| BackgroundThe global incidence of primary hepatocellular carcinoma(HCC)ranks the sixth place in cancer incidence and third in mortality.According to WHO’s prediction,there will be more than one million cases related to liver cancer in the next five years,and the proportion of cases suffering from HCC will be as high as 90%.Chinese herbal formulas are the treasures of traditional Chinese medicine,which has been extensively used in the progress of prevention and treatment of liver diseases and has a great research value.t The role of Chinese herbal formulas has become more and more clear with the increasing understanding of Chinese medicine,especially in immune activation,inflammation improvement,and metabolic regulation.Gansui-Banxia decoction is a classic formula of traditional Chinese medicine,firstly recorded in the Jin Kui Yao Lue.It is composed of four herbs,namely Gan Sui,Han Xia,Bai Shao,and Gan Cao.GansuiBanxia decoction is classified as a medicine for stepping down and expelling water.At present,the research on this formula mainly focuses on the evaluation of the "toxicityeffectiveness" of the combination of Gansui and Glycyrrhiza glabra.There is little research on the mechanism of action of the formula in the treatment of diseases.The mechanism of action of the compound against hepatocellular carcinoma from the perspective of compounds is still blank.Therefore,we proposed to investigate the pharmacological substances and their molecular mechanisms of the anti-liver cancer effect of the compound.Experimental purposeTo identify the main chemical components of the ethanol extract of Gansui-Banxia decoction,the main blood components of the ethanolic extract of Gansui-Banxia decoction was analyzed to predict the pharmacological targets and enrich the pathways of the anti-hepatocellular carcinoma network of Gansui-Banxia decoction,and to validate the experiments in mice.Experimental methodThe chemical composition of the extracts and serum metabolites were analyzed by UPLC-MS,and the pharmacological effects of Gansui-Banxia Decoction were described by combining the results of network pharmacology.ResultsA total of 23 ionic peaks were observed in the ethanol extract of Gansui-Banxia Decoction,which were tentatively corroborated.The main types were flavonoids,glycosides and saponins.Fifteen chemical components of the alcoholic extract of Gansui-Banxia Decoction were identified in serum,which maily were flavonoids and their glycosides,triterpene saponins,and monoterpene glycosides.Subsequently,the adaptive pathways were analyzed by means of network pharmacology:(1)the components of Gansui-Banxia Decoction were searched through the traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),and the active ingredients were screened according to two ADME parameters of oral bioavailability(OB)and drug similarity(DL),combined with literature review to collect the anti-HCC components of Gansui-Banxia Decoction,and finally 254 components were obtained.The active ingredients of the four herbs with good pharmacokinetics and biological activity were finally obtained.The active ingredients were predicted by using STITCH and Swiss Target Prediction database,and 178 key targets of HCC were obtained by mining the relationship between disease and targets using Metascape database.The database analysis showed that the active ingredient targets of Gansui-Banxia Decoction were mainly related to the pathway in cancer,and the c AMP signaling pathway and PI3K-Akt signaling pathway were the most significant.The transplanted tumor model mice was established and divided into model group,sorafenib group(60mg/m L),Gansui banxia decoction high(1.75 mg/kg),middle(0.88 mg/kg),low(0.49 mg/kg)groups for 14 days.The results of Western-blot and H&E dyeing showed that Gansui-Banxia Decoction could significantly inhibit the phosphorylation of Akt and Erk proteins in tumor tissues of mice,which was consistent with the theoretical prediction.ConclusionThe compounds in the ethanol extract of Gansui-Banxia decoction,such as kaempferol,quercetin,and the characteristic compounds of Gansui-Banxia decoction,can regulate the expression of AKT,STAT3,ERK and their phosphorylation levels by binding to proteins,finally,it plays the role of regulating tumor microenvironment and limiting tumor proliferation.However,the specific mechanism still needs to be further confirmed by follow-up experiments.In particular,the compound in medium and high doses can play a similar inhibitory effect to sorafenib,indicating that there is room for further development of the compound. |
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