Celastrol alleviates diabetic vascular injury via Keap1/Nrf2-mediated anti-inflammation DOI Creative Commons
Ning An,

Rixiang Wang,

Lin Li

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 31, 2024

Introduction: Celastrol (Cel) is a widely used main component of Chinese herbal medicine with strong anti-inflammatory, antiviral and antitumor activities. In the present study, we aimed to elucidate cellular molecular protective mechanism Cel against diabetes-induced inflammation endothelial dysfunction. Methods: Type 2 diabetes (T2DM) was induced by db/db mice, osmotic pumps containing (100 μg/kg/day) were implanted intraperitoneally calibrated release drug for 28 days. addition, human umbilical vein cells (HUVECs) cultured in normal or high glucose palmitic acid-containing (HG + PA) media presence absence 48 h. Results: significantly ameliorated hyperglycemia-induced abnormalities nuclear factor (erythroid-derived 2)-like protein (Nrf2) pathway activity alleviated HG PA-induced oxidative damage. However, effect almost completely abolished HUVECs transfected short hairpin (sh)RNA targeting Nrf2, but not nonsense shRNA. Furthermore, PA reduced phosphorylation AMP-activated kinase (AMPK), autophagic degradation p62/Kelch-like ECH-associated 1 (Keap1), localization Nrf2. these catabolic pathways inhibited treatment HUVECs. compound C (AMPK inhibitors) AAV9-sh-Nrf2 Cel-induced Nrf2 activation angiogenesis mice. Discussion: Taking findings together, may be at least part attributed its effects reduce reactive oxygen species (ROS) through p62/Keap1-mediated activation.

Language: Английский

Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ–mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats DOI Creative Commons
Wessam M. Aziz, Samia A. Ahmed,

Sylvia E. Shaker

et al.

Diabetology & Metabolic Syndrome, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 30, 2024

Abstract Background & objective : While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains pillar prophylactic measure. Purslane was extensively described as a potent hypoglycemic and hypolipidemic agent owing to its rich content of antioxidants. Therefore, this report aimed assess renoprotective potentials methanol (MO) methylene chloride (MC) fixed oil extracts purslane seeds in (DN) model. Methods were extracted using absolute chloride, type-1 diabetes induced with single 55 mg/kg dose Streptozotocin (STZ) dissolved 100 mmol/L citrate buffer (pH 4.5), then animals received MO, MC, for 42 consecutive days compare their antidiabetic effect relative reference drug “Losartan”. Renal functions DN biomarkers weekly assessed, expression different oxido-inflammatory mediators quantified kidneys by RT-PCR. Data statistically analyzed GraphPad Prism 9.0.2. Results The oral administration MO MC (250 mg/kg/day) significantly ameliorated body weight loss ( P < 0.0001 / each), fasting blood glucose levels (FBG) urine volume well serum creatinine uric acid = 0.0022, 0.0052), urea nitrogen (BUN) 0.0265, 0.0338); respectively, compared untreated rats. In addition, both restored effectuality antioxidative machinery indicated significant reduction ROS accumulation lipid peroxidation; higher GSH content, promoted activity glutathione reductase superoxide dismutase antioxidant enzymes each). Histologically, alleviated DN-structural alterations including glomerular congestion tubular degeneration, MC-treated showing near normal architecture. transcription profiles all treated revealed downregulated TNF-α, IL-6, Keap1 NF-κB genes, concomitant upregulation SDF-1, IL-10, Nrf2, HO-1, PPARγ gene all). Conclusion These findings highlight remarkable DN-prophylactic mediated neutralizing hyperglycemia-induced accumulation, circumventing downstream inflammatory cascades, surpassing angiotensin receptor blocker; i.e. Losartan.

Language: Английский

Citations

2
Mitochondrial dysfunction in diabetic nephropathy: insights and therapeutic avenues from traditional Chinese medicine DOI Creative Commons

Dan-mai Zhao,

Rui Zhong, Xiaotian Wang

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: July 23, 2024

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. The progressive damage to glomeruli, tubules, and interstitium in the kidneys can lead development chronic kidney disease (CKD) end-stage renal (ESRD). Most energy we need comes from mitochondria. Mitochondria are best known as sites for production respiratory ATP essential eukaryotic life. pathogenesis DN involves variety factors, such altered haemodynamics, oxidative stress, inflammation, studies animal models suggest that mitochondrial dysfunction plays an important role DN. Traditional Chinese medicine (TCM) has history more than 2,500 years rich experience remarkable efficacy treatment Recent have found TCM may great potential regulating This review will elucidate main causes relationship with DN, explore depth mechanisms protect by improving dysfunction. Current pharmacological treatments patients do not prevent inevitable progression ESRD. With herbs, expected be most promising candidate continue learn about incorporate current advances extraction techniques.

Language: Английский

Citations

2
YuNü-Jian attenuates diabetes-induced cardiomyopathy: integrating network pharmacology and experimental validation DOI Creative Commons
Wei Wang, Ruixia Liu, Yingying Zhu

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: May 23, 2023

Diabetic cardiomyopathy (DCM) is one of the most prevalent complications diabetes with complex pathogenesis. YuNü-Jian (YNJ) a traditional Chinese medicinal formula widely used for hypoglycemic and cardioprotective effects. This study aims to investigate actions mechanisms YNJ against DCM which has never been reported. Network pharmacology approach was predict potential pathways targets on DCM. Molecular docking between hub active components performed visualized by AutoDock Vina PyMOL. Then type 2 diabetic model employed intervened 10 weeks further validate these critical targets. First, total 32 main ingredients were identified 700 screened construct herb-compound-target network. 94 differentially expressed genes from GEO database. After that, PPI network generated (SIRT1, Nrf2, NQO1, MYC APP) assessed topology analysis. Next, functional pathway analysis indicated that candidate enriched in response oxidative stress Nrf2 signaling pathway. Furthermore, molecular revealed strong affinity core YNJ. Finally, rats diabetes, obviously attenuated cardiac collagen accumulation degree fibrosis. Meanwhile, significantly upregulated protein expression SIRT1, NQO1 myocardium. Collectively, our findings suggested could effectively ameliorate induced possibly through SIRT1/Nrf2/NQO1 signaling.

Language: Английский

Citations

4
NLRX1 Inhibits LPS-Induced Microglial Death via Inducing p62-Dependent HO-1 Expression, Inhibiting MLKL and Activating PARP-1 DOI Creative Commons
Yu‐Ling Huang, Duen-Yi Huang, Vladlen Klochkov

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 481 - 481

Published: April 17, 2024

The activation of microglia and the production cytokines are key factors contributing to progressive neurodegeneration. Despite well-recognized neuronal programmed cell death regulated by microglial activation, themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions as a scaffolding protein involved in various central nervous system diseases. In this study, we used SM826 cells understand role NLRX1 lipopolysaccharide (LPS)-induced death. We found LPS-induced blocked necrostatin-1 zVAD. Meanwhile, LPS can activate poly (ADP-ribose) polymerase-1 (PARP-1) reduce DNA damage induce heme oxygenase (HO)-1 expression counteract silencing PARP-1 inhibition olaparib enhance an additive manner. Less PARylation higher observed NLRX1-silencing cells. Moreover, HO-1 gene through p62-Keap1-Nrf2 axis attenuated silencing. addition, Nrf2-mediated positive feedback regulation p62 accordingly reduced Of note, does not affect cellular reactive oxygen species (ROS) but increases mixed lineage kinase domain-like pseudokinase (MLKL) necroptosis. blocks bafilomycin A1-induced activation. Taken together, for first time, demonstrate protecting from underlying protective mechanisms include upregulating via Nrf2-dependent downstream Keap1-Nrf2 axis, mediating repair ROS- autophagy-independent pathway, reducing MLKL

Language: Английский

Citations

1
Celastrol alleviates diabetic vascular injury via Keap1/Nrf2-mediated anti-inflammation DOI Creative Commons
Ning An,

Rixiang Wang,

Lin Li

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 31, 2024

Introduction: Celastrol (Cel) is a widely used main component of Chinese herbal medicine with strong anti-inflammatory, antiviral and antitumor activities. In the present study, we aimed to elucidate cellular molecular protective mechanism Cel against diabetes-induced inflammation endothelial dysfunction. Methods: Type 2 diabetes (T2DM) was induced by db/db mice, osmotic pumps containing (100 μg/kg/day) were implanted intraperitoneally calibrated release drug for 28 days. addition, human umbilical vein cells (HUVECs) cultured in normal or high glucose palmitic acid-containing (HG + PA) media presence absence 48 h. Results: significantly ameliorated hyperglycemia-induced abnormalities nuclear factor (erythroid-derived 2)-like protein (Nrf2) pathway activity alleviated HG PA-induced oxidative damage. However, effect almost completely abolished HUVECs transfected short hairpin (sh)RNA targeting Nrf2, but not nonsense shRNA. Furthermore, PA reduced phosphorylation AMP-activated kinase (AMPK), autophagic degradation p62/Kelch-like ECH-associated 1 (Keap1), localization Nrf2. these catabolic pathways inhibited treatment HUVECs. compound C (AMPK inhibitors) AAV9-sh-Nrf2 Cel-induced Nrf2 activation angiogenesis mice. Discussion: Taking findings together, may be at least part attributed its effects reduce reactive oxygen species (ROS) through p62/Keap1-mediated activation.

Language: Английский

Citations

1