Potential Therapeutic Benefits of Aloe barbadensis in Treatment of Rheumatoid Arthritis
DOI:
https://doi.org/10.12970/2310-9874.2014.02.01.6Keywords:
Rheumatoid arthritis, wound healing, anti-inflammatory, anthraquinones, polysaccharides.Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized with a chronic, systemic inflammation which primarily affects synovial joints. A significant percentage of the world population including notably the aged groups suffers from such a disabling and painful condition that can result in substantial loss of normal functioning and mobility, if not adequately treated. Natural products have always been a potential source of alternative therapy and lead compounds for various diseases. A good number of anti-inflammatory or immunomodulatory plant extracts (and phytochemicals thereof) seem to exist whilst several of them have been specially studied in the context of RA. One potential example in this regard includes Aloe barbadensis. Over 75 active components have already been identified in Aloe barbadensis leaf gels and some of them have been implicated as immunomodulatory compounds and as such beneficial against RA, based on animal studies. This paper aims at critically reviewing the evidence of beneficial role as well as possible mechanism of such action of Aloe barbadensis preparations in RA and related complications.
References
Mayada A, Dina E, Marwa S, Wessam EH. Serum Leptin levels in rheumatoid arthritis and relationship with disease activity. Egypt Rheumatol 2014; 36; 1-5. http://dx.doi.org/10.1016/j.ejr.2013.10.002
Samar GS, Tarek EK, Ghada EH, Waleed M. Significance of serum levels of angiopoietin-2 and its relationship to Doppler ultrasonographic findings in rheumatoid arthritis patients. Egypt Rheumatol 2014; 36: 15-20. http://dx.doi.org/10.1016/j.ejr.2013.09.001
Choy EHS, Panayi GS. Cytokine Pathways and Joint Inflammation in Rheumatoid Arthritis. N Engl J Med 2001; 344: 907-16. http://dx.doi.org/10.1056/NEJM200103223441207
Mahajan N, Kaur J, Rawal S, et al. Adult rheumatoid arthritis - a review. Int J of Pharm Res Dev 2010; 2: 1-9.
Reem IES, Hussein SA, Raslan HZ, Elgogary AA. Diagnostic utility of anti-cyclic citrullinated peptide and antimodified citrullinated vimentin antibodies in rheumatoid arthritis. Egypt Rheumatol 2014; 36: 65-70. http://dx.doi.org/10.1016/j.ejr.2013.12.009
Müller-Ladner U, Pap T, Gay RE, Neidhart M, Gay S. Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol 2005; 1: 102-10. http://dx.doi.org/10.1038/ncprheum0047
Kontoyiannis D, Kollias G. Fibroblast biology: Synovial fibroblasts in rheumatoid arthritis- leading role or chorus line? Arthritis Res 2000; 2: 342-3. http://dx.doi.org/10.1186/ar109
Hitoshi I, Soichirou H, Yasuro N, Shigeaki I, Hitoshi K, Osamu O. The role of adhesion molecules in synovial pannus formation in rheumatoid arthritis. Clin Orthop Relat Res 1994; 300: 297-303.
Harris ED Jr. Rheumatoid arthritis: Pathophysiology and implications for therapy. N Engl J Med 1990; 322: 1277-89. http://dx.doi.org/10.1056/NEJM199005033221805
Mullazehi M, Wick MC, Klareskog L, van Vollenhoven R, Rönnelid J. Anti-type II collagen antibodies are associated with early radiographic destruction in rheumatoid arthritis. Arthritis Res Ther 2012; 14: R100. http://dx.doi.org/10.1186/ar3825
Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003; 423: 356-61. http://dx.doi.org/10.1038/nature01661
FitzGerald O, Bresnihan B. Synovial membrane and vascularity. Ann Rheum Dis 1995; 54: 511-5. http://dx.doi.org/10.1136/ard.54.6.511
FitzGerald O, Soden M, Yanni G, Robinson R, Bresnihan B. Morphometric analysis of blood vessels in synovial membranes obtained from clinically affected and unaffected knee joints of patients with rheumatoid arthritis. Ann Rheum Dis 1991; 50: 792-6. http://dx.doi.org/10.1136/ard.50.11.792
McInnes IB, Schett G. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med 2011; 365: 2205-19. http://dx.doi.org/10.1056/NEJMra1004965
McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007; 7: 429-42. http://dx.doi.org/10.1038/nri2094
Van den Berg WB, Pierre M. IL-17 as a future therapeutic target for rheumatoid arthritis. Nat Rev Rheumatol 2009; 5: 549-53. http://dx.doi.org/10.1038/nrrheum.2009.179
Feldmann M, Brennan FM, Maini R. Role of cytokines in rheumatoid arthritis. Ann Rev Immunol 1996; 14: 397-40. http://dx.doi.org/10.1146/annurev.immunol.14.1.397
Arend WP, Malyak M, Guthridge CJ, Gabay C. Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 1998; 16: 27-55. http://dx.doi.org/10.1146/annurev.immunol.16.1.27
Gracie JA, Forsey RJ, Chan WL, et al. A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Invest 1999; 104: 1393-40. http://dx.doi.org/10.1172/JCI7317
Van den Berg WB, Bresnihan B. Pathogenesis of joint damage in rheumatoid arthritis: evidence of a dominant role for interleukin-I. Baillieres Best Pract Res Clin Rheumatol 1999; 13: 577-97. http://dx.doi.org/10.1053/berh.1999.0047
Lubberts E, Joosten LA, Oppers B, et al. IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol 2001; 167: 1004-13.
Gracie JA, Forsey RJ, Chan WL, et al. A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Invest 1999; 104: 1393-401. http://dx.doi.org/10.1172/JCI7317
Albani S, Carson DA. Etiology and pathogenesis of rheumatoid arthritis. In: Koopman WJ, Ed. Arthritis and allied conditions. Lippincott Williams & Wilkins, Baltimore, MD, 1997; p. 979.
Kavanaugh A, Lipsky PE. Rheumatoid arthritis. In: Rich RR, Schwartz BD, Fleisher TA, Shearer WT, Strober W, Eds. Clinical immunology: principles and practice. Mosby-Year Book, St Louis, MO 1996; p. 1093.
Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 1992; 327: 749-54. http://dx.doi.org/10.1056/NEJM199209103271101
Okoli CO, Akah PA, Nwafor SV. Anti-inflammatory activity of plants. J Nat Remedies 2003; 3: 1-30.
Soeken KL, Miller SA, Ernst E. Herbal medicines for the treatment of rheumatoid arthritis: a systematic review. Rheumatology (Oxford) 2003; 42: 652-9. http://dx.doi.org/10.1093/rheumatology/keg183
Rao J, Mihaliak K, Kroenke K, Bradley J, Tierney W, Weinberger M. Use of complementary therapies for arthritis among patients of rheumatologists. Ann Intern Med 1999; 131: 409-16. http://dx.doi.org/10.7326/0003-4819-131-6-199909210-00003
Phillipson JD. Phytochemistry and medicinal plants. Phytochemistry 2001; 56: 237-43. http://dx.doi.org/10.1016/S0031-9422(00)00456-8
Grindlay D, Reynolds T. The Aloe vera phenomenon: a review of the properties and modern uses of leaf parenchyma gel. J Ethnopharmacol 1986; 16: 117-51. http://dx.doi.org/10.1016/0378-8741(86)90085-1
Kong JM, Goh NK, Chia LS, Chia TF. Recent advances in traditional plant drugs and orchids. Acta Pharmacologica Sinica 2003; 24: 7-21.
Traditional medicine strategy launched. (WHO News) 2002; 80: 610.
Benowitz S. As war on cancer hits 25-year mark, scientists see progress, challenges. Scientist 1996; 10: 1-7.
Ni Y, Tizard IR. Analytical methodology: the gel-analysis of aloe pulp and its derivatives. In Aloes The Genus Aloe; Reynolds T, Ed. CRC Press: Boca Raton 2004; pp. 111-26. http://dx.doi.org/10.1016/j.intimp.2004.07.006
Ni Y, Turner D, Yates KM, Tizard I. Isolation and characterisation of structural components of Aloe vera L. leaf pulp. Int Immunopharmacol 2004; 4: 1745-55.
Eshun K, He Q. Aloe vera: A valuable ingredient for the food, pharmaceutical and cosmetic industries – Areview. Crit Rev Food Sci Nutr 2004; 44: 91-6. http://dx.doi.org/10.1080/10408690490424694
Boudreau MD, Beland FA. An evaluation of the biological and toxicological properties of Aloe barbadensis (Miller), Aloe vera. J Environ Sci Health C 2006; l24: 103-54.
Vazquez B, Avila G, Segura D, Escalante B. Antiinflammatory activity of extracts from Aloe vera gel. J Ethnopharmacol 1996; 55: 69-75. http://dx.doi.org/10.1016/S0378-8741(96)01476-6
Reynolds T. Aloe chemistry. In Aloes The Genus Aloe; Reynolds T, Ed. CRC Press: Boca Raton 2004; pp. 39-74.
Femenia A, Sánchez ES, Simal S, Rosselló C. Compositional features of polysacchaides from Aloe vera (Aloe barbadensis Miller) plant tissues. Carbohydr Polym 1999; 39: 109-17. http://dx.doi.org/10.1016/S0144-8617(98)00163-5
Choi S, Chung M-H. A review on the relationship between Aloe vera components and their biologic effects. Semin Integr Med 2003; 1: 53-62. http://dx.doi.org/10.1016/S1543-1150(03)00005-X
Doshi S, Mohan P, Kabra MP, Singh S. Evaluation of analgesic activity of polyherbar leaves extract of Aloe vera and Canabis sativa in experimental animals. World J Phaarmaceutical Res 2013; 2: 2525-34.
Joseph B, Raj SJ. Pharmacogonostic and phytochemical properties of Aloe vera Linn - an overview. Int J Pharm Sci Rev Res 2010; 4: 106-10.
Davis RH, Maro NP. Aloe vera and gibberellin. Anti-inflammatory activity in diabetes. J Am Podiatr Med Assoc 1989; 79: 24-6.
Davis RH, Stewart GJ, Bregman PJ. Aloe vera and the inflamed synovial pouch model. J Am Podiatr Assoc 1992; 82: 140-8.
Budai MM, Varga A, Milesz S, Tőzsér J, Benkő S. Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages. Mol Immunol 2013; 56: 471-9. http://dx.doi.org/10.1016/j.molimm.2013.05.005
Daunsak D, Somboonwong J, Patumraj S. Effects of Aloe vera on leukocyte adhesion and TNF-alpha and IL-6 levels in burn wounded rats. Clin Hemorheol Microcirc 2003; 29: 239-46.
Eamlamnam K, Patumraj S, Visedopas N, Thong-Ngam D. Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats. World J Gastroenterol 2006; 12: 2034-9.
Vázquez B, Avila G, Segura D, Escalante B. Anti-inflammatory activity of extracts from Aloe vera Gel. J Ethnopharmacol 1996; 55: 69-75. http://dx.doi.org/10.1016/S0378-8741(96)01476-6
Vijayalakshmi D, Dhandapani R, Jayaveni S, Jithendra PS, Rose C, Mandal AB. In vitro anti inflammatory activity of Aloe vera by down regulation of MMP-9 in peripheral blood mononuclear cells. J Ethnopharmacol 2012; 141: 542-6. http://dx.doi.org/10.1016/j.jep.2012.02.040
Sarkar D, Dutta A, Das M, Sarkar K, Chatterjee M. Effect of Aloe vera on nitric oxide production by macrophages during inflammation. Ind J Pharmacol 2005; 37: 371-5. http://dx.doi.org/10.4103/0253-7613.19073
Devaraj A, Karpagam T. Evaluation of anti-inflammatory activity and analgesic effect of Aloe vera leaf extract in rat. Int Res J Pharmacy 2011; 2: 103-10.
Yadav KCH, Kumar JR, Basha SI, Deshmukh G, Gujjula R, Santhaman B. Wound healing activity of topical application of Aloe vera gel in experimental animal model. Int J Pharma Bio Sci 2012; 3: 63-72.
Nandanwar R, Gurjar, H, Sahu VK, Saraf H. study on gel healing activity of gel formulation containing ghee and aloe vera. Int J Pharmaceut Sci Res 2010; 1: 50-4.
MendonçaI FAS, Junior JRP, Esquisatto MAM, Mendonça JS, Franchini CC, Santos GMT. Effects of the application of Aloe vera (L.) and microcurrent on the healing of wounds surgically induced in Wistar rats. Acta Cirúrgica Brasileira 2009; 24: 150-5. http://dx.doi.org/10.1590/S0102-86502009000200013
Oryan A, Naeini AT, Nikahval B, Gorjian E. Effect of aqueous extract Aloe vera on experimental cutaneous wound healing in rat. Vet Archiv 2010; 80: 509-22.
Egesie UG, Chima KE, Galam NZ. Anti-inflammatory and Analgesic Effects of Aqueous Extract of Aloe vera (Aloe barbadensis) in Rats. Afr J Biomed Res 2011; 14: 209-12.
Ghosh AK, Banerjee M, Mandal TK, Mishra A, Bhowmik MK. A Study on Analgesic Efficacy and Adverse Effects of Aloe vera in Wistar Rats. Pharmacology online 2011; 1: 1098-8.
Davis RH, Agnew PS, Shapiro E. Anti-Arthritic Activity of Anthraquinones Found In Aloe For Podiatric Medicine. J Am Podiatr Med Assoc 1986; 76: 61-6.
Yagi A, Kabash A, Okamura N, Haraguchi SM, Khalifa TI. Antioxidant, free radical and anti-inflammatory effects of aloesin derivatives in Aloe vera. Planta Med 2002; 68: 957-60. http://dx.doi.org/10.1055/s-2002-35666
Hwang JK, Noh EM, Moon SJ, et al. Emodin suppresses inflammatory responses and joint destruction in collagen-induced arthritic mice. Rheumatology (Oxford) 2013; 52: 1583-91. http://dx.doi.org/10.1093/rheumatology/ket178
Park MY, Kwon HJ, Sung MK. Evaluation of aloin and aloe-emodin as anti-inflammatory agents in aloe by using murine macrophages. Biosci Biotechnol Biochem 2009; 73: 828-32. http://dx.doi.org/10.1271/bbb.80714
Zhu X, Zeng K, Qiu Y, Yan F, Lin C. Therapeutic effect of emodin on collagen-induced arthritis in mice. Inflammation 2013; 36: 1253-9. http://dx.doi.org/10.1007/s10753-013-9663-6
Ha MK, Song YH, Jeong SJ, et al. Emodin inhibits proinflammatory responses and inactivates histone deacetylase 1 in hypoxic rheumatoid synoviocytes. Biol Pharm Bull 2011; 34:1432-7. http://dx.doi.org/10.1248/bpb.34.1432
Hajhashemi V, Ghannadi A, Heidari AH.Anti-inflammatory and wound healing activities of Aloe littoralis in rats. Res Pharm Sci 2012; 7: 73-8.
Junger H, Moore AC, Sorkin LS. Effects of full-thickness burns on nociceptor sensitization in anesthetized rats. Burns 2002; 28: 772-7. http://dx.doi.org/10.1016/S0305-4179(02)00199-7
Somboonwong J, Thanamittramanee S, Jarivapongskul A, Patumraj S. Therapeutic effects of Aloe vera on cutaneous microcirculation and wound healing in second degree burn model in rats. J Med Assoc 2000; 83: 417-25.
Davis RH, Donato JJ, Hartman GM, Haas RC. Anti-inflammatory and wound healing activity of a growth substance in Aloe vera. J Am Podiar Med Assoc 1994; 84: 77-81.
http://www.nature4science.com/AloeVera/1_DescriptionofAloeVera.pdf (accessed February 22, 2014).
Surjushe A, Vasani R, Saple DJ. Aloe vera: A short review. Indian J Dermatol 2008; 53: 163-6. http://dx.doi.org/10.4103/0019-5154.44785
Boonyagul S, Banlunara W, Sangvanich P, Thunyakitpisal P. Effect of acemannan, an extracted polysaccharide from Aloe vera, on BMSCs proliferation, differentiation, extracellular matrix synthesis, mineralization, and bone formation in a tooth extraction model. Odontology 2013; [Epub ahead of print], PMID: 23315202.
Yagi A, Harada N, Shimomura K, Nishioka I. Bradykinin-degrading glycoprotein in Aloe arborescens var. natalensis. Planta Med 1987; 53: 19-21. http://dx.doi.org/10.1055/s-2006-962608
Yagi A, Harada N, Yamada H, Iwadare S, Nishioka I. Antibradykinin active material in Aloe saponaria. J Phar Sci 1982; 71: 1172-4. http://dx.doi.org/10.1002/jps.2600711024
Obata M, Ito S, Beppu H, Fujita K, Nagatsu T. Mechanisms of anti-inflammatory and anti thermal burn action of carboxypeptidase from Aloe aborescens Miller natalensis Berger in rats and mice. Physiother Res 1993; 7: 530-3. http://dx.doi.org/10.1002/ptr.2650070711
Shelton MS. Aloe vera, its chemical and therapeutic properties. Int J Dermatol 1991; 30: 679-83. http://dx.doi.org/10.1111/j.1365-4362.1991.tb02607.x
Davis RH, DiDonato JJ, Johnson RW, Stewart CB. Aloe Vera, hydrocortisone, & sterol influence on wound tensile strength & anti-inflammation. J Am Podiatr Med Assoc 1994; 84: 614-21.
Rajeswari R, Umadevi M, Rahale CS, et al. Aloe vera: the miracle plant its medicinal and traditional uses in India. J Pharmacognosy Phytochem 2012; 1: 118-24.
Hutter JA, Salman M, Stavinoha WB, et al. Anti-inflammatory C-glucosyl chromone from Aloe barbadensis. J Nat Prod 1996; 59: 541-3. http://dx.doi.org/10.1021/np9601519
Saito H, Ishiguro T, Imanishi K, Suzuki I. Pharmacological studies on a plant lectin aloctin A. II. inhibitory effect of aloctin A on experimental models of inflammation in rats. Jpn J Pharmacol 1982; 32: 139-42. http://dx.doi.org/10.1254/jjp.32.139
