Procyanidins are potent inhibitors of LOX-1: a new player in the French Paradox

Nishizuka, Taichi; Fujita, Yoshiko; Sato, Yuko; Nakano, Ana Márcia Spanó; Kakino, Akemi; Ohshima, Shunji; Kanda, Tomomasa; Yoshimoto, Ryo; Sawamura, Tatsuya

doi:10.2183/pjab.87.104

Cited by 55 publications

(34 citation statements)

References 44 publications

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“…Apigenin and procyanidin A2 were dissolved in dimethyl sulfoxide (DMSO). Caffeine, chlorogenic acid and procyanidin A2 and B2 were added at concentrations of 20 μM, 10 μM, 50 μg/mL, and 50 μg/mL, respectively, as reported previously31323334. Apigenin was used at 10 μM unless otherwise specified for in vitro studies, and 40 mg/kg was used for intraperitoneal injection daily for in vivo studies.…”

Section: Methodsmentioning

confidence: 99%

The flavonoid apigenin improves glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice

Ohno

Shibata

Kishikawa

et al. 2013

Sci Rep

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Polyphenols are representative bioactive substances with diverse biological effects. Here, we show that apigenin, a flavonoid, has suppressive effects on microRNA (miRNA) function. The effects were mediated by impaired maturation of a subset of miRNAs, probably through inhibition of the phosphorylation of TRBP, a component of miRNA-generating complexes via impaired mitogen-activated protein kinase (MAPK) Erk activation. While glucose intolerance was observed in miRNA103 (miR103)-overexpressing transgenic mice, administration of apigenin improved this pathogenic status likely through suppression of matured miR103 expression levels. These results suggest that apigenin may have favorable effects on the pathogenic status induced by overexpression of miRNA103, whose maturation is mediated by phosphorylated TRBP.

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Section: Methodsmentioning

confidence: 99%

The flavonoid apigenin improves glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice

Ohno

Shibata

Kishikawa

et al. 2013

Sci Rep

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“…LOX-1 is upregulated in physiologic circumstances highly linked to atherosclerotic disease such as hypertension, hyperlipidemia and diabetes [179]. Utilizing an in vitro model with Chinese hamster ovary cells expressing LOX-1, apple polyphenols inhibited uptake of oxidized LDL by 88%.…”

Section: Bioactive Components Of Polyphenol Rich Foodsmentioning

confidence: 99%

Polyphenols: Benefits to the Cardiovascular System in Health and in Aging

et al. 2013

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Numerous studies have demonstrated the importance of naturally occurring dietary polyphenols in promoting cardiovascular health and emphasized the significant role these compounds play in limiting the effects of cellular aging. Polyphenols such as resveratrol, epigallocatechin gallate (EGCG), and curcumin have been acknowledged for having beneficial effects on cardiovascular health, while some have also been shown to be protective in aging. This review highlights the literature surrounding this topic on the prominently studied and documented polyphenols as pertaining to cardiovascular health and aging.

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“…Decreased expression of ox-LDL may cause the marked reduction of LOX-1 expression seen in the polyphenol group in this study. Additionally, procyanidins have been reported to play a role as an LOX-1 inhibitor by inhibiting ox-LDL from binding to LOX-1, 26 which may assist the inactivation of LOX-1. A vicious cycle of ox-LDL, LOX-1, and ROS can therefore be suppressed by the procyanidins contained in apple polyphenol, resulting in the increased expression of eNOS and a significant increase in the lumen of the basilar artery in a dose-dependent manner as compared with the SAH group.…”

Section: Figmentioning

confidence: 99%

“…1 Of the polyphenols, procyanidin, which is an oligomer of epicatechin, features strong radical scavenging activity due to its many hydroxyl groups, has significant capacity to protect LDL from oxidation, 28,42 and is the only molecule that has been found to exhibit an action directly antagonistic to LOX-1. 26 Procyanidin content is higher in apples than in other commonly consumed foods, and procyanidin is a main component of polyphenols extracted from apples (apple polyphenol).…”

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confidence: 99%

Role of oxidized LDL and lectin-like oxidized LDL receptor-1 in cerebral vasospasm after subarachnoid hemorrhage

Matsuda¹,

Ohkuma²,

Naraoka³

et al. 2014

JNS

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T he consequences of subarachnoid hemorrhage (SAH) after cerebral aneurysm rupture are devastating, with mortality rates as high as 50% and the majority of survivors left with moderate to severe disability. 15 Cerebral vasospasm causes cerebral ischemia and is a major contributor to the high morbidity and mortality rates associated with SAH. The pathogenesis of cerebral vasospasm, however, has not been fully clarified, and potential preventative therapies for this phenomenon have not been established. 7,8,17 Oxyhemoglobin derived from a subarachnoid clot and the free radicals subsequently generated have been considered important causes of cerebral vasospasm. 22,24,33,43 These radicals, by means of a scavenging effect, may be related to cerebral vasospasm by suppressing nitric ox- Object. Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a serious complication. Free radicals derived from subarachnoid clotting are recognized to play an important role. Oxidized low-density lipoprotein (ox-LDL) and lectin-like oxidized LDL receptor-1 (LOX-1) have been shown to be related to the pathogenesis of atherosclerosis and may increase in cerebral arteries after SAH, due to the action of free radicals derived from a subarachnoid clot. These molecules may also affect the pathogenesis of vasospasm, generating intracellular reactive oxygen species and downregulating the expression of endothelial NO synthase (eNOS). If so, apple polyphenol might be effective in the prevention of vasospasm due to an abundant content of procyanidins, which exhibit strong radical scavenging effects, and the ability to suppress ox-LDL and LOX-1. The purposes of this study were to investigate changes in levels of ox-LDL and LOX-1 after SAH and whether administering apple polyphenol can modify cerebral vasospasm.Methods. Forty Japanese white rabbits were assigned randomly to 4 groups: an SAH group (n = 10); a shamoperation group (n = 10), which underwent intracisternal saline injection; a low-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 10 mg/kg per day from Day 0 to Day 3; and a high-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 50 mg/kg per day. At Day 4, the basilar artery and brain was excised from each rabbit. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar artery, and the expression of ox-LDL, LOX-1, and eNOS was examined for each basilar artery by immunohistochemical staining and reverse transcriptase polymerase chain reaction. In addition, neuronal apoptosis in the cerebral cortex was evaluated by TUNEL.Results. Compared with the sham group, the expression of ox-LDL and LOX-1 in the basilar arterial wall was significantly increased in the SAH group, the expression of eNOS was significantly decreased, and the cross-sectional area of basilar artery was significantly decreased. Compared with the SAH group, the cross-sectional area of basilar artery was increased in the polyphenol groups, together with the ...

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Procyanidins are potent inhibitors of LOX-1: a new player in the French Paradox

Cited by 55 publications

References 44 publications

The flavonoid apigenin improves glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice

The flavonoid apigenin improves glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice

Polyphenols: Benefits to the Cardiovascular System in Health and in Aging

Role of oxidized LDL and lectin-like oxidized LDL receptor-1 in cerebral vasospasm after subarachnoid hemorrhage

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