STUDY OF THE EFFECTS OF EUGENIC ACID IN ARTHRITIS AND DIABETES MELLITUS IN EXPERIMENTAL RATS
Main Article Content
Keywords
Rheumatoid arthritis, diabetes mellitus, Eugenic Acid, inflammatory, mediators
Abstract
Background: Systemic inflammatory burden in rheumatoid arthritis (RA) has been shown to predispose to developing both insulin resistance and type 2 diabetes mellitus (DM). Polypharmacy with cumulative side effects are common problems met with in these medical situations of combined diseases.
Aim of the work: the present study evaluates the potential role of Eugenic Acid as a natural product with anti-inflammatory and hypoglycemic activities in combating both DM and RA in experimental animals.
Materials and methods: Twenty four male albino rats were used. Eight male rats were used as a normal control group received saline (group1). Arthritis was induced in 16 male albino rats by intradermal injection of 0.1 ml of Freund’s Complete Adjuvant (FCA) in the right hind paw then diabetes induced by alloxan (arthritic and diabetic animals). Animals were divided into 2 groups. Arthritic and diabetic control received sesame oil oral (group 2). Arthritic and diabetic animals treated with Eugenic Acid 100 mg/kg/day orally (group 3). Treatment was started with Eugenic Acid after diabetes induction for two weeks.
Results: arthritic and diabetic control animals showed significant elevation in serum level of C-reactive protein (CRP), nitric oxide (NO), malondialdehyde (MDA) tumor necrosis factor-α (TNF-α), hyperglycemia and dyslipidemia compared to normal control group. Treatment with Eugenic Acid exhibited significant reduction in serum level of CRP, NO, MDA, TNF-α, blood glucose level, triglycerides, total cholesterol and LDL compared with arthritic diabetic control group. There was insignificant change in HDL serum level.
Conclusion: These results suggested that dietary supplementation with Eugenic Acid could beneficially treat hyperglycemia and dyslipidemia. Also, Eugenic Acid ameliorates RA and could be useful as a beneficial supplement in treatment of RA and DM.
References
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3. Alagona P. and T. A. Ahmad (2015): “Cardiovascular disease risk assessment and prevention: current guidelines and limitations,” Medical Clinics of North America, 99(4): 711–731.
4. Albrecht K. and U. Müller-Ladner (2010): “Side effects and management of side effects of methotrexate in rheumatoid arthritis,” Clinical and Experimental Rheumatology, 28(5): supplement 61, S95–S101.
5. Atef M Al-Attar and Talal A Zari 2007. Modulatory effect of ginger and clove oils on physiological response in streptozotocin induced diabetic rats. International journal of pharmacology, 1(3): 34-40.
6. Azza Abouelella, Hala Madkour and Mahmoud Abdel-Raheem (2011): Effect of Eugenic Acid vs Glibenclamide in Alloxan Induced Diabetic Rats Sci. Med. J., Oct.; 23(4): 35-52.
7. Caraway WT and Watts NB 1987. Carbohydrates In: Tietz NW, ed. Fundamentals of Clinical Chemistry. 3ry ed. Philadephia WB saunders, 422-447.
8. Carrasco FR, Schmidt G, Romero AL, Sartoretto JL, Caparroz- Assef SM, Bersani-Amado CA, Cuman RK. (2009): Immunomodulatory activity of Zingiber officinale ROSCOE, Salvia officinalis L. and Syzygium aromaticum L. essential oils: evidence for humor- and cell-mediated responses. J. Pharm. Pharmacol., 61: 961–967.
9. Chang YC, Chuang LM. (2010): The role of oxidative stress in the pathogenesis of type 2 diabetes: from molecular mechanism to clinical implication. Am J Transl Res., 2: 316–331.
10. Chhanda Mallick, Rajkumar Maiti And Debidas Ghosh (2006): Comparative Study onantihyperglycemic and antihyperlipidemic effects of separate and composite extract of seed of eugenia jambolana and root of musca paradisiaca in streptozotocin-induced diabetic male albino rat. Iranian Journal of Pharmacology & Therapeutics, 5: 27-33.
11. Chung C. P., Annette Oeser, Joseph F. Solus, Tebeb Gebretsadik, Ayumi Shintani, Ingrid Avalos, Tuulikki Sokka, Paolo Raggi, Theodore Pincus and C. Michael Stein (2008): Inflammation- Associated Insulin Resistance: Differential Effects in Rheumatoid Arthritis and Systemic Lupus Erythematosus Define Potential Mechanisms. Arthritis Rheum. Jul; 58(7): 2105–2112.
12. Dix TA and Aikens J, (1993): Mechanisms and biological relevance of lipid peroxidation initiation. Chem Res Toxicol, 6: 2–18.
13. Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M.( 2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci U S A.; 97: 12222–12226.
14. Festa A, D'Agostino R, Jr, Howard G, et al. (2000). Chronic subclinical inflammation as part of the insulin resistancsyndrome: The insulin resistance atherosclerosis study (iras). Circulation, 102(1): 42-7.
15. Fischer R. and O. Maier, (2015) :“Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF,” Oxidative Medicine and Cellular Longevity, 2015; Article ID 610813, 18 pages.
16. Friedewald WT, Levy RI, Fredrickson DS. 1972; Estimation of the concentration of LDL-C in plasma without use of the prepara-tive ultracentrifuge. Clin Chem. 18: 449-502.
17. Giles JT, Bartlett SJ, Andersen RE, Fontaine KR, Bathon JM. (2008): Association of body composition with disability in rheumatoid arthritis: impact of appendicular fat and lean tissue mass. Arthritis Rheum. 14: 1407–1415.
18. Glauce SB Viana, Ana Carolina C Medeiros, Ana Michelle R Lacerda, L Kalyne AM Leal, Tiago G Vale1 and F José de Abreu Matos (2004): Hypoglycemic and anti-lipemic effects of the aqueous extract from Cissus sicyoides BMC Pharmacology, 4: 9.
19. Goldberg RB(2009). Cytokine and cytokine-like inflammation markers, endothelial dysfunction and imbalanced coagulation in development of diabetesand its complications. J Clin Endocrinol Metab, 94(9): 3171-82.
20. Hotamisligil GS. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int J Obes Relat Metab Disord. 2000; 24: S23–S27.
21. Kamezaki F, Yamashita K, Kubara T, et al. (2008): Derivatives of reactive oxygen metabolites correlates with high-sensitivity C-reactive protein. J. Atheroscler Thromb. 15: 206–212.
22. Karuppasamy V., Arumugam R. M., Thangaraj A., Vasanthakumar V. R., Mahalingam S., Ramalingam A., Philip A. Thomas and Pitchairaj Geraldine (2014): Antihyper-cholesterolemic and Antioxidative Potential of an Extract of the Plant, Piper betle and Its Active Constituent, Eugenic Acid, in Triton WR-1339-Induced Hypercholesterolemia in Experimental Rats. Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2014, Article ID 478973, 11 pages.
23. Khazaei M, Roshankhah S, Ghorbani R, Chobsaz F. (2011) Sildenafil effect on nitric oxide secretion by normal human endometrial epithelial cells cultured in vitro. Int J Fertil Steril. 5: 142–147.
24. Kokil G. R., R. N. Veedu, G. A. Ramm, J. B. Prins and H. S. Parekh (2015): “Type 2 diabetes mellitus: limitations of conventional therapies and intervention with nucleic acid-based therapeutics,” Chemical Reviews, 115(11): 4719–4743.
25. Lüscher T. F., (2015): “Ageing, inflammation and oxidative stress: final common pathways of cardiovascular disease,” European Heart Journal, 36(48): 3381–3383.
26. McInnes I. B. and G. Schett, (2011): “The pathogenesis of rheumatoid arthritis,” The New England Journal of Medicine, 2011; 365(23): 2205–2219.
27. Meng, Bo; Li, Jun; Cao, Hong (2013): Antioxidant and Antiinflammatory Activities of Curcumin on Diabetes Mellitus and its Complications. Current Pharmaceutical Design, 19(11): April, pp. 2101- 2113(13).
28. Mnafgui K, Kaanich F, Derbali A, Hamden K, Derbali F, Slama S, et al. Inhibition of key enzymes related to diabetes and hypertension by Eugenic Acid in vitro and in alloxan-induced diabetic rats. Arch Physiol Biochem. 2013; 119(5): 225–33.
29. Murakami Y., Shoji M., Hirata A., Tanaka S., Yokoe I., Fujisawa S. (2005): Dehydrodi- isoEugenic Acid, an isoEugenic Acid dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxy genase-2 expression in macrophages. Arch. Biochem. Biophys. 434: 326–332.
30. Odegaard A. O, D. R. Jacobs, O. A. Sanchez, D. C. Goff, A. P. Reiner and M. D. Gross, (2016): “Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes,” Cardiovascular Diabetology, 15(1): 1–12.
31. Ohkawa H, Ohishi N, Yagi K. (1979) Assay of lipid peroxide in animal tissue by thiobarbituric acid reaction. Ann Biochem. 95: 351–358.
32. Ojezele MO, Abatan OM. (2011). Hypoglycaemic and coronary risk index lowering effects of Bauhinia thoningii in alloxan induced diabetic rats. African Health Sciences, 11(1): 85 – 89.
33. Park S.H., Sim Y.B., Lee J.K., Kim S.M., Kang Y.J., Jung J.S., Suh H.W. (2011): The analgesic effects and mechanisms of orally administered Eugenic Acid. Arch. Pharm. Res., 34: 501–507.
34. Ping Song, Yong Wu, Jian Xu, Zhonglin Xie, Yunzhou Dong, Miao Zhang and Ming-Hui Zou (2007): Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner. Molecular Cardiology Circulation. 2007; 116: 1585-1595.
35. Pourgholami a, M. Kamalinejad b, M. Javadi a, S. Majzoob a, M. Sayyah a, (1999). Evaluation of the anticonvulsant activity of the essential oil of Eugenia caryophyllata in male mice. J Ethnopharmacol. Feb; 64(2): 167-71.
36. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. (2001). C-reactive protein, interleukin 6, andrisk of developing type 2 diabetes mellitus. JAMA, 286(3): 327-34.
37. Prasad SN, Bharath MM, Muralidhara (2016): Neurorestorative effects of Eugenic Acid, a spice bioactive: Evidence in cell model and its efficacy as an intervention molecule to abrogate brain oxidative dysfunctions in the streptozotocin diabetic rat. Neurochem Int. May; 95: 24-36.
38. Pushparaj P, Tan CH, Tan BKH 2000. Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats. J Ethnopharmacol. 72: 69–76. doi: 10.1016/S0378- 8741(00)00200-2.
39. Radhiah Shukri, Suhaila Mohamed, Noordin Mohamed Mustapha (2010): cloves protect the heart, liver and lens of diabetic rats. Food chemistry, October 2010; 122(4): 15 Pages 1116–1121.
40. Rajasekaran S, Ravi K, Savgananam K, Subramanian S. (2006): Beneficial effects of Aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes. Clin Exp Pharmacol Physiol, 33: 232-237.
41. Rajesh Rajaiah, David Y.-W. Lee, Zhongze Ma, Arthur Y. Fan, Lixing Lao, Harry HS Fong, Brian M. Berman, and Kamal D. Moudgil (2009): Huo-Luo-Xiao-Ling Dan modulates antigen-directed immune response in adjuvant-induced inflammation. J. Ethno pharmacol. May 4; 123(1): 40–44.
42. Rhodes B, Fürnrohr BG, Vyse TJ. (2011): C- reactive protein in rheumatology: biology and genetics. Nat Rev Rheumatol. 7: 282–289.
43. Richmond N., Clin Biochem, 1973; 19: 1350-1356.
44. Safwat A. Mangoura, Hala I. Madkour*, Hanan Sayed M. Abozaid, Reda S. Yousef (2015): Eugenic Acid ameliorates freund’s adjuvant induced arthritis in male rats. ejbps, 2(7): 386-392.
45. Santin J.R., Marivane Lemos, Luiz Carlos Klein- Júnior, Isabel Daufenback Machado, Philipe Costa, Ana Paula de Oliveira , Crislaine Tilia, Juliana Paula de Souza et al., (2011): Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component Eugenic Acid in different animal models. Naunyn-Schmiedeberg's Archives of Pharmacology. Feb.; 383(2): 149-158.
46. Singh P, Jayaramaiah RH, Agawane SB, Vannuruswamy G, Korwar AM, Anand A, Dhaygude VS, Shaikh ML, Joshi RS, Boppana R, Kulkarni MJ, Thulasiram HV, Giri AP. (2016): Potential Dual Role of Eugenic Acid in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights. Sci Rep. 2016; 6: 18798.
47. Stein EA; Lipids, (1987) lipoprotein and apolipoproteins, In: NW Tietz, ed, fundamental and clinical chemistry, Philadelphia: WB Saunders, 1087; 448.
48. Stephen A. Adefegha, Ganiyu Oboh, Omowunmi M Adefegha, Aline A Boligon and Margareth L Athayde (2014): Antihyperglycemic, hypolipidemic, hepatoprotective and antioxidative effects of dietary clove (Szyzgium aromaticum) bud powder in a high- fat diet/streptozotocin-induced diabetes rat model. 94(13): October Pages 2726–273.
49. Su S., Jinao Duan, Ting Chen, Xiaochen Huang, Erxin Shang, Li Yu, Kaifeng Wei, Yue Zhu, Jianming Guo, Sheng Guo, Pei Liu, Dawei Qian and Yuping Tang (2015): Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signaling pathway. Scientific Reports | 5:13668 | DOI: 10.1038/srep13668.
50. Tanaka M, Misawa E, Ito Y, Habara N, Nomaguchi K, Yamada M, Toida T, Hayasawa H, Takase M, Inagaki M, Higuchi R. 2006. Identification of five phytosterols from Aloe Vera gel as antidiabetic compounds. Biol Pharmaceut Bull, 29: 1418–1422.
51. Uttara B., A. V. Singh, P. Zamboni and R. T. Mahajan, (2009): “Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options,” Current Neuropharmacology, 7(1): 65–74.
52. Venkadeswaran K, Muralidharan AR, Annadurai T, Ruban VV, Sundararajan M, Anandhi R, et al. (2014): Antihypercholesterolemic and Antioxidative Potential of an Extract of the Plant, Piper betle and Its Active Constituent, Eugenic Acid, in Triton WR-1339- Induced Hypercholester-olemia in Experimental Rats. Evid Based Complement Alternat Med. 2014; 2014: 478973.
53. Wellen KE, Hotamisligil GS. Inflammation, stress and diabetes. J Clin Invest. 2005; 115: 1111–1119.
54. Yao Q. Pi Z, Liu S, Song F, Lin N, Liu Z. (2014): A metabonomic study of adjuvant-induced arthritis in rats using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Mol Biosyst. Oct; 10(10): 2617-25.
55. Yeh ET, Willerson JT. (2003): Coming of age of C- reactive protein: Using inflammation markers in cardiology. Circulation; 107: 370-1.
56. Yogalakshmi B., Viswanathan P., Anuradha C.V. (2010): Investigation of antioxidant, anti- inflammatory and DNA-protective properties of Eugenic Acid in thioacetamide-induced liver injury in rats. Toxicology, 268: 204–212.
2. Aggarwal B. B., S. Krishnan and S. Guha, (2011): Inflammation, Lifestyle and Chronic Diseases: The Silent Link, CRC Press, New York, NY, USA.
3. Alagona P. and T. A. Ahmad (2015): “Cardiovascular disease risk assessment and prevention: current guidelines and limitations,” Medical Clinics of North America, 99(4): 711–731.
4. Albrecht K. and U. Müller-Ladner (2010): “Side effects and management of side effects of methotrexate in rheumatoid arthritis,” Clinical and Experimental Rheumatology, 28(5): supplement 61, S95–S101.
5. Atef M Al-Attar and Talal A Zari 2007. Modulatory effect of ginger and clove oils on physiological response in streptozotocin induced diabetic rats. International journal of pharmacology, 1(3): 34-40.
6. Azza Abouelella, Hala Madkour and Mahmoud Abdel-Raheem (2011): Effect of Eugenic Acid vs Glibenclamide in Alloxan Induced Diabetic Rats Sci. Med. J., Oct.; 23(4): 35-52.
7. Caraway WT and Watts NB 1987. Carbohydrates In: Tietz NW, ed. Fundamentals of Clinical Chemistry. 3ry ed. Philadephia WB saunders, 422-447.
8. Carrasco FR, Schmidt G, Romero AL, Sartoretto JL, Caparroz- Assef SM, Bersani-Amado CA, Cuman RK. (2009): Immunomodulatory activity of Zingiber officinale ROSCOE, Salvia officinalis L. and Syzygium aromaticum L. essential oils: evidence for humor- and cell-mediated responses. J. Pharm. Pharmacol., 61: 961–967.
9. Chang YC, Chuang LM. (2010): The role of oxidative stress in the pathogenesis of type 2 diabetes: from molecular mechanism to clinical implication. Am J Transl Res., 2: 316–331.
10. Chhanda Mallick, Rajkumar Maiti And Debidas Ghosh (2006): Comparative Study onantihyperglycemic and antihyperlipidemic effects of separate and composite extract of seed of eugenia jambolana and root of musca paradisiaca in streptozotocin-induced diabetic male albino rat. Iranian Journal of Pharmacology & Therapeutics, 5: 27-33.
11. Chung C. P., Annette Oeser, Joseph F. Solus, Tebeb Gebretsadik, Ayumi Shintani, Ingrid Avalos, Tuulikki Sokka, Paolo Raggi, Theodore Pincus and C. Michael Stein (2008): Inflammation- Associated Insulin Resistance: Differential Effects in Rheumatoid Arthritis and Systemic Lupus Erythematosus Define Potential Mechanisms. Arthritis Rheum. Jul; 58(7): 2105–2112.
12. Dix TA and Aikens J, (1993): Mechanisms and biological relevance of lipid peroxidation initiation. Chem Res Toxicol, 6: 2–18.
13. Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M.( 2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci U S A.; 97: 12222–12226.
14. Festa A, D'Agostino R, Jr, Howard G, et al. (2000). Chronic subclinical inflammation as part of the insulin resistancsyndrome: The insulin resistance atherosclerosis study (iras). Circulation, 102(1): 42-7.
15. Fischer R. and O. Maier, (2015) :“Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF,” Oxidative Medicine and Cellular Longevity, 2015; Article ID 610813, 18 pages.
16. Friedewald WT, Levy RI, Fredrickson DS. 1972; Estimation of the concentration of LDL-C in plasma without use of the prepara-tive ultracentrifuge. Clin Chem. 18: 449-502.
17. Giles JT, Bartlett SJ, Andersen RE, Fontaine KR, Bathon JM. (2008): Association of body composition with disability in rheumatoid arthritis: impact of appendicular fat and lean tissue mass. Arthritis Rheum. 14: 1407–1415.
18. Glauce SB Viana, Ana Carolina C Medeiros, Ana Michelle R Lacerda, L Kalyne AM Leal, Tiago G Vale1 and F José de Abreu Matos (2004): Hypoglycemic and anti-lipemic effects of the aqueous extract from Cissus sicyoides BMC Pharmacology, 4: 9.
19. Goldberg RB(2009). Cytokine and cytokine-like inflammation markers, endothelial dysfunction and imbalanced coagulation in development of diabetesand its complications. J Clin Endocrinol Metab, 94(9): 3171-82.
20. Hotamisligil GS. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int J Obes Relat Metab Disord. 2000; 24: S23–S27.
21. Kamezaki F, Yamashita K, Kubara T, et al. (2008): Derivatives of reactive oxygen metabolites correlates with high-sensitivity C-reactive protein. J. Atheroscler Thromb. 15: 206–212.
22. Karuppasamy V., Arumugam R. M., Thangaraj A., Vasanthakumar V. R., Mahalingam S., Ramalingam A., Philip A. Thomas and Pitchairaj Geraldine (2014): Antihyper-cholesterolemic and Antioxidative Potential of an Extract of the Plant, Piper betle and Its Active Constituent, Eugenic Acid, in Triton WR-1339-Induced Hypercholesterolemia in Experimental Rats. Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2014, Article ID 478973, 11 pages.
23. Khazaei M, Roshankhah S, Ghorbani R, Chobsaz F. (2011) Sildenafil effect on nitric oxide secretion by normal human endometrial epithelial cells cultured in vitro. Int J Fertil Steril. 5: 142–147.
24. Kokil G. R., R. N. Veedu, G. A. Ramm, J. B. Prins and H. S. Parekh (2015): “Type 2 diabetes mellitus: limitations of conventional therapies and intervention with nucleic acid-based therapeutics,” Chemical Reviews, 115(11): 4719–4743.
25. Lüscher T. F., (2015): “Ageing, inflammation and oxidative stress: final common pathways of cardiovascular disease,” European Heart Journal, 36(48): 3381–3383.
26. McInnes I. B. and G. Schett, (2011): “The pathogenesis of rheumatoid arthritis,” The New England Journal of Medicine, 2011; 365(23): 2205–2219.
27. Meng, Bo; Li, Jun; Cao, Hong (2013): Antioxidant and Antiinflammatory Activities of Curcumin on Diabetes Mellitus and its Complications. Current Pharmaceutical Design, 19(11): April, pp. 2101- 2113(13).
28. Mnafgui K, Kaanich F, Derbali A, Hamden K, Derbali F, Slama S, et al. Inhibition of key enzymes related to diabetes and hypertension by Eugenic Acid in vitro and in alloxan-induced diabetic rats. Arch Physiol Biochem. 2013; 119(5): 225–33.
29. Murakami Y., Shoji M., Hirata A., Tanaka S., Yokoe I., Fujisawa S. (2005): Dehydrodi- isoEugenic Acid, an isoEugenic Acid dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxy genase-2 expression in macrophages. Arch. Biochem. Biophys. 434: 326–332.
30. Odegaard A. O, D. R. Jacobs, O. A. Sanchez, D. C. Goff, A. P. Reiner and M. D. Gross, (2016): “Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes,” Cardiovascular Diabetology, 15(1): 1–12.
31. Ohkawa H, Ohishi N, Yagi K. (1979) Assay of lipid peroxide in animal tissue by thiobarbituric acid reaction. Ann Biochem. 95: 351–358.
32. Ojezele MO, Abatan OM. (2011). Hypoglycaemic and coronary risk index lowering effects of Bauhinia thoningii in alloxan induced diabetic rats. African Health Sciences, 11(1): 85 – 89.
33. Park S.H., Sim Y.B., Lee J.K., Kim S.M., Kang Y.J., Jung J.S., Suh H.W. (2011): The analgesic effects and mechanisms of orally administered Eugenic Acid. Arch. Pharm. Res., 34: 501–507.
34. Ping Song, Yong Wu, Jian Xu, Zhonglin Xie, Yunzhou Dong, Miao Zhang and Ming-Hui Zou (2007): Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner. Molecular Cardiology Circulation. 2007; 116: 1585-1595.
35. Pourgholami a, M. Kamalinejad b, M. Javadi a, S. Majzoob a, M. Sayyah a, (1999). Evaluation of the anticonvulsant activity of the essential oil of Eugenia caryophyllata in male mice. J Ethnopharmacol. Feb; 64(2): 167-71.
36. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. (2001). C-reactive protein, interleukin 6, andrisk of developing type 2 diabetes mellitus. JAMA, 286(3): 327-34.
37. Prasad SN, Bharath MM, Muralidhara (2016): Neurorestorative effects of Eugenic Acid, a spice bioactive: Evidence in cell model and its efficacy as an intervention molecule to abrogate brain oxidative dysfunctions in the streptozotocin diabetic rat. Neurochem Int. May; 95: 24-36.
38. Pushparaj P, Tan CH, Tan BKH 2000. Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats. J Ethnopharmacol. 72: 69–76. doi: 10.1016/S0378- 8741(00)00200-2.
39. Radhiah Shukri, Suhaila Mohamed, Noordin Mohamed Mustapha (2010): cloves protect the heart, liver and lens of diabetic rats. Food chemistry, October 2010; 122(4): 15 Pages 1116–1121.
40. Rajasekaran S, Ravi K, Savgananam K, Subramanian S. (2006): Beneficial effects of Aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes. Clin Exp Pharmacol Physiol, 33: 232-237.
41. Rajesh Rajaiah, David Y.-W. Lee, Zhongze Ma, Arthur Y. Fan, Lixing Lao, Harry HS Fong, Brian M. Berman, and Kamal D. Moudgil (2009): Huo-Luo-Xiao-Ling Dan modulates antigen-directed immune response in adjuvant-induced inflammation. J. Ethno pharmacol. May 4; 123(1): 40–44.
42. Rhodes B, Fürnrohr BG, Vyse TJ. (2011): C- reactive protein in rheumatology: biology and genetics. Nat Rev Rheumatol. 7: 282–289.
43. Richmond N., Clin Biochem, 1973; 19: 1350-1356.
44. Safwat A. Mangoura, Hala I. Madkour*, Hanan Sayed M. Abozaid, Reda S. Yousef (2015): Eugenic Acid ameliorates freund’s adjuvant induced arthritis in male rats. ejbps, 2(7): 386-392.
45. Santin J.R., Marivane Lemos, Luiz Carlos Klein- Júnior, Isabel Daufenback Machado, Philipe Costa, Ana Paula de Oliveira , Crislaine Tilia, Juliana Paula de Souza et al., (2011): Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component Eugenic Acid in different animal models. Naunyn-Schmiedeberg's Archives of Pharmacology. Feb.; 383(2): 149-158.
46. Singh P, Jayaramaiah RH, Agawane SB, Vannuruswamy G, Korwar AM, Anand A, Dhaygude VS, Shaikh ML, Joshi RS, Boppana R, Kulkarni MJ, Thulasiram HV, Giri AP. (2016): Potential Dual Role of Eugenic Acid in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights. Sci Rep. 2016; 6: 18798.
47. Stein EA; Lipids, (1987) lipoprotein and apolipoproteins, In: NW Tietz, ed, fundamental and clinical chemistry, Philadelphia: WB Saunders, 1087; 448.
48. Stephen A. Adefegha, Ganiyu Oboh, Omowunmi M Adefegha, Aline A Boligon and Margareth L Athayde (2014): Antihyperglycemic, hypolipidemic, hepatoprotective and antioxidative effects of dietary clove (Szyzgium aromaticum) bud powder in a high- fat diet/streptozotocin-induced diabetes rat model. 94(13): October Pages 2726–273.
49. Su S., Jinao Duan, Ting Chen, Xiaochen Huang, Erxin Shang, Li Yu, Kaifeng Wei, Yue Zhu, Jianming Guo, Sheng Guo, Pei Liu, Dawei Qian and Yuping Tang (2015): Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signaling pathway. Scientific Reports | 5:13668 | DOI: 10.1038/srep13668.
50. Tanaka M, Misawa E, Ito Y, Habara N, Nomaguchi K, Yamada M, Toida T, Hayasawa H, Takase M, Inagaki M, Higuchi R. 2006. Identification of five phytosterols from Aloe Vera gel as antidiabetic compounds. Biol Pharmaceut Bull, 29: 1418–1422.
51. Uttara B., A. V. Singh, P. Zamboni and R. T. Mahajan, (2009): “Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options,” Current Neuropharmacology, 7(1): 65–74.
52. Venkadeswaran K, Muralidharan AR, Annadurai T, Ruban VV, Sundararajan M, Anandhi R, et al. (2014): Antihypercholesterolemic and Antioxidative Potential of an Extract of the Plant, Piper betle and Its Active Constituent, Eugenic Acid, in Triton WR-1339- Induced Hypercholester-olemia in Experimental Rats. Evid Based Complement Alternat Med. 2014; 2014: 478973.
53. Wellen KE, Hotamisligil GS. Inflammation, stress and diabetes. J Clin Invest. 2005; 115: 1111–1119.
54. Yao Q. Pi Z, Liu S, Song F, Lin N, Liu Z. (2014): A metabonomic study of adjuvant-induced arthritis in rats using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Mol Biosyst. Oct; 10(10): 2617-25.
55. Yeh ET, Willerson JT. (2003): Coming of age of C- reactive protein: Using inflammation markers in cardiology. Circulation; 107: 370-1.
56. Yogalakshmi B., Viswanathan P., Anuradha C.V. (2010): Investigation of antioxidant, anti- inflammatory and DNA-protective properties of Eugenic Acid in thioacetamide-induced liver injury in rats. Toxicology, 268: 204–212.
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Dr. Rajesh R. Patil, Dr. Gaurav Kumar Sharma, Mr. Rajesh Kumar Sinha, & Mrs. Vineeta Chourasia. (2022). STUDY OF THE EFFECTS OF EUGENIC ACID IN ARTHRITIS AND DIABETES MELLITUS IN EXPERIMENTAL RATS. Journal of Population Therapeutics and Clinical Pharmacology, 29(04), 901–912. https://doi.org/10.53555/jptcp.v29i04.3446
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Author Biographies
Dr. Rajesh R. Patil
Associate Professor, Sinhgad Institute of Pharmaceutical Sciences, Lonavala Pune (Maharashtra)
Dr. Gaurav Kumar Sharma
Associate Professor & H.O.D., Faculty of Pharmaceutical Sciences, Mewar University Chittorgarh (Rajasthan)
Mr. Rajesh Kumar Sinha
Associate Professor & H.O.D., Late Pooran Ramprakash Dixit College of Pharmacy, Gahrauli Hamirpur (U.P.)
Mrs. Vineeta Chourasia
Associate Professor, Late Pooran Ramprakash Dixit College of Pharmacy, Gahrauli Hamirpur (U.P.)