Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Dec. 1, 2021

Notoginsenoside R1 (NGR1), the primary bioactive compound found in Panax notoginseng, is believed to have antihypertrophic and antiapoptotic properties, has long been used prevent treat cardiovascular diseases. However, its potential role prevention of diabetic cardiomyopathy remains unclear. The present study aimed investigate mechanism NGR1 action high glucose-induced cell injury. H9c2 cardiomyocytes were cultured a high-glucose medium as an in-vitro model, apoptotic cells visualized using TUNEL staining. Expression Nrf2 HO-1 was measured Western blotting or reverse transcription-quantitative PCR (RT-qPCR). small interfering (si) RNA transfected into Opti-MEM containing Lipofectamine® RNAiMAX. protected from death, apoptosis hypertrophy induced by glucose concentration. auricular natriuretic peptide brain remarkably reduced NGR1-treated H9C2 cells. blot analysis showed that concentration markedly inhibited AMPK, HO-1, this could be reversed treatment. cardioprotective effect attenuated C, which reverses expression levels, suggesting AMPK upregulates gene expression, protein synthesis secretion. Transfection with siRNA via HO-1. These results indicated injury AMPK/Nrf2 signaling downstream target, pathway. We conclude effects result upregulation cardiomyocytes. Our findings suggest treatment might provide novel therapy for cardiomyopathy.

Language: Английский

---

SUMOylation targeting mitophagy in cardiovascular diseases

Journal of Molecular Medicine, Journal Year: 2022, Volume and Issue: 100(11), P. 1511 - 1538

Published: Sept. 26, 2022

Language: Английский

---

Multi-omics insights into potential mechanism of SGLT2 inhibitors cardiovascular benefit in diabetic cardiomyopathy

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Oct. 5, 2022

Background Metabolic and energy disorders are considered central to the etiology of diabetic cardiomyopathy (DCM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) can effectively reduce risk cardiovascular death heart failure in patients with DCM. However, underlying mechanism has not been elucidated. Methods We established a DCM rat model followed by treatment empagliflozin (EMPA) for 12 weeks. Echocardiography, blood tests, histopathology, transmission electron microscopy (TEM) were used evaluate phenotypic characteristics rats. The proteomics metabolomics myocardium performed identify potential targets signaling pathways associated benefit SGLT2i. Results showed pronounced characterized mitochondrial pleomorphic, impaired lipid metabolism, myocardial fibrosis, diastolic systolic functional impairments heart. To some extent, these changes ameliorated after EMPA. A total 43 proteins 34 metabolites identified as rats treated KEGG analysis that arachidonic acid is maximum number related may be target EMPA treatment. Fatty (FA) metabolism was enhanced hearts, perturbation biosynthesis unsaturated FAs enabler Conclusion SGLT2i accumulation damage metabolomic proteomic data revealed SGLT2i, which provides valuable resource

Language: Английский

---

Parkin-mediated mitophagy is negatively regulated by FOXO3A, which inhibits Plk3-mediated mitochondrial ROS generation in STZ diabetic stress-treated pancreatic β cells

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(5), P. e0281496 - e0281496

Published: May 3, 2023

Diabetes mellitus (DM) is one of the most researched metabolic diseases worldwide. It leads to extensive complications such as cardiovascular disease, nephropathy, retinopathy, and peripheral central nervous system through an inability produce or respond insulin. Although oxidative stress-mediated mitophagy has been reported play important role in pathogenesis DM, specific studies are still lacking well remain highly controversial. Here, we found that Parkin-mediated pancreatic β cells under streptozotocin (STZ)-diabetic stress was induced by Polo-like kinase 3 (Plk3) inhibited transcription factor Forkhead Box O3A (FOXO3A). STZ induces mitochondrial recruitment Parkin Plk3-mediated reactive oxygen species (ROS) generation, which causes cell damage. Conversely, FOXO3A acts negative feedback prevent diabetic inhibiting Plk3. Meanwhile, antioxidants including N-acetylcysteine (NAC) natural COA water scientifically block these ROS Through a 3D organoid ex vivo model, confirmed not only inhibitors but also inhibitory factors 3-MA deletion can compensate for growth insulin secretion stress. These findings suggest Plk3-mtROS-PINK1-Parkin axis novel process inhibits β-cell may provide new alternatives effective diabetes treatment strategies future.

Language: Английский

---

Associação entre diabetes e insuficiência cardíaca: mecanismos, fatores de risco e implicações clínicas

Caderno Pedagógico, Journal Year: 2025, Volume and Issue: 22(1), P. e13212 - e13212

Published: Jan. 10, 2025

Introdução: a revisão investigou relação entre diabetes mellitus (DM) e insuficiência cardíaca congestiva (ICC), evidenciando o impacto negativo do DM nos desfechos clínicos, como mortalidade hospitalizações. Mecanismos fisiopatológicos, resistência à insulina, inflamação crônica remodelamento cardíaco, foram destacados fatores que agravam progressão da ICC. Metodologia: analisados estudos publicados 2013 2023, em inglês, português espanhol, selecionados nas bases PubMed, Scopus, Cochrane Library, LILACS SciELO. A seleção incluiu ensaios clínicos randomizados, revisões sistemáticas observacionais, priorizando aqueles com relevância qualidade abordassem ICC, intervenções terapêuticas clínicos. Resultados :os resultados demonstraram exacerba ICC por mecanismos fibrose miocárdica. Novas terapias, os inibidores cotransportadora de sódio-glicose tipo 2 (SGLT2), eficazes na redução hospitalizações mortalidade, além apresentarem benefícios renais significativos. Desenvolvimento: revisados enfatizaram importância um manejo integrado, equilibrando controle glicêmico farmacológicas, para abordar múltiplos fisiopatológicos. Estratégias multidisciplinares são fundamentais otimizar cuidados desfechos. Conclusão: reforça estratégias personalizadas no pacientes foco uso novas terapias cuidado multidisciplinar. Pesquisas futuras devem explorar populações sub-representadas, idosos frágeis renal avançada.

---