Study On The Mechanism Of Action Of Magnolia Officinalis In The Treatment Of Hepatocellular Carcinoma Based On UPLC-Q-TOF/MS And Network Pharmacology

Rationale for topic selection:In recent years,malignant tumors remain a disease with high human mortality rate,and among the high incidence of liver cancer,hepatocellular carcinoma(HCC)is the most common.At present,the treatment of advanced HCC mainly relies on targeted drugs,but tumor recurrence and metastasis,drug resistance and adverse reactions are still the main reasons for the poor survival quality of HCC patients.Magnolia officinalis,a traditional Chinese medicine for strengthening the spleen and regulating Qi.It can treat HCC with evidence of liver depression and spleen deficiency,which is in line with the dialectical treatment of HCC in traditional Chinese medicine.A review of the literature revealed that honokiol is an important target drug of Magnolia officinalis against HCC and drug resistance.Objective:To explore the mechanism of Magnolia officinalis in the treatment of HCC,and to provide a certain basis and reference for further exploration of the medicinal value of Magnolia officinalis.Methods:(1)The UPLC-Q-TOF/MS technique was used to qualitatively analyze the aqueous extract of Magnolia officinalis and its drug-containing serum components,and to analyze the cleavage pathway of each main component.(2)The identified blood-entering components were subjected to network pharmacological analysis to screen the potential active components,key targets,and major signaling pathways of Magnolia officinalis for the treatment of HCC,and the main results were molecularly docked.(3)The effect of honokiol on the proliferation of Hep G2 cells was detected,by cell experiment..(4)PCR and WB were used to detect the expression of MEK,P-MEK,ERK1/2,P-ERK1/2,and VEGF in Hep G2 cells intervened by honokiol.Results:(1)Thirty-eight drug components were identified from the aqueous extract of Magnolia officinalis.Twelve blood-entering components were identified from its drugcontaining serum.(2)Five active ingredients,seven core targets and two major signaling pathways were screened by network pharmacology.Among the molecular docking,honokiol had the strong binding ability to ERK1 targets.(3)The results of in vitro experiments showed that the higher the concentration of honokiol in Hep G2 cells,the higher the rate of inhibition of cell proliferation.(4)The results of PCR and WB assay showed that honokiol could down-regulate the expressions of P-MEK,P-ERK1/2,and VEGF in Hep G2 cells.Conclusion:(1)Honokiol,magnolol,magnolignan,magnoflorine and asimilobin in Magnolia officinalis may be the pharmacological basis of anti-HCC.(2)The anti-HCC effect of Magnolia officinalis has the characteristics of multiple components,multiple targets,and multiple pathways.Its therapeutic mechanism may be to regulate PI3K/Akt,MAPK and other signal pathways.(3)The screened honokiol and MAPK signaling pathway experiments were verified.Honokiol can regulate the MAPK/ERK1/2/VEGF signaling pathway,thereby exerting an anti-HCC effect.