| Liver cancer is a common malignant tumor.According to statistics,the annual mortality rate of liver cancer in China occupies the second place in the mortality rate of all malignant tumors.Surgical resection,chemotherapy drugs or radiotherapy drugs not only destroy tumor cells,but also cause great damage to the human body,while Traditional Chinese Medicine(TCM)in the treatment of liver cancer can inhibit the spread and metastasis of cancer cells.It can also alleviate the side effects of western medicine therapy,so in recent years,more and more researchers pay great attention to the anti-tumor effects of TCM with high efficiency and low toxicity.Traditional Chinese medicine clinical found that Radix Paeoniae Rubra(Paeonia veitchii)promoting blood circulation and removing blood stasis,clearing liver and purging fire,clearing heat and cooling blood,compatibility with North Bupleurum has a good effect on liver cancer.South Bupleurum(Bupleurum scorzonerifolium)is one of the sources of traditional Chinese medicine Bupleurum.Compared with North Bupleurum,it is better at rising Yang and dispelling evil,soothing liver and relieving depression.The compatibility of South Bupleurum and Radix Paeoniae Rubra can relieve depression by entering qi branch,cool blood and break stasis by entering blood,and exert the effect of soothing liver and relieving depression,cooling liver and removing blood stasis,activating blood circulation and relieving pain.Combined with the etiology and pathogenesis of liver qi stagnation,blood stagnation and blood stasis in patients with liver cancer,the effect of the combination of South Bupleurum and Radix Paeoniae Rubra in the treatment of liver cancer will be better than that of South Bupleurum and Radix Paeoniae Rubra.Therefore,in this paper,according to the actual clinical application,the UPLC-Q-TOFMS/MS technology was used to illustrate the pharmacodynamic material basis of herb pair of South Bupleurum-Radix Paeoniae Rubra on the treatment of liver cancer.Through the network pharmacology method and experimental verification preliminary explore the antihepatoma mechanism of the herb pairs.The results will provide a scientific basis for their clinical application in the treatment of liver cancer and the related drug development.In this paper,the inhibitory effects of 30,50,70,95%ethanol extract and 95%ethanol nbutanol extract on the proliferation of human hepatocellular carcinoma cell line HepG2 were investigated.Finally,it was determined that CSYZ had the strongest anti-liver cancer effect,and it was determined as the best anti-liver cancer effective herb pair of South Bupleurum and Radix Paeoniae Rubra.The chemical components of the CSYZ obtained above was analyzed by UPLC-Q-TOFMS/MS technology.A total of 31 chemical constituents were analyzed and identified,of which 20 were derived from South Bupleurum,18 from Radix Paeoniae Rubra,and 7 were common components of South Bupleurum and Radix Paeoniae Rubra.The contents of saikosaponin a,saikosaponin d and paeoniflorin in Paeonia veitchii and Paeonia veitchii were determined.The result showed that the proportion of saikosaponin a,saikosaponin d and paeoniflorin in the single decoction of the two herbs was about 0.3:0.3:14,while that of the combined decoction was 0.2:0.1:14 respectively.On this basis,a total of 14 active components of South Bupleurum and Radix Paeoniae Rubra were obtained by using the method of network pharmacology.There were 72 intersection targets between active components and liver cancer,and 36 core targets were screened.The pathway enrichment analysis of 36 core targets was carried out,and the hepatoma-related signal pathway,PI3K/AKT pathway,which involved the most core targets,was verified by experiments.The results showed that the effective components could indeed inhibit the expression of p-PI3K and p-AKT,and then inhibit the proliferation of human hepatocellular carcinoma HepG2 cells.Finally,human normal hepatocyte L02 was selected as the research object to investigate the effects of effective components of South Bupleurum and Radix Paeoniae Rubra on the activities of glutamic pyruvic transaminase(ALT)and glutamic oxaloacetic transaminase(AST)in the supernatant of L02 cells in vitro.It was found that the effective herb pair of South Bupleurum-Radix Paeoniae Rubra could reduce the activities of AST and ALT in the supernatant of L02 cells,and thereby reduce the damage of normal hepatocytes.It is suggested that the compatibility of South Bupleurum and Radix Paeoniae Rubra may not only be the addition of chemical components,it is speculated that the combination of South Bupleurum and Radix Paeoniae Rubra can reduce the dissolution of saikosaponins,and can not only ensure the efficacy of anti-liver cancer,but also reduce the toxicity to normal cells.To sum up,the best effective fraction of herb pair of South Bupleurum-Radix Paeoniae Rubra against liver cancer is CSYZ,and 14 chemical components are determined as the effective components against liver cancer,including saikosaponin a,saikosaponin d,paeoniflorin,etc.,which can exert its anti-liver cancer effect through multiple pathways including regulation of PI3K/AKT,and South Bupleurum can reduce the dissolution of saikosaponins by combining with Radix Paeoniae Rubra.And the effective components of Radix Paeoniae Rubra can reduce the toxicity of the effective components of Southern Bupleurum on normal hepatocytes. |
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