Different types of effective fractions from Radix Isatidis revealed a multiple-target synergy effect against respiratory syncytial virus through RIG-I and MDA5 signaling pathways, a pilot study to testify the theory of superposition of traditional Chinese Medicine efficacy

被引：19

作者：

Xu, Huiqin ^{[1
]}

He, Liwei ^{[1
,2
]}

Chen, Jing ^{[3
]}

Hou, Xianbang ^{[2
]}

Fan, Fangtian ^{[2
]}

Wu, Hongyan ^{[2
]}

Zhu, Hepeng ^{[2
]}

Guo, Yeqian ^{[2
]}

机构：

[1] Nanjing Univ Chinese Med, Sch Pharm, Dept Pharmacol, Nanjing 210023, Jiangsu, Peoples R China

[2] Nanjing Univ Chinese Med, Dept Pharmacol, Hanlin Coll, POB 225312,6 Xueyuan Rd, Taizhou 225312, Peoples R China

[3] Yangzhou Univ, Inst Translat Med, Med Coll, Yangzhou 225001, Jiangsu, Peoples R China

来源：

JOURNAL OF ETHNOPHARMACOLOGY | 2019年 / 239卷

基金：

中国国家自然科学基金;

关键词：

Radix isatidis; RIG-I; MDA5; respiratory syncytial virus; Synergy; Traditional Chinese medicine; JINXIN ORAL LIQUID; ANTIVIRAL ACTIVITIES; INFECTION; EXTRACT; DRUG;

D O I：

10.1016/j.jep.2019.111901

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Ethnopharmacological relevance: Radix Isatidis, a commonly used traditional Chinese medicine, is also documented in "Dictionary of Chinese Ethnic Medicine" being as an ethnic herb clinically utilized by different nations in China such as Mongol, Uygur, and Dong et al. It has been reported to have a very strong efficacy on respiratory viruses, but to date the mechanism remains unknown. Similarly, it is unclear how different types of effective fractions of Radix Isatidis interact to exert antiviral effects. Aim of study: To reveal the underlying mechanisms for the inhibitory effects of three active fractions from Radix Isatidis, i.e. total alkaloids, lignans and organic acids, on respiratory syncytial virus when used alone or in combination. In addition, we investigated whether these three parts worked synergistically in vivo and in vitro. Materials and methods: A mouse model of RSV infection was constructed by intranasal infection, and the pathological changes of lung tissues in different parts were observed. The level changes of IFN beta and inflammatory cytokines in the mouse alveolar lavage fluid were detected by enzyme-linked immunosorbent assay (ELISA). The anti-RSV effects of different effective fractions were evaluated by the plaque reduction test. The mRNA and protein expressions of RIG-I, MDA-5, MAVS and IRF3 in RAW264.7 cells were detected by RT-PCR and Western blot respectively. Results: HE staining showed that Radix Isatidis extracts alone or in combination relieved virus-induced mouse lung lesions. Compared with individual drugs, the lung lesions were alleviated more significantly after treatment with the three fractions in combination. ELISA demonstrated that the expression levels of IFN beta and inflammatory cytokines were maintained balanced between antiviral and proinflammatory effects. The plaque reduction test indicated that the antiviral effect of combination treatment was much stronger than those of individual drugs. RT-qPCR and Western blot suggested that the mRNA and protein expression levels of key signaling molecules in the RIG-I and MDA5 pathways in mouse macrophages were down-regulated by different effective parts alone or in combination. Conclusions: The three effective fractions of Radix Isatidis have remarkable synergistic anti-RSV effects in vitro and in vivo, and total alkaloids and lignans show multi-target synergistic effects via the RIG-I and MDA5 signaling pathways.

引用

页数：9