Abstract
Objective: San-Cao granule (SCG), a traditional Chinese herb formula, has been used for treating autoimmune hepatitis (AIH) in our clinics for a long time. However, its active ingredients and mechanisms of action were still unknown due to its complicated chemical compositions. In the present study, the pharmacological study of SCG on acute liver injury induced by Concanavalin A (Con A) was performed to provide a scientific evidence for SCG against liver injury.Methods: In order to screen active components and predicate mechanisms of action, an “ingredients-target-disease” interaction network was constructed by network pharmacology. Then, the pharmacological study was performed to evaluate the therapeutic effect and the underlying mechanisms of SCG on Con A-induced liver injury in mice.Results: This research demonstrated the pharmacological effect of SCG on Con A-induced liver injury, which was through improving the liver function, relieving the pathological changes of liver tissue, decreasing the level of pro-inflammatory cytokines, and thus balancing the pro- and anti-inflammatory cytokines. And the anti-inflammatory of SCG may advantage over the ursodeoxycholic acid (UDCA). Network pharmacology analysis revealed that the pharmacological effect of SCG might be related to its active ingredients of taraxanthin, dihydrotanshinone I, isotanshinone I, γ-sitosterol, 3β-acetyl-20,25-epoxydammarane-24α, and δ-7-stigmastenol. The hepatoprotective effect of SCG was reflected by suppressing Con A-induced apoptosis which was mediated by TRAIL and FASL.Conclusion: The combination of network pharmacology and experimental data has revealed the anti-apoptotic effect of SCG against Con A-induced liver injury.
Highlights
Autoimmune hepatitis as a chronic progressive liver disease was characterized by immunological tolerance disorders targeting hepatocytes and inducing inflammation of liver parenchyma, eventually causing cirrhosis and liver failure (Krawitt, 2006; Manns and Vogel, 2006)
This research demonstrated the pharmacological effect of San-Cao granule (SCG) on Concanavalin A (Con A)-induced liver injury, which was through improving the liver function, relieving the pathological changes of liver tissue, decreasing the level of pro-inflammatory cytokines, and balancing the pro- and anti-inflammatory cytokines
Network pharmacology analysis revealed that the pharmacological effect of SCG might be related to its active ingredients of taraxanthin, dihydrotanshinone I, isotanshinone I, γ-sitosterol, 3β-acetyl20,25-epoxydammarane-24α, and δ-7-stigmastenol
Summary
Autoimmune hepatitis as a chronic progressive liver disease was characterized by immunological tolerance disorders targeting hepatocytes and inducing inflammation of liver parenchyma, eventually causing cirrhosis and liver failure (Krawitt, 2006; Manns and Vogel, 2006). Up to now, diversified animal models for AIH study have been used to mimic human liver injury, and the induction reagents include Con A (Tiegs et al, 1992), Poly I:C (Dong et al, 2004), lipopolysaccharide (LPS; Yee et al, 2003), as well as alcohol consumption (Minagawa et al, 2004). Con A-induced immunological liver injury model, established by Tiegs et al (1992) has been widely used for the resemblance of human AIH. There were still limitations that the active ingredients of SCG and their targets were complicated, which caused us hard to illuminate its pharmacological mechanisms. The current research aimed to explore the active ingredients of SCG and illustrate the underlying mechanism by combining network pharmacology and molecular biology technology (Figure 1)
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