San Wu Huangqin decoction regulates inflammation and immune dysfunction induced by influenza virus by regulating the NF-κB signaling pathway in H1N1-infected mice

J Ethnopharmacol. 2021 Jan 10:264:112800. doi: 10.1016/j.jep.2020.112800. Epub 2020 Mar 27.

Abstract

Ethnopharmacological relevance: The San Wu Huangqin Decoction (SWHD), which is made from the dried root of Sophora flavescens Aiton (Kushen in Chinese), the dried root of Scutellaria baicalensis Georgi (Huangqin in Chinese), and the dried root tuber of Rehmannia glutinosa (Gaertn.) DC. (Dihuang in Chinese), is a traditional Chinese formula used to treat prolonged fever and inflammatory diseases in clinics and proven to inhibit influenza virus effectively in our previous study.

Aim of the study: This work was performed to study the regulation of SWHD on inflammation and immune dysfunction induced by the influenza virus and the underlying mechanism in the treatment of SWHD.

Methods: In this study, the influenza virus A/PR/8/34 (H1N1)-infected mouse model was used to investigate the regulation of SWHD on inflammation and immune dysfunction induced by H1N1. The pathological changes, the capacity of proliferation of T and B lymphocytes, the cytotoxicity of natural killer (NK) cells, and the levels of IL-6, TNF-α, IL-1β, IL-4, and IFN-γ in the serum, bronchoalveolar lavage fluid (BALF), and lung were analyzed. The effects of type 1 T helper cell (Th1) and type 2 T helper cell (Th2) immune responses were discussed indirectly. In addition, the expression levels of p-p65, p65, IKKα/β, p-IκBα, and IκBα in relation to the NF-κB pathway were measured using Western blot analysis, or immunohistochemical assay.

Results: SWHD decreased the pathological changes in lung tissues, promoted the proliferation of T and B lymphocytes, enhanced NK cell activity, and accelerated the phagocytic function of macrophages in H1N1-infected mice. At the same time, SWHD decreased the levels of IL-6, TNF-α, IL-1β, IFN-γ, and increased the level of IL-4 in the serum, BALF, and lung of model mice. Moreover, the p-p65, p65, and IκBα protein expression levels were inhibited, whereas the p-IκBα protein expression levels were improved in the lungs of H1N1-infected mice.

Conclusions: SWHD can inhibit the replication of the H1N1 virus and reduced the excessive inflammation and immune dysfunction induced by the H1N1 virus in the body. This work provides rich experimental basis for further anti-inflammation research of SWHD and sets the foundation for the development of a viral inflammation drug of traditional Chinese medicine.

Keywords: H1N1; Inflammation and immune dysfunction; Mouse model; NF-κB pathway; San Wu Huangqin decoction.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Female
  • Immunity, Cellular / drug effects*
  • Immunity, Cellular / physiology
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / physiology*
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Antiviral Agents
  • Drugs, Chinese Herbal
  • NF-kappa B
  • san wu huangqin