidenced z-VAD-fmk-mediated annulment cytotoxicity. Furthermore, reduced levels inherent or interleukin-6-induced tyrosine 705-phosphorylated STAT3 accompanied downregulating BCL-xL, well-established Notably, ectopic expression STAT3-C, dominant-active mutant, BCL-xL thwarted proapoptotic actions. Moreover, at subtoxic dosages enhanced susceptibility Cisplatin-induced apoptosis initially resistant Cisplatin. Remarkably, this Cisplatin-sensitizing effect was abrogated when ectopically expressed STAT3-C BCL-xL. Overall, first time, we proved proapoptotic, cytotoxic, are attributed blockade STAT3/BCL-xL axis. Our findings highlight targeting axis promising strategy eliminate facilitate sensitization, further support incorporating into Cisplatin-based chemotherapy treating cancer.

Язык: Английский

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Fucoxanthin mitigates mercury-induced mitochondrial toxicity in the human ovarian granulosa cell line

Reproductive Toxicology, Год журнала: 2025, Номер 132, С. 108855 - 108855

Опубликована: Фев. 11, 2025

Mercury (Hg) is known to be a hazardous toxin with significant negative impact on female reproduction through mechanisms that remain unclear. The carotenoid fucoxanthin (FX) an antioxidant several positive effects human health. This study aimed examine the potential protective role of FX in reducing Hg-induced bioenergetic disturbances ovarian granulosa cell line model. (methods briefly) Hg was found reduce viability cells concentration-dependent manner, estimated 72-hour EC50 10µM. In contrast, (10 and 20µM) improved viability. (1 10µM) significantly reduced cellular ATP levels, mitochondrial membrane potential, oxygen consumption rates, lactate production. Additionally, impaired activities kinetics complexes I III expression genes ND1, ND5, cytochrome B, C oxidase, synthase subunits 6 8. According tests membranes, increased fluidity by saturated fatty acid levels increasing those unsaturated acids. also promoted swelling enhanced inner permeability hydrogen potassium ions. (10µM) shown mitigate treated cells, bioenergetics parameters, integrity manner. Based these findings, disruption may key underlying cause dysfunction. Furthermore, have therapeutic treating disorders caused bioenergetics.

Язык: Английский

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Carotenoids for Antiaging: Nutraceutical, Pharmaceutical, and Cosmeceutical Applications

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 403 - 403

Опубликована: Март 13, 2025

Background: Carotenoids are bioactive tetraterpenoid C40 pigments that actively synthesized by plants, bacteria, and fungi. Compounds such as α-carotene, β-carotene, lycopene, lutein, astaxanthin, β-cryptoxanthin, fucoxanthin, zeaxanthin have attracted increasing attention for their antiaging properties. They exhibit antioxidant, neuroprotective, anti-inflammatory properties, contributing to the prevention treatment of age-related diseases. Objectives: The aim this study was comprehensively analyze pharmacological potential biological mechanisms carotenoids associated with disorders evaluate application in nutraceuticals, pharmaceuticals, cosmeceuticals. Methods: A systematic review studies published over past two decades conducted using databases PubMed, Scopus, Web Science. selection criteria included clinical, silico, vivo, vitro investigating therapeutic effects carotenoids. Results: demonstrate a variety health benefits, including macular degeneration, cancer, cognitive decline, metabolic disorders, skin aging. Their role nutraceuticals is well supported ability modulate oxidative stress inflammatory pathways. In show promising results formulations targeting neurodegenerative diseases disorders. cosmeceuticals, they improve protecting it against UV radiation damage. However, bioavailability, optimal dosages, toxicity, interactions other compounds remain critical factors maximize efficacy still require careful evaluation scientists. Conclusions: interventions applications fields. Further research needed optimize formulas, confirm long-term safety effectiveness, especially aging population.

Язык: Английский

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Therapeutic Potential of Raspberry Extract in High-Fat Diet-Induced Liver Injury via Apoptosis and AMPK/PPARα Pathways

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

This study aimed to explore the efficacy and mechanisms of raspberry (Rubus idaeus L. fruit) aqueous extract (RE) in alleviating high-fat diet (HFD)-induced metabolic-associated fatty liver disease (MAFLD). The MAFLD mouse model was established examine effects RE through transcriptome metabolomics analysis. In this study, supplementation significantly alleviated HFD-induced injury, hepatosteatosis, inflammation, insulin resistance. Liver analysis demonstrated that favorably regulated signaling pathways involved acid metabolism including AMPK pathway, PPAR apoptosis, etc. Furthermore, injection compound C, an antagonist AMPK, notably reversed hepatoprotective RE, evidenced by increased lipid profile levels, accelerated acid-related gene disorder, positive tunnel staining area. treatment led substantial enrichment tissue metabolite umbelliferone (UMB), which has potential ameliorate accumulation hepatocyte injury pathway. summary, intervention mitigated dysfunction mice, with UMB likely being primary component responsible for its therapeutic liver. addition, provided new insights, suggesting could be used as a promising approach modulating via apoptosis AMPK/PPARα

Язык: Английский

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Fucoxanthinol Mitigates the Cytotoxic Effect of Chlorpyrifos and MPTP on the Dopaminergic Differentiation of SH-SY5Y Human Neuroblastoma Cells

Journal of Molecular Neuroscience, Год журнала: 2025, Номер 75(2)

Опубликована: Апрель 8, 2025

Abstract This study investigates the neuroprotective effects of fucoxanthinol (FXL) against toxic activities two compounds known to induce neurotoxic in humans and animals. MPTP (1-methyl- 4-phenyl- 1,2,3,6-tetrahydropyridine) induces Parkinson’s disease (PD)-like phenotypes by inhibiting mitochondrial complex I dopaminergic neurons. Chlorpyrifos (CPF), another agent, is associated with acute long-term neurotoxicity primarily through acetylcholinesterase (AChE) inhibition. FXL demonstrated ability reverse CPF SH-SY5Y neuronal cell models. Treatment enhances function cells exposed MPTP, as increased levels Adenosine triphosphate (ATP), membrane potential (MMP), complexes activities, oxygen consumption rates, pyruvate dehydrogenase (PDH) mitophagy pathways. improvement highlights FXL’s counteract dysfunction induced these agents. Additionally, reduces oxidative damage viability. At molecular level, were also modulation apoptotic markers, including Bcl- 2 markers. Molecular docking data further support outcomes our vitro studies. Multivariable analysis FXL. These findings indicate mitigate CPF- MPTP-induced neurotoxicity, suggesting its promise a therapeutic agent for managing observe PD.

Язык: Английский

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Potential of siphonaxanthin, a green algal carotenoid, to prevent obesity and related diseases

Journal of Natural Medicines, Год журнала: 2025, Номер unknown

Опубликована: Апрель 12, 2025

Язык: Английский

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Fucoxanthin Targets β1 Integrin to Disrupt Adhesion and Migration in Human Glioma Cells

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Glioblastoma, the most aggressive type of primary brain tumor, is marked by high invasiveness and metastasis, posing significant challenges in treatment. Fucoxanthin, a carotenoid derived from brown macroalgae, has demonstrated therapeutic potential cancer therapy; however, its precise mechanisms action remain unclear. In this study, we explored inhibitory effects fucoxanthin on integrin-mediated adhesion migration human glioma U-87 MG cells, shedding light antimetastatic properties. Our data indicated that at 1 μM did not affect cell viability but inhibited cells to fibronectin, key extracellular matrix (ECM) ligand for integrins, without affecting poly-l-lysine, nonintegrin ligand, indicating selective impact adhesion. Fucoxanthin treatment significantly reduced size number focal adhesions (FA), which play central role migration. addition, impaired migratory capacity, including accumulated distance velocity, determined time-lapse videomicroscopy. Further, remarkably integrin engagement-mediated actin polymerization, Vav3 phosphorylation, downstream activation Rac1, FAK, paxillin, further supporting disrupting signaling cytoskeletal remodeling. Additionally, complementary experiments utilizing protein binding assays, competitive ELISA, CETSA, DARTS, MST collectively confirmed direct interaction between β1 as well affinity fibronectin. The theoretical model molecular docking dynamics simulation align with our experimental findings, providing plausible mechanism competitively inhibits summary, study highlights promising agent impairs glioblastoma directly targeting pathways. These findings offer valuable insights into an

Язык: Английский

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Through its genoprotective, mitochondrial bioenergetic modulation, and antioxidant effects, Fucoxanthin and its metabolite minimize Ochratoxin A-induced nephrotoxicity in HK-2 human kidney cells

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Background Ochratoxin A (OTA) is a mycotoxin with reported multiorgan toxicity, especially kidney toxicity. Fucoxanthin (FX) and its hydrolyzed metabolite Fucoxanthinol (FXL) have reno-protective antioxidant anti-inflammatory properties. This study evaluates the nephroprotective effects of FX FLX on OTA-induced renal cytotoxicity using HK-2 cell line. Methods Molecular docking was used to binding affinities main proteins studied pathways. Various in-vitro assays were test hypothesis, including MTT, mitochondrial bioenergetics, oxidative stress, apoptosis biomarkers. Results Docking revealed tested chemicals mitochondria, apoptosis. Data showed that OTA has dose-dependent cytotoxic effect cells. Notably, FXL improved viability. significant deregulation normal cellular pathways genotoxicity (DNA damage percentage), bioenergetics disruption (PDH, α-KG, MCI MCIII complexes activities, ATP levels membrane potential), downregulation some genes (ND1, ND5, CO-1 ATP6/8) expression, mitophagy inhibition (PARK1 parkin), Oxidative stress induction (ROS TBARS), (HO-1 Nrf2), enzymatic activity reduction CAT), apoptotic mediator markers elevation ( Caspases- 3, 8 9, Bax/Bcl-2 ratio) observed in mono-treated cells compared untreated control All parameters markedly normalized by combining or OTA, providing more protection co-treated samples. Conclusion Our results suggest may be effective novel therapies for treating nephrotoxicity vitro.

Язык: Английский

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