Amalgamated Pharmacoinformatics Study to Investigate the Mechanism of Xiao Jianzhong Tang against Chronic Atrophic Gastritis
- Authors: Lian X.1, Fan K.2, Qin X.3, Liu Y.4
-
Affiliations:
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,, Shanxi University
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,, Shanxi University,
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University,
- Issue: Vol 20, No 5 (2024)
- Pages: 598-615
- Section: Chemistry
- URL: https://rjpbr.com/1573-4099/article/view/644179
- DOI: https://doi.org/10.2174/1573409919666230720141115
- ID: 644179
Cite item
Full Text
Abstract
Background:Traditional Chinese medicine (TCM) Xiaojianzhong Tang (XJZ) has a favorable efficacy in the treatment of chronic atrophic gastritis (CAG). However, its pharmacological mechanism has not been fully explained.
Objective:The purpose of this study was to find the potential mechanism of XJZ in the treatment of CAG using pharmacocoinformatics approaches.
Methods:Network pharmacology was used to screen out the key compounds and key targets, MODELLER and GNNRefine were used to repair and refine proteins, Autodock vina was employed to perform molecular docking, Δ Lin_F9XGB was used to score the docking results, and Gromacs was used to perform molecular dynamics simulations (MD).
Results:Kaempferol, licochalcone A, and naringenin, were obtained as key compounds, while AKT1, MAPK1, MAPK14, RELA, STAT1, and STAT3 were acquired as key targets. Among docking results, 12 complexes scored greater than five. They were run for 50ns MD. The free binding energy of AKT1-licochalcone A and MAPK1-licochalcone A was less than -15 kcal/mol and AKT1-naringenin and STAT3-licochalcone A was less than -9 kcal/mol. These complexes were crucial in XJZ treating CAG.
Conclusion:Our findings suggest that licochalcone A could act on AKT1, MAPK1, and STAT3, and naringenin could act on AKT1 to play the potential therapeutic effect on CAG. The work also provides a powerful approach to interpreting the complex mechanism of TCM through the amalgamation of network pharmacology, deep learning-based protein refinement, molecular docking, machine learning-based binding affinity estimation, MD simulations, and MM-PBSA-based estimation of binding free energy.
About the authors
Xu Lian
Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University
Email: info@benthamscience.net
Kaidi Fan
Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,, Shanxi University
Email: info@benthamscience.net
Xuemei Qin
Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,, Shanxi University,
Author for correspondence.
Email: info@benthamscience.net
Yuetao Liu
Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University,
Author for correspondence.
Email: info@benthamscience.net
References
- Koulis, A.; Buckle, A.; Boussioutas, A. Premalignant lesions and gastric cancer: Current understanding. World J. Gastrointest. Oncol., 2019, 11(9), 665-678. doi: 10.4251/wjgo.v11.i9.665 PMID: 31558972
- Li, Y.; Xia, R.; Zhang, B.; Li, C. Chronic Atrophic Gastritis: A Review. J. Environ. Pathol. Toxicol. Oncol., 2018, 37(3), 241-259. doi: 10.1615/JEnvironPatholToxicolOncol.2018026839 PMID: 30317974
- Rodriguez-Castro, K.I.; Franceschi, M.; Noto, A.; Miraglia, C.; Nouvenne, A.; Leandro, G.; Meschi, T.; De Angelis, G.L.; Di Mario, F. Clinical manifestations of chronic atrophic gastritis. Acta Biomed., 2018, 89(8-S), 88-92. PMID: 30561424
- Woodford, A.M.; Chaudhry, R.; Conte, G.A.; Gupta, V.; Anne, M. Chronic atrophic gastritis presenting as hemolytic anemia due to severe Vitamin B12 deficiency. Case Rep. Hematol., 2021, 2021, 1-5. doi: 10.1155/2021/9571072 PMID: 34373795
- Wei, W.; Lin, S.; Zhu, Y. Effects of Anwei decoction on the protein expression of TFF in rats with chronic atrophic gastritis. Mod. Res. Inflamm., 2014, 3(1), 1-6. doi: 10.4236/mri.2014.31001
- Ou, J.; Wang, L. Efficacy of Self-made Hewei Decoction for chronic atrophic gastritis and its effect on gastrin and pepsinogen expression levels. Contrast Media Mol. Imaging, 2022, 2022, 1-8. doi: 10.1155/2022/1092695 PMID: 35694708
- Wen, J.; Wu, S.; Ma, X.; Zhao, Y. Zuojin Pill attenuates Helicobacter pylori-induced chronic atrophic gastritis in rats and improves gastric epithelial cells function in GES-1 cells. J. Ethnopharmacol., 2022, 285, 114855. doi: 10.1016/j.jep.2021.114855 PMID: 34808298
- Yin, J.; Yi, J.; Yang, C.; Xu, B.; Lin, J.; Hu, H.; Wu, X.; Shi, H.; Fei, X. Weiqi Decoction attenuated chronic atrophic gastritis with precancerous lesion through regulating microcirculation disturbance and HIF-1α signaling pathway. Evid. Based Complement. Alternat. Med., 2019, 2019, 1-12. doi: 10.1155/2019/2651037 PMID: 31320912
- Guo, C.Y. Observation on the curative effect of Xiaojianzhong Decoction in treating chronic gastritis. Mod J Integr Tradit Chin West Med, 2022, 2, 2464-2465.
- Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120. doi: 10.1016/S1875-5364(13)60037-0 PMID: 23787177
- Meng, X.Y.; Zhang, H.X.; Mezei, M.; Cui, M. Molecular docking: A powerful approach for structure-based drug discovery. Curr. Computeraided Drug Des., 2011, 7(2), 146-157. doi: 10.2174/157340911795677602 PMID: 21534921
- Chai, X-L.; Pan, Q.; Zhang, Z-Q.; Tian, C-Y.; Yu, T.; Yang, R. Effect and signaling pathways of Nelumbinis folium in the treatment of hyperlipidemia assessed by network pharmacology. World J. Tradit. Chin. Med., 2021, 7(4), 445-455. doi: 10.4103/2311-8571.328619
- Zhao, T.T.; Lan, R.R.; Liang, S.D.; Schmalzing, G.; Gao, H.W.; Verkhratsky, A.; He, C.H.; Nie, H. An exploration in the potential substance basis and mechanism of Chuanxiong Rhizoma and Angelicae Dahuricae Radix on analgesia based on network pharmacology and molecular docking. World J. Tradit. Chin. Med., 2021, 7(2), 201-208.
- Karplus, M.; McCammon, J.A. Molecular dynamics simulations of biomolecules. Nat. Struct. Biol., 2002, 9(9), 646-652. doi: 10.1038/nsb0902-646 PMID: 12198485
- Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13. doi: 10.1186/1758-2946-6-13 PMID: 24735618
- Xu, H.Y.; Zhang, Y.Q.; Liu, Z.M.; Chen, T.; Lv, C.Y.; Tang, S.H.; Zhang, X.B.; Zhang, W.; Li, Z.Y.; Zhou, R.R.; Yang, H.J.; Wang, X.J.; Huang, L.Q. ETCM: An encyclopaedia of traditional Chinese medicine. Nucleic Acids Res., 2019, 47(D1), D976-D982. doi: 10.1093/nar/gky987 PMID: 30365030
- Xiong, G.; Wu, Z.; Yi, J.; Fu, L.; Yang, Z.; Hsieh, C.; Yin, M.; Zeng, X.; Wu, C.; Lu, A.; Chen, X.; Hou, T.; Cao, D. ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res., 2021, 49(W1), W5-W14. doi: 10.1093/nar/gkab255 PMID: 33893803
- Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7(1), 42717. doi: 10.1038/srep42717 PMID: 28256516
- Nickel, J.; Gohlke, B.O.; Erehman, J.; Banerjee, P.; Rong, W.W.; Goede, A.; Dunkel, M.; Preissner, R. SuperPred: Update on drug classification and target prediction. Nucleic Acids Res., 2014, 42(W1), W26-W31. doi: 10.1093/nar/gku477 PMID: 24878925
- Daina, A.; Michielin, O.; Zoete, V. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res., 2019, 47(W1), W357-W364. doi: 10.1093/nar/gkz382 PMID: 31106366
- Liu, X.; Ouyang, S.; Yu, B.; Liu, Y.; Huang, K.; Gong, J.; Zheng, S.; Li, Z.; Li, H.; Jiang, H. PharmMapper server: A web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res., 2010, 38(Web Server issue)(Suppl.2), W609-W614. doi: 10.1093/nar/gkq300 PMID: 20430828
- Ochoa, D.; Hercules, A.; Carmona, M.; Suveges, D.; Gonzalez-Uriarte, A.; Malangone, C.; Miranda, A.; Fumis, L.; Carvalho-Silva, D.; Spitzer, M.; Baker, J.; Ferrer, J.; Raies, A.; Razuvayevskaya, O.; Faulconbridge, A.; Petsalaki, E.; Mutowo, P.; Machlitt-Northen, S.; Peat, G.; McAuley, E.; Ong, C.K.; Mountjoy, E.; Ghoussaini, M.; Pierleoni, A.; Papa, E.; Pignatelli, M.; Koscielny, G.; Karim, M.; Schwartzentruber, J.; Hulcoop, D.G.; Dunham, I.; McDonagh, E.M. Open Targets Platform: Supporting systematic drugtarget identification and prioritisation. Nucleic Acids Res., 2021, 49(D1), D1302-D1310. doi: 10.1093/nar/gkaa1027 PMID: 33196847
- Hamosh, A.; Scott, A.F.; Amberger, J.S.; Bocchini, C.A.; McKusick, V.A. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res., 2005, 33(Database issue), D514-D517. doi: 10.1093/nar/gki033 PMID: 15608251
- Stelzer, G.; Rosen, N.; Plaschkes, I.; Zimmerman, S.; Twik, M.; Fishilevich, S.; Stein, T.I.; Nudel, R.; Lieder, I.; Mazor, Y.; Kaplan, S.; Dahary, D.; Warshawsky, D.; Guan-Golan, Y.; Kohn, A.; Rappaport, N.; Safran, M.; Lancet, D. The GeneCards Suite.Practical Guide to Life Science Databases; Springer Nature: London, 2022, pp. 27-56.
- Piñero, J.; Bravo, À.; Queralt-Rosinach, N.; Gutiérrez-Sacristán, A.; Deu-Pons, J.; Centeno, E.; García-García, J.; Sanz, F.; Furlong, L.I. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res., 2017, 45(D1), D833-D839. doi: 10.1093/nar/gkw943 PMID: 27924018
- UniProt Consortium. T. UniProt: The universal protein knowledgebase. Nucleic Acids Res., 2018, 46(5), 2699. doi: 10.1093/nar/gky092 PMID: 29425356
- Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504. doi: 10.1101/gr.1239303 PMID: 14597658
- Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57. doi: 10.1038/nprot.2008.211 PMID: 19131956
- Sherman, B.T.; Hao, M.; Qiu, J.; Jiao, X.; Baseler, M.W.; Lane, H.C.; Imamichi, T.; Chang, W. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res., 2022, 50(W1), W216-W221. doi: 10.1093/nar/gkac194 PMID: 35325185
- Bader, G.D.; Hogue, C.W.V. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics, 2003, 4(1), 2. doi: 10.1186/1471-2105-4-2 PMID: 12525261
- Chin, C.H.; Chen, S.H.; Wu, H.H.; Ho, C.W.; Ko, M.T.; Lin, C.Y. cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 2014, 8(S4)(Suppl. 4), S11. doi: 10.1186/1752-0509-8-S4-S11 PMID: 25521941
- Xie, C.; Mao, X.; Huang, J.; Ding, Y.; Wu, J.; Dong, S.; Kong, L.; Gao, G.; Li, C.Y.; Wei, L. KOBAS 2.0: A web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Res., 2011, 39(Web Server issue)(Suppl. 2), W316-W322. doi: 10.1093/nar/gkr483 PMID: 21715386
- Martí-Renom, M.A.; Stuart, A.C.; Fiser, A.; Sánchez, R.; Melo, F.; ali, A. Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct., 2000, 29(1), 291-325. doi: 10.1146/annurev.biophys.29.1.291 PMID: 10940251
- Webb, B.; Sali, A. Comparative protein structure modeling using MODELLER. Curr. Protoc. Bioinformatics, 2016, 5, 5-6. doi: 10.1002/cpbi.3
- Eswar, N.; Webb, B.; Marti-Renom, M.A.; Madhusudhan, M.S.; Eramian, D.; Shen, M.Y.; Pieper, U.; Sali, A. Comparative protein structure modeling using Modeller; Curr. Protoc. Bioinformatics, 2006. Chapter 5, 6. PMID: 18428767
- Jing, X.; Xu, J. Fast and effective protein model refinement using deep graph neural networks. Nature Computational Science, 2021, 1(7), 462-469. doi: 10.1038/s43588-021-00098-9 PMID: 35321360
- Chen, V.B.; Arendall, W.B., III; Headd, J.J.; Keedy, D.A.; Immormino, R.M.; Kapral, G.J.; Murray, L.W.; Richardson, J.S.; Richardson, D.C. MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr., 2010, 66(1), 12-21. doi: 10.1107/S0907444909042073 PMID: 20057044
- Zhang, J.; Zhang, Y. A novel side-chain orientation dependent potential derived from random-walk reference state for protein fold selection and structure prediction. PLoS One, 2010, 5(10), e15386. doi: 10.1371/journal.pone.0015386 PMID: 21060880
- Volkamer, A.; Kuhn, D.; Rippmann, F.; Rarey, M. DoGSiteScorer: A web server for automatic binding site prediction, analysis and druggability assessment. Bioinformatics, 2012, 28(15), 2074-2075. doi: 10.1093/bioinformatics/bts310 PMID: 22628523
- Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461. PMID: 19499576
- Cetin, A. In silico studies on stilbenolignan analogues as SARS-CoV-2 Mpro inhibitors. Chem. Phys. Lett., 2021, 771, 138563. doi: 10.1016/j.cplett.2021.138563 PMID: 33776065
- Cetin, A. Some flavolignans as potent Sars-Cov-2 inhibitors via molecular docking, molecular dynamic simulations and ADME analysis. Curr. Computeraided Drug Des., 2022, 18(5), 337-346. doi: 10.2174/1573409918666220816113516 PMID: 35975852
- Laskowski, R.A.; Swindells, M.B. LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model., 2011, 51(10), 2778-2786. doi: 10.1021/ci200227u PMID: 21919503
- Yang, C.; Zhang, Y. Delta machine learning to improve scoring-ranking-screening performances of proteinligand scoring functions. J. Chem. Inf. Model., 2022, 62(11), 2696-2712. doi: 10.1021/acs.jcim.2c00485 PMID: 35579568
- Abraham, M.J.; Murtola, T.; Schulz, R.; Páll, S.; Smith, J.C.; Hess, B.; Lindahl, E. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 2015, 1-2, 19-25. doi: 10.1016/j.softx.2015.06.001
- Zenodo. GROMACS 2022 Manual. 2020. Available From: https://zenodo.org/record/7037337
- Lu, T.; Chen, F. Multiwfn: A multifunctional wavefunction analyzer. J. Comput. Chem., 2012, 33(5), 580-592. doi: 10.1002/jcc.22885 PMID: 22162017
- Frank, N. Software update: The ORCA program system, version 4.0 Comput. Mol. Sci, 2018, 8(1), e1327. doi: 10.1002/wcms.1327
- Frank, N. Software update: The ORCA program system, version 5.0 Comput. Mol. Sci, 2022, 12(5), e1606. doi: 10.1002/wcms.1606
- Lu, T. Sobtop: A tool of generating forcefield parameters and GROMACS topology file. 2022. Available From: sobereva.com/soft/Sobtop
- Turner, P.J. Center for Coastal And Land-Margin Research (CCALMR); Oregon Graduate Institute of Science and Technology.: Oregon, 2005.
- Jing, X. GNNRefine: Fast and effective protein model refinement by deep graph neural networks; , 2021. Available From: https://codeocean.com/capsule/5769140/tree/v1
- Lobanov, M.Iu.; Bogatyreva, N.S.; Galzitskaia, O.V. Radius of gyration is indicator of compactness of protein structure. Mol. Biol., 2008, 42(4), 701-706. PMID: 18856071
- Borjian Boroujeni, M.; Shahbazi Dastjerdeh, M.; Shokrgozar, M.A.; Rahimi, H.; Omidinia, E. Computational driven molecular dynamics simulation of keratinocyte growth factor behavior at different pH conditions. Informatics in Medicine Unlocked, 2021, 23, 100514. doi: 10.1016/j.imu.2021.100514
- Hao, Y.; Zhang, C.; Sun, Y.; Xu, H. Licochalcone A inhibits cell proliferation, migration, and invasion through regulating the PI3K/AKT signaling pathway in oral squamous cell carcinoma. OncoTargets Ther., 2019, 12, 4427-4435. doi: 10.2147/OTT.S201728 PMID: 31239711
- Chen, X.; Liu, Z.; Meng, R.; Shi, C.; Guo, N. Antioxidative and anticancer properties of Licochalcone A from licorice. J. Ethnopharmacol., 2017, 198, 331-337. doi: 10.1016/j.jep.2017.01.028 PMID: 28111219
- Shu, J.; Cui, X.; Liu, X.; Yu, W.; Zhang, W.; Huo, X.; Lu, C. Licochalcone A inhibits IgE-mediated allergic reaction through PLC/ERK/STAT3 pathway. Int. J. Immunopathol. Pharmacol., 2022, 36, 3946320221135462. doi: 10.1177/03946320221135462 PMID: 36263976
- Wu, J.; Ye, X.; Yang, S.; Yu, H.; Zhong, L.; Gong, Q. Systems pharmacology study of the anti-liver injury mechanism of citri reticulatae pericarpium. Front. Pharmacol., 2021, 12, 618846. doi: 10.3389/fphar.2021.618846 PMID: 33912040
- Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci., 2016, 5, e47. doi: 10.1017/jns.2016.41 PMID: 28620474
- Chu, X.; Ci, X.; Wei, M.; Yang, X.; Cao, Q.; Guan, M.; Li, H.; Deng, Y.; Feng, H.; Deng, X. Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo. J. Agric. Food Chem., 2012, 60(15), 3947-3954. doi: 10.1021/jf2051587 PMID: 22400806
- Furuhashi, I.; Iwata, S.; Sato, T.; Inoue, H.; Shibata, S. Inhibition by licochalcone A, a novel flavonoid isolated from liquorice root, of IL-1β-induced PGE2 production in human skin fibroblasts. J. Pharm. Pharmacol., 2010, 57(12), 1661-1666. doi: 10.1211/jpp.57.12.0017 PMID: 16354411
- Chang, J.; Zhang, Y.; Shen, N.; Zhou, J.; Zhang, H. MiR-129-5p prevents depressive-like behaviors by targeting MAPK1 to suppress inflammation. Exp. Brain Res., 2021, 239(11), 3359-3370. doi: 10.1007/s00221-021-06203-8 PMID: 34482419
- Lee, H.; Jeong, A.J.; Ye, S.K. Highlighted STAT3 as a potential drug target for cancer therapy. BMB Rep., 2019, 52(7), 415-423. doi: 10.5483/BMBRep.2019.52.7.152 PMID: 31186087
- Pan, C.; Liu, Q.; Wu, X. HIF1α/miR-520a-3p/AKT1/mTOR feedback promotes the proliferation and glycolysis of gastric cancer cells. Cancer Manag. Res., 2019, 11, 10145-10156. doi: 10.2147/CMAR.S223473 PMID: 31819647
- Xue, L.; Zhang, W.J.; Fan, Q.X.; Wang, L.X. Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells. Oncol. Lett., 2018, 15(2), 1869-1873. PMID: 29399197
- Huang, C.F.; Yang, S.F.; Chiou, H.L.; Hsu, W.H.; Hsu, J.C.; Liu, C.J.; Hsieh, Y.H. Licochalcone A inhibits the invasive potential of human glioma cells by targeting the MEK/ERK and ADAM9 signaling pathways. Food Funct., 2018, 9(12), 6196-6204. doi: 10.1039/C8FO01643G PMID: 30465574
- Funakoshi-Tago, M.; Tago, K.; Nishizawa, C.; Takahashi, K.; Mashino, T.; Iwata, S.; Inoue, H.; Sonoda, Y.; Kasahara, T. Licochalcone A is a potent inhibitor of TEL-Jak2-mediated transformation through the specific inhibition of Stat3 activation. Biochem. Pharmacol., 2008, 76(12), 1681-1693. doi: 10.1016/j.bcp.2008.09.012 PMID: 18848530
- Fukai, T.; Marumo, A.; Kaitou, K.; Kanda, T.; Terada, S.; Nomura, T. Anti-Helicobacter pylori flavonoids from licorice extract. Life Sci., 2002, 71(12), 1449-1463. doi: 10.1016/S0024-3205(02)01864-7 PMID: 12127165
- Park, J.M.; Park, S.H.; Hong, K.S.; Han, Y.M.; Jang, S.H.; Kim, E.H.; Hahm, K.B. Special licorice extracts containing lowered glycyrrhizin and enhanced licochalcone A prevented Helicobacter pylori-initiated, salt diet-promoted gastric tumorigenesis. Helicobacter, 2014, 19(3), 221-236. doi: 10.1111/hel.12121 PMID: 24646026
- Den Hartogh, D.J.; Tsiani, E. Antidiabetic properties of naringenin: A citrus fruit polyphenol. Biomolecules, 2019, 9(3), 99. doi: 10.3390/biom9030099 PMID: 30871083
- Ge, Y.; Chen, H.; Wang, J.; Liu, G.; Cui, S.W.; Kang, J.; Jiang, Y.; Wang, H. Naringenin prolongs lifespan and delays aging mediated by IIS and MAPK in Caenorhabditis elegans. Food Funct., 2021, 12(23), 12127-12141. doi: 10.1039/D1FO02472H PMID: 34787618
- Wu, J.; Ye, X.; Yang, S.; Yu, H.; Zhong, L.; Gong, Q. Systems pharmacology study of the anti-liver injury mechanism of citri reticulatae pericarpium. Front Pharmacol, 2021, 12, 618846. doi: 10.3389/fphar.2021.61884
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