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BMC Complementary Medicine and Therapies

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Open Access 01-12-2023 | Gastritis | Research

Explore the active ingredients and potential mechanisms of JianPi QingRe HuaYu Methods in the treatment of gastric inflammation-cancer transformation by network pharmacology and experimental validation

Authors: Kechao Nie, Zhihua Zheng, Xiushen Li, Yonglong Chang, FengBin Liu, Xiaoyu Wang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

Abstract

Background

JianPi QingRe HuaYu Methods (JQH) have been long used to treat chronic atrophic gastritis (CAG) and precancerous lesions of gastric cancer (PLGC). However, whether JQH can inhibit the transformation of gastritis to gastric cancer (GC) remains unclear.

Methods

Herein, we first retrieved the active ingredients and targets of JQH from the TCMSP database and the targets related to the gastric inflammation-cancer transformation from public databases. Differentially expressed genes (DEGs) related to gastric inflammation-cancer transformation were identified from the Gene Expression Omnibus (GEO) database. Then, we obtained the potential therapeutic targets of JQH in treating gastric inflammation-cancer transformation by intersecting drugs and disease targets. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) analyses of the potential therapeutic targets were conducted using R software. Next, we conducted molecular docking and in vitro experiments to validate our results.

Results

We obtained 214 potential therapeutic targets of JQH by intersecting drugs and disease targets. We found that the potential mechanisms of JQH in treating gastric inflammation-cancer transformation might be related to JAK-STAT, Wnt, p53 and VEGF signaling pathways. The molecular docking indicated that quercetin, as the main active ingredient of JQH, might inhibit gastric inflammation-cancer transformation by binding with specific receptors. Our experimental results showed that quercetin inhibited cells proliferation (P < 0.001), promoted cell apoptosis (P < 0.001), reduced the secretion of pro-inflammatory cytokines (P < 0.001) and promoted the secretion of anti-inflammatory cytokines (P < 0.001) in MNNG-induced GES-1 cells. Furthermore, quercetin inhibited cells proliferation (P < 0.001) and reduced mRNA and protein level of markers of PLGC (P < 0.001) in CDCA-induced GES-1 cells.

Conclusion

These results provide the material basis and regulatory mechanisms of JQH in treating gastric inflammation-cancer transformation.

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Tan P, Yeoh KG. Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology. 2015;149(5):1153–62.CrossRefPubMed

Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988;48(13):3554–60.PubMed

Collatuzzo G, Pelucchi C, Negri E, Lopez-Carrillo L, Tsugane S, Hidaka A, Shigueaki HG, Hernandez-Ramirez RU, Lopez-Cervantes M, Malekzadeh R, et al. Exploring the interactions between Helicobacter pylori (Hp) infection and other risk factors of gastric cancer: a pooled analysis in the Stomach cancer Pooling (StoP) Project. Int J Cancer. 2021;149(6):1228–38.CrossRefPubMed

Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology. 2015;148(4):719–31.CrossRefPubMed

Ford AC, Forman D, Hunt RH, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014;348:g3174.CrossRefPubMedPubMedCentral

Peng W, Zhang S, Zhang Z, Xu P, Mao D, Huang S, Chen B, Zhang C, Zhang S. Jianpi Jiedu decoction, a traditional Chinese medicine formula, inhibits tumorigenesis, metastasis, and angiogenesis through the mTOR/HIF-1alpha/VEGF pathway. J Ethnopharmacol. 2018;224:140–8.CrossRefPubMed

Hu L, Lao SX, Wang JH: Effect of “Wei Yan Xiao” on bcl-2 Oncogene mRNA Expression in Precancerous Lesion of Gastric Cancer. SH.J.TCM 2006(01):27–28.

Zhuang KH, Li HW, Liu H, Pan JL, Wen Y, Liu FB. Clinical study of Weiweiqing granule in the treatment of chronic atrophic gastritis. Modern Digest Interv. 2018;23(04):479–83.

Zhuang K, Li H, Liu F. Weiweiqing has effect on ultrastructure of gastric mucosa in rats with chronic atrophic gastritis. J New Chinese Med. 2018;50(07):4–7.

10.

Zhuang K, Li H, Liu H, Pan J. LIU F: Effect of invigorating spleen and clearing heat and activating blood circulation on inflammatory pathway factors in rats with atrophic gastritis. Modern Digest Interv. 2018;23(02):145–8.

11.

Wu Z, Li W, Liu G, Tang Y. Network-based methods for prediction of drug-target interactions. Front Pharmacol. 2018;9:1134.CrossRefPubMedPubMedCentral

12.

Pan J, Wen S, Wen Y, Li P, Liu Y, Fu B, Wang X, Liu F. Mechanism research of weiweiqing granules for key mRNA associated with chronic inflammation transforming into gastric adenocarcinoma based on molecular docking technology. CJTCMP. 2019;34(10):4542–6.

13.

Liu X, Sun XH, Qi X. Creation of nitrosamine compounds MNNG induced GES-1 cell model of malignant transformation. Med J Qilu. 2013;28(02):115–6.

14.

Li T, Guo H, Li H, Jiang Y, Zhuang K, Lei C, Wu J, Zhou H, Zhu R, Zhao X, et al. MicroRNA-92a-1-5p increases CDX2 by targeting FOXD1 in bile acids-induced gastric intestinal metaplasia. Gut. 2019;68(10):1751–63.CrossRefPubMed

15.

Zhang P, Yang M, Zhang Y, Xiao S, Lai X, Tan A, Du S, Li S. Dissecting the single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer. Cell Rep. 2019;27(6):1934–47.CrossRefPubMed

16.

Lao SX, Xu XM, Zhou FS, Yu SY, Jia JG. Efficacy analysis of Weiyanxiao in the treatment of precancerous lesions of gastric cancer. Tradition Chinese Drug Res Clin Pharmacol. 1997;02:9–12.

17.

Zou S, Tong Q, Liu B, Huang W, Tian Y, Fu X. Targeting STAT3 in cancer immunotherapy. Mol Cancer. 2020;19(1):145.CrossRefPubMedPubMedCentral

18.

Zhang HX, Xu ZS, Lin H, Li M, Xia T, Cui K, Wang SY, Li Y, Shu HB, Wang YY. TRIM27 mediates STAT3 activation at retromer-positive structures to promote colitis and colitis-associated carcinogenesis. Nat Commun. 2018;9(1):3441.CrossRefPubMedPubMedCentral

19.

Xu ZS, Zhang HX, Li WW, Ran Y, Liu TT, Xiong MG, Li QL, Wang SY, Wu M, Shu HB, et al. FAM64A positively regulates STAT3 activity to promote Th17 differentiation and colitis-associated carcinogenesis. Proc Natl Acad Sci U S A. 2019;116(21):10447–52.CrossRefPubMedPubMedCentral

20.

Liu Y, Liu L, Zhou Y, Zhou P, Yan Q, Chen X, Ding S, Zhu F. CKLF1 enhances inflammation-mediated carcinogenesis and prevents doxorubicin-induced apoptosis via IL6/STAT3 signaling in HCC. Clin Cancer Res. 2019;25(13):4141–54.CrossRefPubMed

21.

Soutto M, Chen Z, Bhat AA, Wang L, Zhu S, Gomaa A, Bates A, Bhat NS, Peng D, Belkhiri A, et al. Activation of STAT3 signaling is mediated by TFF1 silencing in gastric neoplasia. Nat Commun. 2019;10(1):3039.CrossRefPubMedPubMedCentral

22.

Liao W, Wen Y, Wang J, Zhao M, Lv S, Chen N, Li Y, Wan L, Zheng Q, Mou Y, et al. Gallic acid alleviates gastric precancerous lesions through inhibition of epithelial mesenchymal transition via Wnt/beta-catenin signaling pathway. J Ethnopharmacol. 2023;302(Pt A):115885.CrossRefPubMed

23.

Wang P, Xu T, Yan Z, Zheng X, Zhu F. Jian-Pi-Yi-Qi-Fang ameliorates chronic atrophic gastritis in rats through promoting the proliferation and differentiation of gastric stem cells. Ann Transl Med. 2022;10(17):932.CrossRefPubMedPubMedCentral

24.

Yan Z, Xu T, Xu Y, Chen W, An Z, Zhu F. Jianpiyiqi formula ameliorates chronic atrophic gastritis in rats by modulating the Wnt/beta-catenin signaling pathway. Exp Ther Med. 2021;22(2):878.CrossRefPubMedPubMedCentral

25.

Mori J, Tanikawa C, Ohnishi N, Funauchi Y, Toyoshima O, Ueda K, Matsuda K. EPSIN 3, a novel p53 target, regulates the apoptotic pathway and gastric carcinogenesis. Neoplasia. 2017;19(3):185–95.CrossRefPubMedPubMedCentral

26.

Costa L, Corre S, Michel V, Le Luel K, Fernandes J, Ziveri J, Jouvion G, Danckaert A, Mouchet N, Da SBD, et al. USF1 defect drives p53 degradation during Helicobacter pylori infection and accelerates gastric carcinogenesis. Gut. 2020;69(9):1582–91.CrossRefPubMed

27.

Wen JX, Tong YL, Ma X, Wang RL, Li RS, Song HT, Zhao YL. Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N’-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis. Phytomedicine. 2021;91:153619.CrossRefPubMed

28.

Guo SL, Ye H, Teng Y, Wang YL, Yang G, Li XB, Zhang C, Yang X, Yang ZZ, Yang X. Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency. Nat Commun. 2013;4:2544.CrossRefPubMed

29.

Lin FC, Liu YP, Lai CH, Shan YS, Cheng HC, Hsu PI, Lee CH, Lee YC, Wang HY, Wang CH, et al. RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells. Oncogene. 2012;31(39):4302–16.CrossRefPubMed

30.

Silva M, Azenha D, Pereira C, Almeida A, Balseiro S, Sampaio AM, Santos P, Carvalho L. Gastric carcinoma and chronic gastritis: epigenetic regulation of CDH1 (E-Cadherin), CDKN2A (p16INK4A), PTGS2 (COX-2) and EGFR genes through methylation. Acta Med Port. 2010;23(1):5–14.PubMed

31.

Zhang H, Deng T, Liu R, Bai M, Zhou L, Wang X, Li S, Wang X, Yang H, Li J, et al. Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis. Nat Commun. 2017;8:15016.CrossRefPubMedPubMedCentral

32.

Yuan W, Liu B, Wang X, Li T, Xue H, Mo X, Yang S, Ding S, Han W. CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5 activity in gastric cancer. Cancer Lett. 2017;386:77–86.CrossRefPubMed

33.

Zheng L, Liang X, Li S, Li T, Shang W, Ma L, Jia X, Shao W, Sun P, Chen C, et al. CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression. EBioMedicine. 2018;38:69–78.CrossRefPubMedPubMedCentral

34.

Chen XL, Hong LL, Wang KL, Liu X, Wang JL, Lei L, Xu ZY, Cheng XD, Ling ZQ. Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-kappaB pathway. Int J Biol Sci. 2019;15(10):2075–86.CrossRefPubMedPubMedCentral

35.

Zhang S, Huang J, Xie X, He Y, Mo F, Luo Z. Quercetin from polygonum capitatum protects against gastric inflammation and apoptosis associated with helicobacter pylori infection by affecting the levels of p38MAPK, BCL-2 and BAX. Molecules. 2017;22(5):744.CrossRefPubMedPubMedCentral

36.

Hsieh HL, Yu MC, Cheng LC, Chu MY, Huang TH, Yeh TS, Tsai MM. Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-alpha-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells. World J Gastroenterol. 2022;28(11):1139–58.CrossRefPubMedPubMedCentral

37.

Yu C, Lu X, Li L, Wang A. LI X: Mechanisms of quercetin-mediated IRF8/IFN-γ in improving chronic atrophic gastritis induced by Hp infection. Chin J Nosocomio. 2022;20:3073–7.

38.

Zhang JY, Lin MT, Zhou MJ, Yi T, Tang YN, Tang SL, Yang ZJ, Zhao ZZ, Chen HB. Combinational treatment of curcumin and quercetin against gastric cancer MGC-803 cells in vitro. Molecules. 2015;20(6):11524–34.CrossRefPubMedPubMedCentral

39.

Lei CS, Hou YC, Pai MH, Lin MT, Yeh SL. Effects of quercetin combined with anticancer drugs on metastasis-associated factors of gastric cancer cells: in vitro and in vivo studies. J Nutr Biochem. 2018;51:105–13.CrossRefPubMed

Title: Explore the active ingredients and potential mechanisms of JianPi QingRe HuaYu Methods in the treatment of gastric inflammation-cancer transformation by network pharmacology and experimental validation
Authors: Kechao Nie
Zhihua Zheng
Xiushen Li
Yonglong Chang
FengBin Liu
Xiaoyu Wang
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Gastritis
Active Ingredients
Gastric Cancer
Gastric Cancer
Published in: BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-023-04232-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Explore the active ingredients and potential mechanisms of JianPi QingRe HuaYu Methods in the treatment of gastric inflammation-cancer transformation by network pharmacology and experimental validation

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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