Echinocystic acid, a natural plant extract, alleviates cerebral ischemia/reperfusion injury via inhibiting the JNK signaling pathway

Yu, Hailong; Li, Wei; Cao, Xiang; Wang, Xinyue; Zhao, Yuanyuan; Song, Li; Chen, Jian; wang, sushan; Chen, Beilei; Xu, Yun

doi:10.1016/j.ejphar.2019.172610

Cited by 24 publications

(17 citation statements)

References 35 publications

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“…MAPK plays key regulatory roles in the expression and production of pro-inflammatory cytokines (Huang et al 2018). ERK, JNK and p38 have been demonstrated to be activated in ischaemia/reperfusion (I/R) injury (Kovalska et al 2012;Yu et al 2019;Satoh et al 2000;Legos et al 2001). It has been reported that blocking the phosphorylation of ERK, JNK or p38 protects neurons from oxidative stress or reduces acute ischaemic injury in vitro and in vivo, effects that are correlated with decreases in the levels of pro-inflammatory cytokines (IL-1β, IL-6 and iNOS) and increases in the levels of anti-inflammatory cytokines (IL-10 and TGFβ) (Niu et al 2018;Liu et al 2013;Yao et al 2018).…”

Section: Discussionmentioning

confidence: 99%

δ-Opioid receptor activation ameliorates lipopolysaccharide-induced inflammation and apoptosis by inhibiting the MAPK/caspase-3 pathway in BV2 microglial cells

et al. 2020

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Delta-opioid receptor (DOR) is widely distributed in the central nervous system, and its activation protects against ischaemic/hypoxic brain injury. However, the role of DOR in microglia in ischaemic stroke has not yet been fully investigated. We found that DOR was expressed in both human and mouse cerebral microglia, besides, it was upregulated in activated BV2 microglial cells by immunofluorescence staining and Western blot. DOR activation by the specific agonist TAN-67 significantly enhanced BV2 microglial cell viability and reduced apoptosis, as evidenced by decreased cleaved caspase-3 levels and TdT-mediated aUTP-X nick end labelling (TUNEL) staining after LPS stimulation. Furthermore, activation of DOR significantly inhibited inducible nitric oxide synthase (iNOS) production and dose-dependently inhibited the mRNA and protein expression levels of other pro-inflammatory cytokines, including IL-1β and IL-6, whereas it increased the expression of the anti-inflammatory cytokine IL-10 in LPS-stimulated BV2 microglial cells; these effects were correlated with diminished phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Moreover, these effects could be reversed by the DOR antagonist naltrindole. DOR activation can activate microglia to switch to the beneficial phenotype and inhibit LPS-induced inflammation and apoptosis via the mitogen-activated protein kinase (MAPK)/caspase-3 pathway in BV2 microglial cells. This study provides new insight into neuroprotection against and treatment of ischaemic stroke.

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Section: Discussionmentioning

confidence: 99%

δ-Opioid receptor activation ameliorates lipopolysaccharide-induced inflammation and apoptosis by inhibiting the MAPK/caspase-3 pathway in BV2 microglial cells

et al. 2020

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“…Triterpenoid saponins, the glycosides of triterpenoids, are an important form of the bioactive triterpenoids. In total, 20 triterpenoids are found to exhibit neuroprotection in ischemic stroke including arjunolic acid [357], asiatic acid [358,359], boswellic acids [81,360,361], 28-O-caffeoyl betulin [362], celastrol [73,363], echinocystic acid [364], 18β-glycyrrhetinic acid [365], maslinic acid [366], ursolic acid [367], and triterpenoid glycosides: madecassoside [368], astragaloside IV [62,114,369,370], glycyrrhizin [91,[371][372][373], diammonium glycyrrhizinate [374], ginsenoside Rb1 [34,55,115,375,376], ginsenoside Rd [49,[377][378][379][380][381][382][383], ginsenoside Rg1 [384][385][386][387][388][389], ginsenoside Rg3 [390], pseudoginsenoside F11 [391,…”

Section: Triterpenoidsmentioning

confidence: 99%

Neuroprotective Phytochemicals in Experimental Ischemic Stroke: Mechanisms and Potential Clinical Applications

Wang

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ischemic stroke is a challenging disease with high mortality and disability rates, causing a great economic and social burden worldwide. During ischemic stroke, ionic imbalance and excitotoxicity, oxidative stress, and inflammation are developed in a relatively certain order, which then activate the cell death pathways directly or indirectly via the promotion of organelle dysfunction. Neuroprotection, a therapy that is aimed at inhibiting this damaging cascade, is therefore an important therapeutic strategy for ischemic stroke. Notably, phytochemicals showed great neuroprotective potential in preclinical research via various strategies including modulation of calcium levels and antiexcitotoxicity, antioxidation, anti-inflammation and BBB protection, mitochondrial protection and antiapoptosis, autophagy/mitophagy regulation, and regulation of neurotrophin release. In this review, we summarize the research works that report the neuroprotective activity of phytochemicals in the past 10 years and discuss the neuroprotective mechanisms and potential clinical applications of 148 phytochemicals that belong to the categories of flavonoids, stilbenoids, other phenols, terpenoids, and alkaloids. Among them, scutellarin, pinocembrin, puerarin, hydroxysafflor yellow A, salvianolic acids, rosmarinic acid, borneol, bilobalide, ginkgolides, ginsenoside Rd, and vinpocetine show great potential in clinical ischemic stroke treatment. This review will serve as a powerful reference for the screening of phytochemicals with potential clinical applications in ischemic stroke or the synthesis of new neuroprotective agents that take phytochemicals as leading compounds.

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“…The clinical strategy for ischaemia stroke is plagued by the lack of effective neuroprotectants ( Ren et al, 2018 ). Intravenous thrombolysis is limited due to its short window of opportunity for application, and many drugs have failed in clinical trials due to their inefficacy and toxicity ( Yu et al, 2019 ). Therefore, finding new neuroprotectants is crucial for CI/R injury treatment.…”

Section: Discussionmentioning

confidence: 99%

“…TUNEL staining was used to detect the apoptosis of neurons in the ischaemic penumbra. As previously described ( Yu et al, 2019 ), the frozen sections were dried at 37°C for 2 h, washed in PBS 3 times for 5 min each time, soaked in PBS containing 0.25% Triton X-100 for 15 min to permeabilize the cells, and washed with PBS 3 times. The cells were covered with 100 μl of equilibrium buffer and incubated at room temperature for 5‑10 min.…”

Section: Methodsmentioning

confidence: 99%

Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling

Song

Cao

et al. 2020

Front. Pharmacol.

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Cerebral ischaemia/reperfusion (CI/R) injury is a major challenge due to the lack of effective neuroprotective drugs. Hederagenin (HE) is the aglycone part of saponins extracted from Hedera helix Linné that has exhibited anti-apoptotic and anti-inflammatory effects; however, the role of HE in CI/R has not been elucidated. In this study, mice were intraperitoneally (i.p.) injected with HE (26.5, 53, or 106 μmol/kg body weight) for 3 days after middle cerebral artery occlusion (MCAO). Neural function and brain infarct volume were evaluated. HE treatment attenuated CI/R-induced apoptosis and inflammatory cytokine expression within the infarcted areas. HE treatment also decreased the activation of the MLK3 signalling pathway, which potentiates CI/R damage via the MAPK and NFκB pathways. Due to HE’s safety profile, it has potential to be used for the clinical treatment of ischaemic stroke.

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Echinocystic acid, a natural plant extract, alleviates cerebral ischemia/reperfusion injury via inhibiting the JNK signaling pathway

Cited by 24 publications

References 35 publications

δ-Opioid receptor activation ameliorates lipopolysaccharide-induced inflammation and apoptosis by inhibiting the MAPK/caspase-3 pathway in BV2 microglial cells

δ-Opioid receptor activation ameliorates lipopolysaccharide-induced inflammation and apoptosis by inhibiting the MAPK/caspase-3 pathway in BV2 microglial cells

Neuroprotective Phytochemicals in Experimental Ischemic Stroke: Mechanisms and Potential Clinical Applications

Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling

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