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通过靶向NF-κB和p38信号通路,从翼齿六棱菊中分离得到的倍半萜组分对流感病毒的抑制作用。

Inhibition of influenza virus via a sesquiterpene fraction isolated from Laggera pterodonta by targeting the NF-κB and p38 pathways.

作者信息

Wang YuTao, Zhou Beixian, Lu Jingguang, Chen QiaoLian, Ti Huihui, Huang WanYi, Li Jing, Yang ZiFeng, Jiang Zhihong, Wang XinHua

机构信息

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, SAR, China.

出版信息

BMC Complement Altern Med. 2017 Jan 6;17(1):25. doi: 10.1186/s12906-016-1528-8.

Abstract

BACKGROUND

Influenza virus poses serious threats to human health, especially human infection with avian influenza virus. Laggera pterodonta (DC.) Benth is a medicinal plant that is widely used in Traditional Chinese Medicine, especially in Yunnan province, and has been used to treat influenza, pharyngolaryngitis, and bronchitis. However, the compound(s) responsible for the activity and their mechanisms of action against the influenza virus remain to be elucidated.

METHODS

L. pterodonta extract was fractionated, and the active fraction was identified as Fraction 14 (Fr 14). Fr 14 was further analysed and characterized by ultra-high-performance liquid chromatography hyphenated with quadrupole-time of flight mass spectrometry (UHPLC/Q-TOF-MS). The inhibitory effect against influenza virus was evaluated using a cytotoxicity assay. Then, cytokines and chemokines were detected by qRT-PCR and a bio-plex assay. Signalling pathways that inhibited the influenza virus were identified using a western blotting assay.

RESULTS

The active fr 14 showed a wide spectrum of anti-influenza virus activity. The pharmacological mechanisms showed that Fr 14 acts on the early stage of virus replication (0-6 h). It inhibited the p38/MAPK pathway and then inhibited the NF-κB pathway and COX-2. Fr 14 also prevented the increased expression of cytokines and chemokines.

CONCLUSION

This study demonstrated the preliminary mechanisms of fr 14 against the influenza virus. Fr 14 possessed antiviral and anti-inflammatory effects. L. pterodonta can be used to develop innovative antiviral drugs, and further studies will be performed to illustrate the detailed mechanisms.

摘要

背景

流感病毒对人类健康构成严重威胁,尤其是人感染禽流感病毒。翼齿六棱菊是一种药用植物,在传统中药中广泛应用,尤其在云南省,已被用于治疗流感、咽炎和支气管炎。然而,负责该活性的化合物及其抗流感病毒的作用机制仍有待阐明。

方法

对翼齿六棱菊提取物进行分级分离,活性级分被鉴定为级分14(Fr 14)。通过超高效液相色谱-四极杆-飞行时间质谱联用(UHPLC/Q-TOF-MS)对Fr 14进行进一步分析和表征。使用细胞毒性试验评估其对流感病毒的抑制作用。然后,通过qRT-PCR和生物芯片分析检测细胞因子和趋化因子。使用蛋白质印迹试验鉴定抑制流感病毒的信号通路。

结果

活性Fr 14显示出广泛的抗流感病毒活性。药理机制表明,Fr 14作用于病毒复制的早期阶段(0 - 6小时)。它抑制p38/MAPK通路,进而抑制NF-κB通路和COX-2。Fr 14还阻止了细胞因子和趋化因子表达的增加。

结论

本研究证明了Fr 14抗流感病毒的初步机制。Fr 14具有抗病毒和抗炎作用。翼齿六棱菊可用于开发创新型抗病毒药物,后续将进行进一步研究以阐明详细机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a92/5217203/660bb4811dc6/12906_2016_1528_Fig1_HTML.jpg

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