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通过网络药理学和体内外实验探讨金叶败毒颗粒(JYBD)抗甲型流感病毒的作用及机制。

Exploring antiviral effect and mechanism of Jinye Baidu granules(JYBD)against influenza A virus through network pharmacology and in vitro and invivo experiments.

机构信息

NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.

NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China; Sinopharm Zhonglian Pharmaceutical Co., Ltd., Wuhan 430000, PR China.

出版信息

J Ethnopharmacol. 2025 Jan 10;336:118720. doi: 10.1016/j.jep.2024.118720. Epub 2024 Aug 26.

DOI:10.1016/j.jep.2024.118720
PMID:39197802
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Jinye Baidu granules (JYBD) have been used to treat acute respiratory tract infections and demonstrated clinical efficacy for the treatment of emerging or epidemic respiratory viruses such as SARS-CoV-2 and influenza virus.

AIM OF THE STUDY

This study is to investigate the antiviral effect of JYBD against influenza A viruses (IAV) in vitro and in vivo and elucidate its underlying mechanism.

MATERIALS AND METHODS

Ultra-high-performance liquid chromatography connected with Orbitrap mass spectrometer (UHPLC-Orbitrap MS) was employed to describe the chemical profile of JYBD. The potential pathways and targets involved in JYBD against IAV infection were predicted by network pharmacology. The efficacy and mechanism of JYBD were validated through both in vivo and in vitro experiments. Moreover, combination therapy with JYBD and the classic anti-influenza drugs was also investigated.

RESULTS

A total of 126 compounds were identified by UHPLC-Orbitrap MS, of which 9 compounds were unambiguously confirmed with reference standards. JYBD could significantly inhibit the replication of multiple strains of IAV, especially oseltamivir-resistant strains. The results of qRT-PCR and WB demonstrated that JYBD could inhibit the excessive induction of pro-inflammatory cytokines induced by IAV infection and regulate inflammatory response through inhibiting JAK/STAT, NF-κB and MAPK pathways. Moreover, both JYBD monotherapy or in combination with oseltamivir could alleviate IAV-induced severe lung injury in mice.

CONCLUSIONS

JYBD could inhibit IAV replication and mitigate virus-induced excessive inflammatory response. Combinations of JYBD and neuraminidase inhibitors conferred synergistic suppression of IAV both in vitro and in vivo. It might provide a scientific basis for clinical applications of JYBD against influenza virus infected diseases.

摘要

民族药理学相关性

金叶败毒颗粒(JYBD)已被用于治疗急性呼吸道感染,并在治疗 SARS-CoV-2 和流感病毒等新兴或流行的呼吸道病毒方面显示出临床疗效。

研究目的

本研究旨在探讨 JYBD 对甲型流感病毒(IAV)的体外和体内抗病毒作用,并阐明其潜在机制。

材料与方法

采用超高效液相色谱-轨道阱质谱联用(UHPLC-Orbitrap MS)技术描述 JYBD 的化学成分。通过网络药理学预测 JYBD 抗 IAV 感染的潜在途径和靶点。通过体内和体外实验验证 JYBD 的疗效和机制。此外,还研究了 JYBD 与经典抗流感药物的联合治疗。

结果

通过 UHPLC-Orbitrap MS 鉴定出 126 种化合物,其中 9 种化合物通过对照品得到明确确认。JYBD 能显著抑制多种 IAV 株的复制,特别是对奥司他韦耐药株的抑制作用更为明显。qRT-PCR 和 WB 结果表明,JYBD 能抑制 IAV 感染引起的促炎细胞因子的过度诱导,并通过抑制 JAK/STAT、NF-κB 和 MAPK 通路调节炎症反应。此外,JYBD 单药或与奥司他韦联合治疗均可减轻 IAV 诱导的小鼠严重肺损伤。

结论

JYBD 能抑制 IAV 的复制,减轻病毒引起的过度炎症反应。JYBD 与神经氨酸酶抑制剂的联合应用在体外和体内均能协同抑制 IAV。这为 JYBD 临床应用于流感病毒感染性疾病提供了科学依据。

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