Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2017 | Research article

New herbal composition (OA-F2) protects cartilage degeneration in a rat model of collagenase induced osteoarthritis

Authors: Pallavi S. Nirmal, Suresh D. Jagtap, Aarti N. Narkhede, Bhagyashri E. Nagarkar, Abhay M. Harsulkar

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Abstract

Background

Prevalence of osteoarthritis (OA) is on rise on the global scale. At present there are no satisfactory pharmacological agents for treating OA. Our previous study showed that Sida cordifolia L. and Zingiber officinale Rosc. had protective effect on cartilage. Here, we describe the effect of OA-F2, a herbal formulation prepared using combination of these two plants in alleviating OA associated symptoms in a rat model of collagenase-induced OA.

Methods

OA was induced by intra-articular injection of collagenase type II in wistar rats. Diclofenac (10 mg/kg) was used as a reference control. Rats (n = 6) were divided into 6 groups: Healthy control (HC), osteoarthritic control (OAC), diclofenac (DICLO), OA-F2L (135 mg/kg), OA-F2M (270 mg/kg) and OA-F2H (540 mg/kg). The effects of the 20 days treatment were monitored by parameters like knee diameter, paw volume, paw retraction; serum C-reactive protein (CRP), alkaline phosphatase (ALP) and glycosaminoglycan (GAG). Radiography and histopathology of knee joint were also studied. Additionally, gene expression was studied from isolated synovium tissue proving anti-osteoarthritic potential of OA-F2.

Results

Oral administration of OA-F2 has significantly prevented knee swelling compared to OAC; OA-F2 and DICLO, significantly reduced paw volume compared to OAC. Paw latency was remarkably increased by OA-F2 compared to OAC. OA-F2L (−0.670, p < 0.001), M (−0.110, p < 0.05) and H (0.073) has markedly reduced levels of CRP compared to DICLO. OA-F2L (p < 0.05), M (p < 0.001) and H (p < 0.05) significantly reduced ALP levels, compared to DICLO. GAG release in the serum was also significantly lowered in OA-F2 treated group compared to DICLO. Radiological and histopathological observations showed cartilage protection by OA-F2. OA-F2 has upregulated SOD and GPx. Upregulated CAT expression was observed in OA-F2M and H. Considerable down-regulation of expression of MMP-3 and MMP-9 was observed in all the groups. Up-regulation of TIMP-1 was observed in rats treated with OA-F2L, H and DICLO.

Conclusion

OA-F2 has shown therapeutic effects in rat model of collagenase induced OA by demonstrating cartilage protection through controlling MMPs and improving anti-oxidant levels in arthritic synovium and is a potent candidate for further drug development and treatment for OA.

Zhang RX, Renz K, Dubner R. Osteoarthritis pain mechanisms: basic studies in animal models. Osteoarthritis Cartilage. 2013. doi:10.1016/j.joca.2013.06.013.

Mahajan A, Verma S, Tandon V. Osteoarthrits. J Assoc Physicians India. 2005;53:634–41.PubMed

Mujapara AK, Jarullah B. Analysis of the genetic diversity of arthritis patients with reference to the factors inducing its onset. Int J Genet. 2009;1:06–9.

Walsh DA, Bonnet CS, Turner EL, Wilson D, Situ M, McWilliams DF. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis. Osteoarthritis Cartilage. 2007;15:743–51.CrossRefPubMed

Flannery CR, Zollner R, Corcoran C, Jones AR, Root A, Rivera-Bermudez MA, et al. Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin. Arthritis Rheumatol. 2009. doi:10.1002/art.24304.

Henrotin Y, Kurz B, Aigner T. Oxygen and reactive oxygen species in cartilage degradation: friends or foes? Osteoarthritis Cartilage. 2005. doi:10.1016/j.joca.2005.04.002.

Kyostio-Moore S, Bangari DS, Ewing P, Nambiar B, Berthelette P, Sookdeo C, et al. Local gene delivery of heme oxygenase-1 by adeno-associated virus into osteoarthritic mouse joints exhibiting synovial oxidative stress. Osteoarthritis Cartilage. 2013. doi:10.1016/j.joca.2012.11.002.PubMed

Park KC, Park EJ, Kim ER, Kim Y, Chung SH, Cho BW, et al. Therapeutic effects of PG201, an ethanol extract from herbs, through cartilage protection on collagenase-induced arthritis in rabbits. Biochem Biophys Res Commun. 2005;331:1469–77.CrossRefPubMed

Nirmal P, Koppikar S, Bhondave P, Narkhede A, Nagarkar B, Kulkarni V, et al. Influence of six medicinal herbs on collagenase-induced osteoarthritis in rats. Am J Chin Med. 2013. doi:10.1142/S0192415X13500948.PubMed

10.

Jain A, Choubey S, Singour P, Rajak H, Pawar R. Sida cordifolia (Linn) - An overview. J Appl Pharm Sci. 2011;1:23–31.

11.

Anilkumar M. Ethnomedicinal plants as anti-inflammatory and analgesic agents. In: Chattopadhyay D, editor. Ethnomedicine: A Source of Complementary Therapeutics. Trivandrum: Research Signpost; 2010. p. 267–93.

12.

Kumar G, Karthik L, Bhaskara Rao KV. A Review on pharmacological and phytochemical properties of Zingiber officinale Roscoe (Zingiberaceae). J Pharm Res. 2011;4:2963–6.

13.

Shen CL, Hong KJ, Kim SW. Effects of ginger (Zingiber officinale Rosc.) on decreasing the production of inflammatory mediators in sow osteoarthrotic cartilage explants. J Med Food. 2003;6:323–8.CrossRefPubMed

14.

Setty AR, Sigal LH. Herbal medications commonly used in the practice of rheumatology: Mechanisms of action, efficacy and side effects. Arthritis Rheum. 2005;34:773–84.CrossRef

15.

Srivastava N, Sadh R, Jain BK BK, Kolhapure SA SA. Evaluation and comparative clinical efficacy and safety of rumalaya forte in patients suffering from osteoarthritis of the knee. Indian J Clin Pract. 2005;16:19–30.

16.

Pragasam S, Kumar S, Bhoumik M, Sabina E, Rasool M. 6-Gingerol, an active ingredient of ginger suppresses monosodium ureate crystal-induced inflammation: An in vivo and in vitro evaluation. Ann Biol Res. 2011;2:200–8.

17.

Chopra A, Patwardhan L, Chitre D. A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an ayurvedic drug, on osteoarthritis of the knees. J Clin Rheumatol. 2004;10:236–45.CrossRefPubMed

18.

AL-Saffar FJ, Ganabadi S, Yaakub H, Fakurazi S. Collagenase and sodium iodoacetate-induced experimental osteoarthritis model in Sprague dawley rats. Asian J Sci Res. 2009;2:1–13.CrossRef

19.

Hattori K, Ikeuch K, Morita Y, Takakura Y. Quantitative ultrasonic assessment for detecting microscopic cartilage damage in osteoarthritis. Arthritis Res Ther. 2005. doi:10.1186/ar1463.PubMedCentral

20.

Rasool M, Varalakshmi P. Protective effect of Withania somnifera root powder in relation to lipid peroxidation, antioxidant status, glycoproteins and bone collagen on adjuvant-induced arthritis in rats. Fundam Clin Pharmacol. 2007;21:157–64.CrossRefPubMed

21.

Methekar C, Patel BR, Aghera H, Ashok BR, Ravishankar B. A comparative anti-tussive activity of laghugokshura. [Tribulus terrestris Linn.] and brihatgokshura [Pedalium murex Linn.] panchangain swiss albino mice. Global J Res Medicinal Plants Indigenous Med. 2012;1:280–5.

22.

Hoemann CD, Sun J, Chrzanowski V, Bhushman MD. A multivalent assay to detect glycosaminoglycan, protein, collagen, RNA, and DNA content in milligram samples of cartilage or hydrogel-based repair cartilage. Anal Biochem. 2002;300:1–10.CrossRefPubMed

23.

Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101–8.CrossRefPubMed

24.

Sharif M, Shepstone L, Elson CJ, Dieppe PA, Kirwan JR. Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee. Ann Rheum Dis. 2000;59:71–4.CrossRefPubMedPubMedCentral

25.

Sarkar A, Datta P, Gomes A, Das Gupta SC, Gomes A. Anti-Osteoporosis and Anti-Osteoarthritis Activity of Fresh Water Snail (Viviparous bengalensis) Flesh Extract in Experimental Animal Model. Open J Rheumatol Autoimmune Dis. 2013;3:10–7.CrossRef

26.

Kim JK, Park SW, Kang JW, Kim YJ, Lee SY, Shin J, et al. Effect of GCSB-5, a herbal formulation, on monosodium iodoacetate-induced osteoarthritis in rats. Evid Based Complement Alternat Med. 2012. doi:10.1155/2012/730907.

27.

Patel DV, Sawant MG, Ginpreet K. Evaluation of anti-osteoarthritic activity of Vigna mungo in papain induced osteoarthritis model. Indian J Pharmacol. 2015. doi:10.4103/0253-7613.150340.

28.

Wu DQ, Zhong HM, Ding QH, Ba L. Protective effects of biochanin A on articular cartilage: in vitro and in vivo studies. BMC Complement Altern Med. 2014. doi:10.1186/1472-6882-14-444.

29.

Brown KK, Heitmeyer SA, Hookfin EB, Hsieh L, Buchalova M, Taiwo YO, et al. P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm. 2008. doi:10.1186/1476-9255-5-22.

30.

Sturmer T, Brenner H, Koenig W, Gunther KP. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis. 2004. doi:10.1136/ard.2003.007674.PubMed

31.

Wolfe F. The C-reactive protein but not erythrocyte sedimentation rate is associated with clinical severity in patients with osteoarthritis of the knee or hip. J Rheumatol. 1997;24:1486–8.PubMed

32.

Dealy CN. Chondrogenic progenitors for cartilage repair and osteoarthritis treatment. Rheumatol Curr Res. 2012. doi:10.4172/2161-1149.S3-e001.

33.

Jeong YJ, Kim I, Cho JH, Park DW, Kwon JE, Jung MW, et al. Anti-osteoarthritic effects of the litsea japonica fruit in a rat model of osteoarthritis induced by monosodium iodoacetate. PLoS One. 2015. doi:10.1371/journal.pone.0134856.

34.

Park JS, Lee HJ, Lee DY, Jo HS, Jeong JH, Kim DH, et al. Chondroprotective effects of wogonin in experimental models of osteoarthritis in vitro and in vivo. Biolom Ther. 2015. doi:10.4062/biomolther.2015.045.

Title: New herbal composition (OA-F2) protects cartilage degeneration in a rat model of collagenase induced osteoarthritis
Authors: Pallavi S. Nirmal
Suresh D. Jagtap
Aarti N. Narkhede
Bhagyashri E. Nagarkar
Abhay M. Harsulkar
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-016-1535-9

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

New herbal composition (OA-F2) protects cartilage degeneration in a rat model of collagenase induced osteoarthritis

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2017

What intrinsic factors influence responsiveness to acupuncture in pain?: a review of pre-clinical studies that used responder analysis

Rhythm-centred music making in community living elderly: a randomized pilot study

Which potential harms and benefits of using ginger in the management of nausea and vomiting of pregnancy should be addressed? a consensual study among pregnant women and gynecologists

Aqueous root extract of Asparagus cochinchinensis (Lour.) Merr. Has antioxidant activity in D-galactose-induced aging mice

Postnatal treatment using curcumin supplements to amend the damage in VPA-induced rodent models of autism

High prevalence of complementary and alternative medicine use among patients with sickle cell disease in a tertiary hospital in Lagos, South West, Nigeria