α-Mangostin prevents diabetic cardiomyopathy by inhibiting oxidative damage and lipotoxicity through the AKT–FOXO1–CD36 pathway DOI Creative Commons
Xue Bai, Ziqian Zhang, Miao Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Introduction Diabetic cardiomyopathy (DCM), a cardiac complication of diabetes, is the main cause high prevalence heart failure and associated mortality in diabetic patients. Oxidative stress lipid metabolism disorder-induced myocardial cell damage are part pathogenesis DCM. In this study, we investigated effects alpha-mangostin (A-MG), natural antioxidant extracted from mangosteen peel, on vitro vivo DCM models. Methods H9C2 rat cardiomyocytes were treated with glucose (HG) palmitic acid (PA) for 24 h to establish an model. Cell viability cytotoxicity evaluated after treatment varying concentrations A-MG (0.3, 1, 3, 9, or 27 μM) using Counting Kit-8 (CCK8) lactate dehydrogenase (LDH) assays. Flow cytometry assessment was used detect apoptosis. Molecular mechanisms through transcriptome analysis, quantitative PCR (RT-qPCR), Western blotting. Type 2 (T2D) mice, induced by feeding high-fat diet (HFD) combined low-dose streptozotocin (STZ), received either vehicle, (100 mg/kg/d), high-dose (200 mg/kg/d) 6 weeks. Cardiac function assessed echocardiography. H&E Masson’s staining evaluate tissue structure fibrosis, blotting protein expression. Results HG/F-induced cells, (1 3 significantly increased (p < 0.01) reduced LDH release 0.05). (3 attenuated accumulation 0.05), normalized mitochondrial membrane potential 0.01), inhibited reactive oxygen species (ROS) generation malondialdehyde (MDA) production apoptosis also nuclear translocation Forkhead box class O1 (FOXO1) 0.05); expression CD36 PPARα CPT1β 0.05) proteins; enhanced superoxide dismutase (SOD) activity upregulated factor erythroid 2-related (Nrf2) HO-1 SOD2 levels. Further investigation cells indicated that inhibits uptake fatty acids (FAs) regulating AKT/FOXO1/CD36 signaling pathway, reduces excessive β-oxidation FAs mediated PPARα/CPT1β inhibition FOXO1 translocation, stimulates AKT/Nrf2/HO-1 pathway increase cellular capacity. anti-oxidative capacity, decreased accumulation, fibrosis cardiomyocyte apoptosis, improved left ventricular contractile function. Conclusion Using both models, our study demonstrates while enhancing These results suggest may be novel therapeutic option

Language: Английский

GluOC Induced SLC7A11 and SLC38A1 to Activate Redox Processes and Resist Ferroptosis in TNBC DOI Open Access

Jiaojiao Xu,

Xue Bai,

Keting Dong

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 739 - 739

Published: Feb. 21, 2025

Background/Objectives: Ferroptosis, a type of programmed cell death, is mainly associated with disruptions in iron metabolism, imbalances the amino acid antioxidant system, and build-up lipid peroxides. Triple-negative breast cancer (TNBC) has dismal prognosis. Since activating ferroptosis can suppress proliferation, it holds promise as novel therapeutic target for patients. Thus, objective this study was to clarify mechanism TNBC, aiming find new treatment strategies TNBC Methods: We screened out differential genes related after GluOC based on whole-genome sequencing results. At cellular level, we conducted explorations using techniques such quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, fluorescence staining, siRNA transfection. Moreover, further verified role inhibiting through vivo experiments nude mice. Results: The results showed that enhanced glutathione expression levels by inducing SLC7A11 accumulation via specific signaling pathway. Additionally, increased ATP production tricarboxylic flux resistance SLC38A1. Overall, coordinately regulated SLC38A1 inhibit TNBC. Conclusions: This elucidated findings not only provided insights into but also potentially offered concepts development future anticancer therapies, which may contribute improving

Language: Английский

Citations

0
MLC2: Physiological Functions and Potential Roles in Tumorigenesis DOI

Jiaxue Lu,

Nan Li, Wenling Zhang

et al.

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Language: Английский

Citations

0
α-Mangostin prevents diabetic cardiomyopathy by inhibiting oxidative damage and lipotoxicity through the AKT–FOXO1–CD36 pathway DOI Creative Commons
Xue Bai, Ziqian Zhang, Miao Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Introduction Diabetic cardiomyopathy (DCM), a cardiac complication of diabetes, is the main cause high prevalence heart failure and associated mortality in diabetic patients. Oxidative stress lipid metabolism disorder-induced myocardial cell damage are part pathogenesis DCM. In this study, we investigated effects alpha-mangostin (A-MG), natural antioxidant extracted from mangosteen peel, on vitro vivo DCM models. Methods H9C2 rat cardiomyocytes were treated with glucose (HG) palmitic acid (PA) for 24 h to establish an model. Cell viability cytotoxicity evaluated after treatment varying concentrations A-MG (0.3, 1, 3, 9, or 27 μM) using Counting Kit-8 (CCK8) lactate dehydrogenase (LDH) assays. Flow cytometry assessment was used detect apoptosis. Molecular mechanisms through transcriptome analysis, quantitative PCR (RT-qPCR), Western blotting. Type 2 (T2D) mice, induced by feeding high-fat diet (HFD) combined low-dose streptozotocin (STZ), received either vehicle, (100 mg/kg/d), high-dose (200 mg/kg/d) 6 weeks. Cardiac function assessed echocardiography. H&E Masson’s staining evaluate tissue structure fibrosis, blotting protein expression. Results HG/F-induced cells, (1 3 significantly increased (p < 0.01) reduced LDH release 0.05). (3 attenuated accumulation 0.05), normalized mitochondrial membrane potential 0.01), inhibited reactive oxygen species (ROS) generation malondialdehyde (MDA) production apoptosis also nuclear translocation Forkhead box class O1 (FOXO1) 0.05); expression CD36 PPARα CPT1β 0.05) proteins; enhanced superoxide dismutase (SOD) activity upregulated factor erythroid 2-related (Nrf2) HO-1 SOD2 levels. Further investigation cells indicated that inhibits uptake fatty acids (FAs) regulating AKT/FOXO1/CD36 signaling pathway, reduces excessive β-oxidation FAs mediated PPARα/CPT1β inhibition FOXO1 translocation, stimulates AKT/Nrf2/HO-1 pathway increase cellular capacity. anti-oxidative capacity, decreased accumulation, fibrosis cardiomyocyte apoptosis, improved left ventricular contractile function. Conclusion Using both models, our study demonstrates while enhancing These results suggest may be novel therapeutic option

Language: Английский

Citations

0