Exploration of the Mechanism of Chaenomeles speciosa Against Gastric Aging Based on Network Pharmacology and Experimental Validation

WANG Xiao, SHU Heng, LI Jie, HE Yu-min, HE Hai-bo, YUAN Cheng-fu, ZHANG Ji-hong, LI Hao-ran, ZOU Kun, WANG Jun-zhi

Chinese Pharmaceutical Journal ›› 2023, Vol. 58 ›› Issue (13) : 1166-1177.

PDF(3598 KB)
PDF(3598 KB)
Chinese Pharmaceutical Journal ›› 2023, Vol. 58 ›› Issue (13) : 1166-1177. DOI: 10.11669/cpj.2023.13.002

Exploration of the Mechanism of Chaenomeles speciosa Against Gastric Aging Based on Network Pharmacology and Experimental Validation

  • WANG Xiao1, SHU Heng1, LI Jie1, HE Yu-min2, HE Hai-bo1,3*, YUAN Cheng-fu2, ZHANG Ji-hong4, LI Hao-ran4, ZOU Kun1, WANG Jun-zhi1*
Author information +
History +

Abstract

OBJECTIVE To explore the underlying mechanism of Pseudocydonia sinensis against gastric aging by network pharmacology, molecular docking, and in vitro cell experiments. METHODS The composition and potential targets of Pseudocydonia sinensis were obtained by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM), literature review and Swiss ADME; aging related genes were collected using GeneCard database, aging genes and potential targets of Pseudocydonia sinensis were imported into string platform to build protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were completed by using David platform, and then the anti-aging mechanism of Pseudocydonia sinensis was verified by molecular docking and cell experiments. RESULTS According to the prediction results, 35 main components and 65 chief targets of Chaenomeles speciosa against gastric aging were obtained, the mechanism of action may be related to the cancer pathway, phosphatidylinositol 3-kiases/protein kinase B(PI3K/AKT) signaling pathway. In vitro experiments demonstrated that the extract of Pseudocydonia sinensis could significantly reduce the level of reative oxygen species(ROS) and β-galactosidase, elevate the protein expressions of p-PI3K, p-AKT, p-GSK3β, β-catenin and alleviate G0/G1 cell cycle arrest in D-galactose induced human gastric epithelial cells (GES-1). CONCLUSION This study manifested the characteristics of multi-component, multi-target and multi-channelsynergistic action of Pseudocydonia sinensis against gastric aging, and also provided experimental basis for drug development and clinical application of anti-gastric senescence.

Key words

Pseudocydonia sinensis / gastric aging / network pharmacology / molecular docking / molecular mechanism

Cite this article

Download Citations
WANG Xiao, SHU Heng, LI Jie, HE Yu-min, HE Hai-bo, YUAN Cheng-fu, ZHANG Ji-hong, LI Hao-ran, ZOU Kun, WANG Jun-zhi. Exploration of the Mechanism of Chaenomeles speciosa Against Gastric Aging Based on Network Pharmacology and Experimental Validation[J]. Chinese Pharmaceutical Journal, 2023, 58(13): 1166-1177 https://doi.org/10.11669/cpj.2023.13.002

References

[1] TONG X L. Traditional Chinese medicine and aging health [J]. Healthy China Obs(健康中国观察), 2022, 34 (11):32-35.
[2] CREEVY K E, AKEY J M, KAEBERLEIN M, et al. An open science study of ageing in companion dogs [J]. Nature, 2022, 602 (7895):51-57.
[3] MA D, ZHAO B, ZHOU B. Clinical experience of ZHOU Bin in treating chronic atrophic gastritis with the theory of ‘stomach nature year’ [J]. Chin J Tradit Chin Med Pharm (中华中医药杂志), 2019, 34(9):4093-4095.
[4] Ch.P(2020) Vol Ⅰ(中国药典2020年版.一部) [S]. 2020:62-63.
[5] HE H B, LI X Q, LI X M, et al. Therapeutic effect of total triterpenoids of Chaenomeles speciosa combined with omeprazole on gastric ulcer induced by indomethacin in rats [J]. China J Chin Mater Med (中国中药杂志), 2019, 44 (11):2338-2347.
[6] SHI M Q, HE J Y, WANG X, et al. Protective effect of total triterpenoids from Chaenomeles speciosa against Helicobacter pylori-induced gastritis in mice [J]. China J Chin Mater Med (中国中药杂志), 2021, 46 (18):4782-4792.
[7] XIONG X J, LI X M, HE Y M, et al. Effect of total triterpenoids of Chaenomeles speciosa on PPARγ/SIRT1 /NF-κBp65 signaling pathway and intestinal mucosal barrier of ulcerative colitis induced by DSS in mice [J]. China J Chin Mater Med (中国中药杂志), 2018, 43 (21):4295-4304.
[8] HE H B, LI X M, YU H L, et al. Gastroprotective effect of araloside A on ethanol and aspirin-induced gastric ulcer in mice:involvement of H+/K+-ATPase and mitochondrial-mediated signaling pathway [J]. J Nat Med, 2019, 73 (2):339-352.
[9] HE HB, FENG ML, XU HY, et al. Total triterpenoids from the fruits of Chaenomeles speciosa exerted gastroprotective activities on indomethacin-induced gastric damage via modulating microRNA-423-5p-mediated TFF/NAG-1 and apoptotic pathways [J]. Food Funct, 2020, 11 (1):662-679.
[10] ZHANG Y Y, XU H Y, HE H B, et al. Total triterpenes from the fruits of Chaenomeles speciosa (Sweet) Nakai protects against indomethacin-induced gastric mucosal injury:involvement of TFF1-mediated EGF/EGFR and apoptotic pathways [J]. J Pharm Pharmacol, 2020, 72(3):409-423.
[11] HE H B, ZHANG Y F, LI X M, et al. The clinical research of triterpenoids from the fruits of Chaenomeles speciosa combined with omeprazole on upper gastrointestinal bleeding caused by NSAIDs [J]. Pharmacol Clin Chin Mater Med (中药药理与临床), 2017, 33 (2):209-212.
[12] HE H B, LI X M, LI X Q, et al. The clinical research of triterpenoids from the fruits of Chaenomeles speciosa combined with rebamipide on small bowel injury caused by NSAIDs caused by NSAIDs [J]. Pharmacol Clin Chin Mater Med (中药药理与临床), 2018, 34 (4):172-176.
[13] ZHANG JH, LI XM, SHI MQ, et al. Effects of Muguasantie combined with mesalazine on the clinical efficacy, inflammatory and intestinal barrier protective factors of ulcerative colitis [J]. Chin J Clin Pharm Ther (中国临床药理学与治疗学), 2018, 23 (10):1165-1173.
[14] GUO L, XIA D Z, LUO Y J, et al. Mechanism of Smilax glabra in treatment of gout based on network pharmacology[J]. Chin Tradit Herb Drugs (中草药), 2019, 50 (6):1413-1418.
[15] ZHANG H C, ZHOU R, TANG Z S, et al. Prediction of hepatoprotective mechanism of Panacis majoris Rhizoma based on network pharmacology,molecular docking and in vitro cellular test [J]. Chin Tradit Pat Med (中成药), 2021, 43 (9):2342-2351.
[16] BAI Y X, WANG T Q, DING S, et al. Mechanism of cyclocarya paliurus regulating blood glucose based on network pharmacology [J]. World Sci Technol Mod Tradit Chin Med (世界科学技术-中医药现代化), 2021, 23 (11):4017-4030.
[17] SUN Z Y, HUANG L, LIAO J Q, et al. Prediction of molecular mechanism of Shengjie Tongyu decoction in the treatment of chronic heart failure based on network pharmacology and molecular docking technology[J]. Chin Pharm J (中国药学杂志), 2021, 56 (18):1486-1495.
[18] NIU Y H, LIAO J L, ZHOU H T, et al. Flavonoids from Lycium barbarum leaves exhibit anti-aging effects through the redox-modulation [J]. Molecules, 2022, 27(15):4952. Doi:10.3390/molecules27154952.
[19] CUI Z F, ZHAO X T, AMEVOR F K, et al. Therapeutic application of quercetin in aging-related diseases:SIRT1 as a potential mechanism [J]. Front Immunol, 2022, 13(7):943321. Doi:10.3389/fimmu.2022.943321.
[20] EL-FAR A H, LEBDA M A, NORELDIN A E, et al. Quercetin attenuates pancreatic and renal D-galactose-induced aging-related oxidative alterations in rats [J]. Int J Mol Sci, 2020, 21(12):4348. Doi:10.3390/ijms21124348.
[21] DA POZZO E, COSTA B, CAVALLINI C, et al. The citrus flavanone naringenin protects myocardial cells against age-associated damage [J]. Oxid Med Cell Longev, 2017, 9536148. Doi:10.1155/2017/9536148.
[22] ISHAQ A, TCHKONIA T, KIRKLAND J L, et al. Palmitate induces DNA damage and senescence in human adipocytes in vitro that can be alleviated by oleic acid but not inorganic nitrate [J]. Exp Gerontol, 2022,163 (6):111798. Doi:10.1016/j.exger.2022.111798.
[23] SUH W S, PARK K J, KIM D H, et al. A biphenyl derivative from the twigs of Chaenomeles speciosa[J]. Bioorg Chem, 2017, 72 (6):156-160.
[24] LI W S, LIN S C, CHU C H, et al. The gastroprotective effect of naringenin against ethanol-induced gastric ulcers in mice through inhibiting oxidative and inflammatory responses [J]. Int J Mol Sci, 2021, 22(21):11985. Doi:10.3390/ijms222111985.
[25] CAMPOS-VIDAL Y, HERRERA-RUIZ M, TREJO-TAPIA G, et al. Gastroprotective activity of kaempferol glycosides from Malvaviscus arboreus Cav [J]. J Ethnopharmacol,2021, 268 (3):113633. Doi:10.1016/j.jep.2020.113633.
[26] WANG L, HUANG Y, HUANG C H, et al. A marine alkaloid, ascomylactam A, suppresses lung tumorigenesis via inducing cell cycle G1/S arrest through ROS/Akt/Rb pathway [J]. Mar Drugs,2020,18 (10):494. Doi:10.3390/md18100494.
[27] YANG S S, NIE T J, SHE H, et al. Regulation of TFEB nuclear localization by HSP90AA1 promotes autophagy and longevity [J]. Autophagy, 2023, 19(3):822-838.
[28] CHEN K Q, LI Y Q, ZHANG X H, et al. The role of the PI3K/AKT signalling pathway in the corneal epithelium:recent updates[J]. Cell Death Dis, 2022, 13 (5):513. Doi:10.1038/s41419-022-04963-x.
[29] SIKORA E, BIELAK-ZMIJEWSKA A, MOSIENIAK G. A common signature of cellular senescence; does it exist? [J]. Ageing Res Rev, 2021, 71 (11):101458. Doi:10.1016/j.arr.2021.101458.
[30] LIU S Z, HU J P, SHI C L, et al. Sparstolonin B exerts beneficial effects on prostate cancer by acting on the reactive oxygen species-mediated PI3K/AKT pathway [J]. J Cell Mol Med, 2021, 25 (12):5511-5524.
[31] YANG Y F, PENG S X, WANG K Y, et al. Effect of Mailuo Shutong Pills in treatment of ischemic stroke based on network pharmacological analysis and experimental verification [J]. China J Chin Mater Med (中国中药杂志), 2022, 47 (23):6466-6475.
[32] LEZCANO V, MORELLI S, GONZÁLEZ-PARDO V. Molecular and cellular outcomes of quercetin actions on healthy and tumor osteoblasts [J]. Biochimie, 2022, 199 (8):46-59.
[33] DU J, ZHU X X, GUO R, et al. Autophagy induces G0/G1 arrest and apoptosis in menstrual blood-derived endometrial stem cells via GSK3-β/β-catenin pathway [J]. Stem Cell Res Ther, 2018, 9(1):330. Doi:10.1186/s13287-018-1073-0.
[34] LIU W H, ZHAO Z Q, WANG Y Q, et al. Dioscin inhibits stem-cell-like properties and tumor growth of osteosarcoma through Akt/GSK3/β-catenin signaling pathway[J]. Cell Death Dis, 2018, 9(3):343. Doi:10.1038/s41419-018-0363-x.
PDF(3598 KB)

Accesses

Citation

Detail

Sections
Recommended

/