BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2023
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IF 3.1
Qiuxia Zhu,Yong Luo,Yuetao Wen,Ding Wang,Jing Li,Zhongcai Fan
Apoptosis is a major pathophysiological change following myocardial ischemia/reperfusion (I/R) injury. Glucagon-like peptide 1 (GLP-1) and its receptor GLP-1R are widely expressed in the cardiovascular system and GLP-1/GLP-1R activates the protein kinase G (PKG)-related signaling pathway. Therefore, this study tested whether semaglutide, a new GLP-1 analog, inhibits I/R injury-induced cardiomyocyte apoptosis by activating the PKG/PKCε/ERK1/2 pathway. We induced myocardial I/R injury in rats and hypoxia/reoxygenation (H/R) injury in H9C2 cells and detected the effects of semaglutide, a PKG analog (8-Br-cGMP), and a PKG inhibitor (KT-5823) on the PKG/PKCε/ERK1/2 pathway and cardiomyocyte apoptosis. We found that semaglutide upregulated GLP-1R levels, and both semaglutide and 8-Br-cGMP activated the PKG/PKCε/ERK1/2 pathway, inhibited myocardial infarction (MI), decreased hs-cTNT levels, increased NT-proBNP levels, and suppressed cardiomyocyte apoptosis in I/R rats and H/R H9C2 cells. However, KT-5823 exerted contrasting effects with semaglutide and 8-Br-cGMP, and KT-5823 weakened the cardioprotective effects of semaglutide. In conclusion, semaglutide inhibits I/R injury-induced cardiomyocyte apoptosis by activating the PKG/PKCε/ERK1/2 pathway. The beneficial effect of GLP-1/GLP-1R, involved in the activation of the PKG/PKCε/ERK1/2 pathway, may provide a novel treatment method for myocardial I/R injury.
研究领域:
心脏病学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Xin Gao,Zhen-Zi Shang,Qiang-Ming Li,Feng-Yun Zhang,Xue-Qiang Zha,Jian-Ping Luo
Ethnopharmacological relevance Dendrobium huoshanense has been long used to treat gastrointestinal disorders including ulcerative colitis (UC) in traditional Chinese medicine. Polysaccharides as its main active components can alleviate UC by reducing inflammation, and promote the secretion of glucagon-like peptide-1 (GLP-1), which possesses anti-inflammatory effects via GLP-1 receptor (GLP-1R). However, it remains unclear whether polysaccharides from different parts of this herb are equally effective in alleviating UC and whether polysaccharides function via GLP-1/GLP-1R axis. Aim of the study To identify the part in which the polysaccharide is most effective in alleviating UC and to explore its mechanism of action through GLP-1/GLP-1R axis. Materials and methods The physicochemical properties of polysaccharides were analyzed. A dextran sulfate sodium (DSS)-induced UC mouse model was used to assess colitis-associated damage via morphological scoring, histopathological evaluation and inflammatory examination with multi-cytokine array and western blotting. Gut microbiota compositions, short-chain fatty acid contents and GLP-1 levels were measured, and their roles were checked using antibiotic mixture and GLP-1R antagonist Exendin (9-39). Results Stem, leaf and flower polysaccharides, with different molecular weight, monosaccharide composition and spatial conformation, differentially alleviated UC symptoms, and stem polysaccharide (DHPS) showed the strongest efficacy, as evidenced by improved epithelial integrity, mucus barrier and inflammatory disorder. DHPS-alleviated UC was independent of DHPS-altered gut microbiota and positively correlated with DHPS-elevated GLP-1 levels, which could be abolished by Exendin (9-39), suggesting that GLP-1-activated GLP-1R signaling mediated the effects of DHPS against UC. Conclusions DHPS is the most effective polysaccharide for alleviating DSS-induced UC through GLP-1/GLP-1R axis, proposing DHPS is a valid candidate for UC treatment using D. huoshanense .
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Yinan Zhang,Qilei Chen,Yaning Xu,Yanming Lv,Yini Wang,Xin-yu Shi,Jiaqi Liu,Jie Wen,Xueting Li,Baixiang Li
Atrazine (ATR), a widely used herbicide, is linked to dopaminergic neurotoxicity and persistent gut microbiota dysbiosis after early life exposure. However, whether the gut microbiota mediates ATR-induced loss of dopaminergic neurons remains unclear. Mice were exposed to ATR from juvenility (4 th week) until adulthood (12 th week), after which exposure ceased until the 20 th week. The role of gut microbiota was confirmed through fecal microbiota transplantation (FMT), which was classified into different groups based on the donor's ATR treatment status. 16S rRNA sequencing revealed that Akkermansia , which exhibited significant differences across FMT groups, is a classic short-chain fatty acid (SCFA)-producing bacteria. FMT recipients receiving ATR-donor microbiota exhibited reduced colonic G Protein-Coupled Receptor 43 (GPR43), serum Glucagon-like Peptide-1 (GLP-1), and substantia nigra Glucagon-like Peptide-1 receptor (GLP-1R)/Tyrosine hydroxylase (TH) levels. Soy isoflavones (SIF), selected for their dual prebiotic and neuroprotective effects, attenuated ATR-induced dopaminergic neurotoxicity by enriching SCFA-producing gut microbiota and the level of SCFAs, thereby activating the GPR43/GLP-1/GLP-1R axis and reducing neuronal loss. These findings demonstrate the critical role of gut microbiota in ATR-induced dopaminergic neurodegeneration, positioning SIF-mediated microbiota modulation as a promising therapeutic approach within the "food-medicine homology" framework.
研究领域:
神经毒理学
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环境健康
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微生物组研究
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神经药理学
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营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）