International Journal of Nanomedicine
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2023
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IF 8
Ning-Ke Guo,Han She,Lei Tan,Yuan-Qun Zhou,Chun-Qiong Tang,Xiao-Yong Peng,Chun-Hua Ma,Tao Li,Liang-Ming Liu
Background Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured.Methods In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis.Results The encapsulation rate of Nano PTL was 95±1.5%, the drug loading rate was 11±0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL.Conclusion Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.
研究领域:
药理学
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免疫学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2020
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IF 4.225
Wang Lulu,Fan Xiangcheng,Han Jichun,Cai Minxuan,Wang Xiaozhong,Wang Yan,Shang Jing
The precipitous increase in occurrence of non-alcoholic steatohepatitis (NASH) is a serious threat to public health worldwide. The pathogenesis of NASH has not yet been thoroughly studied. We aimed to elucidate the interplay between serotonin (5-hydroxytryptamine, 5-HT) and NASH. The serum 5-HT levels in patients with non-alcoholic fatty liver disease (NAFLD) and a rat fed with high fat-sucrose diet (HFSD) were evaluated using liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF MS)/MS. The peripheral Tph1 inhibitor, LP533401, and a tryptophan (TRP)-free diet were administered to rats with NASH, induced by HFSD. BRL-3A cells were treated with 1 mM free fatty acids (FFAs) and/or 50 μM 5-HT, and then small interfering RNA (siRNA) targeting the 5-HT2A receptor (HTR2A) and the PPARγ pharmaceutical agonist, pioglitazone, were applied. We found a marked correlation between 5-HT and NASH. The absence of 5-HT, through the pharmaceutical blockade of Tph1 (LP533401) and dietary control (TRP-free diet), suppressed hepatic lipid load and the expression of inflammatory factors (Tnfα, Il6, and Mcp-1). In BRL-3A cells, 50 μM 5-HT induced lipid accumulation and upregulated the expression of lipogenesis-ralated genes (Fas, Cd36, and Plin2) and the inflammatory response. Specifically, HTR2A knockdown and evaluation of PPARγ agonist activity revealed that HTR2A promoted hepatic steatosis and inflammation by activating PPARγ2. These results suggested that duodenal 5-HT was a risk factor in the pathological progression of NASH. Correspondingly, it may represent an attractive therapeutic target for preventing the development of NASH via the regulation of the HTR2A/PPARγ2 signaling pathway.
研究领域:
肝病学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Chen Dongliang,Wang Yuanfei,Yang Jianmei,Ou Wanyi,Lin Guiru,Zeng Ze,Lu Xiaomin,Chen Zumin,Zou Lili,Tian Yaling,Wu Aiping,Keating Shelley,Yang Qinhe,Lin Chenli,Liang Yinji
The prevalence of non-alcoholic fatty liver disease (NAFLD) and related mortality are increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment for NAFLD. This study examined the new mechanism of "Shenling Baizhu San" (SLBZS) in the prevention and treatment of NAFLD at the preclinical level.The male C57BL/6J mice were randomly divided into three groups: ND (normal diet), WDC (Western Diet+CCl4 injection) and WDC+SLBZS (SLBZS intervention). Body weight, energy intake, liver enzymes, pro-inflammatory factors and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A and HTR2B were tested by qRT-PCR or ELISA. Dynamic changes in gut microbiota and metabolites were further detected through 16S rRNA gene and untargeted metabolomics.
研究领域:
药理学
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胃肠病学
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微生物学
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代谢组学
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中医
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）