Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

The Xiaogu San Attenuates Pain and Cartilage Damage in Rats with Monosodium Iodoacetate Induced Osteoarthritis

Author(s): Xiaoyun Zhang, Rilan Chen*, Zilong Liao, Ying Zhu, Yueping Chen, Jianhang Liu and Xia Chen

Volume 25, Issue 11, 2022

Published on: 11 January, 2022

Page: [1914 - 1951] Pages: 38

DOI: 10.2174/1386207325666211008130312

Price: $65

Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease with an increasing incidence associated with increased life expectancy. The application of traditional Chinese medicine in the treatment of OA has become a research hotspot.

Objective: This study investigated the effects of XGS externally applied to osteoarthritic joints and analyze its effect on pain in monosodium iodoacetate (MIA)-induced OA rats. This study also evaluates potential mechanisms behind the anti-osteoarthritic effects of XGS.

Methods: A total of 24 Sprague Dawley rats were evenly and randomly divided into three separate groups, including the normal control (NC), OA and XGS groups. MIA (50 μL, 10 mg/mL) was injected into the left knee joints of the rats to induce OA. After 7 days, The rats of XGS group were given XGS (0.45 g) that was externally applied to the left knee joint, were fixed with gauze, and continuously administered XGS for 28 days. Morphological changes in tissues and organs were examined using H&E staining. Biochemical indicators were measured using an automatic biochemical analyzer. Inflammatory cytokines were detected using ELISA kits and immunohistochemistry. RNA-based high-throughput sequencing (RNA-seq) was performed to detect differential expression of mRNAs in normal and MIA–induced OA rats.

Results: Stride of the left leg was extended in rats, matrix increased on cartilage tissue surfaces, and inflammatory cytokines were reduced when treated with XGS. RNA-seq results revealed that the PI3K-Akt signaling pathway is activated in the OA model. The qRT-PCR showed that the expression levels of Tnn, Col6a6, Igf1 and Lamb1 were up-regulated by XGS.

Conclusion: Altogether, this work demonstrated the potential therapeutic effects of XGS in rats with OA induced by MIA. The XGS may be considered an alternative therapy to manage OA.

Keywords: Osteoarthritis, Xiaogu San, PI3K/AKT signaling pathway, pain, cartilage damage, knee joint.

Graphical Abstract

[1]
Ondrésik, M.; Maia, F.; Morais, A.D.S.; Gertrudes, A.; Bacelar, A.; Reis, R.L.; Correia, C. Gon?Alves, C; Radhouani, H; Sousa, R; Oliveira, J Management of knee Osteoarthritis. Current status and future trends. Biotechnol. Bioeng., 2016, 114(4), 717-739.
[http://dx.doi.org/10.1002/bit.26182] [PMID: 27618194]
[2]
Li, G.; Yin, J.; Gao, J.; Cheng, T.S.; Pavlos, N.J.; Zhang, C.; Zheng, M.H. Subchondral bone in osteoarthritis: Insight into risk factors and microstructural changes. Arthritis Res. Ther., 2013, 15(6), 223.
[http://dx.doi.org/10.1186/ar4405] [PMID: 24321104]
[3]
Leong, D.J.; Choudhury, M.; Hirsh, D.M.; Hardin, J.A.; Cobelli, N.J.; Sun, H.B. Nutraceuticals: Potential for chondroprotection and mo-lecular targeting of osteoarthritis. Int. J. Mol. Sci., 2013, 14(11), 23063-23085.
[http://dx.doi.org/10.3390/ijms141123063] [PMID: 24284399]
[4]
Maiese, K. Picking a bone with WISP1 (CCN4): New strategies against degenerative joint disease. J. Transl. Sci., 2016, 1(3), 83-85.
[http://dx.doi.org/10.15761/JTS.1000120] [PMID: 26893943]
[5]
Fauci, A.; Fauci, A.S.; Braunwald, E.; Kasper, D.; Hauser, S.; Dan, L.; Jameson, J.; Loscalzo, J. Harrison’s Principles of Internal Medi-cine; Mcgraw-hill, 2014.
[6]
Jin, C.; Lee, A.; Joong, K.; Goya, C.; Seung-Hyung, K. Protective effects of peucedanum japonicum extract against osteoarthritis in an animal model using a combined systems approach for compound-target prediction. Nutrients, 2018, 10(6), 754.
[7]
Chen, Z.; Li, X-P.; Li, Z-J.; Xu, L.; Li, X-M. Reduced hepatotoxicity by total glucosides of paeony in combination treatment with lefluno-mide and methotrexate for patients with active rheumatoid arthritis. Int. Immunopharmacol., 2013, 15(3), 474-477.
[http://dx.doi.org/10.1016/j.intimp.2013.01.021] [PMID: 23415907]
[8]
Hamidpour, M.; Hamidpour, R.; Hamidpour, S.; Shahlari, M. Chemistry, pharmacology, and medicinal property of sage (salvia) to prevent and cure illnesses such as obesity, diabetes, depression, dementia, lupus, autism, heart disease, and cancer. J. Tradit. Complement. Med., 2014, 4(2), 82-88.
[http://dx.doi.org/10.4103/2225-4110.130373] [PMID: 24860730]
[9]
Maione, F.; Mascolo, N. Danshen and the cardiovascular system: New advances for an old remedy. Semin. Thromb. Hemost., 2016, 42(3), 321-322.
[http://dx.doi.org/10.1055/s-0036-1580086] [PMID: 26951502]
[10]
Chen, Z.; Zhang, C.; Gao, F.; Fu, Q.; Fu, C.; He, Y.; Zhang, J. A systematic review on the rhizome of Ligusticum chuanxiong Hort. (Chuanxiong). Food Chem. Toxicol., 2018, 119, 309-325.
[http://dx.doi.org/10.1016/j.fct.2018.02.050] [PMID: 29486278]
[11]
Zheng, H.P. Clinical observation on the therapeutic effect of percutaneous application of “xiaogu san” (osteophyte-eliminating powder) in the treatment of 105 cases of ankylosing spondylitis. Int. Convention Trad. Med., 2004. Available from: http://223.220.252.164:888/KCMS/detail/detail.aspx?filename=ZYKY200411001739&dbcode=IPFD&dbname=IP FD2006
[12]
Guo, C.L. Ma Bai Xiao Gu San in the treatment of bone hyperplasia. J. Intern. Med., 1993, 04.
[13]
Yang, S.W. Clinical experience in treating 128 cases of osteophytes with Xiao Gu San. Chin. Med. J., 2014, 8, 139-140.
[14]
Tong, L.K.; Huang, J.S. Treatment of 221 cases of bone hyperplasia with Xiao Gu San plus manipulation. Hebei Trad. Chin. Med., 2000, 7, 503-503.
[15]
Kuyinu, E.L.; Narayanan, G.; Nair, L.S.; Laurencin, C.T. Animal models of osteoarthritis: Classification, update, and measurement of outcomes. J. Orthop. Surg. Res., 2016, 11(1), 19.
[http://dx.doi.org/10.1186/s13018-016-0346-5] [PMID: 26837951]
[16]
Piel, M.J.; Kroin, J.S.; van Wijnen, A.J.; Kc, R. Im, H-J. Pain assessment in animal models of osteoarthritis. Gene, 2014, 537(2), 184-188.
[http://dx.doi.org/10.1016/j.gene.2013.11.091] [PMID: 24333346]
[17]
Kullander, K.; Croll, S.D.; Zimmer, M.; Pan, L.; McClain, J.; Hughes, V.; Zabski, S.; DeChiara, T.M.; Klein, R.; Yancopoulos, G.D.; Gale, N.W. Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control. Genes Dev., 2001, 15(7), 877-888.
[http://dx.doi.org/10.1101/gad.868901] [PMID: 11297511]
[18]
Lin, J.; Hou, Y.; Huang, S.; Wang, Z.; Sun, C.; Wang, Z.; He, X.; Tam, N.L.; Wu, C.; Wu, L. Exportin-T promotes tumor proliferation and invasion in hepatocellular carcinoma. Mol. Carcinog., 2019, 58(2), 293-304.
[http://dx.doi.org/10.1002/mc.22928] [PMID: 30334580]
[19]
Jamieson, S.E.; de Roubaix, L-A.; Cortina-Borja, M.; Tan, H.K.; Mui, E.J.; Cordell, H.J.; Kirisits, M.J.; Miller, E.N.; Peacock, C.S.; Har-grave, A.C.; Coyne, J.J.; Boyer, K.; Bessieres, M-H.; Buffolano, W.; Ferret, N.; Franck, J.; Kieffer, F.; Meier, P.; Nowakowska, D.E.; Paul, M.; Peyron, F.; Stray-Pedersen, B.; Prusa, A-R.; Thulliez, P.; Wallon, M.; Petersen, E.; McLeod, R.; Gilbert, R.E.; Blackwell, J.M. Genetic and epigenetic factors at COL2A1 and ABCA4 influence clinical outcome in congenital toxoplasmosis. PLoS One, 2008, 3(6), e2285-e2285.
[http://dx.doi.org/10.1371/journal.pone.0002285] [PMID: 18523590]
[20]
McAlinden, A.; Majava, M.; Bishop, P.N.; Perveen, R.; Black, G.C.M.; Pierpont, M.E.; Ala-Kokko, L.; Männikkö, M. Missense and non-sense mutations in the alternatively-spliced exon 2 of COL2A1 cause the ocular variant of Stickler syndrome. Hum. Mutat., 2008, 29(1), 83-90.
[http://dx.doi.org/10.1002/humu.20603] [PMID: 17721977]
[21]
Sandell, L.J.; Aigner, T. Articular cartilage and changes in arthritis. An introduction: Cell biology of osteoarthritis. Arthritis Res., 2001, 3(2), 107-113.
[http://dx.doi.org/10.1186/ar148] [PMID: 11178118]
[22]
Goldring, M.B. The role of the chondrocyte in osteoarthritis. Arthritis Rheum., 2000, 43(9), 1916-1926.
[http://dx.doi.org/10.1002/1529-0131(200009)43:9<1916:AID-ANR2>3.0.CO;2-I] [PMID: 11014341]
[23]
Huang, K.; Wu, L.D. Aggrecanase and aggrecan degradation in osteoarthritis: a review. J. Int. Med. Res., 2008, 36(6), 1149-1160.
[http://dx.doi.org/10.1177/147323000803600601] [PMID: 19094423]
[24]
Poole, A.R.; Kobayashi, M.; Yasuda, T.; Laverty, S.; Mwale, F.; Kojima, T.; Sakai, T.; Wahl, C.; El-Maadawy, S.; Webb, G.; Tchetina, E.; Wu, W. Type II collagen degradation and its regulation in articular cartilage in osteoarthritis. Ann. Rheum. Dis., 2002, 61(Suppl. 2), ii78-ii81.
[http://dx.doi.org/10.1136/ard.61.suppl_2.ii78] [PMID: 12379630]
[25]
Ryu, J-H.; Yang, S.; Shin, Y.; Rhee, J.; Chun, C-H.; Chun, J-S. Interleukin-6 plays an essential role in hypoxia-inducible factor 2α-induced experimental osteoarthritic cartilage destruction in mice. Arthritis Rheum., 2011, 63(9), 2732-2743.
[http://dx.doi.org/10.1002/art.30451] [PMID: 21590680]
[26]
Latourte, A.; Cherifi, C.; Maillet, J.; Ea, H-K.; Bouaziz, W.; Funck-Brentano, T.; Cohen-Solal, M.; Hay, E.; Richette, P. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann. Rheum. Dis., 2017, 76(4), 748-755.
[http://dx.doi.org/10.1136/annrheumdis-2016-209757] [PMID: 27789465]
[27]
Yokota, K.; Sato, K.; Miyazaki, T.; Kitaura, H.; Kayama, H.; Miyoshi, F.; Araki, Y.; Akiyama, Y.; Takeda, K.; Mimura, T. Combination of tumor necrosis factor α and interleukin-6 induces mouse osteoclast-like cells with bone resorption activity both in vitro and in vivo. Arthritis Rheumatol., 2014, 66(1), 121-129.
[http://dx.doi.org/10.1002/art.38218] [PMID: 24431283]
[28]
Rowan, A.D.; Koshy, P.J.; Shingleton, W.D.; Degnan, B.A.; Heath, J.K.; Vernallis, A.B.; Spaull, J.R.; Life, P.F.; Hudson, K.; Cawston, T.E. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum., 2001, 44(7), 1620-1632.
[http://dx.doi.org/10.1002/1529-0131(200107)44:7<1620:AID-ART285>3.0.CO;2-B] [PMID: 11465713]
[29]
Zhang, Q.; Wang, J.; Chen, C.; Kong, Y.; Yan, H.; Duan, J.; Wang, C.; Sha, Y.; Wen, X.; Wang, C. Perfluorooctanoic acid induces migration and invasion and inhibits apoptosis through the PI3K/AKT signaling pathway in human rhabdomyosarcoma cells. Oncol. Rep., 2019, 42(4), 1558-1568.
[http://dx.doi.org/10.3892/or.2019.7265] [PMID: 31524277]
[30]
Chen, J.; Jiang, C.; Fu, L.; Zhu, C.L.; Xiang, Y.Q.; Jiang, L.X.; Chen, Q.; Liu, W.M.; Chen, J.N.; Zhang, L.Y.; Liu, M.; Chen, C.; Tang, H.; Wang, B.; Tsao, S.W.; Kwong, D.L.; Guan, X.Y. CHL1 suppresses tumor growth and metastasis in nasopharyngeal carcinoma by repress-ing PI3K/AKT signaling pathwayvia interaction with Integrin β1 and Merlin. Int. J. Biol. Sci., 2019, 15(9), 1802-1815.
[http://dx.doi.org/10.7150/ijbs.34785] [PMID: 31523184]
[31]
Khan, M.A.; Jain, V.K.; Rizwanullah, M.; Ahmad, J.; Jain, K. PI3K/AKT/mTOR pathway inhibitors in triple-negative breast cancer: a re-view on drug discovery and future challenges. Drug Discov. Today, 2019, 24(11), 2181-2191.
[http://dx.doi.org/10.1016/j.drudis.2019.09.001] [PMID: 31520748]
[32]
Ahmed, S.; Wang, N.; Hafeez, B.B.; Cheruvu, V.K.; Haqqi, T.M. Punica granatum L. extract inhibits IL-1beta-induced expression of ma-trix metalloproteinases by inhibiting the activation of MAP kinases and NF-kappaB in human chondrocytes in vitro. J. Nutr., 2005, 135(9), 2096-2102.
[http://dx.doi.org/10.1093/jn/135.9.2096] [PMID: 16140882]
[33]
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.
[http://dx.doi.org/10.1007/s10753-016-0309-3] [PMID: 26846886]
[34]
Cai, C.; Min, S.; Yan, B.; Liu, W.; Yang, X.; Li, L.; Wang, T.; Jin, A. MiR-27a promotes the autophagy and apoptosis of IL-1β treated-articular chondrocytes in osteoarthritis through PI3K/AKT/mTOR signaling. Aging (Albany NY), 2019, 11(16), 6371-6384.
[http://dx.doi.org/10.18632/aging.102194] [PMID: 31460867]
[35]
Hashimoto, M.; Nakasa, T.; Hikata, T.; Asahara, H. Molecular network of cartilage homeostasis and osteoarthritis. Med. Res. Rev., 2008, 28(3), 464-481.
[http://dx.doi.org/10.1002/med.20113] [PMID: 17880012]
[36]
Vincenti, M.P.; Brinckerhoff, C.E. Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: Integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res., 2002, 4(3), 157-164.
[http://dx.doi.org/10.1186/ar401] [PMID: 12010565]

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