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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Network Pharmacology Analysis on the Mechanism of Xihuangwan in Treating Rectal Cancer and Radiation Enteritis

Author(s): Minghe Lv, Rong Ding, Peizhen Ma, Yue Feng, Su Zeng, Yang Zhang, Wenhao Shen, Wenhui Guan, Xiangyu E., Hongwei Zeng* and Jingping Yu*

Volume 30, Issue 9, 2024

Published on: 19 February, 2024

Page: [683 - 701] Pages: 19

DOI: 10.2174/0113816128287232240213105913

Abstract

Background: Recent studies have shown that XihuangWan (XHW) is a kind of Chinese medicine with significant anti-tumor and anti-inflammatory activities. However, its mechanism for preventing and treating radiation proctitis in rectal cancer patients during radiotherapy remains unclear.

Methods: This study employed the network pharmacology to establish a “drug-active ingredient-target genedisease” network via using TCMSP, SymMap, GeneCard, and OMIM databases. The PPI network was conducted by the String tool. The core targets of XHW in the treatment of rectal cancer and radiation enteritis were identified by topological analysis, and the functional annotation analysis and pathway enrichment analysis were performed.

Results: A total of 61 active ingredients of XHW ingredients, 4607 rectal cancer-related genes, 5803 radiation enteritis-related genes, and 68 common targets of XHW in the treatment of rectal cancer and radiation enteritis were obtained. PTGS1 and NR3C2, as identified potential targets, were significantly associated with OS of colorectal cancer patients. GO and KEGG enrichment analysis showed that bioinformatics annotation of these common genes was mainly involved in DNA-binding transcription factor, PI3K/Akt, TNF, HIF-1 signaling pathway, and colorectal cancer pathway.

Conclusion: The active ingredients of XHW, mainly including Quercetin, Ellagic acid, and Stigmasterol, might act on common targets of rectal cancer and radiation enteritis, such as PTGS1, NR3C2, IL-6, EGFR, HIF-1A, CASP3, BCL2, ESR1, MYC, and PPARG, and regulate multiple signaling pathways like PI3K-Akt, TNF, and HIF-1 to inhibit tumor proliferation, tumor angiogenesis, inflammatory responses, and oxidative stress, thereby achieving prevention and treatment of radiation enteritis in rectal cancer patients during radiotherapy. It provided an important reference for further elucidating the anti-inflammation and anti-tumor mechanism and clinical application of XHW.

Keywords: Network pharmacology, Xihuangwan (XHW), rectal cancer, radiation enteritis, anti-tumor activity, radiotherapy.

« Previous Next »
[1]
Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin 2023; 73(3): 233-54.
[http://dx.doi.org/10.3322/caac.21772] [PMID: 36856579]
[2]
Cao M, Li H, Sun D, Chen W. Cancer burden of major cancers in China: A need for sustainable actions. Cancer Commun 2020; 40(5): 205-10.
[http://dx.doi.org/10.1002/cac2.12025] [PMID: 32359212]
[3]
Rahma OE, Yothers G, Hong TS, et al. Use of total neoadjuvant therapy for locally advanced rectal cancer: Initial results from the pembrolizumab arm of a phase 2 randomized clinical trial. JAMA Oncol 2021; 7(8): 1225-30.
[http://dx.doi.org/10.1001/jamaoncol.2021.1683] [PMID: 34196693]
[4]
Wang A, Zhou J, Wang G, Zhang B, Xin H, Zhou H. Deep learning of endoscopic features for the assessment of neoadjuvant therapy response in locally advanced rectal cancer. Asian J Surg 2023; 46(9): 3568-74.
[http://dx.doi.org/10.1016/j.asjsur.2023.03.165] [PMID: 37062601]
[5]
Ju HE, Lee CS, Bae JH, et al. High incidence of late anastomosis leakage in patients for rectal cancer after neoadjuvant chemoradiotherapy: A comparative study. Asian J Surg 2022; 45(10): 1832-42.
[http://dx.doi.org/10.1016/j.asjsur.2021.10.039] [PMID: 34815142]
[6]
Schrag D, Shi Q, Weiser MR, et al. Preoperative treatment of locally advanced rectal cancer. N Engl J Med 2023; 389(4): 322-34.
[http://dx.doi.org/10.1056/NEJMoa2303269] [PMID: 37272534]
[7]
Serra-Aracil X, Pericay C, Badia-Closa J, et al. Short-term outcomes of chemoradiotherapy and local excision versus total mesorectal excision in T2-T3ab,N,M rectal cancer: A multicentre randomised, controlled, phase III trial (the TAU-TEM study). Ann Oncol 2023; 34(1): 78-90.
[http://dx.doi.org/10.1016/j.annonc.2022.09.160] [PMID: 36220461]
[8]
Hauer-Jensen M, Denham JW, Andreyev HJN. Radiation enteropathy-pathogenesis, treatment and prevention. Nat Rev Gastroenterol Hepatol 2014; 11(8): 470-9.
[http://dx.doi.org/10.1038/nrgastro.2014.46] [PMID: 24686268]
[9]
Hale MF. Radiation enteritis: From diagnosis to management. Curr Opin Gastroenterol 2020; 36(3): 208-14.
[http://dx.doi.org/10.1097/MOG.0000000000000632] [PMID: 32141897]
[10]
Xu HB, Chen XZ, Wang X, Pan J, Yi-Zhuo Z, Zhou CH. Xihuang pill in the treatment of cancer: TCM theories, pharmacological activities, chemical compounds and clinical applications. J Ethnopharmacol 2023; 316: 116699.
[http://dx.doi.org/10.1016/j.jep.2023.116699] [PMID: 37257709]
[11]
Chen Z, Li Z, Yang S, Wei Y, An J. The prospect of Xihuang pill in the treatment of cancers. Heliyon 2023; 9(4): e15490.
[http://dx.doi.org/10.1016/j.heliyon.2023.e15490] [PMID: 37128341]
[12]
Guo Q, Lin J, Liu R, et al. Review on the applications and molecular mechanisms of Xihuang pill in tumor treatment. Evid Based Complement Alternat Med 2015; 2015: 1-10.
[http://dx.doi.org/10.1155/2015/854307] [PMID: 26170886]
[13]
Chen C, Yuan S, Chen X, Xie J, Wei Z. Xihuang pill induces pyroptosis and inhibits progression of breast cancer cells via activating the cAMP/PKA signalling pathway. Am J Cancer Res 2023; 13(4): 1347-62.
[PMID: 37168335]
[14]
Zhang YZ, Yang JY, Wu RX, et al. Network pharmacology-based identification of key mechanisms of Xihuang pill in the treatment of triple-negative breast cancer stem cells. Front Pharmacol 2021; 12: 714628.
[http://dx.doi.org/10.3389/fphar.2021.714628] [PMID: 34737698]
[15]
Cao B, Wang S, Li R, et al. Xihuang Pill enhances anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway. Biomed Pharmacother 2022; 151: 113081.
[http://dx.doi.org/10.1016/j.biopha.2022.113081] [PMID: 35605293]
[16]
Liao YH, Li CI, Lin CC, Lin JG, Chiang JH, Li TC. Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients. J Cancer Res Clin Oncol 2017; 143(12): 2425-35.
[http://dx.doi.org/10.1007/s00432-017-2491-6] [PMID: 28803328]
[17]
Zhao X, Hao J, Chen S. Network pharmacology-based strategy for predicting therapy targets of traditional Chinese medicine Xihuang pill on liver cancer. Evid Based Complement Alternat Med 2020; 2020: 1-12.
[http://dx.doi.org/10.1155/2020/6076572] [PMID: 32256653]
[18]
Yu D, An GY. Clinical effects of Xihuang pill combined with chemotherapy in patients with advanced colorectal cancer. Evid Based Complement Alternat Med 2017; 2017: 1-5.
[http://dx.doi.org/10.1155/2017/5936086] [PMID: 28458715]
[19]
Lv M, Zhuang X, Zhang Q, et al. Acetyl-11-keto-β-boswellic acid enhances the cisplatin sensitivity of non-small cell lung cancer cells through cell cycle arrest, apoptosis induction, and autophagy suppression via p21-dependent signaling pathway. Cell Biol Toxicol 2021; 37(2): 209-28.
[http://dx.doi.org/10.1007/s10565-020-09541-5] [PMID: 32562082]
[20]
Lv M, Shao S, Zhang Q, Zhuang X, Qiao T. Acetyl-11-keto-beta- boswellic acid exerts the anti-cancer effects via cell cycle arrest, apoptosis induction and autophagy suppression in non-small cell lung cancer cells. OncoTargets Ther 2020; 13: 733-44.
[http://dx.doi.org/10.2147/OTT.S236346] [PMID: 32158225]
[21]
Su S, Duan J, Chen T, et al. Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signaling pathway. Sci Rep 2015; 5(1): 13668.
[http://dx.doi.org/10.1038/srep13668] [PMID: 26329643]
[22]
Hu ML, Liao QZ, Liu BT, et al. Xihuang pill ameliorates colitis in mice by improving mucosal barrier injury and inhibiting inflammatory cell filtration through network regulation. J Ethnopharmacol 2024; 319(Pt 1): 117098.
[http://dx.doi.org/10.1016/j.jep.2023.117098] [PMID: 37640256]
[23]
Nogales C, Mamdouh ZM, List M, Kiel C, Casas AI, Schmidt HHHW. Network pharmacology: Curing causal mechanisms instead of treating symptoms. Trends Pharmacol Sci 2022; 43(2): 136-50.
[http://dx.doi.org/10.1016/j.tips.2021.11.004] [PMID: 34895945]
[24]
Zhang R, Zhu X, Bai H, Ning K. Network pharmacology databases for traditional Chinese medicine: Review and assessment. Front Pharmacol 2019; 10: 123.
[http://dx.doi.org/10.3389/fphar.2019.00123] [PMID: 30846939]
[25]
Blum A, Wang P, Zenklusen JC. SnapShot: TCGA-analyzed tumors. Cell 2018; 173(2): 530.
[http://dx.doi.org/10.1016/j.cell.2018.03.059] [PMID: 29625059]
[26]
Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487(7407): 330-7.
[http://dx.doi.org/10.1038/nature11252] [PMID: 22810696]
[27]
Allen C, Her S, Jaffray DA. Radiotherapy for cancer: Present and future. Adv Drug Deliv Rev 2017; 109: 1-2.
[http://dx.doi.org/10.1016/j.addr.2017.01.004] [PMID: 28189183]
[28]
Kavanagh BD, Pan CC, Dawson LA, et al. Radiation dose-volume effects in the stomach and small bowel. Int J Radiat Oncol Biol Phys 2010; 76(3): S101-7.
[http://dx.doi.org/10.1016/j.ijrobp.2009.05.071] [PMID: 20171503]
[29]
Tang SM, Deng XT, Zhou J, Li QP, Ge XX, Miao L. Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. Biomed Pharmacother 2020; 121: 109604.
[http://dx.doi.org/10.1016/j.biopha.2019.109604] [PMID: 31733570]
[30]
Dower JI, Geleijnse JM, Gijsbers L, Schalkwijk C, Kromhout D, Hollman PC. Supplementation of the pure flavonoids epicatechin and quercetin affects some biomarkers of endothelial dysfunction and inflammation in (pre)hypertensive adults: A randomized double-blind, placebo-controlled, crossover trial. J Nutr 2015; 145(7): 1459-63.
[http://dx.doi.org/10.3945/jn.115.211888] [PMID: 25972527]
[31]
Xiao L, Luo G, Tang Y, Yao P. Quercetin and iron metabolism: What we know and what we need to know. Food Chem Toxicol 2018; 114: 190-203.
[http://dx.doi.org/10.1016/j.fct.2018.02.022] [PMID: 29432835]
[32]
Kim SH, Yoo ES, Woo JS, et al. Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation. Eur J Pharmacol 2019; 860: 172568.
[http://dx.doi.org/10.1016/j.ejphar.2019.172568] [PMID: 31348906]
[33]
Xue P, Zhang G, Zhang J, Ren L. Synergism of ellagic acid in combination with radiotherapy and chemotherapy for cancer treatment. Phytomedicine 2022; 99: 153998.
[http://dx.doi.org/10.1016/j.phymed.2022.153998] [PMID: 35217437]
[34]
Baradaran Rahimi V, Ghadiri M, Ramezani M, Askari VR. Antiinflammatory and anti-cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies. Phytother Res 2020; 34(4): 685-720.
[http://dx.doi.org/10.1002/ptr.6565] [PMID: 31908068]
[35]
Djedjibegovic J, Marjanovic A, Panieri E, Saso L. Ellagic acid-derived urolithins as modulators of oxidative stress. Oxid Med Cell Longev 2020; 2020: 1-15.
[http://dx.doi.org/10.1155/2020/5194508] [PMID: 32774676]
[36]
Bae H, Song G, Lim W. Stigmasterol causes ovarian cancer cell apoptosis by inducing endoplasmic reticulum and mitochondrial dysfunction. Pharmaceutics 2020; 12(6): 488.
[http://dx.doi.org/10.3390/pharmaceutics12060488] [PMID: 32481565]
[37]
Zhang J, Zhang C, Miao L, Meng Z, Gu N, Song G. Stigmasterol alleviates allergic airway inflammation and airway hyperresponsiveness in asthma mice through inhibiting substance-P receptor. Pharm Biol 2023; 61(1): 449-58.
[http://dx.doi.org/10.1080/13880209.2023.2173252] [PMID: 36788676]
[38]
Li J, Xu Z. NR3C2 suppresses the proliferation, migration, invasion and angiogenesis of colon cancer cells by inhibiting the AKT/ERK signaling pathway. Mol Med Rep 2022; 25(4): 133.
[http://dx.doi.org/10.3892/mmr.2022.12649] [PMID: 35191517]
[39]
Liu H, Lei W, Li Z, Wang X, Zhou L. NR3C2 inhibits the proliferation of colorectal cancer via regulating glucose metabolism and phosphorylating AMPK. J Cell Mol Med 2023; 27(8): 1069-82.
[http://dx.doi.org/10.1111/jcmm.17706] [PMID: 36950803]
[40]
Huang Y, Wang Y, Ouyang Y. Elevated microRNA-135b-5p relieves neuronal injury and inflammation in post-stroke cognitive impairment by targeting NR3C2. Int J Neurosci 2022; 132(1): 58-66.
[http://dx.doi.org/10.1080/00207454.2020.1802265] [PMID: 32713242]
[41]
Vara JÁF, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 2004; 30(2): 193-204.
[http://dx.doi.org/10.1016/j.ctrv.2003.07.007] [PMID: 15023437]
[42]
Sul OJ, Ra SW. Quercetin prevents Lps-induced oxidative stress and inflammation by modulating NOX2/ROS/NF-kB in lung epithelial cells. Molecules 2021; 26(22): 6949.
[http://dx.doi.org/10.3390/molecules26226949] [PMID: 34834040]
[43]
Wu Y, Zhou BP. TNF-α/NF-κB/Snail pathway in cancer cell migration and invasion. Br J Cancer 2010; 102(4): 639-44.
[http://dx.doi.org/10.1038/sj.bjc.6605530] [PMID: 20087353]
[44]
Balamurugan K. HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer 2016; 138(5): 1058-66.
[http://dx.doi.org/10.1002/ijc.29519] [PMID: 25784597]

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