response time. Moreover, primary safety evaluation demonstrates that a high dose of cordycepin adjuvanted with HBsAg accelerated antibody production more rapidly than the existing vaccine without any side effects Enhancement of celluar immunity is also important for defense of HBV infection especially T cell responses and T cell related cytokines which involved in B cell activation and antibody production. The Thl-type of cellular immune response damages the virus, whereas the main function of the Th2-type of cellular immune response is to promote B cell production of antibodies. IFN-y is a multifunctional cytokine that is primarily produced by Thl cells, CTLs and natural killer cells with antiviral and immunomodulatory activities. IL-4 controls Th2 differentiation and plays an important role in antibody class switching.68. Enhanced cytokine production by cordycepin suggests that it accelerates Thl and Th2 cell responses at the same time Jeong et al. also demonstrated that cordycepin increases the levels of different cytokines in vitro, contributing to the enhancement of immunity. The Th2 cell activation results in b cell maturation which consistent with the b cell classification experiments To sum it up, the systems pharmacology analysis offers us a new way to discover effective adjuvants from certain TCMs. Here we get a comprehensive understanding of function mechanism of Ophiocordyceps sinensis in a molecular-target level In the component-target network, the active components showed enormous polypharmacology, and after pathway enrichment analysis, multiple targets were found to participate in many physiological activities, including ion transport and
11 response time. Moreover, primary safety evaluation demonstrates that a high dose of cordycepin adjuvanted with HBsAg accelerated antibody production more rapidly than the existing vaccine without any side effects. Enhancement of celluar immunity is also important for defense of HBV infection, especially T cell responses and T cell related cytokines which involved in B cell activation and antibody production63. The Th1-type of cellular immune response damages the virus, whereas the main function of the Th2-type of cellular immune response is to promote B cell production of antibodies. IFN-γ is a multifunctional cytokine that is primarily produced by Th1 cells, CTLs and natural killer cells with antiviral and immunomodulatory activities64-66. IL-4 controls Th2 differentiation and plays an important role in antibody class switching67,68. Enhanced cytokine production by cordycepin suggests that it accelerates Th1 and Th2 cell responses at the same time. Jeong et al. also demonstrated that cordycepin increases the levels of different cytokines in vitro, contributing to the enhancement of immunity69. The Th2 cell activation results in B cell maturation which consistent with the B cell classification experiments. To sum it up, the systems pharmacology analysis offers us a new way to discover effective adjuvants from certain TCMs. Here we get a comprehensive understanding of function mechanism of Ophiocordyceps sinensis in a molecular-target level. In the component-target network, the active components showed enormous polypharmacology, and after pathway enrichment analysis, multiple targets were found to participate in many physiological activities, including ion transport and
stimulus response. To enhance the immune response, we selected cordycepin as a potential adjuvant of the hepatitis B vaccine. The results of our experiments showed that cordycepin significantly enhances humoral and cellular immunity in balB/c mice without any side effects. Our results lay the foundation for the investigation of new combined vaccines Method Dataset construction. All the ingredients of Ophiocordyceps sinensis were extracted from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(http://sp.nwsuafedu.cn/tcmsp.php)andtheAnticancerHerbsDatabaseof SystemsPharmacology(http://sp.nwsuaf.edu.cn/cancerhspphp).Twentypotential compounds with OB 2 30%, DL 20.18 or HL 4 were selected. Additionally, three compounds in the CancerHSP Database with potential anti-cancer activities and ob> 30% were also selected as candidate compounds for further analysis. Duplicate compounds in the two databases were eliminated, yielding 23 readily-absorbed ds from a total pounds. After eliminating the additional compounds without targets, the 190 targets in the database were assembled and ranked for the 17 Its present in O. siner Network construction. To obtain a better understanding of the complex relationship between the compounds and targets, a network was constructed. The candidate compounds and potential targets were used to construct the compound-target network The network was generated and analyzed by Cytoscape 3. 2. 1. The degree of a node
12 stimulus response. To enhance the immune response, we selected cordycepin as a potential adjuvant of the hepatitis B vaccine. The results of our experiments showed that cordycepin significantly enhances humoral and cellular immunity in BALB/c mice without any side effects. Our results lay the foundation for the investigation of new combined vaccines. Methods Dataset construction. All the ingredients of Ophiocordyceps sinensis were extracted from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (http://lsp.nwsuaf.edu.cn/tcmsp.php) and the Anticancer Herbs Database of Systems Pharmacology (http://lsp.nwsuaf.edu.cn/CancerHSP.php). Twenty potential compounds with OB ≥ 30%, DL ≥ 0.18 or HL ≥ 4 were selected. Additionally, three compounds in the CancerHSP Database with potential anti-cancer activities and OB ≥ 30% were also selected as candidate compounds for further analysis. Duplicate compounds in the two databases were eliminated, yielding 23 readily-absorbed compounds from a total of 40 compounds. After eliminating the additional compounds without targets, the 190 targets in the database were assembled and ranked for the 17 components present in O. sinensis. Network construction. To obtain a better understanding of the complex relationships between the compounds and targets, a network was constructed. The candidate compounds and potential targets were used to construct the compound-target network. The network was generated and analyzed by Cytoscape 3.2.170. The degree of a node