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Luteolin Ameliorates Experimental Pulmonary Arterial Hypertension via Suppressing Hippo-YAP/PI3K/AKT Signaling Pathway.

ABSTRACT: Luteolin is a flavonoid compound with a variety of pharmacological effects. In this study, we explored the effects of luteolin on monocrotaline (MCT) induced rat pulmonary arterial hypertension (PAH) and underlying mechanisms. A rat PAH model was generated through MCT injection. In this model, luteolin improved pulmonary vascular remodeling and right ventricular hypertrophy, meanwhile, luteolin could inhibit the proliferation and migration of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB (PDGF-BB) in a dose-dependent manner. Moreover, our results showed that luteolin could downregulate the expression of LATS1 and YAP, decrease YAP nuclear localization, reduce the expression of PI3K, and thereby restrain the phosphorylation of AKT induced by PDGF-BB. In conclusion, luteolin ameliorated experimental PAH, which was at least partly mediated through suppressing HIPPO-YAP/PI3K/AKT signaling pathway. Therefore, luteolin might become a promising candidate for treatment of PAH.

SUBMITTER: Zuo W

PROVIDER: S-EPMC8082250 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Luteolin Ameliorates Experimental Pulmonary Arterial Hypertension via Suppressing Hippo-YAP/PI3K/AKT Signaling Pathway.

Zuo Wanyun W Liu Na N Zeng Yunhong Y Xiao Zhenghui Z Wu Keke K Yang Fan F Li Biao B Song Qingqing Q Xiao Yunbin Y Liu Qiming Q

Frontiers in pharmacology 20210415

Luteolin is a flavonoid compound with a variety of pharmacological effects. In this study, we explored the effects of luteolin on monocrotaline (MCT) induced rat pulmonary arterial hypertension (PAH) and underlying mechanisms. A rat PAH model was generated through MCT injection. In this model, luteolin improved pulmonary vascular remodeling and right ventricular hypertrophy, meanwhile, luteolin could inhibit the proliferation and migration of pulmonary artery smooth muscle cells induced by plate ...[more]

PMID: 33935785

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Project description:BackgroundLuteolin is widely distributed among a number of vegetal species worldwide. The pharmacological effects of luteolin are diverse and amongst antioxidant, free radical scavenging, and anti-inflammatory activities. Preliminary study showed that luteolin can ameliorate hypertension. However, the precise mechanism needs further investigation. There is no evidence that luteolin affects the paraventricular nucleus of the hypothalamus (PVN), a brain nucleus associated with a critical neural regulator of blood pressure. Our main aim was to explore the effect of luteolin on the PI3K/Akt/NF-κB signaling pathway within the PVN of hypertensive rats.Methodsspontaneously hypertensive rats (SHRs) and corresponding normotensive control rats, the Wistar Kyoto (WKY) rats were divided into four groups and subsequently treated for 4 weeks with bilateral PVN injections of either luteolin (20 µg/0.11 µL, volume: 0.11 µL/h) or vehicle (artificial cerebrospinal fluid).Resultsluteolin infusion to the PVN significantly decreased some hemodynamic parameters including the mean arterial pressure (MAP), heart rate (HR), circulating plasma norepinephrine (NE) and epinephrine (EPI). Additionally, there was a decrease in the expressions of the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT), levels of reactive oxygen species (ROS), NAD(P)H oxidase subunit (NOX2, NOX4) in the PVN of SHRs. Meanwhile, the expression of inflammatory cytokines and the activity of nuclear factor κB (NF-κB) p65 in the PVN of SHRs were lowered. Furthermore, immunofluorescence results showed that injection of luteolin in the PVN reduced the expression of tyrosine hydroxylase (TH), and increased that of superoxide dismutase (SOD1) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN of SHRs.ConclusionOur novel findings revealed that luteolin lowered hypertension via inhibiting NF-κB-mediated inflammation and PI3K/Akt signaling pathway in the PVN.

Dataset Information

Luteolin Ameliorates Experimental Pulmonary Arterial Hypertension via Suppressing Hippo-YAP/PI3K/AKT Signaling Pathway.

Publications

Luteolin Ameliorates Experimental Pulmonary Arterial Hypertension via Suppressing Hippo-YAP/PI3K/AKT Signaling Pathway.

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