Scutellarin attenuates oxidative stress and neuroinflammation in cerebral ischemia/reperfusion injury through PI3K/Akt-mediated Nrf2 signaling pathways

Xie, Xueheng; Wang, Fan; Ge, Wenxiu; Meng, Xiangbao; Fan, Lijuan; Zhang, Wei; Wang, Zhen; Ding, Meng; Gu, Shengliang; Xing, Xiaoyan; Sun, Xiaobo

doi:10.1016/j.ejphar.2023.175979

Cited by 14 publications

(3 citation statements)

References 79 publications

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“…It is also an upstream signaling molecule of Nrf2, which can activate Nrf2 and regulate its downstream gene transcription. Exogenous stimuli can promote PI3K/Akt phosphorylation by activating tyrosine kinase receptors, thereby activating Nrf2 (55). There is evidence to suggest that PI3K is located upstream of Nrf2 and can regulate its activity.…”

Section: Discussionmentioning

confidence: 99%

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

Jia,

Yang,

Jia

et al. 2024

Preprint

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Long term hypertension seriously affects target organ damage such as the brain, heart, and kidneys, and has become an increasingly serious public health problem worldwide. Capsaicin has been proven to improve blood pressure. However, whether capsaicin can reduce salt induced hypertension and the mechanism has yet to be elucidated. This study aimed to identify the AMPK/Akt/iNOS pathway in hypothalamic paraventricular nucleus (PVN) mediates capsaicin in improving the process of high salt induced hypertension. Dahl salt-sensitive (Dahl S) rats were uesed as the animal model for the present study. All rats were randomly divided into four groups based on their dietary regimen (0.3% salt diet and 8% salt diet) and treatment methods. Chronic administration capsaicin to the PVN during the process of blood pressure rise in rats. The entire process lasted for 6 weeks. Our results demonstrated that PVN pretreatment with capsaicin can slow down the blood pressure elevation and heart rate (HR) of Dahl S hypertensive rats. Interestingly, The cardiac hypertrophy was significantly improved. Furthermore, PVN pretreatment with capsaicin induced decrease in mRNA expression of NOX2, Inducible nitric oxide synthase (iNOS), NOX4 and proinfammatory cytokines and increase in positive cell level of Nrf2, p-IKKβ, iNOS and HO-1 in the PVN of Dahl S hypertensive rats. Additionally, the protein expressions of phosphorylated adenosine Monophosphate-activated protein kinase (p-AMPK), the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT) were attenuated after PVN pretreatment with capsaicin. Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/iNOS pathway in the PVN.

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Section: Discussionmentioning

confidence: 99%

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

Jia,

Yang,

Jia

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…PI3K/Akt is an important member of the growth factor receptor superfamily signaling pathway that is an upstream signaling molecule of Nrf2, which can activate Nrf2 and regulate its downstream gene transcription. For example, PI3K activators can activate and promote Nrf2 nuclear translocation ( Xie et al, 2023 ). Also, some neuroprotective agents were reported to activate Nrf2 by activating the PI3K/Akt signaling pathway in order to exert a neuroprotective effect on Parkinson’s model cells ( Han et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

Jia,

Yang,

Jia

et al. 2024

Front. Neurosci.

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BackgroundLong term hypertension seriously promotes target organ damage in the brain and heart, and has increasingly become serious public health problem worldwide. The anti-hypertensive effects of capsaicin has been reported, however, the role and mechanism of capsaicin within the brain on salt-induced hypertension have yet to be elucidated. This study aimed to verify the hypothesis that capsaicin attenuates salt-induced hypertension via the AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus (PVN).MethodsDahl salt-sensitive (Dahl S) rats were used as animal model for the present study. Rats were randomly divided into four groups based on their dietary regimen (0.3% normal salt diet and 8% high salt diet) and treatment methods (infusion of vehicle or capsaicin in the PVN). Capsaicin was chronically administered in the PVN throughout the animal experiment phase of the study that lasted 6 weeks.ResultsOur results demonstrated that PVN pretreatment with capsaicin can slow down raise of the blood pressure elevation and heart rate (HR) of Dahl S hypertensive rats given high salt diet. Interestingly, the cardiac hypertrophy was significantly improved. Furthermore, PVN pretreatment with capsaicin induced decrease in the expression of mRNA expression of NADPH oxidase-2 (NOX2), inducible nitric oxide synthase (iNOS), NOX4, p-IKKβ and proinflammatory cytokines and increase in number of positive cell level for Nrf2 and HO-1 in the PVN of Dahl S hypertensive rats. Additionally, the protein expressions of phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT) were decreased, phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were increased after the PVN pretreatment with capsaicin.ConclusionCapsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/iNOS pathway in the PVN.

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“…Jia et al [ 32 ] found through network pharmacology and experimental validation that Scutellarin exerts therapeutic effects on cerebral ischemia by activating astrocyte JAK2/STAT3 signaling, which provides a solid experimental basis for its clinical application. Xie et al [ 33 ] found that Scutellarin exhibited antioxidant, anti-inflammatory, and neuroprotective effects in cerebral ischemia/reperfusion injury (CIRI) through PI3K/Akt pathway-mediated Nrf2 activation. Zhang et al [ 34 ] found that scutellarin inhibits the inflammatory process through nuclear factor κ-B p65 and p38 mitogen-activated protein kinase signaling pathways and protects against brain damage in ischemically injured rats.…”

Section: Pharmacological Effectsmentioning

confidence: 99%

Current advances on the therapeutic potential of scutellarin: an updated review

Xie,

Sun,

Tao

et al. 2024

Nat. Prod. Bioprospect.

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Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed. Graphical Abstract

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Scutellarin attenuates oxidative stress and neuroinflammation in cerebral ischemia/reperfusion injury through PI3K/Akt-mediated Nrf2 signaling pathways

Cited by 14 publications

References 79 publications

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

Current advances on the therapeutic potential of scutellarin: an updated review

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