Systems pharmacology uncovers Janus functions of botanical drugs: activation of host defense system and inhibition of influenza virus replication.

Integr Biol (Camb). 2013 Feb; 5(2):351-71. doi: 10.1039/c2ib20204b.

 

Xia Wang, Xue Xu, Yan Li, Xiuxiu Li,Weiyang Tao, Bohui Li,Yonghua Wang*, and Ling Yang

College of Life Sciences, Northwest A&F University, Yangling, 712100 Shaanxi, China.

 

Abstract

Given the imminent threat of influenza pandemics and continuing emergence of new drug-resistant influenza virus strains, novel strategies for preventing and treating influenza disease are urgently needed. Herbal medicine, used for thousands of years in combinational therapies (Herb Formula), plays a significant role in stimulating the host immune system in vivo, and meanwhile, in fighting against the pandemic by directly inhibiting influenza virus in vitro. Such potential Janus functions may spark interest in therapeutic manipulation of virus diseases. Unfortunately, the molecular mechanism of the Janus functions of the medicinal herbs in the treatment of influenza remains unclear. In this work, to illustrate the therapeutic concept of Janus functions in the treatment of influenza, we have introduced a novel systems pharmacology model that integrates pharmacokinetic screening, targeting and network analysis of two representative herbs Lonicera japonica and Fructus Forsythiae that are efficient in the treatment of influenza, inflammation and other diseases. 50 Chemicals with favorable pharmacokinetic profiles have been identified for the two herbs, and the ligand-target network was constructed by complementing the literature-based experimental data deposited in DrugBank. The annotation of these chemicals was assigned using a novel drug targeting approach, and mapped to target-disease and drug-target-pathway networks. The overall data suggest that the medicinal herbs function by indirectly suppressing the virus proliferation via regulating the immune systems in hosts, and also, by directly inhibiting virus proliferation through targeting viral proteins essential for the viral life cycle. For the first time, we have demonstrated the mechanism of medicinal herbs in prevention and treatment of virus diseases via the Janus functions on a systematic level.

 

Supplementary

Understanding how the diverse chemical components in medicinal herbs contribute to the overall pharmacological effect is a major challenge for current studies. Additionally, some components play dual, even multiple roles, during fighting against influenza virus which added another layer of complexity to pharmacological researches. Herein, Wang et.al introduced a novel systems pharmacology model which integrates pharmacokinetic screening, targeting and network analysis. By using this model, two representative herbs Lonicera japonica and Fructus Forsythiae were analyzed regarding their pharmacological effect on influenza, inflammation and other diseases. Of noted, Janus function is a striking pharmacological characteristic of these chemical compounds in both herbs: directly inhibiting virus replication and simultaneously promoting host immune response. It is seen by some as a perfect match for YinYang theory of TCM (Traditional Chinese Medicine), in which Yin and Yang are complementary opposites emphasizing all physiological functions are the equilibrium of bipolar Yin and Yang characteristics. Indeed, TCM always uses mixtures of plant extracts in a holistic approach to disease which is well consistent to the systems-based approach of modern science that integrates all the potential related factors involved in the pathologies and disease treatment in a network framework (1, 2).

Yonghua Wang-1

References

1 Hopkins A L. Network pharmacology: the next paradigm in drug discovery [J]. Nature chemical biology, 2008, 4(11): 682-690.

2 Huang C, Zheng C, Li Y, et al. Systems pharmacology in drug discovery and therapeutic insight for herbal medicines[J]. Briefings in bioinformatics, 2013.

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