Age Related Osteoarthritis: Regenerative Therapy, Synthetic Drugs, and
Naturopathy to Combat Abnormal Signal Transduction

Tamanna      Ahmed; Rishita      Dey; Jhumpa      Mukherjee; Asmita      Samadder; Sisir      Nandi

Abstract

Introduction: Osteoarthritis (OA) is a common chronic inflammatory neurodegenerative joint disorder that causes disability among the geriatric population. It involves the loss of the articular cartilage that covers the end of a long bone thereby failing to prevent the friction between the joints.

Methods: The literature on the prevalence of OA and different risk factors like physical inactivity, obesity, and joint injury was searched through Google scholar, PubMed, research gate, Wikipedia, etc for the review.

Results: OA has affected around 303 million people globally. It affects the knee, hip, hands, and spine joints owing to common symptoms like pain, swelling, and disability. Further, OA-associated disability causes depression leading to an economic and social burden with physical isolation, thus making it more severe for older people in their day-to-day lifestyle. Presently, no permanent cure has been developed for OA. Although, there are many risk factors of OA, among them, the most prominent one is considered to be “aging”. Most people crossing the age of 65–70 years have been associated with changes in the joints (one or more) about the development of OA. Several theories related to cellular aging and cell senescence with OA development. However, aging alone does not cause this condition; it is accelerated by the abnormal signal transduction followed by the progression of OA. The blueprint of possible management of OA by the different approaches has been the prime concern of this review work.

Conclusion: An outline of the risk factors of abnormal signal transduction and different treatment approaches, including regenerative therapy, synthetic drugs, and naturopathy manipulating them concerning OA are discussed in this review which might be an answer to the age-old issue of geriatrics.

Keywords: Osteoarthritis, aging, abnormal signal transduction, regenerative treatment, synthetic drugs, naturopathy.

Graphical Abstract

[1]
Jiang Y. Osteoarthritis year in review 2021: Biology Osteoarthritis Cartilage 2021; S1063-4584(21): 970-5.

[2]
Shane Anderson A, Loeser RF. Why is osteoarthritis an age-related disease? Best Pract Res Clin Rheumatol  2010; 24(1): 15-26.
 [http://dx.doi.org/10.1016/j.berh.2009.08.006] [PMID:  20129196]

[3]
Hawker GA. Osteoarthritis is a serious disease. Clin Exp Rheumatol  2019; 37(5) (Suppl. 120): 3-6.
 [PMID:  31621562]

[4]
Heidari B. Knee osteoarthritis prevalence, risk factors, pathogenesis and features: Part I. Caspian J Intern Med  2011; 2(2): 205-12.
 [PMID:  24024017]

[5]
Roos EM, Arden NK. Strategies for the prevention of knee osteoarthritis. Nat Rev Rheumatol  2016; 12(2): 92-101.
 [http://dx.doi.org/10.1038/nrrheum.2015.135] [PMID:  26439406]

[6]
Ashraf S, Cha BH, Kim JS, et al. Regulation of senescence associated signaling mechanisms in chondrocytes for cartilage tissue regenera-tion. Osteoarthritis Cartilage  2016; 24(2): 196-205.
 [http://dx.doi.org/10.1016/j.joca.2015.07.008] [PMID:  26190795]

[7]
Liu H, Zhao Z, Clarke RB, Gao J, Garrett IR, Margerrison EE. Enhanced tissue regeneration potential of juvenile articular cartilage. Am J Sports Med  2013; 41(11): 2658-67.
 [http://dx.doi.org/10.1177/0363546513502945] [PMID:  24043472]

[8]
Loeser RF. Aging and osteoarthritis: The role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis Cartilage  2009; 17(8): 971-9.
 [http://dx.doi.org/10.1016/j.joca.2009.03.002] [PMID:  19303469]

[9]
Livshits G, Zhai G, Hart DJ, et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: The Chingford Study. Arthritis Rheum  2009; 60(7): 2037-45.
 [http://dx.doi.org/10.1002/art.24598] [PMID:  19565477]

[10]
Philipot D, Guérit D, Platano D, et al. p16INK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation-associated matrix remodeling in osteoarthritis. Arthritis Res Ther  2014; 16(1): R58.
 [http://dx.doi.org/10.1186/ar4494] [PMID:  24572376]

[11]
O’Sullivan RJ, Karlseder J. Telomeres: Protecting chromosomes against genome instability. Nat Rev Mol Cell Biol  2010; 11(3): 171-81.
 [http://dx.doi.org/10.1038/nrm2848] [PMID:  20125188]

[12]
Diotti R, Loayza D. Shelterin complex and associated factors at human telomeres. Nucleus  2011; 2(2): 119-35.
 [http://dx.doi.org/10.4161/nucl.2.2.15135] [PMID:  21738835]

[13]
Martin JA, Buckwalter JA. The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair. J Bone Joint Surg Am  2003; 85-A (Suppl. 2): 106-10.
 [http://dx.doi.org/10.2106/00004623-200300002-00014] [PMID:  12721352]

[14]
Kuszel L, Trzeciak T, Richter M, Czarny-Ratajczak M. Osteoarthritis and telomere shortening. J Appl Genet  2015; 56(2): 169-76.
 [http://dx.doi.org/10.1007/s13353-014-0251-8] [PMID:  25366419]

[15]
Yu SM, Kim SJ. Thymoquinone-induced reactive oxygen species causes apoptosis of chondrocytes via PI3K/Akt and p38kinase pathway. Exp Biol Med (Maywood)  2013; 238(7): 811-20.
 [http://dx.doi.org/10.1177/1535370213492685] [PMID:  23788172]

[16]
Yudoh K, Nguyen T, Nakamura H, Hongo-Masuko K, Kato T, Nishioka K. Potential involvement of oxidative stress in cartilage senes-cence and development of osteoarthritis: Oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function. Arthritis Res Ther  2005; 7(2): R380-91.
 [http://dx.doi.org/10.1186/ar1499] [PMID:  15743486]

[17]
Yao X, Zhang J, Jing X, et al. Fibroblast growth factor 18 exerts anti-osteoarthritic effects through PI3K-AKT signaling and mitochondrial fusion and fission. Pharmacol Res  2019; 139: 314-24.
 [http://dx.doi.org/10.1016/j.phrs.2018.09.026] [PMID:  30273654]

[18]
Huang J, Zhao L, Chen D. Growth factor signalling in osteoarthritis. Growth Factors  2018; 36(5-6): 187-95.
 [http://dx.doi.org/10.1080/08977194.2018.1548444] [PMID:  30624091]

[19]
Shapiro IM, Layfield R, Lotz M, Settembre C, Whitehouse C. Boning up on autophagy: The role of autophagy in skeletal biology. Autophagy  2014; 10(1): 7-19.
 [http://dx.doi.org/10.4161/auto.26679] [PMID:  24225636]

[20]
Caramés B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum  2010; 62(3): 791-801.
 [http://dx.doi.org/10.1002/art.27305] [PMID:  20187128]

[21]
Murrow L, Debnath J. Autophagy as a stress-response and quality-control mechanism: Implications for cell injury and human disease. Annu Rev Pathol  2013; 8(1): 105-37.
 [http://dx.doi.org/10.1146/annurev-pathol-020712-163918] [PMID:  23072311]

[22]
Michael JW, Schlüter-Brust KU, Eysel P. The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. Dtsch Arztebl Int  2010; 107(9): 152-62.
 [http://dx.doi.org/10.3238/arztebl.2010.0152] [PMID:  20305774]

[23]
Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: Latest findings and interpretations. Ther Adv Musculoskelet Dis  2013; 5(2): 77-94.
 [http://dx.doi.org/10.1177/1759720X12467868] [PMID:  23641259]

[24]
Loef M, Kroon FPB, Bergstra SA, et al. TNF inhibitor treatment is associated with a lower risk of hand osteoarthritis progression in rheu-matoid arthritis patients after 10 years. Rheumatology (Oxford)  2018; 57(11): 1917-24.
 [http://dx.doi.org/10.1093/rheumatology/key016] [PMID:  29471377]

[25]
Mimpen JY, Baldwin MJ, Cribbs AP, et al. Interleukin-17A causes osteoarthritis-like transcriptional changes in human osteoarthritis-derived chondrocytes and synovial fibroblasts in vitro. Front Immunol  2021; 12: 676173.
 [http://dx.doi.org/10.3389/fimmu.2021.676173] [PMID:  34054865]

[26]
Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta  2012; 1824(1): 133-45.
 [http://dx.doi.org/10.1016/j.bbapap.2011.06.020] [PMID:  21777704]

[27]
Patel JM, Saleh KS, Burdick JA, Mauck RL. Bioactive factors for cartilage repair and regeneration: Improving delivery, retention, and ac-tivity. Acta Biomater  2019; 93: 222-38.
 [http://dx.doi.org/10.1016/j.actbio.2019.01.061] [PMID:  30711660]

[28]
Bernardes de Jesus B, Blasco MA. Telomerase at the intersection of cancer and aging. Trends Genet  2013; 29(9): 513-20.
 [http://dx.doi.org/10.1016/j.tig.2013.06.007] [PMID:  23876621]

[29]
Tan BL, Norhaizan ME, Liew WP, Sulaiman Rahman H. Antioxidant and oxidative stress: A mutual interplay in age-related diseases. Front Pharmacol  2018; 9: 1162.
 [http://dx.doi.org/10.3389/fphar.2018.01162] [PMID:  30405405]

[30]
Lepetsos P, Papavassiliou AG. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta  2016; 1862(4): 576-91.
 [http://dx.doi.org/10.1016/j.bbadis.2016.01.003] [PMID:  26769361]

[31]
Li XZ, Zhang SN. Recent advance in treatment of osteoarthritis by bioactive components from herbal medicine. Chin Med  2020; 15(1): 80.
 [http://dx.doi.org/10.1186/s13020-020-00363-5] [PMID:  32765641]

[32]
Xu X, Liu X, Yang Y, et al. Resveratrol exerts anti-osteoarthritic effect by inhibiting tlr4/nf-κb signaling pathway via the tlr4/akt/foxo1 axis in il-1β-stimulated sw1353 cells. Drug Des Devel Ther  2020; 14: 2079-90.
 [http://dx.doi.org/10.2147/DDDT.S244059] [PMID:  32581510]

[33]
Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clin Interv Aging  2018; 13: 757-72.
 [http://dx.doi.org/10.2147/CIA.S158513] [PMID:  29731617]

[34]
van Osch GJ, Brittberg M, Dennis JE, et al. Cartilage repair: Past and future--lessons for regenerative medicine. J Cell Mol Med  2009; 13(5): 792-810.
 [http://dx.doi.org/10.1111/j.1582-4934.2009.00789.x] [PMID:  19453519]

[35]
Medvedeva EV, Grebenik EA, Gornostaeva SN, et al. Repair of damaged articular cartilage: Current approaches and future directions. Int J Mol Sci  2018; 19(8): 2366.
 [http://dx.doi.org/10.3390/ijms19082366] [PMID:  30103493]

[36]
Mistry H, Connock M, Pink J, et al. Autologous chondrocyte implantation in the knee: Systematic review and economic evaluation. Health Technol Assess  2017; 21(6): 1-294.
 [http://dx.doi.org/10.3310/hta21060] [PMID:  28244303]

[37]
Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep  2015; 35(2): e00191.
 [http://dx.doi.org/10.1042/BSR20150025] [PMID:  25797907]

[38]
Choi KM, Seo YK, Yoon HH, et al. Effect of ascorbic acid on bone marrow-derived mesenchymal stem cell proliferation and differentia-tion. J Biosci Bioeng  2008; 105(6): 586-94.
 [http://dx.doi.org/10.1263/jbb.105.586] [PMID:  18640597]

[39]
Ikada Y. Challenges in tissue engineering. J R Soc Interface  2006; 3(10): 589-601.
 [http://dx.doi.org/10.1098/rsif.2006.0124] [PMID:  16971328]

[40]
Chan BP, Leong KW. Scaffolding in tissue engineering: General approaches and tissue-specific considerations. Eur Spine J  2008; 17(S4) (Suppl. 4): 467-79.
 [http://dx.doi.org/10.1007/s00586-008-0745-3] [PMID:  19005702]

[41]
Zhang W, Ouyang H, Dass CR, Xu J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res  2016; 4(1): 15040.
 [http://dx.doi.org/10.1038/boneres.2015.40] [PMID:  26962464]

[42]
Sarzi-Puttini P, Cimmino MA, Scarpa R, et al. Osteoarthritis: An overview of the disease and its treatment strategies. Semin Arthritis Rheum  2005; 35(1) (Suppl. 1): 1-10.
 [http://dx.doi.org/10.1016/j.semarthrit.2005.01.013] [PMID:  16084227]

[43]
Evans CH, Christopher H. Gene therapies for osteoarthritis. Curr Rheumatol Rep  2004; 6(1): 31-40.
 [http://dx.doi.org/10.1007/s11926-004-0081-5] [PMID:  14713400]

[44]
Tomita T, Hashimoto H, Tomita N, et al. In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (Sendai virus) and liposomes. Arthritis Rheum  1997; 40(5): 901-6.
 [http://dx.doi.org/10.1002/art.1780400518] [PMID:  9153552]

[45]
Schwartz E. The adeno-associated virus vector for orthopaedic gene therapy. Clin Orthop Relat Res  2000; 379(379) (Suppl.): 31-40.
 [http://dx.doi.org/10.1097/00003086-200010001-00005]

[46]
Caron JP, Fernandes JC, Martel-Pelletier J, et al. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. Suppression of collagenase-1 expression. Arthritis Rheum  1996; 39(9): 1535-44.
 [http://dx.doi.org/10.1002/art.1780390914] [PMID:  8814066]

[47]
Fernandes J, Tardif G, Martel-Pelletier J, et al. In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: Prevention of osteoarthritis progression. Am J Pathol  1999; 154(4): 1159-69.
 [http://dx.doi.org/10.1016/S0002-9440(10)65368-0] [PMID:  10233854]

[48]
Frisbie DD, Ghivizzani SC, Robbins PD, Evans CH, McIlwraith CW. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Ther  2002; 9(1): 12-20.
 [http://dx.doi.org/10.1038/sj.gt.3301608] [PMID:  11850718]

[49]
Steinert AF, Nöth U, Tuan RS. Concepts in gene therapy for cartilage repair. Injury  2008; 39 (Suppl. 1): S97-S113.
 [http://dx.doi.org/10.1016/j.injury.2008.01.034] [PMID:  18313477]

[50]
Cherian JJ, Parvizi J, Bramlet D, Lee KH, Romness DW, Mont MA. Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-β1 in patients with grade 3 chronic degenera-tive joint disease of the knee. Osteoarthritis Cartilage  2015; 23(12): 2109-18.
 [http://dx.doi.org/10.1016/j.joca.2015.06.019] [PMID:  26188189]

[51]
Grässel S, Muschter D. Recent advances in the treatment of osteoarthritis. F1000 Res  2020; 9: F1000-325.
 [http://dx.doi.org/10.12688/f1000research.22115.1] [PMID:  32419923]

[52]
Primorac D, Molnar V, Matišić V, et al. Comprehensive review of knee osteoarthritis pharmacological treatment and the latest professional societies’ guidelines. Pharmaceuticals (Basel)  2021; 14(3): 205.
 [http://dx.doi.org/10.3390/ph14030205] [PMID:  33801304]

[53]
Derwich M, Mitus-Kenig M, Pawlowska E. Orally administered nsaids-general characteristics and usage in the treatment of temporoman-dibular joint osteoarthritis-a narrative review. Pharmaceuticals (Basel)  2021; 14(3): 219.
 [http://dx.doi.org/10.3390/ph14030219] [PMID:  33807930]

[54]
Katz JN, Smith SR, Collins JE, et al. Cost-effectiveness of nonsteroidal anti-inflammatory drugs and opioids in the treatment of knee oste-oarthritis in older patients with multiple comorbidities. Osteoarthritis Cartilage  2016; 24(3): 409-18.
 [http://dx.doi.org/10.1016/j.joca.2015.10.006] [PMID:  26525846]

[55]
Maity S, Misra A, Wairkar S. Novel injectable carrier based corticosteroid therapy for treatment of rheumatoid arthritis and osteoarthritis. J Drug Deliv Sci Technol  2021; 61: 102309.
 [http://dx.doi.org/10.1016/j.jddst.2020.102309]

[56]
Ravina E. The evolution of drug discovery. In: Traditional Medicines to Modern Drugs.  John Wiley & Sons 2011; p. 24.

[57]
Brien S, Lewith GT, McGregor G. Devil’s Claw (Harpagophytum procumbens) as a treatment for osteoarthritis: A review of efficacy and safety. J Altern Complement Med  2006; 12(10): 981-93.
 [http://dx.doi.org/10.1089/acm.2006.12.981] [PMID:  17212570]

[58]
Conrozier T, Mathieu P, Bonjean M, Marc JF, Renevier JL, Balblanc JC. A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain. Altern Ther Health Med  2014; 20 (Suppl. 1): 32-7.
 [PMID:  24473984]

[59]
Gagnier JJ, van Tulder MW, Berman B, Bombardier C. Herbal medicine for low back pain: A Cochrane review. Spine  2007; 32(1): 82-92.
 [http://dx.doi.org/10.1097/01.brs.0000249525.70011.fe] [PMID:  17202897]

[60]
van Wyk BE. A broad review of commercially important southern African medicinal plants. J Ethnopharmacol  2008; 119(3): 342-55.
 [http://dx.doi.org/10.1016/j.jep.2008.05.029] [PMID:  18577439]

[61]
Clarkson C, Staerk D, Hansen SH, Smith PJ, Jaroszewski JW. Identification of major and minor constituents of Harpagophytum procum-bens (Devil’s claw) using HPLC-SPE-NMR and HPLC-ESIMS/APCIMS. J Nat Prod  2006; 69(9): 1280-8.
 [http://dx.doi.org/10.1021/np0601612] [PMID:  16989520]

[62]
Fiebich BL, Heinrich M, Hiller KO, Kammerer N. Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69. Phytomedicine  2001; 8(1): 28-30.
 [http://dx.doi.org/10.1078/0944-7113-00002] [PMID:  11292236]

[63]
Schulze-Tanzil G, Hansen C, Shakibaei M. Effect of a harpagophytum procumbens dc extract on matrix metalloproteinases in human chondrocytes in vitro. Arzneimittelforschung  2004; 54(4): 213-20.
 [PMID:  15146934]

[64]
Jang MH, Lim S, Han SM, et al. Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. J Pharmacol Sci  2003; 93(3): 367-71.
 [http://dx.doi.org/10.1254/jphs.93.367] [PMID:  14646256]

[65]
Kundu JK, Mossanda KS, Na HK, Surh YJ. Inhibitory effects of the extracts of Sutherlandia frutescens (L.) R. Br. and Harpagophytum procumbens DC. on phorbol ester-induced COX-2 expression in mouse skin: AP-1 and CREB as potential upstream targets. Cancer Lett  2005; 218(1): 21-31.
 [http://dx.doi.org/10.1016/j.canlet.2004.07.029] [PMID:  15639337]

[66]
Na HK, Mossanda KS, Lee JY, Surh YJ. Inhibition of phorbol ester-induced COX-2 expression by some edible African plants. Biofactors  2004; 21(1-4): 149-53.
 [http://dx.doi.org/10.1002/biof.552210130] [PMID:  15630188]

[67]
Tan BH, Ong CE. The use of natural remedies to treat osteoarthritis TANG  2016; 6(1): 1.1-9.

[68]
Kumar K, Thakur AK, Verma S, Yadav V, Chatterjee SS. Potential of some traditionally used edible plants for prevention and cure of diabesity associated comorbidities. TANG  2015; 5(2): e8.
 [http://dx.doi.org/10.5667/tang.2014.0026]

[69]
Park SY, Kim YH, Kim Y, Lee SJ. Aromatic-turmerone attenuates invasion and expression of MMP-9 and COX-2 through inhibition of NF-κB activation in TPA-induced breast cancer cells. J Cell Biochem  2012; 113(12): 3653-62.
 [http://dx.doi.org/10.1002/jcb.24238] [PMID:  22740037]

[70]
Huang G, Xu Z, Huang Y, et al. Curcumin protects against collagen-induced arthritis via suppression of BAFF production. J Clin Immunol  2013; 33(3): 550-7.
 [http://dx.doi.org/10.1007/s10875-012-9839-0] [PMID:  23184090]

[71]
Park C, Moon DO, Choi IW, et al. Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of pa-tients with rheumatoid arthritis. Int J Mol Med  2007; 20(3): 365-72.
 [http://dx.doi.org/10.3892/ijmm.20.3.365] [PMID:  17671742]

[72]
Kim JH, Gupta SC, Park B, Yadav VR, Aggarwal BB. Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed os-teoclastogenesis. Mol Nutr Food Res  2012; 56(3): 454-65.
 [http://dx.doi.org/10.1002/mnfr.201100270] [PMID:  22147524]

[73]
Deodhar SD, Sethi R, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res  1980; 71: 632-4.
 [PMID:  7390600]

[74]
Kiuchi F, Iwakami S, Shibuya M, Hanaoka F, Sankawa U. Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and dia-rylheptanoids. Chem Pharm Bull (Tokyo)  1992; 40(2): 387-91.
 [http://dx.doi.org/10.1248/cpb.40.387] [PMID:  1606634]

[75]
Imtiyaz S, Rahman K, Sultana A, Tariq M, Chaudhary SS. Zingiber officinale Rosc.: A traditional herb with medicinal properties. TANG  2013; 3(4): e26.
 [http://dx.doi.org/10.5667/tang.2013.0009]

[76]
Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum  2001; 44(11): 2531-8.
 [http://dx.doi.org/10.1002/1529-0131(200111)44:11<2531:AID-ART433>3.0.CO;2-J] [PMID:  11710709]

[77]
Bliddal H, Rosetzsky A, Schlichting P, et al. A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in oste-oarthritis. Osteoarthritis Cartilage  2000; 8(1): 9-12.
 [http://dx.doi.org/10.1053/joca.1999.0264] [PMID:  10607493]

[78]
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature  1997; 389(6653): 816-24.
 [http://dx.doi.org/10.1038/39807] [PMID:  9349813]

[79]
Knotkova H, Pappagallo M, Szallasi A. Capsaicin (TRPV1 Agonist) therapy for pain relief: Farewell or revival? Clin J Pain  2008; 24(2): 142-54.
 [http://dx.doi.org/10.1097/AJP.0b013e318158ed9e] [PMID:  18209521]

[80]
O’Neill J, Brock C, Olesen AE, Andresen T, Nilsson M, Dickenson AH. Unravelling the mystery of capsaicin: A tool to understand and treat pain. Pharmacol Rev  2012; 64(4): 939-71.
 [http://dx.doi.org/10.1124/pr.112.006163] [PMID:  23023032]

[81]
Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev  1999; 51(2): 159-212.
 [PMID:  10353985]

[82]
Joe B, Rao UJ, Lokesh BR. Presence of an acidic glycoprotein in the serum of arthritic rats: Modulation by capsaicin and curcumin. Mol Cell Biochem  1997; 169(1-2): 125-34.
 [http://dx.doi.org/10.1023/A:1006877928703] [PMID:  9089639]

[83]
Park JS, Choi MA, Kim BS, Han IS, Kurata T, Yu R. Capsaicin protects against ethanol-induced oxidative injury in the gastric mucosa of rats. Life Sci  2000; 67(25): 3087-93.
 [http://dx.doi.org/10.1016/S0024-3205(00)00890-0] [PMID:  11125845]

[84]
Kim CS, Kawada T, Kim BS, et al. Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peri-toneal macrophages. Cell Signal  2003; 15(3): 299-306.
 [http://dx.doi.org/10.1016/S0898-6568(02)00086-4] [PMID:  12531428]

[85]
Siemoneit U, Koeberle A, Rossi A, et al. Inhibition of microsomal prostaglandin E2 synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense. Br J Pharmacol  2011; 162(1): 147-62.
 [http://dx.doi.org/10.1111/j.1476-5381.2010.01020.x] [PMID:  20840544]

[86]
Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, Ammon HP. Boswellic acids: Novel, specific, nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther  1992; 261(3): 1143-6.
 [PMID:  1602379]

[87]
Majeed M, Majeed S, Narayanan NK, Nagabhushanam K. A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee. Phytother Res  2019; 33(5): 1457-68.
 [http://dx.doi.org/10.1002/ptr.6338] [PMID:  30838706]

[88]
Majeed M, Vaidyanathan P, Natarajan S, Majeed S, Vuppala KK. Effect of Boswellin® Super on knee pain in Japanese adults: A random-ized, double-blind, placebo-controlled trial. Eur J Biomed  2016; 3: 293-8.

[89]
Lindler BN, Long KE, Taylor NA, Lei W. Use of herbal medications for treatment of osteoarthritis and rheumatoid arthritis. Medicines (Basel)  2020; 7(11): 67.
 [http://dx.doi.org/10.3390/medicines7110067] [PMID:  33126603]

[90]
Delazar A, Sarker SD, Nahar L, et al. Rhizomes of eremostachys laciniata: Isolation and structure elucidation of chemical constituents and a clinical trial on inflammatory diseases. Adv Pharm Bull  2013; 3(2): 385-93.
 [PMID:  24312865]

[91]
Khan S, Nisar M, Rehman W, Khan R, Nasir F. Anti-inflammatory study on crude methanol extract and different fractions of Eremosta-chys laciniata. Pharm Biol  2010; 48(10): 1115-8.
 [http://dx.doi.org/10.3109/13880200903517950] [PMID:  20818928]

[92]
Erdemoglu N, Turan NN, Cakici I, Şener B, Aydin A. Antioxidant activities of some Lamiaceae plant extracts. Phytother Res  2006; 20(1): 9-13.
 [http://dx.doi.org/10.1002/ptr.1816] [PMID:  16397914]

[93]
Koh W, Shin J-S, Lee J, et al. Anti-inflammatory effect of Cortex Eucommiae via modulation of the toll-like receptor 4 pathway in lipo-polysaccharide-stimulated RAW 264.7 macrophages. J Ethnopharmacol  2017; 209: 255-63.
 [http://dx.doi.org/10.1016/j.jep.2017.08.001] [PMID:  28782620]

[94]
Kim M-C, Kim D-S, Kim S-J, et al. Eucommiae cortex inhibits TNF-α and IL-6 through the suppression of caspase-1 in lipopolysaccha-ride-stimulated mouse peritoneal macrophages. Am J Chin Med  2012; 40(1): 135-49.
 [http://dx.doi.org/10.1142/S0192415X12500115] [PMID:  22298454]

[95]
Xia T, Gao R, Zhou G, Liu J, Li J, Shen J. Trans-cinnamaldehyde inhibits il-1β-stimulated inflammation in chondrocytes by suppressing nf-κb and p38-jnk pathways and exerts chondrocyte protective effects in a rat model of osteoarthritis. BioMed Res Int  2019; 2019: 4039472-12.
 [http://dx.doi.org/10.1155/2019/4039472] [PMID:  31205941]

[96]
Wang ZY, Shi SY, Li SJ, et al. Efficacy and safety of duloxetine on osteoarthritis knee pain: A meta-analysis of randomized controlled trials. Pain Med  2015; 16(7): 1373-85.
 [http://dx.doi.org/10.1111/pme.12800] [PMID:  26176791]

[97]
Lu H, Jiang J, Xie G, Liu W, Yan G. Effects of an aqueous extract of Eucommia on articular cartilage in a rat model of osteoarthritis of the knee. Exp Ther Med  2013; 6(3): 684-8.
 [http://dx.doi.org/10.3892/etm.2013.1223] [PMID:  24137247]

[98]
Shoara R, Hashempur MH, Ashraf A, Salehi A, Dehshahri S, Habibagahi Z. Efficacy and safety of topical Matricaria chamomilla L. (chamomile) oil for knee osteoarthritis: A randomized controlled clinical trial. Complement Ther Clin Pract  2015; 21(3): 181-7.
 [http://dx.doi.org/10.1016/j.ctcp.2015.06.003] [PMID:  26256137]

[99]
Pirouzpanah S, Mahboob S, Sanayei M, Hajaliloo M, Safaeiyan A. The effect of chamomile tea consumption on inflammation among rheumatoid arthritis patients: Randomized clinical trial. Prog Nutr  2017; 19: 27-33.

[100]
Srivastava JK, Shankar E, Gupta S. Chamomile: A herbal medicine of the past with bright future. Mol Med Rep  2010; 3(6): 895-901.
 [PMID:  21132119]

[101]
Gupta A, Singh S. Evaluation of anti-inflammatory effect of Withania somnifera root on collagen-induced arthritis in rats. Pharm Biol  2014; 52(3): 308-20.
 [http://dx.doi.org/10.3109/13880209.2013.835325] [PMID:  24188460]

[102]
Singh D, Aggarwal A, Maurya R, Naik S. Withania somnifera inhibits NF-kappaB and AP-1 transcription factors in human peripheral blood and synovial fluid mononuclear cells. Phytother Res  2007; 21(10): 905-13.
 [http://dx.doi.org/10.1002/ptr.2180] [PMID: 17562568]

Rights & Permissions Print Cite

Article Metrics

17

2

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1574362417666220610153540	Print ISSN 1574-3624
Publisher Name Bentham Science Publisher	Online ISSN 2212-389X

Current Signal Transduction Therapy

Age Related Osteoarthritis: Regenerative Therapy, Synthetic Drugs, and Naturopathy to Combat Abnormal Signal Transduction

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles