Dietary polyphenol morin rescues endothelial dysfunction in a diabetic mouse model by activating the Akt/eNOS pathway

Taguchi, Kumiko; Hida, Mari; Hasegawa, Mami; Matsumoto, Takayuki; Kobayashi, Tsuneo

doi:10.1002/mnfr.201500618

Cited by 36 publications

(14 citation statements)

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“…endothelial no synthase (enoS) is a critical enzyme for the synthesis of vasoprotective molecule no in the endothelial cells (27). The main features of endothelial dysfunction are loss of no production and impaired enoS activity (28). Therefore, it was hypothesized that nac may also affect the function of vascular endothelial cells by regulating the production of no derived from endothelial no synthase.…”

Section: Introductionmentioning

confidence: 99%

N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway

et al. 2019

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lipopolysaccharide (lPS) can regulate the expression of apoptotic factors, including caspase-3, Bcl-2 and Bcl-2-associated X protein (Bax). nitric oxide (no) plays an important role in apoptosis. n-acetyl cysteine (nac) has been shown to exhibit antioxidant effects in vitro. However, the effects of nac on lPS-induced apoptosis of human umbilical vein endothelial cells (HuVecs) and the associated mechanisms are not well characterized. The present study explored the effect of nac on lPS-induced apoptosis of HuVecs and determined the participation of the p38 mitogen-activated protein kinase (MaPK) pathway in the process of apoptosis. cell viability was assessed using the cell counting Kit-8 (ccK-8) assay. The expression of caspase-3, Bax, Bcl-2, phosphorylated (p)-p38MaPK/total (t-)p38MaPK and p-endothelial e nitric oxide synthase (enoS)/t-enoS proteins were determined by western blotting. The expression levels of caspase-3, Bax and Bcl-2 mrna were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The rate of apoptosis was determined using flow cytometry. an no detection kit (nitric reductase method) was used to determine no concentration. The results of ccK-8 and flow cytometric analyses showed that pretreatment of HuVecs with nac or p38MaPK inhibitor (SB203580) attenuated lPS-induced decrease in cell viability and increase in cell apoptosis. rT-qPcr and western blotting showed that lPS promoted caspase-3 and Bax expression, but inhibited that of Bcl-2 in HuVecs; however, these effects were attenuated by pretreatment with nac or SB203580. lPS stimulation significantly enhanced the expression of p-p38MAPK protein and reduced the expression of p-enoS protein; however, these effects were attenuated by pretreatment with nac or SB203580. nac pretreatment attenuated lPS-induced inhibition of no synthesis, which was consistent with the effects of SB203580. The results demonstrated that nac pretreatment alleviated lPS-induced apoptosis and inhibition of no production in HuVecs. Furthermore, these effects were proposed to be mediated via the p38MaPK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway

et al. 2019

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“…These may have beneficial actions in cancer (Nandhakumar et al, 2012), liver fibrosis (Heeba and Mahmoud, 2014;MadanKumar et al, 2014), Alzheimer's disease (Noor et al, 2012), Parkson's disease (Lee et al, 2016), and many other chronic diseases. Recently, morin was shown to reduce blood pressure (Prahalathan et al, 2012), improve endothelial dysfunction in diabetic animals (Taguchi et al, 2016), ameliorate blood glucose, serum lipid and liver TG levels (Vanitha et al, 2014;Naowaboot et al, 2016), mimic the effects of insulin (Paoli et al, 2013) and inhibit fatty acid synthase (FAS) (Tian, 2006). However, the underlying mechanisms of morin's effects have not been elucidated In a screening of LXR ligands from natural products with a reporter assay, we found that morin inhibited both the transactivities of both LXRα and LXRβ.…”

Section: Introductionmentioning

confidence: 99%

Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases

Zhang

Liu

et al. 2017

British J Pharmacology

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“…Resveratrol has been shown to increase endothelial NO production, thereby improving endothelial dysfunction and lowering BP in hypertensive rats, which is explained by calcium-dependent eNOS activation [178]. Morin, a flavonol present in the Moraceae family, protects against endothelial dysfunction through an Akt (protein kinase B) -dependent activation of eNOS signaling in a diabetic mouse model [179].…”

Section: Impact On Mechanisms Contributing To Asmentioning

confidence: 99%

Dietary Polyphenols Targeting Arterial Stiffness: Interplay of Contributing Mechanisms and Gut Microbiome-Related Metabolism

et al. 2019

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Increased arterial stiffness is a degenerative vascular process, progressing with age that leads to a reduced capability of arteries to expand and contract in response to pressure changes. This progressive degeneration mainly affects the extracellular matrix of elastic arteries and causes loss of vascular elasticity. Recent studies point to significant interference of dietary polyphenols with mechanisms involved in the pathophysiology and progression of arterial stiffness. This review summarizes data from epidemiological and interventional studies on the effect of polyphenols on vascular stiffness as an illustration of current research and addresses possible etiological factors targeted by polyphenols, including pathways of vascular functionality, oxidative status, inflammation, glycation, and autophagy. Effects can either be inflicted directly by the dietary polyphenols or indirectly by metabolites originated from the host or microbial metabolic processes. The composition of the gut microbiome, therefore, determines the resulting metabolome and, as a consequence, the observed activity. On the other hand, polyphenols also influence the intestinal microbial composition, and therefore the metabolites available for interaction with relevant targets. As such, targeting the gut microbiome is another potential treatment option for arterial stiffness.

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Dietary polyphenol morin rescues endothelial dysfunction in a diabetic mouse model by activating the Akt/eNOS pathway

Abstract: These results indicate a novel role for MO in protection against endothelial dysfunction in diabetes. The protective effects of MO are dependent on Akt-dependent activation of eNOS signaling.

Cited by 36 publications

References 40 publications

N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway

N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway

Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases

Dietary Polyphenols Targeting Arterial Stiffness: Interplay of Contributing Mechanisms and Gut Microbiome-Related Metabolism

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