GYY4137 protects against MCAO via p38 MAPK mediated anti-apoptotic signaling pathways in rats

Han, Xu; Mao, Zhengchun; Wang, Shan; Xin, Yanming; Li, Ping; Maharjan, Surendra; Zhang, Bing

doi:10.1016/j.brainresbull.2020.02.015

Cited by 21 publications

(9 citation statements)

References 35 publications

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“…Furthermore, GYY4137 interfered with platelet activation and adhesion molecule-mediated aggregation reducing the formation of the microvascular thrombus and stabilizing atherosclerosis plaque [ 147 ]. It seems to protect against diabetic myocardial I/R injury (activating the PHLPP-1/Akt/Nrf2 pathway) [ 148 ] and against cerebral I/R injury (via the p38 MAPK mediated anti-apoptotic signaling pathways) in rats [ 149 ]. It has been proven that GYY4137 slowly releases H 2 S upon hydrolysis.…”

Section: H 2 S Donors and Diseasesmentioning

confidence: 99%

H2S Donors and Their Use in Medicinal Chemistry

Magli¹,

Perissutti²,

Santagada³

et al. 2021

Biomolecules

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Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their -biological applications.

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Section: H 2 S Donors and Diseasesmentioning

confidence: 99%

H2S Donors and Their Use in Medicinal Chemistry

Magli¹,

Perissutti²,

Santagada³

et al. 2021

Biomolecules

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“…The PI3K-Akt signaling pathway could reduce neuronal apoptosis during stoke or OGD/R (Xie W. et al, 2020;Miao et al, 2020;Wu et al, 2020). The MAPK signaling pathway could inhibit the apoptosis of nerve cells (Han et al, 2013;Han et al, 2020), increase the activities of ERK, JNK, and p38 (Hong et al, 2020), reduce the activities of PLA2, IL1, TNF, IL1β, IL6, and IL8 (Dong et al, 2019;Ding Y. et al, 2020), and regulate the synthesis of proteins such as ASPK/JNK, p38, and P-SAPK/JNK (Zeng et al, 2019).…”

Section: Kyoto Encyclopedia Of Genes and Genomes Enrichment Analysis ...mentioning

confidence: 99%

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke

Chen

Wang

Cai

et al. 2022

Front. Cell Dev. Biol.

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Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM.

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“…The appropriate conclusion is drawn that the gut microbiota is the main target pool for berberine, having well‐known pharmacological actions in metabolic disease, inflammation condition and central nervous system disorders (Habtemariam, 2020). GYY4137, a slow‐releasing donor of H 2 S, and NaHS, another donor of H 2 S, both showed neuroprotection in the transient model of focal cerebral ischemia via lateral cerebral ventricle or intraperitoneal injection, which are fulfilled through maintaining a certain concentration in the brain (Gheibi et al, 2014; Han et al, 2020). In the present investigation, the immediate concentration of H 2 S determined in the feces is at nanomole levels, which inadequately provides the concentration contributing to the directional protection of the neuron.…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulated by microbiota‐derived hydrogen sulfide mediates the regulation of berberine on microglia in transient middle cerebral artery occlusion rats

Yao

Wei

et al. 2022

Phytotherapy Research

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Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut–brain axis signals in berberine‐modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine‐induced H2S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c‐fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota‐dependent manner. H2S stimulates the vagus nerve through TRPV1 is responsible for the berberine‐induced gut–brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.

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GYY4137 protects against MCAO via p38 MAPK mediated anti-apoptotic signaling pathways in rats

Cited by 21 publications

References 35 publications

H2S Donors and Their Use in Medicinal Chemistry

H2S Donors and Their Use in Medicinal Chemistry

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke

Vagus nerve stimulated by microbiota‐derived hydrogen sulfide mediates the regulation of berberine on microglia in transient middle cerebral artery occlusion rats

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