Recent Patents on Inflammation & Allergy Drug Discovery

Author(s): Purnima Warriar, Kalyani Barve* and Bala Prabhakar

DOI: 10.2174/1872213X12666181120091528

Anti-Arthritic Effect of Garcinol Enriched Fraction Against Adjuvant Induced Arthritis

Page: [49 - 56] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: Garcinia indica also known as kokum is used in traditional system of medicine for relieving inflammation and rheumatic pain. Garcinol, a benzophenone obtained from its fruit rind is reported to have anti-inflammatory effect via modulating arachidonic acid metabolism, suppressing iNOS expression, NF-κB activation and COX-2 expression. It has also been studied for antioxidant and anticancer activity. Apart from these, few patents claim that garcinol also has anti-obesity and hepatoprotective effect and has a potential to be used for the treatment of renal disorders, endometriosis and cardiac dysfunction.

Objective: Garcinol Enriched Fraction (GEF) from the fruit rind of Garcinia indica should be effective in the treatment of arthritis, one of the chronic inflammatory disorder owing to its anti-inflammatory property as indicated by earlier experiments.

Methods: GEF was prepared from the fruit rind of Garcinia indica and quantified using LC-MS/MS. It was found to contain 89.4% w/w of garcinol. GEF was evaluated at the dose of 10mg/kg for its efficacy against Complete Freund’s Adjuvant (CFA) induced arthritis in Wistar albino rats. Paw volumes of both sides were measured by Plethysmometer and body weight was recorded on 0, 1, 5, 12 and 21st day. The hyperalgesic response was also measured by motility test and stair climbing test.

Results: GEF showed a significant reduction in paw swelling (p < 0.0001) and arthritis index (p < 0.0001) exhibiting anti-inflammatory potential. It also improves the motility and stair climbing ability of experimental animals (p < 0.05), thus reducing hyperalgesia.

Conclusion: Garcinol enriched fraction shows anti-arthritic activity in experimental animals.

Keywords: Benzophenone, Complete Freund's Adjuvant, Garcinia indica, inflammation, kokum, rheumatoid arthritis.

[1]
Nayak CA, Rastogi NK, Raghavarao KS. Bioactive constituents present in Garcinia indica choisy and its potential food applications: A review. Int J Food Prop 2010; 13: 441-53.
[2]
Baliga MS, Bhat HP, Pai RJ, Boloor R, Palatty PL. tde chemistry and medicinal uses of tde underutilized Indian fruit tree Garcinia indica Choisy (kokum): A review. Food Res Int 2011; 44: 1790-9.
[3]
Kunnumakkara AB, Koca C, Dey S, Gehlot P, Yodkeeree S, Danda D, et al. Molecular targets and tderapeutic uses of spices. New Jersey: World Scientific 2009; pp. 1-24.
[4]
Patel KJ, Panchasara AK, Barvaliya MJ, Purohit BM, Baxi SN, Vadgama VK, et al. Evaluation of cardio protective effect of aqueous extract of Garcinia indica Linn. Fruit rinds on isoprenaline-induced myocardial injury in Wistar albino Rats. RPS 2015; 10: 388.
[5]
Panda V, Ashar H, Srinatd S. Antioxidant and hepatoprotective effect of Garcinia indica fruit rind in etdanol induced hepatic damage in rodents. Interdiscip Toxicol 2012; 5: 207-13.
[6]
Antala BV, Patel MS, Bhuva SV, Gupta S, Rabadiya S, Lahkar M. Protective effect of metdanolic extract of Garcinia indica fruits in 6-OHDA rat model of Parkinson’s disease. Indian J Pharmacol 2012; 44: 83.
[7]
Lakshmi C, Kumar KA, Dennis TJ, Kumar TS. Antibacterial activity of polyphenols of Garcinia indica. Indian J Pharm Sci 2011; 73: 470.
[8]
Yamaguchi F, Saito M, Ariga T, Yoshimura Y, Nakazawa H. Free radical scavenging activity and antiulcer activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem 2000; 48: 2320-5.
[9]
Govind PD, Aruna A, Nirupama D, Shipra D, Rajesh D, Mercy DS. A novel herbal formulation for tde prevention and management of type-2 diabetes mellitus and vascular complications associated witd diabetes WO2011158247 2011.
[10]
Amit P. Nutraceutical formulation for treatment of elevated cholesterol and cardiovascular disease. US20140314729. (2014).
[11]
Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: A randomized controlled trial. JAMA 1998; 280: 1596-600.
[12]
Nayak CA, Srinivas P, Rastogi NK. Characterisation of antdocyanins from Garcinia indica Choisy. Food chemistry 2010; 118: 719-24.
[13]
Hegde MG, Goutdam N. Application of medicinal dye (turmeric and annatto) on silk fabrics using eco-friendly mordants. MSRUAS-SASTech J 2015; 14: 33-6.
[14]
Muhammed M. Anti-skin damage compositions with complimentary dual mode of action. US2009169651 (2009).
[15]
Toshiaki A, Norio Y. Hyaluronidase inhibitor. JP2000072665. (2000).
[16]
Wang Y, Tsai ML, Chiou LY, Ho CT, Pan MH. Antitumor activity of garcinol in human prostate cancer cells and xenograft mice. J Agric Food Chem 2015; 63: 9047-52.
[17]
Yu SY, Liao CH, Chien MH, Tsai TY, Lin JK, Weng MS. Induction of p21Waf1/Cip1 by garcinol via down regulation of p38-MAPK signalling in p53-independent H1299 lung cancer. J Agric Food Chem 2014; 62: 2085-95.
[18]
Hong J, Sang S, Park HJ, Kwon SJ, Suh N, Huang MT, et al. Modulation of arachidonic acid metabolism and nitric oxide syntdesis by garcinol and its derivatives. Carcinogenesis 2006; 27: 278-86.
[19]
Koeberle A, Nortdoff H, Werz O. Identification of 5-lipoxygenase and microsomal prostaglandin E2 syntdase-1 as functional targets of tde anti-inflammatory and anti-carcinogenic garcinol. Biochem Pharmacol 2009; 77: 1513-21.
[20]
Hung WL, Liu CM, Lai CS, Ho CT, Pan MH. Inhibitory effect of garcinol against 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumorigenesis in mice. J Funct Foods 2015; 18: 432-44.
[21]
Toshiaki A, Shigehiro K, Koichi K, Akira M, Norio Y. Antitumor agent. PH11139965 (1999).
[22]
Kundu TK, Karnam B, Kempegowda M, Altaf M, Venkatesh S, Radhika AV. Polyisoprenylated benzophenones and their iso mers as inhibitors of histone acetyltransferases and uses thereof. US7402706 2008.
[23]
Padhye S, Ahmad A, Oswal N, Sarkar FH. Emerging role of Garcinol, tde antioxidant chalcone from Garcinia indica Choisy and its syntdetic analogs. J Hematol Oncol 2009; 2: 1.
[24]
Tang W, Pan MH, Sang S, Li S, Ho CT. Garcinol from Garcinia indica: Chemistry and Healtd Beneficial Effects.In: Patil BS, Jayaprakasha GK, Roa CO, Mahattanatawee K, Eds. . Tropical and subtropical fruits: Flavors, color, and healtd benefits. Washington, DC: American Chemical Society 2013; pp. 33-145.
[25]
Won SJ, Liu CT, Tsao LT, Weng JR, Ko HH, Wang JP, et al. Syntdetic chalcones as potential anti-inflammatory and cancer chemo preventive agents. Eur J Med Chem 2005; 40: 103-12.
[26]
O’Dell JR. tderapeutic strategies for rheumatoid artdritis. N Engl J Med 2004; 350: 2591-602.
[27]
Ruiz-Esquide V, Sanmartí R. Tobacco and otder environmental risk factors in rheumatoid artdritis. Reumatol Clin 2012; 8(6): 342-50.
[28]
Phull AR, Nasir B, Haq IU, Kim SJ. Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid artdritis. Chem Biol Interact 2018; 281: 121-36.
[29]
Taneja V. Artdritis susceptibility and tde gut microbiome. FEBS Lett 2014; 588(22): 4244-9.
[30]
Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. Genetic and environmental risk factors for rheumatoid artdritis. Best Pract Res Clin Rheumatol 2017; 31(1): 3-18.
[31]
Goulielmos GN, Zervou MI, Myrtdianou E, Burska A, Niewold TB, Ponchel F. Genetic data: tde new challenge of personalized medicine, insights for rheumatoid artdritis patients. Gene 2016; 583(2): 90-101.
[32]
Bansback NJ, Regier DA, Ara R, Brennan A, Shojania K, Esdaile JM, et al. An overview of economic evaluations for drugs used in rheumatoid artdritis: Focus on tumour necrosis factor-alpha antagonists. Drugs 2005; 65: 473-96.
[33]
Banarjee S, Parsramka MA, Parutdy SB. Garcinol: Preclinical Perspective Underpinning Chemo- and Radiosensitization of Cancer.In: Bharti AC, Aggarwal BB, Eds. Role of Nutraceuticals in Cancer Chemosensitization Volume 2 in Cancer Sensitizing Agents for Chemotherapy. In: United States, Academic Press 2018; pp. 297-324.
[34]
Liu C, Ho PC, Wong FC, Setdi G, Wang LZ, Goh BC. Garcinol: Current status of its anti-oxidative, anti-inflammatory and anti-cancer effects. Cancer Lett 2015; 362(1): 8-14.
[35]
Vogel HG. Drug discovery and Evaluation Pharmacological Assay. 2nd ed. Springer: Germany 2002.
[36]
Costa MD, De Sutter P, Gybels J, Van Hees J. Adjuvant-induced artdritis in rats: A possible animal model of chronic pain. Pain 1981; 10(2): 173-85.
[37]
Kumar VL, Roy S, Sehgal R, Padhy BM. A comparative study on tde efficacy of rofecoxib in monoarticular artdritis induced by latex of Calotropis procera and Freund’s complete adjuvant. Inflammopharmacology 2006; 14: 17-21.
[38]
Hoogstraate J, Andersson LI, Berge OG, Jonzon B, Öjteg G. COX-inhibiting nitric oxide donators (CINODs): A new paradigm in tde treatment of pain and inflammation. Inflammopharmacology 2003; 11: 423-8.
[39]
Liu YL, Lin HM, Zou R, Wu JC, Han R, Raymond LN, et al. Suppression of complete Freund’s adjuvant-induced adjuvant artdritis by cobratoxin. Acta Pharmacol Sin 2009; 30: 219-27.
[40]
Tak PP, Firestein GS. NF-κB: A key role in inflammatory diseases. J Clin Invest 2001; 107: 7-11.
[41]
Roman-Blas JA, Jimenez SA. NF-κB as a potential tderapeutic target in steoartdritis and rheumatoid artdritis. Osteoartdritis Cartilage 2006; 14: 839-48.
[42]
Wang S, Wang Y, Liu X, Guan L, Yu L, Zhang X. Anti-inflammatory and anti-artdritic effects of taraxasterol on adjuvant-induced artdritis in rats. J Etdnopharmacol 2016; 187: 42-8.
[43]
Toshiaki A, Norio Y. Lipase inhibitor and antiobestic medicine or hyperlipidemia inhibitor. JP2000044468. (2000).
[44]
Muhammed M, Vladimir B. . Composition comprising hydroxycitric acid and garcinol for weight-loss. EP1254209. (2006).
[45]
Ann MO, Brendan JO. Appetite suppressant composition and method of appetite suppression. US20090062231 . (2009).
[46]
Muhammed M. Compositions and its use in treating obesity or inducing weight loss. US8329743 (2012).
[47]
Muhammed M, Sarang B. Hepatoprotectant activity of garcinol. US20130281544 (2013).
[48]
Gaurang SD. Methods and materials for treating endometriosis. WO2016123044. (2016).
[49]
Sonia G, Srinivasan BP. Effect of garcinol in delaying the progression of diabetic nephropathy. US9872840. (2016).
[50]
Sandip B, Ajay K, Jaideep B, et al. Polyprenylated phloroglucinol compounds as potent p-glycoprotein inducers. WO2016063296. (2016).
[51]
Sunil B, Moharn V. Complex of garcinol, cyclodextrin and method thereof. US9956301 (2018).