Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling

Yu, Hailong; Song, Li; Cao, Xiang; Li, Wei; Zhao, Yuanyuan; Chen, Jian; Li, Jun; Chen, Yingzhu; Yu, Wenkui; Xu, Yun

doi:10.3389/fphar.2020.01173

Cited by 34 publications

(17 citation statements)

References 37 publications

(47 reference statements)

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“…Hederagenin, as a naturally occurring triterpene, induces (drug-resistant head and neck cancer (HNC) cell apoptosis) resistant HNC cell death through the Nrf2-ARE antioxidant pathway [ 41 ]. In animal models of cerebral ischemia/reperfusion injury, hederagenin exerts antiapoptotic and anti-inflammatory effects through the MAPK and NF κ B pathways [ 42 ]. Formononetin has antioxidant and neuroprotective effects [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

Exploring the Oxidative Stress Mechanism of Buyang Huanwu Decoction in Intervention of Vascular Dementia Based on Systems Biology Strategy

Yang

Zeng

et al. 2021

Oxidative Medicine and Cellular Longevity

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Objective. To explore the oxidative stress mechanism of modified Buyang Huanwu decoction (MBHD) in intervention of vascular dementia (VD) based on systems biology strategy. Methods. In this study, through the reverse virtual target prediction technology and transcriptomics integration strategy, the active ingredients and potential targets of MBHD treatment of VD were analyzed, and the drug-disease protein-protein interaction (PPI) network was constructed. Then, bioinformatics analysis methods are used for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis, and finally find the core biological process. After that, in animal models, low-throughput technology is used to detect gene expression and protein expression of key molecular targets in oxidative stress-mediated inflammation and apoptosis signaling pathways to verify the mechanism of MBHD treatment of VD rats. Finally, the potential interaction relationship between MBHD and VD-related molecules is further explored through molecular docking technology. Results. There are a total of 54 MBHD components, 252 potential targets, and 360 VD genes. The results of GO enrichment analysis and pathway enrichment analysis showed that MBHD may regulate neuronal apoptosis, nitric oxide synthesis and metabolism, platelet activation, NF-κB signaling pathway-mediated inflammation, oxidative stress, angiogenesis, etc. Among them, SIRT1, NF-κB, BAX, BCL-2, CASP3, and APP may be important targets for MBHD to treat VD. Low-throughput technology (qRT-PCR/WB/immunohistochemical technology) detects oxidative stress-mediated inflammation and apoptosis-related signaling pathway molecules. The molecular docking results showed that 64474-51-7, cycloartenol, ferulic acid, formononetin, kaempferol, liquiritigenin, senkyunone, wallichilide, xanthinin, and other molecules can directly interact with NF-κB p65, BAX, BCL-2, and CASP3. Conclusion. The active compounds of MBHD interact with multiple targets and multiple pathways in a synergistic manner, and have important therapeutic effects on VD mainly by balancing oxidative stress/anti-inflammatory and antiapoptotic, enhancing metabolism, and enhancing the immune system.

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Section: Resultsmentioning

confidence: 99%

Exploring the Oxidative Stress Mechanism of Buyang Huanwu Decoction in Intervention of Vascular Dementia Based on Systems Biology Strategy

Yang

Zeng

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Apoptosis is a vital pathophysiological mechanism associated with I/R, and reperfusion could accelerate the apoptotic death process induced by ischaemia (Villa et al 2003). Compelling findings indicate the inhibition of apoptosis as a key protective mechanism against cerebral I/R injury (Baldrati et al 2020;Yu et al 2020). Wen et al (2019) demonstrated that N-Myc downstream-regulated gene 4 (NDRG4) protected cerebral IR injury by inhibiting cell apoptosis and regulated cerebral cell apoptosis by increasing BDNF expression.…”

Section: Discussionmentioning

confidence: 99%

Myrtenol improves brain damage and promotes angiogenesis in rats with cerebral infarction by activating the ERK1/2 signalling pathway

Huang

Zhanguo

Cai

et al. 2021

Pharmaceutical Biology

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Context: Cerebral ischaemia/reperfusion (I/R) injury has a high disability and fatality worldwide. Myrtenol has protective effects on myocardial I/R injury through antioxidant and anti-apoptotic effects.Objective: This study investigated the effect of myrtenol on cerebral ischaemia/reperfusion (I/R) injury and the underlying mechanism. Materials and methods: Cerebral I/R injury was induced in adult Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) for 90 min. MCAO rats were treated with or without myrtenol (10, 30, or 50 mg/ kg/day) or/and U0126 (10 lL) intraperitoneally for 7 days. Results: In the present study, myrtenol had no toxicity at concentrations up to 1.3 g/kg. Myrtenol treatment improved neurological function of MCAO rats, with significantly (p < 0.05) improved neurological deficits (4.31 ± 1.29 vs. 0.00) and reduced brain edoema (78.95 ± 2.27% vs. 85.48 ± 1.24%). Myrtenol extenuated brain tissue injury and neuronal apoptosis, with increased Bcl-2 expression (0.48-fold) and decreased Bax expression (2.02-fold) and caspase-3 activity (1.36-fold). Myrtenol promoted angiogenesis in the brain tissues of MCAO rats, which was reflected by increased VEGF (0.86-fold) and FGF2 (0.51-fold). Myrtenol promoted the phosphorylation of MEK1/2 (0.80-fold) and ERK1/2 (0.97-fold) in MCAO rats. U0126, the inhibitor of ERK1/2 pathway, reversed the protective effects of myrtenol on brain tissue damage and angiogenesis in MCAO rats. Discussion and conclusions: Myrtenol reduced brain damage and angiogenesis through activating the ERK1/2 signalling pathway, which may provide a novel alternative strategy for preventing cerebral I/R injury. Further in vitro work detailing its mechanism-of-action for improving ischaemic cerebral infarction is needed.

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“…ED also stabilized ABCA1, a key transporter for cholesterol efflux, in THP-1-derived human macrophages [ 144 ]. Yu et al reported that intraperitoneal injection of HG attenuated cerebral ischemia/reperfusion-induced apoptosis and inflammatory cytokine expression and reduced cerebral infarction via the MLK3 signaling pathway [ 145 ]. HG also reduced bleomycin-induced pulmonary fibrosis in rats by decreasing the levels of α-SMA, collagen I, hydroxyproline, and decreased inflammatory cytokines (TNF-α and IL-6) as well as phosphorylation of JNK and NFAT4 in a dose-dependent manner [ 146 ].…”

Section: Biological Effects Of Naturally Occurring Analogues Of Uamentioning

confidence: 99%

Ursolic Acid and Related Analogues: Triterpenoids with Broad Health Benefits

et al. 2021

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Ursolic acid (UA) is a well-studied natural pentacyclic triterpenoid found in herbs, fruit and a number of traditional Chinese medicinal plants. UA has a broad range of biological activities and numerous potential health benefits. In this review, we summarize the current data on the bioavailability and pharmacokinetics of UA and review the literature on the biological activities of UA and its closest analogues in the context of inflammation, metabolic diseases, including liver and kidney diseases, obesity and diabetes, cardiovascular diseases, cancer, and neurological disorders. We end with a brief overview of UA’s main analogues with a special focus on a newly discovered naturally occurring analogue with intriguing biological properties and potential health benefits, 23-hydroxy ursolic acid.

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Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling

Cited by 34 publications

References 37 publications

Exploring the Oxidative Stress Mechanism of Buyang Huanwu Decoction in Intervention of Vascular Dementia Based on Systems Biology Strategy

Exploring the Oxidative Stress Mechanism of Buyang Huanwu Decoction in Intervention of Vascular Dementia Based on Systems Biology Strategy

Myrtenol improves brain damage and promotes angiogenesis in rats with cerebral infarction by activating the ERK1/2 signalling pathway

Ursolic Acid and Related Analogues: Triterpenoids with Broad Health Benefits

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