Honokiol improves endothelial function in type 2 diabetic rats via alleviating oxidative stress and insulin resistance

He, An; Yu, Hongwei; Yu, Huimei; Hui-ling, Chen; Li, Xiang; Shen, Jian; Zhuang, Rongjuan; Chen, Yi; Sasmita, Bryan Richard; Luo, Minghao; Lv, Dingyi

doi:10.1016/j.bbrc.2022.02.057

Cited by 10 publications

(5 citation statements)

References 31 publications

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“…As documented in our previous investigation [ 1 ], the relaxation evoked by carbachol was significantly increased in HCD/SLS Meriones as compared to normal Meriones (NC + DW). These results contrast with the finding of previous data describing the reduction of endothelium-dependent relaxation of T2D patients [ 48 ] and T2D/hypertensive rats [ 49 ]. In general, the impaired vascular relaxation could be attributed to one or multiple mechanisms of action, including the decrease of NO sensitivity/exogenous NO evoked relaxation and/or the alteration of the NO/cyclic guanosine monophosphate (cGMP) pathway [ 50 ].…”

Section: Discussioncontrasting

confidence: 99%

Hypoglycemic and Hypotensive Effects of Calycotome villosa Subsp. intermedia Seeds in Meriones shawi Rats: In Vivo, Ex Vivo, and In Vitro Investigations

Lyoussi

Laaroussi

Cherkaoui-Tangi

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Calycotome villosa subsp. intermedia is used in traditional medicine for the prevention and self-treatment of a variety of illnesses, including diabetes mellitus, obesity, and hypertension. The present study aims to investigate the in vivo, ex vivo, and in vitro hypoglycemic and hypotensive effects of the lyophilized aqueous extract of Calycotome villosa subsp. intermedia seeds (CV) on Meriones shawi submitted to hypercaloric diet and physical inactivity (HCD/PI) for 12 weeks. This diet induces a type 2 diabetes/metabolic syndrome phenotype with hypertension. Furthermore, HCD/PI decreased aorta contraction due to noradrenaline, enhanced L-arginine, and depressed insulin-evoked relaxation, while the relaxing effects of the NO donor SNAP and of diazoxide were unchanged. In vivo experiments showed that the oral administration of the CV extract (50 mg/kg b.wt) for 3 consecutive weeks significantly attenuated the development of type 2 diabetes, obesity, dyslipidemia, and hypertension. These effects may involve the improvement of lipid metabolism, insulin sensitivity, systolic arterial pressure, and urine output. Additionally, ex vivo and in vitro investigations revealed that CV treatment improved vascular contraction to noradrenaline, induced a slight aorta relaxation in response to carbachol, increased the vasorelaxation effect evoked by insulin, and depressed the L-arginine evoked relaxation. However, CV did not change the endothelium-independent vasorelaxation response evoked by SNAP or diazoxide. Hence, the present study provides useful information and supports the traditional use of CV in the prevention and self-treatment of numerous ailments. Overall, it can be concluded that Calycotome villosa subsp. intermedia seed extracts might be useful in the management of type 2 diabetes and hypertension.

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Section: Discussioncontrasting

confidence: 99%

Hypoglycemic and Hypotensive Effects of Calycotome villosa Subsp. intermedia Seeds in Meriones shawi Rats: In Vivo, Ex Vivo, and In Vitro Investigations

Lyoussi

Laaroussi

Cherkaoui-Tangi

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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“…Vascular vasodilation function was measured as described previously [ 26 , 27 ]. In brief, aortic rings were mounted and isometric tension recordings were performed using a DMT620 system (Denmark).…”

Section: Methodsmentioning

confidence: 99%

Role of the cGAS-STING Pathway in Aging-related Endothelial Dysfunction

Yu¹,

Liao²,

Yu³

et al. 2022

Aging and disease

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Endothelial dysfunction develops gradually with age, and is the foundation of many age-related diseases in the elderly. The purpose of this study was to investigate the role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in aging-related endothelial dysfunction. Endothelial functional parameters and biochemical indices of vascular function were examined in 2-, 6-, 12- and 24-month-old mice. Then, 6-month-old mice were administered RU.521, a specific inhibitor of cGAS, for 6 months, and endothelial functional parameters and biochemical indices of vascular function were re-examined. An in vitro model of cell senescence was established by treating human aortic endothelial cells (HAECs) with D-Galactose (D-GAL). Using inhibitors or siRNA interference, cGAS and STING were suppressed or silenced in senescent HAECs, and changes in the expression of eNOS, the senescence markers, p53, p21 and p16, components of the cGAS-STING pathway and Senescence-Associated β-galactosidase (SA-β-gal) staining were examined. Finally, cGAS, STING and p-IRF3 levels were measured in aorta tissue sections from eight patients. A decline in endothelial function, up-regulation of p53, p21 and p16 expression, and activation of the cGAS-STING pathway were observed in aging mice. Inhibition of cGAS was found to improve endothelial function and reverse the increased expression of aging markers. Our in vitro data demonstrated that D-GAL induced a decrease in eNOS expression and cell senescence, which could be partly reversed by cGAS inhibitor, STING inhibitor, siRNA-cGAS and siRNA-STING treatment. Higher expression levels of cGAS, STING and p-IRF3 were observed in aged human aortic intima tissue compared to young aortic intima tissue. Our study demonstrated that activation of the cGAS-STING pathway played a vital role in aging-related endothelial dysfunction. Thus, the cGAS-STING pathway may be a potential target for the prevention of cardiovascular diseases in the elderly.

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“…Collectively, these data highlight an unprecedented role of SIRT3 in preserving the glomerular endothelium homeostasis by regulating the cellular crosstalk between podocytes and endothelial cells. For this reason, modulating SIRT3 by means of specific activators, such as honokiol [ 32 ], may represent a promising intervention to preserve glomerular endothelial cell function during kidney disease [ 12 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Sirt3 deficiency promotes endothelial dysfunction and aggravates renal injury

Pezzotta,

Perico,

Corna

et al. 2023

PLoS ONE

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Sirtuin 3 (SIRT3), the main deacetylase of mitochondria, modulates the acetylation levels of substrates governing metabolism and oxidative stress. In the kidney, we showed that SIRT3 affects the proper functioning of high energy-demanding cells, such as tubular cells and podocytes. Less is known about the role of SIRT3 in regulating endothelial cell function and its impact on the progression of kidney disease. Here, we found that whole body Sirt3-deficient mice exhibited reduced renal capillary density, reflecting endothelial dysfunction, and VEGFA expression compared to wild-type mice. This was paralleled by activation of hypoxia signaling, upregulation of HIF-1α and Angiopietin-2, and oxidative stress increase. These alterations did not result in kidney disease. However, when Sirt3-deficient mice were exposed to the nephrotoxic stimulus Adriamycin (ADR) they developed aggravated endothelial rarefaction, altered VEGFA signaling, and higher oxidative stress compared to wild-type mice receiving ADR. As a result, ADR-treated Sirt3-deficient mice experienced a more severe injury with exacerbated albuminuria, podocyte loss and fibrotic lesions. These data suggest that SIRT3 is a crucial regulator of renal vascular homeostasis and its dysregulation is a predisposing factor for kidney disease. By extension, our findings indicate SIRT3 as a pharmacologic target in progressive renal disease whose treatments are still imperfect.

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Honokiol improves endothelial function in type 2 diabetic rats via alleviating oxidative stress and insulin resistance

Cited by 10 publications

References 31 publications

Hypoglycemic and Hypotensive Effects of Calycotome villosa Subsp. intermedia Seeds in Meriones shawi Rats: In Vivo, Ex Vivo, and In Vitro Investigations

Hypoglycemic and Hypotensive Effects of Calycotome villosa Subsp. intermedia Seeds in Meriones shawi Rats: In Vivo, Ex Vivo, and In Vitro Investigations

Role of the cGAS-STING Pathway in Aging-related Endothelial Dysfunction

Sirt3 deficiency promotes endothelial dysfunction and aggravates renal injury

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