Influenza caused by influenza virus,seriously threaten human life and health.Drug treatment is one of the effective measurement.However,there are only two classes of drugs,one class is M2 blockers and another is neura...Influenza caused by influenza virus,seriously threaten human life and health.Drug treatment is one of the effective measurement.However,there are only two classes of drugs,one class is M2 blockers and another is neuraminidase(NA) inhibitors.The recent antiviral surveillance studies reported a global significant increase in M2 blocker resistance among influenza viruses,and the resistant virus strains against NA inhibitor are also reported in clinical treatment.Therefore thediscovery of new medicines with low resistance has become very urgent.As all known,traditional medicines with multi-target features and network mechanism often possess low resistance.Compound Yizhihao,which consists of radix isatidis,folium isatidis,Artemisia rupestris,is one of the famous traditional medicine for influenza treatment in China,however its mechanism of action against influenza is unclear.In this study,the multiple targets related with influenza disease and the known chemical constituents from Compound Yizhihao were collected,and multi-target QSAR(mt-QSAR) classification models were developed by Na?e Bayesian algorithm and verified by various datasets.Then the classification models were applied to predict the effective constituents and their drug targets.Finally,the constituent-target-pathway network was constructed,which revealed the effective constituents and their network mechanism in Compound Yizhihao.This study will lay important basis for the clinical uses for influenza treatment and for the further research and development of the effective constituents.展开更多
Objective To research the anti-influenza effect of active ingredients in Compound Yizhihao Granule （CYG）. Methods The cytotoxicity and cytopathic effects （CPE） were observed under the phase-contrast microscope, be...Objective To research the anti-influenza effect of active ingredients in Compound Yizhihao Granule （CYG）. Methods The cytotoxicity and cytopathic effects （CPE） were observed under the phase-contrast microscope, besides 50% toxicity concentration （TC50） and 50% inhibitory concentration （IC50） were also calculated using Reed-Muench method, then the antiviral activity in vitro according to Selection Index （SI = TC50/IC50） was evaluated. In PR8 virus-infected mice, survival time, death rate, and lung index were observed in order to evaluate the protective effect. Besides, the effective ingredients were determined using HPLC method, and their contents were calculated by external standard method. Results CYG could inhibit the influenza virus-induced CPE, with ICso of 4.6 mg/mL （equal to herbal extracts 262.2 μg/mL）, and no direct cytotoxic effect at this concentration. PR8-infected mice were ig given CYG, the lung index and mortality were significantly reduced, and survival time was obviously prolonged. HPLC analysis indicated CYG contained many kinds of antivirus active components, including rupestonic acid, epigoitrin, and adenosine. Conclusion CYG is an effective natural anti-influenza medicine, its antiviral effect should be the synergic effect of a variety of antiviral active ingredients.展开更多
基金supported by National Natural Science Foundation of China(81673480) Project of Urumqi science and Technology Bureau of the Xinjiang Uygur Autonomous Region(Y151310010)
文摘Influenza caused by influenza virus,seriously threaten human life and health.Drug treatment is one of the effective measurement.However,there are only two classes of drugs,one class is M2 blockers and another is neuraminidase(NA) inhibitors.The recent antiviral surveillance studies reported a global significant increase in M2 blocker resistance among influenza viruses,and the resistant virus strains against NA inhibitor are also reported in clinical treatment.Therefore thediscovery of new medicines with low resistance has become very urgent.As all known,traditional medicines with multi-target features and network mechanism often possess low resistance.Compound Yizhihao,which consists of radix isatidis,folium isatidis,Artemisia rupestris,is one of the famous traditional medicine for influenza treatment in China,however its mechanism of action against influenza is unclear.In this study,the multiple targets related with influenza disease and the known chemical constituents from Compound Yizhihao were collected,and multi-target QSAR(mt-QSAR) classification models were developed by Na?e Bayesian algorithm and verified by various datasets.Then the classification models were applied to predict the effective constituents and their drug targets.Finally,the constituent-target-pathway network was constructed,which revealed the effective constituents and their network mechanism in Compound Yizhihao.This study will lay important basis for the clinical uses for influenza treatment and for the further research and development of the effective constituents.
基金National Natural Science Foundation of China-NSFC-Xinjiang Joint Fund Project(No.U1303224)
文摘Objective To research the anti-influenza effect of active ingredients in Compound Yizhihao Granule （CYG）. Methods The cytotoxicity and cytopathic effects （CPE） were observed under the phase-contrast microscope, besides 50% toxicity concentration （TC50） and 50% inhibitory concentration （IC50） were also calculated using Reed-Muench method, then the antiviral activity in vitro according to Selection Index （SI = TC50/IC50） was evaluated. In PR8 virus-infected mice, survival time, death rate, and lung index were observed in order to evaluate the protective effect. Besides, the effective ingredients were determined using HPLC method, and their contents were calculated by external standard method. Results CYG could inhibit the influenza virus-induced CPE, with ICso of 4.6 mg/mL （equal to herbal extracts 262.2 μg/mL）, and no direct cytotoxic effect at this concentration. PR8-infected mice were ig given CYG, the lung index and mortality were significantly reduced, and survival time was obviously prolonged. HPLC analysis indicated CYG contained many kinds of antivirus active components, including rupestonic acid, epigoitrin, and adenosine. Conclusion CYG is an effective natural anti-influenza medicine, its antiviral effect should be the synergic effect of a variety of antiviral active ingredients.
文摘目的通过免疫因子水平变化考察复方一枝蒿滴鼻剂对卵清蛋白(Ovalbumin,OVA)致小鼠变应性鼻炎模型的疗效及其作用机制。方法50只BALB/c小鼠随机分为5组:对照组(PBS),模型组(OVA+PBS),阳性药组(丙酸氟替卡松鼻喷雾剂0.008 mg/kg体质量),复方一枝蒿滴鼻剂低剂量组(64 mg/kg体质量)和复方一枝蒿滴鼻剂高剂量组(256 mg/kg体质量)。采用OVA全身致敏及局部攻击相结合的方法构建变应性鼻炎小鼠模型,分别滴鼻给于阳性药、复方一枝蒿滴鼻剂低剂量、复方一枝蒿滴鼻剂高剂量,观察小鼠抓鼻次数、喷嚏次数、脏器指数和鼻腔灌洗液细胞;ELISA法定量检测血清免疫球蛋白E(IgE)、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)和干扰素-γ(IFN-γ)的含量;显微镜观察鼻黏膜组织病理学变化;制备脾细胞悬液对比脾细胞悬液CD4^+CD25^+T细胞变化。结果第25天时,与对照组比较,各组小鼠抓鼻与喷嚏次数增多,差异有统计学意义(P<0.01)。第28天时,与模型组比较,阳性药组、复方一枝蒿滴鼻剂高剂量组、复方一枝蒿滴鼻剂低剂量组小鼠抓鼻与喷嚏次数减少,差异有统计学意义(P<0.01)。第29天时,与对照组比较,模型组小鼠鼻腔灌洗液中嗜酸粒细胞和肥大细胞增多,血清IgE、IL-4、IL-10水平增大,IFN-γ水平和CD4^+CD25^+T细胞含量减小,血清IFN-γ/IL-4比值增大,差异有统计学意义(P<0.05)。与模型组比较,阳性药组、复方一枝蒿滴鼻剂高、低剂量组小鼠脾脏指数减小,嗜酸粒细胞和肥大细胞含量减少,血清IgE、IL-4、IL-10水平减小,血清IFN-γ水平增大,血清IFN-γ/IL-4比值增大,差异有统计学意义(P<0.01)。与模型组比较,复方一枝蒿滴鼻剂高、低剂量组小鼠脾细胞悬液CD4^+CD25^+T细胞比例增大,差异有统计学意义(P<0.01)。结论复方一枝蒿滴鼻剂对变应性鼻炎具有一定的疗效,通过改善1型辅助性T细胞(Helper T cells 1,Th1)/2型辅助性T细胞(Helper T cells 2,Th2)平衡治疗变应性鼻炎。
