Exploration of the mechanisms of Ge Gen Decoction against influenza A virus infection

Abstract

Ge Gen Decoction (GGD), a Traditional Chinese Medicine prescription, is mainly used to treat infectious respiratory diseases and can relieve the symptoms of influenza A virus (IAV) infection. However, the underlying mechanism of GGD against IAV infection remains unclear. In this study, we found that GGD had moderate anti-IAV activity in vitro. GGD was more effective when given before the viral infection and targeted the viral attachment and replication stages rather than the internalization stage. In vivo, GGD treatment reduced the virus titers of lung tissue significantly and improved the survival rate, lung index, and pulmonary histopathological changes in H1N1-infected mice. We observed the changes in several key immuno-related indexes in GGD administrated H1N1-infected mice with anti-IAV drug oseltamivir phosphate as the control. GGD treatment decreased the expression of TNF-α and improved Th1/Th2 immune balance to reduce the excessive immune response in H1N1-infected mice. Besides, the expression of the toll-like receptor 7 signaling pathway in H1N1-infected mice decreased after GGD treatment. Our results showed that GGD has anti-IAV activity and can modulate the immune system to relieve lung inflammation.

Role of Traditional Chinese Medicine in the Management of Viral Pneumonia

“…Based on the data from time-of-addition experiments and on release tests of progeny viruses, arctigenin was assumed to interfere the early event(s) of viral replication after viral penetration into cells, and to suppress the release of progeny viruses from the host cells (p<0.01 or p<0.001) (Hayashi et al, 2010). The classical Chinese medical formula, Pueraria Decoction (Gegen Tang) can play an antiviral role in the adsorption stage of virus (p<0.01), and Pueraria decoction and its antiviral activity are positively correlated with dose (Geng et al, 2019). Neuraminidase (NA) can be another target molecule FIGURE 2 | Usage frequency of Chinese medical formulas and proprietary traditional Chinese medicine products in traditional Chinese medicine (TCM) part of the China National Guidelines of Diagnosis and Treatment for SARS-CoV, MERS-CoV, SARS-CoV-2, and influenza virus (The statistical data were based on the analysis of Chinese medical formulas and proprietary traditional Chinese medicine products involved in different syndromes of viral pneumonia in China's National Guidelines for TCM treatment of SARS-CoV, MERS-CoV, SARS-CoV-2, and influenza virus).…”

“…Whether the different distribution of this functional domain is related to its antiviral effect needs further study. After virus invasion, both TLR3mediated MyD88 independent signaling and TLR7-mediated MyD88-dependent signaling ultimately activate the nuclear transcription factor NF-kB, which induces and promotes the expression of preinflammatory factors (Sanjeewa et al, 2020 (Lai et al, 2011;Liu et al, 2014;Li et al, 2018;Geng et al, 2019).…”

“…Hypericum perforatum L. extract can improve the immunologic function of influenza virus-infected mice by enhancing T and B lymphocyte conversion, phagocytic function of macrophages and NK killing activity (p<0.05 or p<0.01) (Xu et al, 2016). Gegen decoction can regulate the ratio of CD3+CD4+/CD3 +CD8+ and CD4+IFN-g+/CD4+IL-4+ in peripheral blood of virus-infected mice (p<0.01) (Geng et al, 2019). Shengjiang Power can increase the percentage of CD8+ in peripheral blood, regulate the radio of CD4+/CD8+, and improve the immune function of the body (p<0.05 or p<0.01) (Nan et al, 2016b).…”

The effects of the Xijiao Dihuang decoction combined with Yinqiao powder on miRNA-mRNA profiles in mice infected with influenza a virus

“…IAV infection triggers activation of TLR, PKC, MAPK and inflammasome pathways, leading to production of proinflammatory cytokines. Many traditional Chinese medicine formulas, such as San Wu Huangqin Decoction, Gegen Qinlian Decoction, and Ma Huang Tang have been indicated to have protective effects on IAV-infected mice by modulating the TLR pathway to maintain a balanced inflammatory response [ 54 – 56 ]. Previous studies have indicated that XDY could inhibit the overreaction of TLR, PKC and inflammasome pathways to exert therapeutic efficacy on viral pneumonia induced by IAV challenge [ 30 – 32 , 34 ].…”

Traditional Chinese Medicine in Treating Influenza: From Basic Science to Clinical Applications

“…ex DC ., 6 g of paeonia lactiflora pall., 9 g of zingiber officinale roscoe, and 22 g of ziziphus jujuba mill .] decreased the expression of TNF-α and toll-like receptor 7 signaling pathways in influenza virus infected mice thereby reducing lung inflammation ( Geng et al., 2019 ). Research endorsed that Gui Zhi Ma Huang Ge Ban Tang [9 g of ephedra sinica stapf, 6 g of cinnamomum cassia (L.) J.Presl , 9 g of prunus amygdalus batsch , and 6 g of glycyrrhiza uralensis fisch.…”