Oral mucositis(OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of ...Oral mucositis(OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life.Shuanghua Baihe Tablet(SBT) is a traditional Chinese medicine(TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg;·d;. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17(IL-17) and tumor necrosis factor-α(TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues.After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates that SBT regulates inoleic acid metabolism, glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.展开更多
An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid(CGA) and taurocholic acid(TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatogra...An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid(CGA) and taurocholic acid(TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L^(-1) of ammonium acetate buffer solution containing 0.5% of formic acid- acetonitrile as mobile phase at a flow rate of 300 μL·min-1. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1–10 ng·m L^(-1) for CGA and 2–150 ng·m L^(-1) for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets(SBTs). In the single-dose study, the maximum plasma concentration(C_(max)), time to reach C_(max)(T_(max)) and elimination half-life(t_(1/2)) of CGA were(0.763 8 ± 0.542 0) ng·m L^(-1),(1.0 ± 0.5) h, and(1.3 ± 0.6) h, respectively. In the multiple-dose study, the C_(max), T_(max) and t_(1/2) of CGA were(0.663 7 ± 0.583 3) ng·m L^(-1),(1.1 ± 0.5) h, and(1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient.展开更多
Objective: To study the effect and mechanism of Shuanghua aerosol (SHA) in treating infantile upper respiratory tract infection. Methods: In the clinical study, 276 patients were randomly divided into two groups. The ...Objective: To study the effect and mechanism of Shuanghua aerosol (SHA) in treating infantile upper respiratory tract infection. Methods: In the clinical study, 276 patients were randomly divided into two groups. The treated group was treated with SHA and the control group was treated with Shuanghuanglian aerosol (SHLA, 双黄连气雾剂). In the experimental study, the effects of SHA on anti-inflammation and anti-virus were observed. Results: The clinical total effective rate of SHA was 99.03% and its cure rate 65.38%, while those of the SHLA were 94.11% and 44.12% respectively, significant difference was shown between the two groups (P<0.01). Experimental study showed that SHA could inhibit the xylol induced ear swelling and the egg white induced paw swelling in mice obviously, and inhibit the proliferation of influenza virus in rat's lung. Conclusion: SHA has obvious anti-inflammatory and anti-viral effect, and has good curative effect in treating infantile upper respiratory tract infection.展开更多
目的:借助网络药理学手段探究复方双花片治疗流行性腮腺炎的主要活性成分和作用机制。方法:在中药系统药理学数据库和分析平台以及GeneCards数据库分别获取复方双花片的化学成分及作用靶点和流行性腮腺炎的靶点后获得共同靶点。采用STR...目的:借助网络药理学手段探究复方双花片治疗流行性腮腺炎的主要活性成分和作用机制。方法:在中药系统药理学数据库和分析平台以及GeneCards数据库分别获取复方双花片的化学成分及作用靶点和流行性腮腺炎的靶点后获得共同靶点。采用STRING软件构建共同靶点蛋白互作图后进行基因本体论功能富集分析和京都基因与基因组百科全书通路富集分析,并构建“药物-成分-靶点-通路”网络图,拓扑分析获得主要活性成分与关键靶点,进行分子对接。结果:获得活性成分包括槲皮素、毛地黄黄酮、山奈酚等11个黄酮类,荷包牡丹碱、清风藤碱、去氧喜树碱3个生物碱,β-谷甾醇和豆甾醇2个植物甾醇,牛蒡子苷、异落叶松脂素等4个木脂素类。关键靶点前列腺素内过氧化物合酶2(Prostaglandin-endoperoxide Synthase 2,PTGS2)、热休克蛋白90AB1(Heat Shock Protein 90 k Da Alpha,Class B member 1,HSP90AB1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等11个。主要富集在T细胞受体信号通路、Toll样受体信号通路、NF-κB信号通路等分子信号通路,主要涉及促进RNA聚合酶Ⅱ启动子转录、炎症反应及调节NO生物合成等生物过程。分子对接表明活性成分与关键靶点有一定的作用力。结论:复方双花片中的槲皮素、山奈酚、β-谷甾醇等成分可能通过PTGS2、HSP90AB1、TNF等靶点和T细胞受体信号通路、Toll样受体信号通路等阻止病毒复制,降低炎性反应和提高机体免疫力而发挥治疗流行性腮腺炎的作用。展开更多
基金supported by the Clinical Research Special Fund of Wu Jieping Medical Foundation(No.320.6750.2020-04-9)the National Key Research and Development Program of China(No.2017YFC0909900)+2 种基金the National Natural Science Foundation of China(No.82002433)the Science and Technology Project of Henan Provincial Department of Education(Nos.18A320044 and 21A320036)Henan Province Medical Science and Technology Research Project Joint Construction Project(Nos.LHGJ20190003 and LHGJ20190055)。
文摘Oral mucositis(OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life.Shuanghua Baihe Tablet(SBT) is a traditional Chinese medicine(TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg;·d;. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17(IL-17) and tumor necrosis factor-α(TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues.After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates that SBT regulates inoleic acid metabolism, glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.
基金supported financially by National Natural Science Foundation of China(No.81273482)the Graduate Innovation Fund of Zhejiang Huahai Pharmaceuticals Co.,Ltd
文摘An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid(CGA) and taurocholic acid(TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L^(-1) of ammonium acetate buffer solution containing 0.5% of formic acid- acetonitrile as mobile phase at a flow rate of 300 μL·min-1. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1–10 ng·m L^(-1) for CGA and 2–150 ng·m L^(-1) for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets(SBTs). In the single-dose study, the maximum plasma concentration(C_(max)), time to reach C_(max)(T_(max)) and elimination half-life(t_(1/2)) of CGA were(0.763 8 ± 0.542 0) ng·m L^(-1),(1.0 ± 0.5) h, and(1.3 ± 0.6) h, respectively. In the multiple-dose study, the C_(max), T_(max) and t_(1/2) of CGA were(0.663 7 ± 0.583 3) ng·m L^(-1),(1.1 ± 0.5) h, and(1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient.
文摘Objective: To study the effect and mechanism of Shuanghua aerosol (SHA) in treating infantile upper respiratory tract infection. Methods: In the clinical study, 276 patients were randomly divided into two groups. The treated group was treated with SHA and the control group was treated with Shuanghuanglian aerosol (SHLA, 双黄连气雾剂). In the experimental study, the effects of SHA on anti-inflammation and anti-virus were observed. Results: The clinical total effective rate of SHA was 99.03% and its cure rate 65.38%, while those of the SHLA were 94.11% and 44.12% respectively, significant difference was shown between the two groups (P<0.01). Experimental study showed that SHA could inhibit the xylol induced ear swelling and the egg white induced paw swelling in mice obviously, and inhibit the proliferation of influenza virus in rat's lung. Conclusion: SHA has obvious anti-inflammatory and anti-viral effect, and has good curative effect in treating infantile upper respiratory tract infection.
文摘目的:借助网络药理学手段探究复方双花片治疗流行性腮腺炎的主要活性成分和作用机制。方法:在中药系统药理学数据库和分析平台以及GeneCards数据库分别获取复方双花片的化学成分及作用靶点和流行性腮腺炎的靶点后获得共同靶点。采用STRING软件构建共同靶点蛋白互作图后进行基因本体论功能富集分析和京都基因与基因组百科全书通路富集分析,并构建“药物-成分-靶点-通路”网络图,拓扑分析获得主要活性成分与关键靶点,进行分子对接。结果:获得活性成分包括槲皮素、毛地黄黄酮、山奈酚等11个黄酮类,荷包牡丹碱、清风藤碱、去氧喜树碱3个生物碱,β-谷甾醇和豆甾醇2个植物甾醇,牛蒡子苷、异落叶松脂素等4个木脂素类。关键靶点前列腺素内过氧化物合酶2(Prostaglandin-endoperoxide Synthase 2,PTGS2)、热休克蛋白90AB1(Heat Shock Protein 90 k Da Alpha,Class B member 1,HSP90AB1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等11个。主要富集在T细胞受体信号通路、Toll样受体信号通路、NF-κB信号通路等分子信号通路,主要涉及促进RNA聚合酶Ⅱ启动子转录、炎症反应及调节NO生物合成等生物过程。分子对接表明活性成分与关键靶点有一定的作用力。结论:复方双花片中的槲皮素、山奈酚、β-谷甾醇等成分可能通过PTGS2、HSP90AB1、TNF等靶点和T细胞受体信号通路、Toll样受体信号通路等阻止病毒复制,降低炎性反应和提高机体免疫力而发挥治疗流行性腮腺炎的作用。
