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In this study the drug corallocarpus epigaeus was evaluated for acute and chronic inflammation and the results of phytochemical studies shows the presence of alkaloids, carbohydrates, glycosides, tannins, flavonoids, fixed oils, saponins, proteins, steroids present in hydro alcoholic extract. The acute oral toxicity studies shows the LD50 value >2000 mg/kg. In carrageenan induced rat paw edema method the significant percentage inhibition of paw edema was obtained. The results obtained from the complete Freund’s Adjuvant induced arthritis model showed the significant inhibition of inflammation and there is no significant changes in biochemical and haematological parameters.


Inflammation Percentage inhibition

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R. Sarojini, S. Selvakumar, & N. Chidambaranathan. (2024). Preclinical Evaluation of Hydro alcoholic extract of Corallocarpus epigaeus for Anti inflammatory activity. International Journal of Research in Pharmacology & Pharmacotherapeutics, 13(2), 176-202. Retrieved from


  1. 1. Hurley JV. Acute inflammation. Edinburgh, London: Churchill Livingstone; 1972. [Google Scholar]
  2. 2. Sanderson JB. A system of Surgery. 2. London Longmans: Green and Co; 1871. [Google Scholar]
  3. 3. Spector WG, Willoughby DA. The Inflammatory Response. Bacteriological Reviews. 1963;27:117– 149. [PMC free article] [PubMed] [Google Scholar]
  4. 4. Winter CA, Risley EA, Nuss GV. Carrageenin-induced edema in hind paw of the rat as an assay for anti inflammatory drugs. Proc Soc Exp Biol Med. 1962;111:544–547. [PubMed] [Google Scholar]
  5. 5. Newbould BB. Chemotherapy of arthritis induced in rats by mycobaterial adjuvant. Br J Pharmacol. 1963;21:127–136. [PMC free article] [PubMed] [Google Scholar]
  6. 6. Pearson CM, Wood FD. Studies of polyarthritis and other lesions induced in rats by injection of mycobacterial adjuvant. Arth Rheum. 1959;2:440. [Google Scholar]
  7. 7. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin like drugs. Nature New Biology. 1971;231:232–235. [PubMed] [Google Scholar]
  8. 8. Hawkey CJ, Jackson L, Harper SE, Simon TJ, Mortensen E, Lines CR. Review article: the gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2 in humans. Aliment Pharmacol Ther. 2001;15:1–9. doi: 10.1046/j.1365-2036.2001.00894.x. [PubMed] [CrossRef] [Google Scholar]
  9. 9. Whelan CJ. Will non-steroid approaches to the treatment of inflammation replace our need for glucocorticoids? Current Opinion in Investigational Drugs. 2003;4:536–543. [PubMed] [Google Scholar]
  10. 10. Gilroy DW, Lawrence T, Perretti M, Rossi AG. Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov. 2004;3:401–16. doi: 10.1038/nrd1383. [PubMed] [CrossRef] [Google Scholar]
  11. 11. Kumar S, Boehm J, Lee JC. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov. 2003;2:717–26. doi: 10.1038/nrd1177. [PubMed] [CrossRef] [Google Scholar]
  12. 12. Ward SG, Finan P. Isoform-specific phosphoinositide 3-kinase inhibitors as therapeutic agents. Curr Opin Pharmacol. 2003;3:426–34. doi: 10.1016/S1471-4892(03)00078-X. [PubMed] [CrossRef] [Google Scholar]
  13. 13. Manning AM, Davis RJ. Targeting JNK for therapeutic benefit: from junk to gold? Nat Rev Drug
  14. Discov. 2003;2:554–65. doi: 10.1038/nrd1132. [PubMed] [CrossRef] [Google Scholar]
  15. 14. Karin M, Yamamoto Y, Wang QM. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov. 2004;3:17–26. doi: 10.1038/nrd1279. [PubMed] [CrossRef] [Google Scholar]
  16. 15. Leung DY, Bloom JW. Update on glucocorticoid action and resistance. J Allergy Clin Immunol. 2003;111:3–22. doi: 10.1067/mai.2003.97. [PubMed] [CrossRef] [Google Scholar]
  17. 16. Barnes PJ, Adcock IM. How do corticosteroids work in asthma? Ann Intern Med. 2003;139:359– 70. [PubMed] [Google Scholar]
  18. 17. Baldwin AS Jr. Series introduction: the transcription factor NF-kappaB and human disease. J Clin
  19. Invest. 2001;107:3–6. [PMC free article] [PubMed] [Google Scholar]
  20. 18. BioMed Central Open Access Charter
  21. 19. PubMed Central
  22. 20. Potsdam
  23. 21. INIST
  24. 22. e-Depot
  25. 23. Lawrence S. Free online availability substantially increases a paper's impact. Nature. 2001;411:521.
  26. doi: 10.1038/35079151. [PubMed] [CrossRef] [Google Scholar]
  27. 24. Velterop J. Should scholarly societies embrace Open Access (or is it the kiss of death)? Learned
  28. Publishing. 2003;16:167–169. doi: 10.1087/095315103322110932. [CrossRef] [Google Scholar]
  29. 25. Open Access law introduced
  30. 26. Tan-Torres Edejer T. Disseminating health information in developing countries: the role of the internet. BMJ. 2000;321:797–800. doi: 10.1136/bmj.321.7264.797. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  31. 27. Silman, A. J. & Pearson, J. E. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 4(Suppl. 3), S265–S272 (2002)
  32. 28. Van der Linden, M. P. et al. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum. 62, 3537–3546 (2010)
  33. 29. Moura, C. S. et al. Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study. Arthritis Res. Ther. 17, 197 (2015)
  34. 30. Cho, S. K. et al. Factors associated with time to diagnosis from symptom onset in patients with early rheumatoid arthritis. Korean J. Intern. Med. 113, (2017).
  35. 31. Raza, K. et al. Delays in assessment of patients with rheumatoid arthritis:variations across Europe. Ann. Rheum. Dis. 70, 1822–1825 (2011)
  36. 32. Ometto, F. et al. Methods used to assess remission and low disease activity in rheumatoid arthritis. Autoimmun. Rev. 9, 161–164 (2010)
  37. 33. Grennan, D. M., Gray, J., Loudon, J. & Fear, S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann. Rheum. Dis. 60, 214– 217 (2001).
  38. 34. Nishimura, K. et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann. Intern. Med. 146, 797–808 (2005)
  39. 35. Bizzaro, N. et al. Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis: results from a 2-year prospective study. Arthritis Res. Ther. 15, R16 (2013)
  40. 36. Malmstrom, V., Catrina, A. I. & Klareskog, L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nat. Rev. Immunol. 17, 60–75 (2017)
  41. 37. Padyukov, L. et al. A genome-wide association study suggests contrasting associations in ACPApositive versus ACPA-negative rheumatoid arthritis. Ann. Rheum. Dis. 70, 259–265 (2011)
  42. 38. Schuerwegh, A. J. et al. Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 107, 2586–2591 (2010)
  43. 39. Van Dongen, H. et al. Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 56, 1424–1432 (2007).
  44. 40. Sellam, J. et al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 63, 933–938 (2011).
  45. 41. Seegobin, S. D. et al. ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial. Arthritis Res. Ther. 16, R13 (2011)
  46. 42. Raychaudhuri, S. et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat. Genet. 44, 291–296 (2012)
  47. 43. Okada, Y. et al. Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations. Hum. Mol. Genet. 23, 6916–6926 (2014)
  48. 44. Mori, M., Yamada, R., Kobayashi, K., Kawaida, R. & Yamamoto, K. Ethnic differences in allele frequency of autoimmune-disease-associated SNPs. J. Hum. Genet. 50, 264–266 (2005)
  49. 45. Nabi, G. et al. Meta-analysis reveals PTPN22 1858C/T polymorphism confers susceptibility to rheumatoid arthritis in Caucasian but not in Asian population. Autoimmunity 49, 197–210 (2016).
  50. 46. Goh, L. L. et al. NLRP1, PTPN22 and PADI4 gene polymorphisms and rheumatoid arthritis in ACPApositive Singaporean Chinese. Rheumatol. Int. 37, 1295–1302 (2017)
  51. 47. McCarthy, C. et al. Brief report: genetic variation of the alpha1 -antitrypsin gene is associated with increased autoantibody production in rheumatoid arthritis. Arthritis Rheumatol. 69, 1576–1579 (2017).
  52. 48. Castaneda-Delgado, J. E. et al. Type I interferon gene response is increased in early and established rheumatoid arthritis and correlates with autoantibody production. Front. Immunol. 8, 285 (2017).
  53. 49. Ding, B. et al. Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region. Arthritis Rheum. 60, 30–38 (2009).
  54. 50. Schiff, M. H. et al. Long-term experience with etanercept in the treatment of rheumatoid arthritis in elderly and younger patients: patient-reported outcomes from multiple controlled and open-label extension studies. Drugs Aging 23, 167–178 (2006).
  55. 51. Frisell, T. et al. Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anticitrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum. 65, 2773–2782 (2013).
  56. 52. Kuo, C. F. et al. Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: a nationwide population-based study. Rheumatology 56, 928–933 (2017).
  57. 53. Svendsen, A. J. et al. On the origin of rheumatoid arthritis: the impact of environment and genes--a population based twin study. PLoS ONE 8, e57304 (2013).
  58. 54. Aletaha, D.; Smolen, J.S. Diagnosis and management of rheumatoid arthritis: A review. JAMA 2018, 320, 1360–1372. [CrossRef] [PubMed]
  59. 55. Fiehn, C.; Holle, J.; Iking-Konert, C.; Leipe, J.; Weseloh, C.; Frerix, M.; Alten, R.; Behrens, F.; Baerwald, C.; Braun, J.; et al. S2e guideline: Treatment of rheumatoid arthritis with disease-modifying drugs. Z. Rheumatol. 2018, 77, 3553.
  60. 56. Verschueren, P.; De Cock, D.; Corluy, L.; Joos, R.; Langenaken, C.; Taelman, V.; Raeman, F.; Ravelingien, I.; Vandevyvere, K.; Lenaerts, J.; et al. Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial. Ann. Rheum. Dis.2017, 76, 511–520. [PubMed]
  61. 57. Smolen, J.S.; Kalden, J.R.; Scott, D.L.; Rozman, B.; Kvien, T.K.; Larsen, A.; Loew-Friedrich, I.; Oed, C.; Rosenburg, R. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: A double-blind, randomised, multicentre trial. Lancet 1999, 353, 259–266. [CrossRef]
  62. 58. Brown, P.M.; Pratt, A.G.; Isaacs, J.D. Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers. Nat. Rev. Rheumatol. 2016, 12, 731–742. [CrossRef]
  63. 59. Kruger, K.; Albrecht, K.; Rehart, S.; Scholz, R. Recommendations of the German society for rheumatology on the perioperative approach under therapy with DMARDs and biologicals in inflammatory rheumatic diseases. Z. Rheumatol. 2014, 73, 77–84. [CrossRef]
  64. 60. Østensen, M.; Khamashta, M.; Lockshin, M.; Parke, A.; Brucato, A.; Carp, H.; Doria, A.; Rai, R.;
  65. Meroni, P.L.; Cetin, I.; et al. Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res. Ther. 2006, 8, 209. [CrossRef] [PubMed]
  66. 61. Breedveld, F.C.; Dayer, J. Leflunomide: Mode of action in the treatment of rheumatoid arthritis. Ann. Rheum. Dis. 2000, 59, 841–849. [CrossRef] [PubMed]
  67. 62. Kruger, K.; Bolten, W. Treatment with leflunomide in rheumatoid arthritis. Z. Rheumatol. 2005, 64, 96–101. [CrossRef] [PubMed]
  68. 63. Fox, R.; Helfgott, S.M. Pharmacology, Dosing, and Adverse Effects of Leflunomide in the Treatment of Rheumatoid Arthritis. Available online: (accessed on 2 April 2019).
  69. 64. Smedegård, G.; Björk, J. Sulphasalazine: Mechanism of Action in Rheumatoid Arthritis. Rheumatology 1995, 34, 7–15. [CrossRef]
  70. 65. Michael, H.; Weisman, R.Z.R. Sulfasalazine: Pharmacology, Administration, and Adverse Effects in the Treatment of Rheumatoid Arthritis. Available online: (accessed on 2 April 2019).
  71. 66. Pullar, T.; A Box, S. Sulphasalazine in the treatment of rheumatoid arthritis. Rheumatology 1997, 36, 382–386.
  72. 67. Fachinformation Sulfasalazin HEXAL. Available online:
  73. (accessed on 2 April 2019).
  74. 68. Keffer, J.; Probert, L.; Cazlaris, H.; Georgopoulos, S.; Kaslaris, E.; Kioussis, D.; Kollias, G. Transgenic mice expressing human tumour necrosis factor: A predictive genetic model of arthritis. EMBO J. 1991, 10, 4025–4031. [CrossRef] [PubMed]
  75. 69. Emery, P. Infliximab: A new treatment for rheumatoid arthritis. Hosp. Med. 2001, 62, 150–152. [CrossRef]
  76. 70. Fleischmann, R.; Vencovsky, J.; van Vollenhoven, R.F.; Borenstein, D.; Box, J.; Coteur, G.; Goel, N.; Brezinschek, H.P.; Innes, A.; Strand, V. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: The FAST4WARD study. Ann. Rheum. Dis. 2009, 68, 805–811. [CrossRef]
  77. 71. Cheifetz, A.; Mayer, L.Monoclonal antibodies, immunogenicity, and associated infusion reactions.
  78. Mount Sinai J. Med. 2005, 72, 250–256.
  79. 72. Weinblatt, M.E.; Schiff, M.; Valente, R.; van der Heijde, D.; Citera, G.; Zhao, C.; Maldonado, M.; Fleischmann, R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: Findings of a phase IIIb, multinational, prospective, randomized study. Arthritis
  80. Rheum. 2013, 65, 28–38. [CrossRef]
  81. 73. Konttinen, L.; Kankaanpää, E.; Luosujärvi, R.; Blåfield, H.; Vuori, K.; Hakala, M.; Rantalaiho, V.; Savolainen, E.; Uutela, T.; Nordström, D.; et al. Effectiveness of anakinra in rheumatic disease in patients naive to biological drugs or previously on TNF blocking drugs: An observational study. Clin. Rheumatol. 2006, 25, 882–884. [CrossRef] [PubMed]
  82. 74. Mertens, M.; Singh, J.A. Anakinra for Rheumatoid Arthritis: A Systematic Review. J. Rheumatol. 2009, 36, 1118–1125. [CrossRef] [PubMed]
  83. 75. Gratton, S.B.; Scalapino, K.J.; Fye, K.H. Case of anakinra as a steroid-sparing agent for gout inflammation. Arthritis Rheum.2009, 61, 1268–1270. [CrossRef] [PubMed]
  84. 76. Fleischmann, R.M.; Tesser, J.; Schiff, M.H.; Schechtman, J.; Burmester, G.-R.; Bennett, R.; Modafferi, D.; Zhou, L.; Bell, D.; Appleton, B. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann. Rheum. Dis. 2006, 65, 1006–1012. [CrossRef] [PubMed]
  85. 77. Nisha SC, Balaji JS, Venkatramanan K, Madhumathi L. Pharmacognostical and preliminary phytochemical screening of the root and rhizome of Corallocarpus epigaeus. Int J Pharm Biomed Res.
  86. 2010;1(1):24-7.
  87. 78. Ellof JN. Which extractant should be used for the screening and isolation of antimicrobial components from plants? J Ethnopharmacol.1998;60:1-6.
  88. 79. Agnihotri S, Wakode S, Agnihotri A. An overview on anti-inflammatory properties and chemo-profile of plants used in traditional medicine. Indian Journal of Natural products and Resources. 2010;1(2):150.
  89. 80. Arnous A, Makris DP, Kefalas P. Effect of principal polyphenolic components in relation to antioxidant characteristics of aged red wines.J Agric Food Chem. 2001;49:5736-42.
  90. 81. Subramanion LJ, Zuraini Z, Sasidharan S. Phytochemicals screening,DPPH free radical scavenging and xanthine oxidase inhibitiory activities of Cassia fistula seeds extract. J Med Plants Res.
  91. 2011;5(10):1941-7.
  92. 82. Dunnill PM, Fowden L. The Amino Acids of Seeds of the Cucurbitaceae.Phytochemistry (1965) 4(6):933–44. doi: 10.1016/S0031-9422(00)86271-8
  93. 83. Gupta J, Ali M, Pillai KK, Velasco-Negueruela A, Pérez-Alonso MJ, Contreras FÓ. The Occurrence of
  94. Ishwarane and Ishwarone in the Roof Oil of Corallocarpus Epigaeus Benth. Ex Hook. F. J Essential Oil
  95. Res (1997) 9 (6):667–72. doi: 10.1080/10412905.1997.9700808
  96. 84. Bhavani M, Leelavathi S. Investigation on In Vitro Cytotoxic Activity of a Selected Wild Cucurbitaceae
  97. Plant Corallocarpus Epigeaus Against Cancer. Int J Pharm Sci Res (2015) 6(8):3554–57. doi: 10.13040/IJPSR.0975-8232.6 (8).3554-57
  98. 85. Aiyelero OM, Ibrahim ZG and Yaro AH. Analgesic and anti-inflammatory properties of the methanol leaf extract of Ficus ingens (moraceae) in rodents. Nig Journ Pharm Sci. 8(2), 2009, 79-86.
  99. 86. Pearson CM. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Bio Med 1956;91(1):95e101.
  100. 87. Johnson PM, Faulk WP. Rheumatoid factor: its nature, specificity, and production in rheumatoid arthritis. Clin Immunol Immunopathol 1976;6(3):414e30.
  101. 88. Gavrilov VB, Gavrilova AR, Mazhul LM. Methods of determining lipid peroxidation products in the serum using a thiobarbituric acid test. Vopr Med Khim 1987;33:118e22.
  102. 89. Ekambaram S, Perumal SS, Subramanian V. Evaluation of antiarthritic activity of Strychnos potatorum Linn seeds in Freund’s adjuvant induced arthritic rat model. BMC Complementary and Alternative Medicine. 2010;10:56.
  103. 90. Narendhirakannan RT, Subramanian S, Kandaswamy M. Evaluation of anti-inflammatory activity of Cleome gynandra L. leaf extract on acute and chronic inflammatory arthritis studied in rats. Journal of Pharmacology and Toxicology. 2007;2(1):44-53.
  104. 91. Azza Z, Oudghiri M. In vivo anti-inflammatory and anti-arthritic activities of aqueous extracts from Thymelaea hirsuta. Pharmacognosy Res. 2015;7(2):213-6. doi:10.4103/0974-8490.150510.
  105. 92. Phanse MA, Chaudhari PD, Patel B, Patil MJ, Abbulu K. Anti-inflammatory activity of sparagus cochinchinensis root extract in mice. J Appl Pharm Sci. 2012;2(7):19-33. doi: 10.7324/JAPS.2012.2704.
  106. 93. Daniela Placha, and Josef Jampilek. Chronic Inflammatory Diseases, Anti-Inflammatory Agents and
  107. Their Delivery Nanosystems. Journal of pharmaceutics. 2021;13(1):64.
  108. doi: 10.3390/pharmaceutics13010064.
  109. 94. Patil KR, Mahajan UB, Unger BS, Goyal SN, Belemkar S. Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals. Int J Mol Sci.2019;20(18):4367. doi: 10.3390/ijms20184367.
  110. 95. Kalpesh Ishnava, Ruchi Kotadia, Sandip Patel.Nutritional Properties and Chemical Composition of Corallocarpus epigaeus (Arn.) Cl : As Remedy to Control Diabetes mellitus. Indian journal of pharmaceutical science.2015; 42(4) : 806-815.
  111. 96. T.Sivkumar, K. Kannan, R. Manavalan. Pharmacognostical Investigations of Corallocarpus Epigaeus (Rotter) C.B. Clark. Rasayan Journal of chemistry. 2009; 2(1): 159-166.
  112. 97. Retrieved from hepatotoxicity.
  113. 98. Rajes,M.G., Latha, M.S.Hepatoprotection by Elephanto pusscaber Linn. In CCl4 induced liver injury Ind. J. Physiol. Pharmacology, 2001,Vol( 45):81-486.
  114. 99. Vishal gupta, S.K., Yadav., Dinesh singh., Naveen gupta. Evaluation of wound healing activity of herbal drug combination of Rubia cordifolia, Centella asiatica, TerminaliBelerica, Plumbago zeylanica and Withania somnifera. Int. J. of pharm. & life sci. 2011, 952-954.
  115. 100. Navneet kishore., Bhuwan, B., Mishra., Vinod, K. Tiwari., Vyasji tripathi. ifuranonaphthoquinones from Plumbago zeylanica roots, Journal of Phytochemistry. 2010,3: 62-65.
  116. 101. Ravikumar V., Sudaha, T. Phytochemical and Antimicromial studies in plumbago zeylanica.
  117. International journal of research in pharmacy and chemistry. 2011: 185-18.
  118. 102. Meena. K., Brijendra singh, Ramanjeet Kaur. Pharmacognostic and physicochemical Studies on plumbago zeylanica Linn. Research Article Drug Invention Today. 2009, Vol.2(4): 217-219.
  119. 103. Kattamanchi G., Kontham Ramakanth R.,Gudur Pavan K., Bheemanapally K.,Karka Srinivas R. and Avvari Sanjeeva K.,Int. Curr. Pharm. J., 2013; 2(3): 53-56.
  120. 104. Kirtikar K.R. and Basu B.D., Indian Medicinal Plants, International Book Distributors, Dehradun, 1988.
  121. 105. Heinrich M., Barnes J., Gibbons S. and Williamson E.M., Fundamentals of Pharmacognosy and Phytotherapy, Churchill Livingstone, Elsevier Science Ltd, 2004.
  122. 106. Shukla RK, Painuly D, Shukla A, Kumar V, Singh J, Porval A, Vats S. Physical evaluation, proximate analysis and antimicrobial activity of Morus Nigra seeds. International Journal of Pharmacy and Pharmaceutical Sciences. 2015; 7(1):191-7.
  123. 107. Aborisade AB, Adetutu A, Owoade AO. Phytochemical and Proximate Analysis of Some Medicinal Leaves. Clinical Medicine Research. 2017; 6(6):209.
  124. 108. Bansode TS, Salalkar BK. Phytochemical analysis of some selected Indian medicinal plants. Int J Pharm Bio Sci. 2015; 6(1):550-6.
  125. 109. Bhargava VV, Saluja AK, Dholwani KK. Detection of heavy metal contents and proximate analysis of roots of Anogeissus latifolia. Journal of Pharmacognosy and Phytochemistry. 2013; 1(6).
  126. 110. Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phytochemistry. 2000; 55:481-504.
  127. 111. Salehi-Surmaghi MH, Aynehchi Y, Amin GH, Mahhmoodi Z (1992). Survey of Iranian plants for saponins, alkaloids, flavonoids and tannins IV. Daru Journal of Pharmaceutical Sciences 2: 281-291.
  128. 112. Smolenski SJ, Silinis H, Farnsworth NR (1972). Alkaloid screening. I. Lloydia 35:1-34.
  129. 113. Ajaiyeoba EO (2002). Phytochemical and antibacterial properties of Parkia biglobosa and Parkia bicolor leaf extracts. African Journal of Biomedical Research 5: 125-129.
  130. 114. Harborne JB (1973). Phytochemical methods, Champman and Hall Ltd. London, pp.49-188.
  131. 115. Kapoor LD, Singh A, Kapoor SL, Shrivastava SN (1969). Survey of Indian plants for saponins, alkaloids and flavonoids. I. Lloydia 32: 297-304.
  132. 116. Segelman AB, Farnsworth NR, Quimby MD (1969). False negative saponins test results induced by the presence of tannins I. Lloydia 32: 52-58.
  133. 117. McDonald S, Prenzler PD, Antolovich M, Robards K (2001). Phenolic content and antioxidant activity of olive extracts. Food Chemistry 73: 73-84.
  134. 118. Chang C, Yang M, Wen H, Chern J (2002). Estimation of total flavonoid content in propolis by two complementary colorimetric methods. Journal of Food and Drug Analysis 10: 178-182.
  135. 119. Anonymous. Organization for economic Co-operation and development Guidance Document on Acute toxicity testing. Environment Directorate, OECD. Peris: 2001, 1-24.
  136. 120. Aiyelero OM, Ibrahim ZG and Yaro AH. Analgesic and anti-inflammatory properties of the methanol leaf extract of Ficus ingens (moraceae) in rodents. Nig Journ Pharm Sci. 8(2), 2009, 79-86.
  137. 121. Winter CA, Risley EA, Nuss GW (1962). Carrageenan-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proceedings of the Society for Experimental Biology and Medicine 111: 544-547.
  138. 122. Pearson CM. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Bio Med 1956;91(1):95e101.
  139. 123. Winter CA, Risley EA, Nuss CW. Carageenan induced edema in hind paw of the rats as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med.1962;111:544–7.
  140. 124. Bihani GV, Rojatkar SR, Bodhankar SL. Anti-arthritic activity of methanol extract of Cyathocline purpurea (whole plant) in Freund’s complete adjuvant-induced arthritis in rats. Biomedicine & Aging Pathology. 2014;4:197–206.
  141. 125. Gabriella C, Maristella A, Elena G, Iwan JP. de Esch, Rob L. Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenaninduced acute inflammation. Eur J Pharmacol. 2007;563:240–4.
  142. 126. Foyet HS, Tsala DE, Zogo Essono Bodo JC, Carine AN, Heroyne LT, Oben EK.Anti-inflammatory and antiarthritic activity of a methanol extract from Vitellaria paradoxa stem bark. Phcog Res.
  143. 2015;7:367–77.
  144. 127. Mythilypriya R, Shanthi P, Sachdanandam P. Salubrious effect of Kalpaamruthaa, a modified indigenous preparation in adjuvant-induced arthritis in rats – A biochemical approach. Chem Biol Interact. 2008;173:148–58.
  145. 128. Mehta A, Sethiya N, Mehta C, Shah G. Anti-arthritis activity of roots of Hemidesmus indicus R. Br. (Anantmul) in rats. Asian Pac J Trop Med. 2012;5(2):130–5.
  146. 129. Zheng CJ, Zhao XX, Ai HW, et al. Therapeutic effects of standardized Vitex negundo seeds extract on complete Freund’s adjuvant induced arthritis in rats. Phytomedicine. 2014;21:838–846.
  147. 130. Devasagayam TP, Tarachand U. Decreased lipid peroxidation in the rat kidney during gestation. Biochem Biophys Res Commun.1987;145:134–138.
  148. 131. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem.1974;47:469-474.
  149. 132. Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47:389–394.
  150. 133. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582:67–78.
  151. 134. Roth SH. Coming to terms with nonsteroidal anti-inflammatory drug gastropathy. Drugs. 2012; 72: 873-879.
  152. 135. Nagatomi H, Ando K. Studies on the anti-inflammatory activity and ulcerogenic adverse effect of thiazole derivatives, especially 2-amino-thiazoleacetic acid derivatives. Arzneimittelforschung. 1984; 34:
  153. 599-603.
  154. 136. Simon RA. Prevention and treatment of reactions to NSAIDs. Clin Rev Allergy Immunol. 2003; 24:189-198.
  155. 137. John H, Nodine MD (1999). Chicago: Year Book Medical. Publishers Inc, p. 492.
  156. 138. Marzouk B, Marzouk Z, Haloui E, Fenina N, Bouraoui A, Aouni M (2010). Screening of analgesic and anti inflammatory activities of Citrullus colocynthisfrom southern Tunisia. Journal of Ethnopharmacology 128: 15-19.
  157. 139. Morebise O, Fafunso MA, Makinde JM, Olajide OA, Awe EO (2002).Antiinflammatory property of the leaves of Gongronema latifolium. Phytotherapy Research 16: S75-S77.
  158. 140. Erdemoglu N, Turan NN, Akkol EK, Sener B, Abacioglu N (2009). Estimation of anti-inflammatory, antinociceptive and antioxidant activities on Arctium minus (Hill) Bernh. ssp. minus. Journal of Ethnopharmacology 121: 318-323.
  159. 141. Thomazzi SM, Silva CB, Silveira DCR, Vasconcellos CLC, Lira AF, Cambui EVF (2010). Antinociceptive and anti-inflammatory activities of Bowdichia virgilioides (sucupira). Journal of Ethnopharmacology 127: 451-456.
  160. 142. McInnes IB, Schett G. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med. 2011;365:2205–19.
  161. 143. Rhee DK, Marcelino J, Baker M, et al. The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Invest. 2005;115:62231.
  162. 144. van der Heijde DM. Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol.
  163. 1995;34 Suppl 2:74–8.
  164. 145. Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum. 2002;46:357–65.
  165. 146. Benslay DN, Bendele AM. Development of a rapid screen for detecting and differentiating immunomodulatory vs anti-inflammatory compounds in rats.Agents Actions. 1991;34:254–6.
  166. 147. Colpaert FC, Meert T, Witte P, Schmitt P. Further evidence validating adjuvant arthritis as an experimental model of chronic pain in the rat. Life Sci. 1982;31:67–75.
  167. 148. Singh S, Majumdar DK. Effect of fixed oil of Ocimum sanctum against experimentally induced arthritis and joint edema in laboratory animals. Int J Pharmacogn. 1996;34:218–22.
  168. 149. Milovanoic M, Nilson E, Jaremo P. Relationship between platelets and inflammatory markers in rheumatoid arthritis. Clin Chim Acta J. 2004;343:237–40.
  169. 150. Pepys MB, Hirchfield GM. C-reactive protein: a critical update. J Clin Invest.2003;111(12):1805–12.
  170. 151. Yildirim K, Karatay S, Melikoglu MA, Gureser G, Ugur M, Senel K. Associations between acute phase reactant levels and disease activity score (DAS28) in patient with rheumatoid arthritis. Ann Clin Lab Sci. 2004;34(4):423–6.
  171. 152. Rainsford KD. Adjuvant polyarthritis in rats. Is this a satisfactory model for screening anti-arthritic drugs? Agents Actions. 1982;12:452–8.
  172. 153. Glenn EM, Gray J, Kooyers W. Chemical changes in adjuvant induced polyarthritis of rats. Am J Vet Res.1965;26(114):1195–203.
  173. 154. Niino-Nanke Y, Akama H, Hara M, Kashiwazaki S. Alkaline phasphatase (ALP) activity in rheumatoid arthritis-its clinical significance and synthesis of ALP in RA synovium. Ryumachi. 1998;38(4):581–8.
  174. 155. Rehman Q, Lane NE. Bone loss. Therapeutic approaches for preventing bone loss in inflammatory arthritis. Arthritis Res. 2001;3:221–7.
  175. 156. Aida S. Relation between Rheumatoid Arthritis and Alkaline Phosphatase Isoenzymes. Ann Rheum Dis. 1993;52(7):511–6.
  176. 157. Harris ED. Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med. 1990;322:1277–89.
  177. 158. Ferraccioli G, Bracci-Laudiero L, Alivernini S, et al. Interleukin-1 b and Interleukin-6 in arthritis animal models: roles in the early phase of transition from acute to chronic inflammation and relevance for human rheumatoid arthritis. Mol Med. 2010;16:552–557.
  178. 159. Hackett TL, Holloway R, Holgate ST, et al. Dynamics of proinflammatory and anti-inflammatory cytokine release during acute inflammation in chronic obstructive pulmonary disease: an ex vivo study.
  179. Respir Res. 2008;9:47.
  180. 160. Zuo J, Xia Y, Li X, et al. Therapeutic effects of dichloromethane fraction of Securidaca inappendiculata on adjuvant-induced arthritis in rat. J Ethnopharmacol. 2014;153:352–358.
  181. 161. Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996; 14:397–440.
  182. 162. Ho CY, Weng CJ, Jhang JJ, et al. Diallyl sulfide as a potential dietary agent to reduce TNF-a- and histamine-induced proinflammatory responses in A7r5 cells. Mol Nutr Food Res. 2014;58:1069–1078.
  183. 163. Kausik B, Ishita C, Ranjiit K, et al. Biological activities and medicinal properties of neem (Azadirachta indica). Curr Sci. 2002;82:1336–1345.
  184. 164. Hodge G, Hodge S, Han P. Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease.Cytometry.
  185. 2002;48:209–215.
  186. 165. Halliwell B, Aeschbach R, L€oliger J, et al. The characterization of antioxidants. Food Chem Toxicol. 1995;33:601–617.
  187. 166. Arivazhagan S, Balasenthil S, Nagini S. Modulatory effects of garlic and neem leaf extracts on Nmethyl-N?-nitro-N-nitrosoguanidine (MNNG)-induced oxidative stress in Wistar rats. Cell Biochem Funct.
  188. 2000;18:17–21.
  189. 167. Arivazhagan S, Balasenthil S, Nagini S. Garlic and neem leaf extracts enhance hepatic glutathione and glutathione dependent enzymes duringN-methyl-N?-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats. Phytother Res. 2000;14:291–293.
  190. 168. Fahmy SR, Hamdi S. Antioxidant effect of the Egyptian freshwater Procambarus clarkii extract in rat liver and erythrocytes. Afr J Pharm Pharmacol. 2011;5:776–785.
  191. 169. Lim_on-Pacheco JH, Hern_andez NA, Fanjul-Moles ML, et al.Glutathione depletion activates mitogen-activated protein kinase (MAPK) pathways that display organ-specific responses and brain protection in mice. Free Radic Biol Med. 2007; 43:1335–1347.
  192. 170. Rao AD, Devi KN, Thyagaraju K. Isolation of antioxidant principle from Azadirachta seed kernels: determination of its role on plant lipoxygenases. J Enzyme Inhib. 1998;14:85–86.