Protocatechualdehyde restores endothelial dysfunction in streptozotocin-induced diabetic rats

Ji, Bin; Yuan, Kaiming; Li, Jun; Ku, Bon Jeong; Leung, Po Sing; He, Wei

doi:10.21037/atm-21-1431

Cited by 9 publications

(6 citation statements)

References 21 publications

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“…Acetylcholine produces the relaxation of the vessel smooth muscle layer through an endothelium-dependent mechanism by increasing the synthesis and release of vasodilator substances from this layer, including the NO and prostacyclin. Several studies showed the overreaction to Ach of the diabetic vessels in rats [33][34][35][36], but in our study the diabetic aortas' response to this neurotransmitter was decreased. The group of rats with DM and moderate swimming training had an improved vascular function.…”

Section: Discussioncontrasting

confidence: 81%

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The Beneficial Effect of Swimming Training Associated with Quercetin Administration on the Endothelial Nitric Oxide-Dependent Relaxation in the Aorta of Rats with Experimentally Induced Type 1 Diabetes Mellitus

et al. 2023

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Type 1 diabetes mellitus is related to the vascular oxidative and nitrosative stress, the trigger for atherosclerosis and cardiovascular complications. The effects of moderate swimming training associated with quercetin oral administration were evaluated in aorta of rats with experimentally induced type 1 diabetes mellitus (T1DM), by analysing the nitric oxide-endothelial dependent relaxation (NO-EDR). T1DM rats received daily quercetin 30 mg/kg and followed the protocol of 5-weeks swimming exercise (30 min/day; 5 days/week). Aorta relaxation to acetylcholine (Ach) and sodium nitroprusside (SNP) were measured at the end of the experiment. Ach-induced endothelial dependent relaxation was significantly decreased in phenylephrine (PE) pre-contracted aorta of diabetic rats. Swimming exercise with quercetin administration preserved Ach-induced EDR but did not have any impact on SNP-induced endothelium-independent relaxation in the diabetic aorta. These findings suggest that quercetin administration associated with moderate swimming exercise could improve the endothelial NO-dependent relaxation in the aorta of rats with experimentally induced type 1 diabetes mellitus, showing that this therapeutical combination may improve and even prevent the vascular complications that occur in diabetic patients.

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Section: Discussioncontrasting

confidence: 81%

“…Therefore, the iNOS (inducible nitric oxide synthase) expression increases, leading to NO increased synthesis. Nitric oxide reacts with superoxide anion radical producing peroxynitrite, a strong oxidant with numerous noxious effects [ 7 , 33 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

The Beneficial Effect of Swimming Training Associated with Quercetin Administration on the Endothelial Nitric Oxide-Dependent Relaxation in the Aorta of Rats with Experimentally Induced Type 1 Diabetes Mellitus

et al. 2023

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“…Active ingredients extracted from Astragalus membranaceus , including baicalin, baicalein, and wogonin, relieved high glucose-induced endothelial inflammation to prevent and treat diabetic complications ( 34 ). Treating rats with protocatechualdehyde effectively relieved streptozotocin-induced endothelial dysfunction ( 35 ). In this study, we demonstrated the anti-apoptotic and anti-inflammatory properties of bergenin in pancreatic β-cells, suggesting it as a potential agent for treating T2DM.…”

Section: Discussionmentioning

confidence: 99%

Bergenin inhibits palmitic acid-induced pancreatic β-cell inflammatory death via regulating NLRP3 inflammasome activation

Lei¹,

Sun²,

Liu³

et al. 2022

Ann Transl Med

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Background: Bergenin, an active constituent of plants of the genus Bergenia, has been reported to have antidiabetic properties. This study investigated whether bergenin is beneficial for treating type 2 diabetes mellitus (T2DM) via regulating NOD-like receptor family-pyrin domain containing 3 (NLRP3) inflammasome.Methods: Two pancreatic β-cell lines, INS-1 and MIN6, were treated with 1, 3, or 10 μM bergenin in the absence or presence of palmitic acid (PA). Cell Counting Kit (CCK)-8, flow cytometry, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescent staining were performed.Results: Bergenin with concentrations of 1, 3, and 10 μM had no cytotoxicity in INS-1 and MIN6 cells.However, bergenin dose-dependently relieved PA-induced pancreatic β-cell loss and apoptosis. Bergenin dose-dependently inhibited NLRP3 inflammasome-related inflammation, as observed by the downregulation of NLRP3, apoptosis associated speck like protein (ASC), cleaved caspase-1, and gasdermin-D (GSDMD)-N, as well as the decreased release of cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, and IL-18. The NOD-like receptor signaling pathway was predicted to be a downstream signaling pathway regulated by bergenin. Autodock Vina software docked bergenin with NLRP3. The binding energy of interaction was −5.101 kcal/mol and the root-mean-square deviation (RMSD) score was 1.5901A. Treating pancreatic β-cells with bergenin accelerated the degeneration of NLRP3. Furthermore, restoration of NLRP3 expression using plasmid transfection reversed the protective effects of bergenin on pancreatic β-cells.Conclusions: Our data suggests that bergenin is a potential agent for treating T2DM through preventing NLRP3 inflammasome-related inflammation in pancreatic β-cells.

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“…The oxidative stress-generated reactive oxygen species (ROS) leads to mitochondrial damage that induces endothelial dysfunction [ 35 ]. PCA can also protect against oxidative stress and restore endothelial function in diabetic conditions [ 36 ]. Additionally, PCA attenuates endothelial dysfunction and atherosclerosis, in vitro and in vivo [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Therapeutic Effects of Protocatechuic Aldehyde in Diabetic Nephropathy

Chang

Chung

Hsieh

et al. 2021

Toxins

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Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice. Kidney morphology, renal function indicators, and Western blot, immunohistochemistry, and hematoxylin and eosin (H&E) staining data were analyzed. The results revealed that treatment with PCA could reduce diabetic-induced renal dysfunction, as indicated by the urine albumin-to-creatinine ratio (db/m: 120.1 ± 46.1μg/mg, db/db: 453.8 ± 78.7 µg/mg, db/db + 30 mg/kg PCA: 196.6 ± 52.9 µg/mg, db/db + 60 mg/kg PCA: 163.3 ± 24.6 μg/mg, p < 0.001). However, PCA did not decrease body weight, fasting plasma glucose, or food and water intake in db/db mice. H&E staining data revealed that PCA reduced glomerular size in db/db mice (db/m: 3506.3 ± 789.3 μm2, db/db: 6538.5 ± 1818.6 μm2, db/db + 30 mg/kg PCA: 4916.9 ± 1149.6 μm2, db/db + 60 mg/kg PCA: 4160.4 ± 1186.5 μm2p < 0.001). Western blot and immunohistochemistry staining indicated that PCA restored the normal levels of diabetes-induced fibrosis markers, such as transforming growth factor-beta (TGF-β) and type IV collagen. Similar results were observed for epithelial–mesenchymal transition-related markers, including fibronectin, E-cadherin, and α-smooth muscle actin (α-SMA). PCA also decreased oxidative stress and inflammation in the kidney of db/db mice. This research provides a foundation for using PCA as an alternative therapy for DN in the future.

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Protocatechualdehyde restores endothelial dysfunction in streptozotocin-induced diabetic rats

Cited by 9 publications

References 21 publications

The Beneficial Effect of Swimming Training Associated with Quercetin Administration on the Endothelial Nitric Oxide-Dependent Relaxation in the Aorta of Rats with Experimentally Induced Type 1 Diabetes Mellitus

The Beneficial Effect of Swimming Training Associated with Quercetin Administration on the Endothelial Nitric Oxide-Dependent Relaxation in the Aorta of Rats with Experimentally Induced Type 1 Diabetes Mellitus

Bergenin inhibits palmitic acid-induced pancreatic β-cell inflammatory death via regulating NLRP3 inflammasome activation

Evaluation of the Therapeutic Effects of Protocatechuic Aldehyde in Diabetic Nephropathy

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