Bee Venom Apitoxin Alleviates Collagen-Induced Arthritis In DBA-1J Mice
Abstract
The anti-inflammatory, antibacterial effect, and anti-aging properties of the venom of honey bee Apis mellifera L. have been investigated and exploited for pharmaceutical and cosmetic applications for decades. Apitoxin, a drug based on bee venom, is administered via injection and is permitted for use in humans for its antipyretic, analgesic, and anti-inflammatory properties. This study was conducted to expand the scope of apitoxin application to arthritis. We used a DBA-1J mouse model of collagen-induced arthritis (CIA). Apitoxin was injected intradermally into the mice twice a week, and the body weight, arthritis score, and hindlimb paw edema were recorded once a week for 4 weeks in mice with CIA. The body weight of the groups with CIA was significantly lower than that of the group without CIA during the experimental period. Although the arthritis scores of all groups with CIA were higher than those of the group without CIA, the high dose apitoxin-treated group had a significantly improved arthritis score than the vehicle group on days 14 and 28. A significant reduction in edema was observed in the hindlimb paws in the apitoxin-treated group compared with that in the vehicle group. Additionally, inflammatory cytokines, such as IL-6 and IL-1β, and IgG antibodies to type II collagen, were detected in the articular tissue of mice with CIA on day 28. Both IL-6 and anti-type II collagen IgG levels significantly decreased in the apitoxin-treated group compared with those in the vehicle group. Histopathological analysis of the articular tissue also revealed similar improved results in the apitoxin-treated group. In conclusion, these results suggested that apitoxin has potential therapeutic application in patients with arthritis.
Keywords:
Apitoxin, Arthritis, Bee venom, CIA mouse, InflammationDOI
https://doi.org/10.25004/IJPSDR.2022.140510References
Billingham ME, Morley J, Hanson JM, Shipolini RA, Vernon CA. Letter: An Anti-Inflammatory Peptide from Bee Venom. Nature. 1973;245:163-164. Available from: doi.org/10.1038/245163a0
Moreno M, Giralt E. Three Valuable Peptides from Bee and Wasp Venoms for Therapeutic and Biotechnological Use: Melittin, Apamin and Mastoparan. Toxins (Basel). 2015;7:1126-1150. Available from: doi.org/10.3390/toxins7041126
Lariviere WR, Melzack R. The Bee Venom Test: A New Tonic-Pain Test. Pain. 1996;66:271-277. Available from: doi.org/10.1016/0304- 3959(96)03075-8
Lee G, Bae H. Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects. Molecules. 2016;21:616. Available from: doi. org/10.3390/molecules21050616
Jung KH, Baek H, Kang M, Kim N, Lee SY, Bae H. Bee Venom Phos¬pholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice. Toxins (Basel). 2017;9:68. Available from: doi.org/10.3390/toxins9020068
Lee JD, Kim SY, Kim TW, Lee SH, Yang HI, Lee DI, Lee YH. Anti-inflammatory Effect of Bee Venom on Type II Collagen-Induced Arthritis. Am J Chin Med. 2004;32:361-367. Available from: doi. org/10.1142/S0192415X04002016
Choi GM, Lee B, Hong R, Park SY, Cho DE, Yeom M, Park HJ, Bae H, Hahm DH. Bee Venom Phospholipase A2 Alleviates Collagen-Induced Polyarthritis by Inducing Foxp3(+) Regulatory T Cell Polarization in Mice. Sci Rep. 2021;11:3511. Available from: doi.org/10.1038/ s41598-021-82298-x
Roos EM, Arden NK. Strategies for the Prevention of Knee Osteo¬arthritis. Nat Rev Rheumatol. 2016;12:92-101. Available from: doi. org/10.1038/nrrheum.2015.135
Barbour KE, Murphy LB, Helmick CG, Hootman JM, Renner JB, Jordan JM. ¬oject. Arthritis Care Res (Hoboken). 2017;69:1863-1870. Avail¬able from: doi.org/10.1002/acr.23211
Cho HJ, Morey V, Kang JY, Kim KW, Kim TK. Prevalence and Risk Factors of Spine, Shoulder, Hand, Hip, and Knee Osteoarthritis in Community-dwelling Koreans Older Than Age 65 Years. Clin Orthop Relat Res. 2015;473:3307-3314. Available from: doi.org/10.1007/ s11999-015-4450-3
Egloff C, Hugle T, Valderrabano V. Biomechanics and Pathomechanisms of Osteoarthritis. Swiss Med Wkly. 2012;142:w13583. Available from: doi.org/10.4414/smw.2012.13583
Scott D, Smith C, Lohmander S, Chard J. Osteoarthritis. Clin Evid. 2003;10:1402-1430.
Rahman MM, Kim HK, Kim SE, Kim MJ, Kim DH, Lee HS. Chondroprotective Effects of a Standardized Extract (KBH-JP- 040) from Kalopanax pictus, Hericium erinaceus, and Astragalus membranaceus in Experimentally Induced In Vitro and In Vivo Osteoarthritis Models. Nutrients. 2018;10:356. Available from: doi. org/10.3390/nu10030356
Sarzi-Puttini P, Cimmino MA, Scarpa R, Caporali R, Parazzini F, Zaninelli A, Atzeni F, Canesi B. Osteoarthritis: An Overview of the Disease and Its Treatment Strategies. Semin Arthritis Rheum. 2005;35:1-10. Available from: doi.org/10.1016/j. semarthrit.2005.01.013
van Haselen RA. Topical Treatment of Osteoarthritis of the Knee with Herbal Products: Promising Results but Still Questions. J Clin Rheumatol. 2003;9:140-141. Available from: doi.org/10.1097/01. RHU.0000073438.41609.4b
Huh JE, Baek YH, Lee JD, Choi DY, Park DS. Therapeutic Effect of Siegesbeckia Pubescens on Cartilage Protection in a Rabbit Collagenase-Induced Model of Osteoarthritis. J Pharmacol Sci. 2008;107:317-328. Available from: doi.org/10.1254/jphs.08010fp
Park DS, Huh JE, Baek YH. Therapeutic Effect of Aralia Cordata Extracts on Cartilage Protection in Collagenase-Induced Inflammatory Arthritis Rabbit Model. J Ethnopharmacol. 2009;125:207-217. Available from: doi.org/10.1016/j.jep.2009.07.010
Scales HE, Ierna M, Smith KM, Ross K, Meiklejohn GR, Patterson- Kane JC, McInnes IB, Brewer JM, Garside P, Maffia P. Assessment of Murine Collagen-Induced Arthritis by Longitudinal Non-Invasive Duplexed Molecular Optical Imaging. Rheumatology (Oxford). 2016;55:564-572. Available from: doi.org/10.1093/rheumatology/ kev361
Jag ua-Gualdron A , Pena-Latorre JA , Fernadez-Bernal R E . Apitherapy for Osteoarthritis: Perspectives from Basic Research. Complement Med Res. 2020;27:184-192. Available from: doi. org/10.1159/000505015
Kim Y, Lee YW, Kim H, Chung DK. Bee Venom Alleviates Atopic Dermatitis Symptoms through the Upregulation of Decay- Accelerating Factor (DAF/CD55). Toxins (Basel). 2019;11:239. Available from: doi.org/10.3390/toxins11050239
El-Aarag B, Magdy M, AlAjmi MF, Khalifa SAM, El-Seedi HR. Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries In Mice by Modifying Oxidative Stress and Apoptosis. Molecules. 2019;24:1498. Available from: doi.org/10.3390/molecules24081498
Trentham DE, Townes AS, Kang AH. Autoimmunity to Type II Collagen an Experimental Model of Arthritis. J Exp Med. 1977;146:857-868. Available from: doi.org/10.1084/jem.146.3.857
El-Tedawy DM, Abd-Alhaseeb MM, Helmy MW, Ghoneim AI. Systemic Bee Venom Exerts Anti-Arthritic and Anti-Inflammatory Properties in a Rat Model of Arthritis. Biomed Rep. 2020;13:20. Available from: doi.org/10.3892/br.2020.1327
Lee JA, Son MJ, Choi J, Jun JH, Kim JI, Lee MS. Bee Venom Acupuncture for Rheumatoid Arthritis: A Systematic Review of Randomised Clinical Trials. BMJ Open. 2014;4:e006140. Available from: doi. org/10.1136/bmjopen-2014-006140
Ozlem Nisbet H, Ozak A, Yardimci C, Nisbet C, Yarim M, Bayrak IK, Sirin YS. Evaluation of Bee Venom and Hyaluronic Acid in the Intra-Articular Treatment of Osteoarthritis in an Experimental Rabbit Model. Res Vet Sci. 2012;93:488-493. Available from: doi. org/10.1016/j.rvsc.2011.08.007
Lee SH, Kwon GS, Kang MS, Yoon HM, Kim CH. Comparative Study on the Effects of Bee Venom Pharmacopuncture according to the Treatment Method for Knee Osteoarthritis. J Pharmacopuncture. 2012;15:7-14. Available from: doi.org/10.3831/KPI.2012.15.011
Li Y, Kakkar R, Wang J. In vivo and in vitro Approach to Anti-arthritic and Anti-inflammatory Effect of Crocetin by Alteration of Nuclear Factor-E2-Related Factor 2/hem Oxygenase (HO)-1 and NF-kappaB Expression. Front Pharmacol. 2018;9:1341. Available from: doi. org/10.3389/fphar.2018.01341
Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010;376:1094-1108. Available from: doi.org/10.1016/S0140- 6736(10)60826-4
Mori T, Miyamoto T, Yoshida H, Asakawa M, Kawasumi M, Kobayashi T, Morioka H, Chiba K, Toyama Y, Yoshimura A. IL-1beta and TNFalpha-initiated IL-6-STAT3 Pathway is Critical in Mediating Inflammatory Cytokines and RANKL Expression in Inflammatory Arthritis. Int Immunol. 2011;23:701-712. Available from: doi. org/10.1093/intimm/dxr077
Yang S, Hollister AM, Orchard EA, Chaudhery SI, Ostanin DV, Lokitz SJ, Mathis JM. Quantification of Bone Changes in a Collagen-Induced Arthritis Mouse Model by Reconstructed Three Dimensional Micro-CT. Biol Proced Online. 2013;15:8. Available from: doi. org/10.1186/1480-9222-15-8
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