Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

To Explore the Mechanism of “Fuzi-Guizhi” for the Treatment of Osteoarthritis on the Basis of Network Pharmacology and Molecular Docking

Author(s): De-Ta Chen*, Xue Shen*, Yu-Mei Li, Lin Chen, Yan-Bin Pan, Xiao-Ping Sheng, Wu Rao, Xiao-Liang Xie, Jing-Liang Gu, Hai-Xia Zhu, Tian-You Fan and Min-Lei Qiu

Volume 26, Issue 4, 2023

Published on: 29 August, 2022

Page: [743 - 755] Pages: 13

DOI: 10.2174/1386207325666220512000940

Price: $65

conference banner
Abstract

Objective: The objective of this study is to analyze and verify the main drug components and targets of "Fuzi-Guizhi" in the treatment of osteoarthritis by using the network pharmacology platform.

Methods: The integrated pharmacology of "Fuzi-Guizhi" was analyzed by using the platform of integrated pharmacology of traditional Chinese medicine to explore its mechanism in the treatment of osteoarthritis. By establishing an arthritis model in vitro, the pharmacological effect of "aconitecassia twigs" on articular cartilage was evaluated and conducted for molecular docking.

Results: 28 candidate active components, 37 compound targets, and 583 osteoarthritis-related potential targets were screened, and 10 key target processes were screened in the protein interaction network model. Enrichment analysis showed that the 10 core targets involved 958 GO biologic function items and 76 KEGG signal pathways, which were mainly related to apoptosis and mitochondrial functional metabolism and "Fuzi-Guizhi" drug-containing serum inhibited the expression of Caspase-3 mRNA and protein in chondrocytes and promoted the synthesis of ATP.

Conclusion: Our research is preliminary that the mechanism of action of "Fuzi-Guizhi" may inhibit chondrocyte degeneration by resisting mitochondrial apoptosis, and further experimental research is required to determine.

Keywords: Traditional chinese medicine, cartilage degeneration, apoptosis, atp, caspase-3, Fuzi-Guizhi.

« Previous Next »
Graphical Abstract

[1]
Muraki, S; Tanaka, S; Yoshimura, N. Epidemiology of knee osteoarthritis. OA Sports Med., 2013, 3(1), 21.
[2]
Marini, J-C.; Forlino, A. Replenishing cartilage from endogenous stem cells. N. Engl. J. Med., 2012, 366(26), 2522-2524.
[http://dx.doi.org/10.1056/NEJMcibr1204283] [PMID: 22738103]
[3]
Hunter, D.J. Pharmacologic therapy for osteoarthritis-the era of disease modification. Nat. Rev. Rheumatol., 2011, 7(1), 13-22.
[http://dx.doi.org/10.1038/nrrheum.2010.178] [PMID: 21079644]
[4]
Chen, D.; Li, Y.; Lin, C. Research progress of Fuzi compound in animal model of rheumatoid arthritis. Liaoning. J. Trad. Chinese Med., 2019, 46(12), 2675-2678.
[5]
Fu, W. 200 cases of commonly used drugs in clinical practice; Chemical Industry Press: Beijing, 2010.
[6]
Lin, S.; Liu, K.; Wu, W.; Chen, C.; Wang, Z.; Zhang, X. Study on pretreatment of FPS-1 in rats with hepatic ischemia-reperfusion injury. Am. J. Chin. Med., 2009, 37(2), 323-337.
[http://dx.doi.org/10.1142/S0192415X09006874] [PMID: 19507275]
[7]
Zhang, C.; Lei, J.; Chen, H. Effect of Guizhi Fuzi Decoction on MAPK signaling pathway in synovium of CIA rats. Chinese J. Exper. Prescript., 2017, 23(5), 130-134.
[8]
Fang, H.; Hui, Z.; Tao, Y. Study on the mechanism of Angelica sinensis against atherosclerosis based on integrated pharmacology. Prac. Drugs Clin., 2021, 24(2), 122-127.
[9]
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.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[10]
Pinero, J; Queralt-Rosinach, N; Bravo, A DisGeNET: A discovery platform for the dynamical exploration of human diseases and their genes. Database, 2015, 28, av028.
[11]
Berenbaum, F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr. Cartil., 2013, 21(1), 16-21.
[http://dx.doi.org/10.1016/j.joca.2012.11.012] [PMID: 23194896]
[12]
Habiballa, L.; Salmonowicz, H.; Passos, J-F. Mitochondria and cellular senescence: Implications for musculoskeletal ageing. Free Radic. Biol. Med., 2019, 132, 3-10.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.10.417] [PMID: 30336251]
[13]
Thomas, C-M.; Fuller, C-J.; Whittles, C-E.; Sharif, M. Chondrocyte death by apoptosis is associated with the initiation and severity of articular cartilage degradation. Int. J. Rheum. Dis., 2011, 14(2), 191-198.
[http://dx.doi.org/10.1111/j.1756-185X.2010.01578.x] [PMID: 21518319]
[14]
Blanco, F-J.; Rego-Pérez, I. Mitochondria and mitophagy: Biosensors for cartilage degradation and osteoarthritis. Osteoarthr. Cartil., 2018, 26(8), 989-991.
[http://dx.doi.org/10.1016/j.joca.2018.05.018] [PMID: 29857157]
[15]
Liu, H.; Li, Z.; Cao, Y.; Cui, Y.; Yang, X.; Meng, Z.; Wang, R. Effect of chondrocyte mitochondrial dysfunction on cartilage degeneration: A possible pathway for osteoarthritis pathology at the subcellular level. Mol. Med. Rep., 2019, 20(4), 3308-3316.
[http://dx.doi.org/10.3892/mmr.2019.10559] [PMID: 31432161]
[16]
Blanco, F.J.; June, R.K. II cartilage metabolism, mitochondria, and osteoarthritis. J. Am. Acad. Orthop. Surg., 2020, 28(6), e242-e244.
[http://dx.doi.org/10.5435/JAAOS-D-19-00442] [PMID: 31688367]
[17]
Huang, L-W.; Huang, T-C.; Hu, Y-C.; Hsieh, B.S.; Chiu, P.R.; Cheng, H.L.; Chang, K.L. Zinc protects chondrocytes from monosodium iodoacetate-induced damage by enhancing ATP and mitophagy. Biochem. Biophys. Res. Commun., 2020, 521(1), 50-56.
[http://dx.doi.org/10.1016/j.bbrc.2019.10.066] [PMID: 31610916]
[18]
Gupta, S.; Kass, G-E.; Szegezdi, E.; Joseph, B. The mitochondrial death pathway: a promising therapeutic target in diseases. J. Cell. Mol. Med., 2009, 13(6), 1004-1033.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00697.x] [PMID: 19220575]
[19]
Mao, X.; Fu, P.; Wang, L.; Xiang, C. Mitochondria: Potential targets for osteoarthritis. Front. Med. (Lausanne), 2020, 7, 581402.
[http://dx.doi.org/10.3389/fmed.2020.581402] [PMID: 33324661]
[20]
Yi, D.; Yu, H.; Lu, K.; Ruan, C.; Ding, C.; Tong, L.; Zhao, X.; Chen, D. AMPK signaling in energy control, cartilage biology, and osteoarthritis. Front. Cell Dev. Biol., 2021, 9, 696602.
[http://dx.doi.org/10.3389/fcell.2021.696602] [PMID: 34239878]
[21]
White, R.; Gibson, J-S. The effect of oxygen tension on calcium homeostasis in bovine articular chondrocytes. J. Orthop. Surg. Res., 2010, 5(1), 27.
[http://dx.doi.org/10.1186/1749-799X-5-27] [PMID: 20420658]
[22]
Kan, S.; Duan, M.; Liu, Y.; Wang, C.; Xie, J. Role of mitochondria in physiology of chondrocytes and diseases of osteoarthritis and rheumatoid arthritis. Cartilage, 2021, 13(2), 1102S-1121S.
[http://dx.doi.org/10.1177/19476035211063858] [PMID: 34894777]
[23]
Yi, H.; Zhang, W.; Cui, Z-M.; Cui, S.Y.; Fan, J.B.; Zhu, X.H.; Liu, W. Resveratrol alleviates the interleukin-1β-induced chondrocytes injury through the NF-κB signaling pathway. J. Orthop. Surg. Res., 2020, 15(1), 424.
[http://dx.doi.org/10.1186/s13018-020-01944-8] [PMID: 32948212]
[24]
Shao, X.; Chen, Q.; Dou, X.; Chen, L.; Wu, J.; Zhang, W.; Shao, H.; Ling, P.; Liu, F.; Wang, F. Lower range of molecular weight of xanthan gum inhibits cartilage matrix destruction via intrinsic bax-mitochondria cytochrome c-caspase pathway. Carbohydr. Polym., 2018, 198, 354-363.
[http://dx.doi.org/10.1016/j.carbpol.2018.06.108] [PMID: 30093011]
[25]
Liu, Q.; Wang, J.; Sun, Y.; Han, S. Chondroitin sulfate from sturgeon bone protects chondrocytes via inhibiting apoptosis in osteoarthritis. Int. J. Biol. Macromol., 2019, 134, 1113-1119.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.05.110] [PMID: 31121225]
[26]
Xia, S.; Song, G. Experimental study on the effect of Guizhi Fuzi Decoction on IL-6 level in adjuvant arthritis rats. Liaoning Zhongyiyao Daxue Xuebao, 2011, 13(06), 250-251.
[27]
Lu, Q. Effect and mechanism of modified Guizhi Fuzi Decoction combined with external medicine on rheumatic cold arthritis. Chinese Prac. Med., 2015, 10(16), 206-208.
[28]
Jiang, G.; Yi, C.; Hu, H. Clinical study on Guizhi Fuzi Decoction in treating osteoarthritis of cold-dampness obstruction type. Mod. Distance Educ. Chinese Trad. Med., 2020, 18(22), 76-78.
[29]
Zhou, G.; Tang, L.; Zhou, X.; Wang, T.; Kou, Z.; Wang, Z. A review on phytochemistry and pharmacological activities of the processed lateral root of Aconitum carmichaelii Debeaux. J. Ethnopharmacol., 2015, 160, 173-193.
[http://dx.doi.org/10.1016/j.jep.2014.11.043] [PMID: 25479152]
[30]
Zheng, Q.; Zhao, Y.; Wang, J.; Liu, T.; Zhang, B.; Gong, M.; Li, J.; Liu, H.; Han, B.; Zhang, Y.; Song, X.; Li, Y.; Xiao, X. Spectrum-effect relationships between UPLC fingerprints and bioactivities of crude secondary roots of Aconitum carmichaelii Debeaux (Fuzi) and its three processed products on mitochondrial growth coupled with canonical correlation analysis. J. Ethnopharmacol., 2014, 153(3), 615-623.
[http://dx.doi.org/10.1016/j.jep.2014.03.011] [PMID: 24632114]
[31]
Ying, L.; Chao, J.; Wu, W. Protective mechanism of Fuzi polysaccharide on myocardial cells of neonatal rats with hypoxia/reoxygenation. Chinese J. Mod. Appl. Pharm., 2012, 29(04), 281-284.
[32]
Huang, L.; Peng, S.; Zhang, S.; Hu, Q.; Yu, R.; Liu, H.; Sun, J. Hepatic energy metabolism on rats by six traditional Chinese medicine with hot property. Zhongguo Zhongyao Zazhi, 2010, 35(11), 1470-1473.
[PMID: 20822023]
[33]
Shen, D. Effect of Guizhi Gancao Decoction on myocardial apoptosis and expression of TGF-β 1 and ICAM-1 in rats with heart failure. Chinese J. Trad. Chinese Med., 2018, 36(04), 932-935.
[34]
Liu, G.; Yan, Y.; Miao, G. Effect of Guizhi Jiajian Decoction on cardiomyocyte apoptosis and Bax mRNA and Caspase 3 mRNA gene expression in MRL mice. J. Clin. Cardiovas. Dis., 2011, 27(07), 549-551.
[35]
Isemura, M. Catechin in human health and disease. Molecules, 2019, 24(3), E528.
[http://dx.doi.org/10.3390/molecules24030528] [PMID: 30717121]
[36]
Nakanishi, T.; Mukai, K.; Hosokawa, Y.; Takegawa, D.; Matsuo, T. Catechins inhibit vascular endothelial growth factor production and cyclooxygenase-2 expression in human dental pulp cells. Int. Endod. J., 2015, 48(3), 277-282.
[http://dx.doi.org/10.1111/iej.12312] [PMID: 24847951]
[37]
Heinecke, L-F.; Grzanna, M-W.; Au, A-Y.; Mochal, C.A.; Rashmir-Raven, A.; Frondoza, C.G. Inhibition of cyclooxygenase-2 expression and prostaglandin E2 production in chondrocytes by avocado soybean unsaponifiables and epigallocatechin gallate. Osteoarthritis Cartilage, 2010, 18(2), 220-227.
[http://dx.doi.org/10.1016/j.joca.2009.08.015] [PMID: 19748608]
[38]
Tang, L-Q.; Wei, W.; Wang, X-Y. Effects and mechanisms of catechin for adjuvant arthritis in rats. Adv. Ther., 2007, 24(3), 679-690.
[http://dx.doi.org/10.1007/BF02848793] [PMID: 17660179]
[39]
Singh, R.; Akhtar, N.; Haqqi, T-M. Green tea polyphenol epigallocatechin-3-gallate: Inflammation and arthritis. [corrected]. Life Sci., 2010, 86(25-26), 907-918.
[http://dx.doi.org/10.1016/j.lfs.2010.04.013] [PMID: 20462508]
[40]
Yin, Y.; Liu, X.; Liu, J.; Cai, E.; Zhu, H.; Li, H.; Zhang, L.; Li, P.; Zhao, Y. Beta-sitosterol and its derivatives repress lipopolysaccharide/d-galactosamine-induced acute hepatic injury by inhibiting the oxidation and inflammation in mice. Bioorg. Med. Chem. Lett., 2018, 28(9), 1525-1533.
[http://dx.doi.org/10.1016/j.bmcl.2018.03.073] [PMID: 29622518]
[41]
Rajavel, T.; Mohankumar, R.; Archunan, G.; Ruckmani, K.; Devi, K.P. Beta sitosterol and Daucosterol (phytosterols identified in Grewia tiliaefolia) perturbs cell cycle and induces apoptotic cell death in A549 cells. Sci. Rep., 2017, 7(1), 3418.
[http://dx.doi.org/10.1038/s41598-017-03511-4] [PMID: 28611451]
[42]
Loizou, S.; Lekakis, I.; Chrousos, G.P.; Moutsatsou, P. β-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol. Nutr. Food Res., 2010, 54(4), 551-558.
[http://dx.doi.org/10.1002/mnfr.200900012] [PMID: 19937850]
[43]
Choi, Y-H.; Kong, K-R.; Kim, Y-A.; Jung, K.O.; Kil, J.H.; Rhee, S.H.; Park, K.Y. Induction of Bax and activation of caspases during beta-sitosterol-mediated apoptosis in human colon cancer cells. Int. J. Oncol., 2003, 23(6), 1657-1662.
[PMID: 14612938]
[44]
Zhang, F.; Liu, Z.; He, X.; Li, Z.; Shi, B.; Cai, F. β-Sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund’s adjuvant-induced arthritis in rats: involvement of NF-кB and HO-1/Nrf-2 pathway. Drug Deliv., 2020, 27(1), 1329-1341.
[http://dx.doi.org/10.1080/10717544.2020.1818883] [PMID: 32945205]
[45]
Ma, Y.; Liu, R.; Hui, Y. Observation on nursing effect of moxibustion separated from aconite cake combined with bean burying at auricular points on knee osteoarthritis. World Latest Med. Inform. Digest, 2019, 19(95), 282-285.
[46]
Guo, J-R.; Chen, Q-Q.; Lam, C.W.; Zhang, W. Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and HL-60 cancer cells. Biol. Res., 2015, 48(1), 40.
[http://dx.doi.org/10.1186/s40659-015-0031-x] [PMID: 26209237]
[47]
Bose, M.; Chakraborty, M.; Bhattacharya, S.; Mukherjee, D.; Mandal, S.; Mishra, R. Prevention of arthritis markers in experimental animal and inflammation signalling in macrophage by Karanjin isolated from Pongamia pinnata seed extract. Phytother. Res., 2014, 28(8), 1188-1195.
[http://dx.doi.org/10.1002/ptr.5113] [PMID: 24399783]
[48]
Anita-Elaine, W. Dihydroquercetin: More than just an impurity? Eur. J. Pharmacol., 2012, 684(1-3), 19-26.
[49]
Xiao, S.; Rong-chang, C.; Zhi-hong, Y.; Gui-bo, S.; Min, W.; Xiao-jun, M.; Li-juan, Y.; Xiao-bo, S. Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis. Food Chem. Toxicol., 2014, 63, 221-232.
[50]
Kim, A.; Yoon-Jeong, N.; Chung-Soo, L. Taxifolin reduces the cholesterol oxidation product-induced neuronal apoptosis by suppressing the Akt and NF-κB activation-mediated cell death. Brain Res. Bull., 2017, 134, 13463-13471.
[http://dx.doi.org/10.1016/j.brainresbull.2017.07.008]
[51]
Turovskaya, M-V.; Gaidin, S-G.; Mal’tseva, V.N.; Zinchenko, V.P.; Turovsky, E.A. Taxifolin protects neurons against ischemic injury in vitro via the activation of antioxidant systems and signal transduction pathways of GABAergic neurons. Mol. Cell. Neurosci., 2019, 96, 10-24.
[http://dx.doi.org/10.1016/j.mcn.2019.01.005] [PMID: 30776416]

Rights & Permissions Print Cite
Article Metrics
11
© 2024 Bentham Science Publishers | Privacy Policy