Exploring the mechanism of action of rehmannia glutinosa for the treatment of gastric cancer based on network pharmacology
DOI:
https://doi.org/10.1590/s2175-97902025e24651Keywords:
Network pharmacology, Rehmannia glutinosa, Gastric cancer, MechanismAbstract
This study investigates the molecular mechanisms of Rehmannia glutinosa in gastric cancer treatment using network pharmacology, supported by experimental validation. Network pharmacology methods, including active ingredient prescreening, target prediction, gene enrichment analysis, network analysis, and cell-based experiments, were applied to explore the therapeutic action of Rehmannia glutinosa against gastric cancer. Analysis revealed 33 active components and identified 41 potential targets. Gene Ontology analysis indicated that these targets were primarily associated with the biological processes “positive regulation of cell death,” “apoptotic signaling pathway,” and “response to mechanical stimulus.” Kyoto Encyclopedia of Genes and Genomes analysis showed that the targets were enriched in the cancer signaling, prostate cancer, tumor necrosis factor signaling, endocrine resistance–related signaling, and PI3K-Akt signaling pathways. In vitro experiments demonstrated that R. glutinosa total glycosides upregulated Caspase-3 activity, reduced PARP expression levels, and induced cell apoptosis. In conclusion, network pharmacology and experimental results suggest that R. glutinosa may exert its antigastric cancer effects through multiple biological processes and signaling pathways.
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Bhattamisra SK, Yap KH, Rao V, Choudhury H. Multiple biological effects of an iridoid glucoside, catalpol and its underlying molecular mechanisms. Biomolecules. 2019;10(1):32.
Boezio B, Audouze K, Ducrot P, Taboureau O. Network-based approaches in pharmacology. Mol Inform. 2017;36(10):1700048.
Cao M, Li H, Sun D, Lei L, Peng J, Chen W. Analysis of epidemiological trends of gastric cancer in China from 2000 to 2019. Chin J Gastro Surg. 2021;20(01):102-109.
Chandra R, Balachandar N, Wang S, Reznik S, Zeh H, Porembka M. The changing face of gastric cancer: epidemiologic trends and advances in novel therapies. Cancer Gene Ther. 2020.
Chao JC, Chiang SW, Wang CC, Tsai YH, Wu MS. Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells. World J Gastroenterol. 2006;(28):4478-4484.
Clatot F, Augusto L, Di Fiore F. ESR1 mutations in breast cancer. AGING-US. 2017;9(1):3-4.
Cui QL, Hu YH, Ma DY, Zhang JH, Liu BR. Research on the key anti-gastric cancer targets and regulatory networks of volatile oil constituents of ginseng based on network pharmacology. Acta Medica Mediterr. 2022;38(03):1509-1514.
Giannopoulou L, Mastoraki S, Buderath P, Strati A, Pavlakis K, Kasimir-Bauer S, et al. ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer. Gynecol Oncol. 2018;150(2):355-360.
Hu M, Zhu S, Xiong S, Xue X, Zhou X. MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (review). Oncol Rep. 2019; 41(3):1439-1454.
Huang B, Liu J, Ding F, Li Y. Epidemiology, risk areas and macro determinants of gastric cancer: a study based on geospatial analysis. Int J Health Geogr. 2023;22(1):32.
Jiang L, Liao J, Han Y. Study on the role and pharmacology of cuproptosis in gastric cancer. Front Oncol. 2023;13:1145446.
Li M, Wang X, Zhang Z, Zhang J, Zhao X, Zheng X, et al. Three new alkaloids and a new iridoid glycoside from the roots of Rehmannia glutinosa. Phytochem Lett. 2017;21:157-162.
Liu H, Zhou Y, Tang L. Caffeine induces sustained apoptosis of human gastric cancer cells by activating the caspase-9/caspase-3 signalling pathway. Mol Med Rep. 2017;16: 2445-2454.
Liu W, Chen X, Ge Y, Wang H, Phosat C, Li J, et al. Network pharmacology strategy for revealing the pharmacological mechanism of pharmacokinetic target components of San-Ye-Tang-Zhi-Qing formula for the treatment of type 2 diabetes mellitus. J Ethnopharmacol. 2020; 5(260):113044.
Lyons K, Le LC, Pham YT, Borron C, Park JY, Tran CTD, et al. Gastric cancer: epidemiology, biology, and prevention: a mini review. Eur J Cancer Prev. 2019;28(5):397-412.
Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. Int J Mol Sci. 2020;21(11):4012-4012.
Pandian J, Ganesan K. Delineation of gastric tumors with activated ERK/MAPK signaling cascades for the development of targeted therapeutics. Exp Cell Res. 2022;410:112956.
Rajaram P, Chandra P, Ticku S, Pallavi BK, Rudresh KB, Mansabdar P. Epidermal growth factor receptor: role in human cancer. Indian J Dent Res. 2017;28(6):687-694.
Shang L, Chen X, Zhu T, Chong S, Liu H, Huang W, et al. Cancer-associated fibroblast-secreted exosomes promote gastric cancer cell migration and invasion via the IL-32/ESR1 axis. Appl Biochem Biotech. 2024;1-14.
Shu P, Cai S, Zhao X, Zang S, Li R, Ge Y, et al. Chemical constituents from the roots of Rehmannia glutinosa. Rec Nat Prod. 2023;17(4):615-621.
Shi CJ, Wen XS, Gao HF, Liu ZH, Xu XK, Li LF, et al. Steamed root of Rehmannia glutinosa Libosch (Plantaginaceae) alleviates methotrexate-induced intestinal mucositis in rats. J Ethnopharmacol. 2016;183:143-150.
Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. The Lancet. 2020;396(10251):635-648.
Tian H, Ketkar R, Tao P. ADMETboost: a web server for accurate ADMET prediction. J Mol Model. 2022;28(12):408.
Thrift AP, Nguyen TH. Gastric Cancer Epidemiology. Gastrointest Endosc Clin N Am. 2021;31(3):425-439.
Wagner W, Ochman B, Wagner W. Semaphorin 6 family—an important yet overlooked group of signaling proteins involved in cancerogenesis. Cancers. 2023;15(23):5536.
Wang YK, Hong YJ, Wei M, Wu Y, Huang ZQ, Chen RZ, et al. Curculigoside attenuates human umbilical vein endothelial cell injury induced by H2O2. J Ethnopharmacol. 2010;132(1):233-239.
Wang Z, Wang R, Na Z, Liang S, Wu F, Xie H, et al. Network pharmacology analysis of liquid-cultured armillaria ostoyae mycelial metabolites and their molecular mechanism of action against gastric cancer. Molecules. 2024;29(7):1668.
Xu H, Shen X, Li X, Yang X, Chen C, Luo D. The natural product dehydrocurvularin induces apoptosis of gastric cancer cells by activating PARP-1 and caspase-3. Apoptosis. 2023;28(3-4):525-538.
Xu W, Li B, Xu M, Yang T, Hao X. Traditional Chinese medicine for precancerous lesions of gastric cancer: a review. Biomed Pharmacother. 2022;146:112542.
Xu X, Yu Z, Zeng S. Investigating the therapeutic mechanism of Xiaotan Sanjie Formula for gastric cancer via network pharmacology and molecular docking: a review. Medicine. 2023;102(46):e35986.
Xu Z, Dai X, Su S, Yan H, Guo S, Qian D, et al. Investigation of dynamic accumulation and regularity of nine glycosides and saccharides in Rehmannia glutinosa by rapid quantitative analysis technology. J Sep Sci. 2019;42(8):1489-1499.
Xu Z, Dai XX, Zhang QY, Su SL, Yan H, Zhu Y, et al. Protective effects and mechanisms of Rehmannia glutinosa leaves total glycoside on early kidney injury in db/db mice. Biomed Pharmacother. 2020;125:109926.
Yang L, Sun H, Bai Y, Sun S, Wu X, Gan Z, et al. Trends and projections of stomach cancer incidence in Hong Kong: a population-based study. Cancer Invest. 2023;41(4):319–329.
Zhao L, Zhang H, Li N, Chen J, Xu H, Wang Y, et al. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. J Ethnopharmacol. 2023;309:116306.
Zhang RX, Li MX, Jia ZP. Rehmannia glutinosa: review of botany, chemistry and pharmacology. J Ethnopharmacol. 2008;117(2):199-214.
Zheng, Y. The therapeutic effects of rehmannia oral liquid for the syndrome of heat accumulation with Yin consumption in esophagus cancer patients undergoing radiotherapy--a report of 60 cases. J Tradit Chin Med. 2007;27(4):248-254.
Zhu P, Wu Y, Yang A, Fu X, Mao M, Liu Z. Catalpol suppressed proliferation, growth and invasion of CT26 colon cancer by inhibiting inflammation and tumor angiogenesis. Biomed Pharmacother. 2017;95:68-76.
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