Potential Mechanisms Underlying the Therapeutic Roles of Gancao fuzi Decoction in Cold-dampness Obstruction Syndrome-type Knee Osteoarthritis
- Authors: Zhao J.1, Liang G.1, Huang H.2, Yang W.3, Pan J.3, Luo M.3, Zeng L.1, Liu J.4
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Affiliations:
- , The Second Clinical College of Guangzhou University of Chinese Medicine
- , The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, 510120, China
- , The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)
- , The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences
- Issue: Vol 20, No 4 (2024)
- Pages: 384-395
- Section: Chemistry
- URL: https://rjeid.com/1573-4099/article/view/644050
- DOI: https://doi.org/10.2174/1573409919666230605115940
- ID: 644050
Cite item
Full Text
Abstract
Background:The key active components and potential molecular mechanism of Gancao Fuzi decoction (GFD) in the treatment of cold-dampness obstruction-type knee osteoarthritis (KOA) remain unclear.
Objective:To explore the mechanism of GFD in the treatment of cold-dampness obstruction syndrome-type KOA by network pharmacology.
Methods:The potential active components and targets of the four herbs in GFD (Fuzi, Guizhi, Baizhu, and Gancao) were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The targets of KOA were obtained with the Comparative Toxicogenomics Database (CTD), the GeneCards database, and the DisGeNET database, and the common targets of the drugs and disease were ultimately obtained. Cytoscape (v.3.7.1) was used to draw the active component-target network, and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) (v.11.0) database was used to construct the protein interaction network. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the intersecting targets.
Results:A total of 102 potential active components and 208 targets of GFD in the treatment of cold-dampness obstruction syndrome-type KOA were screened. GFD treatment was found to be closely related to many inflammatory signalling pathways in the treatment of KOA.
Conclusion:The effect of GFD on cold-dampness obstruction syndrome-type KOA is mediated by multicomponent, multitarget, and multichannel mechanisms, which provides the basis for further experimental study of its pharmacodynamic material basis and mechanism.
About the authors
Jinlong Zhao
, The Second Clinical College of Guangzhou University of Chinese Medicine
Email: info@benthamscience.net
Guihong Liang
, The Second Clinical College of Guangzhou University of Chinese Medicine
Email: info@benthamscience.net
Hetao Huang
, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, 510120, China
Email: info@benthamscience.net
Weiyi Yang
, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)
Email: info@benthamscience.net
Jianke Pan
, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)
Email: info@benthamscience.net
Minghui Luo
, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)
Email: info@benthamscience.net
Lingfeng Zeng
, The Second Clinical College of Guangzhou University of Chinese Medicine
Author for correspondence.
Email: info@benthamscience.net
Jun Liu
, The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences
Author for correspondence.
Email: info@benthamscience.net
References
- Bichsel, D.; Liechti, F.D.; Schlapbach, J.M.; Wertli, M.M. Cross-sectional analysis of recommendations for the treatment of hip and knee osteoarthritis in clinical guidelines. Arch. Phys. Med. Rehabil., 2022, 103(3), 559-569.e5. doi: 10.1016/j.apmr.2021.07.801 PMID: 34411512
- Carlesso, L.C.; Feldman, D.E.; Vendittoli, P.A.; LaVoie, F.; Choinière, M.; Bolduc, M.È.; Fernandes, J.; Newman, N.; Sabouret, P. Use of IMMPACT recommendations to explore pain phenotypes in people with knee osteoarthritis. Pain Med., 2022, 23(10), 1708-1716. doi: 10.1093/pm/pnac044 PMID: 35266543
- Filardo, G.; Kon, E.; Longo, U.G.; Madry, H.; Marchettini, P.; Marmotti, A.; Van Assche, D.; Zanon, G.; Peretti, G.M. Non-surgical treatments for the management of early osteoarthritis. Knee Surg. Sports Traumatol. Arthrosc., 2016, 24(6), 1775-1785. doi: 10.1007/s00167-016-4089-y PMID: 27043347
- Litwic, A.; Edwards, M.H.; Dennison, E.M.; Cooper, C. Epidemiology and burden of osteoarthritis. Br. Med. Bull., 2013, 105(1), 185-199. doi: 10.1093/bmb/lds038 PMID: 23337796
- Murphy, L.; Helmick, C.G. The impact of osteoarthritis in the United States: A population-health perspective: A population-based review of the fourth most common cause of hospitalization in U.S. adults. Orthop. Nurs., 2012, 31(2), 85-91. doi: 10.1097/NOR.0b013e31824fcd42 PMID: 22446800
- Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation-United States, 2010-2012. MMWR Morb. Mortal. Wkly. Rep., 2013, 62(44), 869-873. PMID: 24196662
- Razumov, A.N. Purigа, A.O.; Yurova, O.V. The long-term results of the application of the combined rehabilitative treatment in the patients presenting with knee osteoarthrosis. Vopr. Kurortol. Fizioter. Lech. Fiz. Kult., 2015, 92(6), 42-44. doi: 10.17116/kurort2015642-44 PMID: 26841528
- Farpour, H.R.; Fereydooni, F. Comparative effectiveness of intra-articular prolotherapy versus peri-articular prolotherapy on pain reduction and improving function in patients with knee osteoarthritis: A randomized clinical trial. Electron. Physician, 2017, 9(11), 5663-5669. doi: 10.19082/5663 PMID: 29403602
- Deng, W. Clinical research on Gancao fuzi decoction in treating osteoarthritis of knee joint. Zhong Yao Cai, 2008, 31(7), 1107-1110. doi: 10.13863/j.issn1001-4454.2008.07.007 PMID: 18973027
- Nazari, G. Knee osteoarthritis. J. Physiother., 2017, 63(3), 188. doi: 10.1016/j.jphys.2017.04.004 PMID: 28633882
- Farber, J.M. The knee, osteoarthritis and biomarkers. Osteoarthritis Cartilage, 2018, 26(7), 845-846. doi: 10.1016/j.joca.2018.01.023 PMID: 29426011
- 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
- Hong, M.; Zhang, Y.; Li, S.; Tan, H.; Wang, N.; Mu, S.; Hao, X.; Feng, Y. A network pharmacology-based study on the hepatoprotective effect of Fructus Schisandrae. Molecules, 2017, 22(10), 1617. doi: 10.3390/molecules22101617 PMID: 28956809
- Tao, W.; Xu, X.; Wang, X.; Li, B.; Wang, Y.; Li, Y.; Yang, L. Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease. J. Ethnopharmacol., 2013, 145(1), 1-10. doi: 10.1016/j.jep.2012.09.051 PMID: 23142198
- 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
- Dimmer, E.C.; Huntley, R.P.; Alam-Faruque, Y.; Sawford, T.; ODonovan, C.; Martin, M.J.; Bely, B.; Browne, P.; Mun Chan, W.; Eberhardt, R.; Gardner, M.; Laiho, K.; Legge, D.; Magrane, M.; Pichler, K.; Poggioli, D.; Sehra, H.; Auchincloss, A.; Axelsen, K.; Blatter, M.C.; Boutet, E.; Braconi-Quintaje, S.; Breuza, L.; Bridge, A.; Coudert, E.; Estreicher, A.; Famiglietti, L.; Ferro-Rojas, S.; Feuermann, M.; Gos, A.; Gruaz-Gumowski, N.; Hinz, U.; Hulo, C.; James, J.; Jimenez, S.; Jungo, F.; Keller, G.; Lemercier, P.; Lieberherr, D.; Masson, P.; Moinat, M.; Pedruzzi, I.; Poux, S.; Rivoire, C.; Roechert, B.; Schneider, M.; Stutz, A.; Sundaram, S.; Tognolli, M.; Bougueleret, L.; Argoud-Puy, G.; Cusin, I. Duek- Roggli, P.; Xenarios, I.; Apweiler, R. The UniProt-GO Annotation database in 2011. Nucleic Acids Res., 2012, 40(D1), D565-D570. doi: 10.1093/nar/gkr1048 PMID: 22123736
- Davis, A.P.; Wiegers, T.C.; Johnson, R.J.; Sciaky, D.; Wiegers, J.; Mattingly, C.J. Comparative Toxicogenomics Database (CTD): Update 2023. Nucleic Acids Res., 2023, 51(D1), D1257-D1262. doi: 10.1093/nar/gkac833 PMID: 36169237
- Fishilevich, S.; Nudel, R.; Rappaport, N.; Hadar, R.; Plaschkes, I.; Iny Stein, T.; Rosen, N.; Kohn, A.; Twik, M.; Safran, M.; Lancet, D.; Cohen, D. GeneHancer: Genome-wide integration of enhancers and target genes in GeneCards. Database (Oxford), 2017, 2017, bax028. doi: 10.1093/database/bax028 PMID: 28605766
- Piñero, J.; Ramírez-Anguita, J.M.; Saüch-Pitarch, J.; Ronzano, F.; Centeno, E.; Sanz, F.; Furlong, L.I. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res., 2019, 48(D1), gkz1021. doi: 10.1093/nar/gkz1021 PMID: 31680165
- Oliveros, J.C. Venny. An interactive tool for comparing lists with Venn's diagrams. , 2007-2015. Avialable from:https://bioinfogp.cnb.csic.es/tools/venny/index.html
- Doncheva, N.T.; Morris, J.H.; Holze, H.; Kirsch, R.; Nastou, K.C.; Cuesta-Astroz, Y.; Rattei, T.; Szklarczyk, D.; von Mering, C.; Jensen, L.J. Cytoscape stringApp 2.0: Analysis and visualization of heterogeneous biological networks. J. Proteome Res., 2023, 22(2), 637-646. doi: 10.1021/acs.jproteome.2c00651 PMID: 36512705
- Gfeller, D.; Grosdidier, A.; Wirth, M.; Daina, A.; Michielin, O.; Zoete, V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Res., 2014, 42(W1), W32-W38. doi: 10.1093/nar/gku293 PMID: 24792161
- Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable proteinprotein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612. doi: 10.1093/nar/gkaa1074 PMID: 33237311
- Dennis, G., Jr; Sherman, B.T.; Hosack, D.A.; Yang, J.; Gao, W.; Lane, H.C.; Lempicki, R.A. DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol., 2003, 4(5), P3. doi: 10.1186/gb-2003-4-5-p3 PMID: 12734009
- Loeser, R.F.; Goldring, S.R.; Scanzello, C.R.; Goldring, M.B. Osteoarthritis: A disease of the joint as an organ. Arthritis Rheum., 2012, 64(6), 1697-1707. doi: 10.1002/art.34453 PMID: 22392533
- Yang, M. Oral Gancao fuzi Decoction on combined with injection of sodium hyaluronate in the treatment of 60 patients with knee osteoarthritis. Chin. J. Traumatol., 2012, 20, 9-11.
- Xiang, X.; Zhou, Y.; Sun, H.; Tan, S.; Lu, Z.; Huang, L.; Wang, W. Ivabradine abrogates TNF-α-induced degradation of articular cartilage matrix. Int. Immunopharmacol., 2019, 66, 347-353. doi: 10.1016/j.intimp.2018.11.035 PMID: 30521963
- Zhou, J.; Liu, S.; Qiu, B.; Hu, Q.; Ming, J.; Peng, H. Effects of hyaluronan on vascular endothelial growth factor and receptor-2 expression in a rabbit osteoarthritis model. J. Orthop. Sci., 2009, 14(3), 313-319. doi: 10.1007/s00776-009-1329-8 PMID: 19499299
- Chen, X.; Hao, Y.; Wang, Z.; Zhou, J.; Jia, Q.; Qiu, B. The effect of vascular endothelial growth factor on aggrecan and type II collagen expression in rat articular chondrocytes. Rheumatol. Int., 2012, 32(11), 3359-3364. doi: 10.1007/s00296-011-2178-2 PMID: 22045519
- Jansen, H.; Meffert, R.H.; Birkenfeld, F.; Petersen, W.; Pufe, T. Detection of vascular endothelial growth factor (VEGF) in moderate osteoarthritis in a rabbit model. Ann. Anat., 2012, 194(5), 452-456. doi: 10.1016/j.aanat.2012.01.006 PMID: 22429866
- Jin, Q.; Zhu, Q.; Wang, K.; Chen, M.; Li, X. Allisartan isoproxil attenuates oxidative stress and inflammation through the SIRT1/Nrf2/NF κB signalling pathway in diabetic cardiomyopathy rats. Mol. Med. Rep., 2021, 23(3), 215. doi: 10.3892/mmr.2021.11854 PMID: 33495841
- Song, W.; Zhang, Y.; Wang, J.; Ma, T.; Hao, L.; Wang, K. Antagonism of cysteinyl leukotriene receptor 1 (cysLTR1) by montelukast suppresses cell senescence of chondrocytes. Cytokine, 2018, 103, 83-89. doi: 10.1016/j.cyto.2017.12.021 PMID: 29331588
- Labuschagne, C.F.; Zani, F.; Vousden, K.H. Control of metabolism by p53 - Cancer and beyond. Biochim. Biophys. Acta Rev. Cancer, 2018, 1870(1), 32-42. doi: 10.1016/j.bbcan.2018.06.001 PMID: 29883595
- Lee, Y.J.; Kim, S.A.; Lee, S.H. Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway. Acta Pharmacol. Sin., 2016, 37(5), 664-673. doi: 10.1038/aps.2015.151 PMID: 27041463
- Chen, W.P.; Xiong, Y.; Hu, P.F.; Bao, J.P.; Wu, L.D. Baicalein inhibits MMPs expression via a MAPK-dependent mechanism in chondrocytes. Cell. Physiol. Biochem., 2015, 36(1), 325-333. doi: 10.1159/000374075 PMID: 25967971
- Wang, C.; Zeng, L.; Zhang, T.; Liu, J.; Wang, W. Tenuigenin prevents IL-1β-induced inflammation in human osteoarthritis chondrocytes by suppressing PI3K/AKT/NF-κB signaling pathway. Inflammation, 2016, 39(2), 807-812. doi: 10.1007/s10753-016-0309-3 PMID: 26846886
- Zhang, Q.; Lai, S.; Hou, X.; Cao, W.; Zhang, Y.; Zhang, Z. Protective effects of PI3K/Akt signal pathway induced cell autophagy in rat knee joint cartilage injury. Am. J. Transl. Res., 2018, 10(3), 762-770. PMID: 29636866
- Yang, Y.; Wang, Y.; Zhao, M.; Jia, H.; Li, B.; Xing, D. Tormentic acid inhibits IL-1β-induced chondrocyte apoptosis by activating the PI3K/Akt signaling pathway. Mol. Med. Rep., 2018, 17(3), 4753-4758. doi: 10.3892/mmr.2018.8425 PMID: 29328385
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