PHYTOMEDICINE
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2024
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IF 6.7
Sheng Zhang,Rongrong Huang,Junsong Jing,Xueping Wei,Yu Zhang,Youping Wu,Guoteng Ou,Jingjin Hu,Yueguo Wu,Yuanyuan Li,Shibo Ying,Zhenqiang You
ABSTRACT Background Acute respiratory distress syndrome (ARDS) is an acute respiratory disease characterized by bilateral chest radiolucency and severe hypoxemia. Quzhou Fructus Aurantii ethyl acetate extract (QFAEE), which is prepared from the traditional Chinese respiratory anti-inflammatory natural herb Quzhou Fructus Arantii, has the potential to alleviate ARDS. In this work, we aimed to investigate the potential and mechanism underlying the action of QFAEE on ARDS and how QFAEE modulates the STING pathway to reduce type I interferon release to alleviate the inflammatory response. Methods Lipopolysaccharide (LPS), a potential proinflammatory stimulant capable of causing pulmonary inflammation with edema after nasal drops, was employed to model ARDS in vitro and in vivo . Under QFAEE intervention, the mechanism of action of QFAEE to alleviate ARDS was explored in this study. TREX1 −/− mice were sued as a research model for the activation of the congenital STING signaling pathway. The effect of QFAEE on TREX1 −/− mice could explain the STING-targeted effect of QFAEE on alleviating the inflammatory response. Our explorations covered several techniques, Western blot, histological assays, immunofluorescence staining, transcriptomic assays and qRT-PCR to determine the potential mechanism of action of QFAEE in antagonizing the inflammatory response in the lungs, as well as the mechanism of action of QFAEE in targeting the STING signaling pathway to regulate the release of type I interferon. Results QFAEE effectively alleviates ARDS symptoms in LPS-induced ARDS. We revealed that the mechanism underlying LPS-induced ARDS is the STING-TBK1 signaling pathway and further elucidated the molecular mechanism of QFAEE in the prevention and treatment of ARDS. QFAEE reduced the release of type I interferons by inhibiting the STING-TBK1-IRF3 axis, thus alleviating LPS-induced pneumonia and lung cell death in mice. Another key finding is that activation of the STING pathway by activators or targeted knockdown of the TREX1 gene can also induce ARDS. As expected, QFAEE was found to be an effective protective agent in alleviating ARDS and the antagonistic effect of QFAEE on ARDS was achieved by inhibiting the STING signaling pathway. Conclusions The main anti-inflammatory effect of QFAEE was achieved by inhibiting the STING signaling pathway and reducing the release of type I interferons. According to this mechanism of effect, QFAEE can effectively alleviate ARDS and can be considered a potential therapeutic agent. In addition, the STING pathway plays an essential role in the development and progression of ARDS, and it is a potential target for ARDS therapy.
研究领域:
药理学
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免疫学
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呼吸医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
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2018
·Vol. 8
·期 1
·1-11
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IF 4.122
Li Lili,Zhang Sheng,Xin Yanfei,Sun Junying,Xie Feng,Yang Lin,Chen Zhiqin,Chen Hao,Liu Fang,Xuan Yaoxian,You Zhenqiang
Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO 4 ·5H 2 O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO 4 ·5H 2 O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro . In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO 4 ·5H 2 O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.
研究领域:
药理学
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免疫学
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呼吸医学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2023
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IF 8.1
Xiaomin Cao,Kaixin Shi,Yang Xu,Peipei Zhang,Hongyan Zhang,Siyi Pan
The benefits of citrus herbs are strongly associated with their secondary metabolites. In the study, we conducted widely-targeted metabolomics and ultra-high performance liquid chromatography (UPLC) to compare the variability of ingredients in four citrus herbs. In total, we discovered 1126 secondary metabolites, primarily comprising flavonoids, phenolic acids, lignans and coumarins, and alkaloids. Differential metabolites of citrus herbs were searched by multivariate statistical analysis. Notably, Citri Reticulatae Pericarpium contained higher levels of flavonoids, while Zhique and Huajuhong demonstrated a greater abundance of coumarins. Among the flavonoids determined by UPLC, Guangchenpi demonstrated significantly elevated levels of polymethoxyflavones (tangeretin and nobiletin) compared to other citrus herbs. Additionally, we determined their antioxidant capacity (Chenpi > Guangchenpi > Huajuhong > Zhique) using in vitro assays. Finally, we utilized network pharmacology to explore the antioxidant mechanisms and potential pharmacological ingredients, providing a basis for future preventive and therapeutic applications of these metabolites.
研究领域:
药理学
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代谢组学
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植物科学
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生物化学
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网络分析
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Qixuan Mu,Yaping Zhang,Ying Cui,Xin Chai,Junlian Liu,Yongzhi Li,Huijuan Yu,Yuefei Wang
As the representatives of closely related Chinese medicinal materials (CMMs) originated from Rutaceae family, Aurantii fructus immaturus (AFI), Aurantii fructus (AF), Citri reticulatae pericarpium viride (CRPV), and Citri reticulatae pericarpium (CRP) have better functions in regulating qi and promoting gastrointestinal motility. However, differences in the quality of closely related Citrus CMMs have not yet been revealed until now. Herein, this study focused on the systematic differentiation and in-depth understanding of closely related Citrus CMMs by a strategy integrating chemometrics and network pharmacology. Determined by ultra performance liquid chromatography, the content of nine flavonoids showed obvious fluctuations in the decoction pieces from different species (Citrus aurantium Linnaeus and Citrus reticulate Blanco) with decreasing levels in the samples of ripe fruits. Decoction pieces from the different species and ripening stages were well distinguished by orthogonal projection to latent structure-discriminate analysis (OPLS-DA) and cluster analysis. As a result, four active components including narirutin, naringenin, hesperidin, and 3,5,6,7,8,3′,4′-heptemthoxyflavone were filtered out by variable importance for the projection (VIP) value (VIP > 1.0), which were regarded as chemotaxonomic markers. Furthermore, a components-targets-diseases network was constructed via ingenuity pathway analysis (IPA), and the correlations were predicted between four chemotaxonomic markers, 223 targets, and three diseases including colitis, breast cancer, and colorectal cancer. The obtained results will be of great significance for identifying closely related Citrus CMMs and conduce to improving the resource utilization of CMMs.
研究领域:
药理学
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分析化学
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网络生物学
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中医药
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植物科学
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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）