Identifying medication regularity of traditional Chinese medicine and potential pharmacological mechanism of Jiedu Sangen decoction in colorectal cancer treatment by data mining and network pharmacology

Objective:Colorectal cancer(CRC)is one of the most common malignancies in the world,and traditional Chinese medicine(TCM)is widely used in its treatment in China.However,the medication rules of TCM for CRC treatment remain unclear.Therefore,data mining combined with network pharmacology was utilized to establish treatment principles and rules.Methods:The CRC cases treated at Zhejiang Provincial Hospital of Chinese Medicine from January 1,2016 to October 31,2021 were analyzed using data mining methods.UPLC-Q/TOF-MS analysis was performed to identify the chemical composition of Jiedu Sangen decoction(JSD).Network pharmacology was used to reveal the therapeutic mechanism of JSD.Results:A total of 312 cases 2,998 prescriptions that met the inclusion criteria used 343 kinds of traditional Chinese medicines.The nature of the herbs used in treatment was mainly warm and mild.The taste was mainly sweet,bitter,and pungent.The meridian tropisms were mainly the spleen meridian,followed by lung and stomach meridians.Tonifying and replenishing herbs were the most frequently used in treatment.High-frequency herbs were classified into 11 categories by cluster analysis,and 42 association rules were obtained by association rule analysis.Combined with complex network analysis,3 core prescriptions for clinical CRC treatment were obtained.Jiedu Sangen decoction contains 64 chemical ingredients,out of which 31 active ingredients were identified,including polydatin,caffeic acid,and glutamic acid,along with 130 potential targets such as AKT1,SRC,and MAPK1.Jiedu Sangen decoction may play a role in regulating inflammation,immunity,metabolism,and hormones in the development of CRC via pathways such as the relaxin signaling pathway,IL-17 signaling pathway,prolactin signaling pathway,and T cell receptor signaling pathway.Conclusions:This study summarizes the treatment and medication principles for clinical CRC treatment,promoting the inheritance and development of the traditional Chinese medical experience.

Jiedu Sangen decoction inhibits chemoresistance to 5-fluorouracil of colorectal cancer cells by suppressing glycolysis via PI3K/AKT/HIF-1αsignaling pathway

Drug resistance is a major obstacle in the development of effective colorectal cancer(CRC)therapy.Our study aimed to explore the reversal abilities of Jiedu Sangen decoction(JSD)on the 5-fluorouracil(5-FU)resistance and its underlying molecular mechanisms.Expression changes in HIF-1 of CRC tissues were firstly revealed by bioinformatics analysis.Afterwards,cell viabilities of JSD and 5-FU treatments on 5-FU resistant human colon cancer cells(HCT-8/5-FU)were determined.Expressions of phosphoinositide 3-kinase(PI3K),protein kinase B(AKT)/p-AKT,hypoxia-inducible factor 1(HIF-1α),as well as glycolysis related proteins such as L-lactate dehydrogenase A(LDHA),Glucose transporter type 1(Glut1),Hexokinase 2(HKII),and cysteinyl aspartate specific proteinase(Caspase)family members in HCT-8/5-FU cells,HIF-1αsilenced HCT-8/5-FU cells and tumor tissues were detected by western blotting.HIF-1αwas found over expressed in CRC tissues according to public available datasets in Oncomine.Growth inhibition rates of HCT-8/5-FU cells were increased along with the increase of JSD concentrations.JSD caused down-regulated HIF-1α,PI3K,AKT/p-AKT,HKII and Glut1,as well as up-regulated Caspase3 and Caspase9 in HCT-8/5-FU cells and tumor tissues.In HIF-1αsilenced HCT-8/5-FU cells,synergistic group showed significantly reduced expression levels of PI3K,AKT,p-AKT.Additionally,up-regulated expressions of Caspase6 and Caspase7 were observed.JSD combined with 5-FU also exhibited obvious inhibitory efficiency on tumor growth in vivo.JSD may reverse 5-FU resistance by suppressing glycolysis via PI3K/AKT/HIF-1αsignaling pathway,thereby inhibiting glycolysis and induce apoptosis to enhance anti-tumor activity.