Open Access
Review (Published online: 15-05-2018)
9. The crucial roles of inflammatory mediators in inflammation: A review
L. A. Abdulkhaleq, M. A. Assi, Rasedee Abdullah, M. Zamri-Saad, Y. H. Taufiq-Yap, and M. N. M. Hezmee
Veterinary World, 11(5): 627-635

L. A. Abdulkhaleq: Department of Pathology and Poultry Diseases, Faculty of Veterinary Medicine, Baghdad University, Baghdad, Iraq; Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Malaysia.
M. A. Assi: Department of Community Health, College of Health and Medical Techniques, Al-Furat Al-Awsat Technical University, Iraq; Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Malaysia.
Rasedee Abdullah: Department of Veterinary Laboratory Diagnostics, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Malaysia.
M. Zamri-Saad: Department of Veterinary Laboratory Diagnostics, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Malaysia.
Y. H. Taufiq-Yap: Department of Chemistry, Faculty of Sains, Universiti Putra Malaysia, Malaysia.
M. N. M. Hezmee: Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Malaysia.

doi: 10.14202/vetworld.2018.627-635

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Article history: Received: 24-01-2018, Accepted: 10-04-2018, Published online: 15-05-2018

Corresponding author: Rasedee Abdullah


Citation: Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq Yap YH, Hezmee MNM (2018) The crucial roles of inflammatory mediators in inflammation: A review, Veterinary World, 11(5): 627-635.

The inflammatory response is a crucial aspect of the tissues' responses to deleterious inflammogens. This complex response involves leukocytes cells such as macrophages, neutrophils, and lymphocytes, also known as inflammatory cells. In response to the inflammatory process, these cells release specialized substances which include vasoactive amines and peptides, eicosanoids, proinflammatory cytokines, and acute-phase proteins, which mediate the inflammatory process by preventing further tissue damage and ultimately resulting in healing and restoration of tissue function. This review discusses the role of the inflammatory cells as well as their by-products in the mediation of inflammatory process. A brief insight into the role of natural anti-inflammatory agents is also discussed. The significance of this study is to explore further and understand the potential mechanism of inflammatory processes to take full advantage of vast and advanced anti-inflammatory therapies. This review aimed to reemphasize the importance on the knowledge of inflammatory processes with the addition of newest and current issues pertaining to this phenomenon.

Keywords: chemokines, cytokines, inflammatory mediators, inflammatory response.


1. Isailovic, N., Daigo, K., Mantovani, A. and Selmi, C. (2015) Interleukin-17 and innate immunity in infections and chronic inflammation. J. Autoimmun., 60: 1-11. [Crossref] [PubMed]

2. Todd, I., Spickett, G. and Fairclough, L. (2015), Lecture Notes: Immunology. John Wiley & Sons, New York.

3. Serhan, C.N., Dalli, J., Colas, R.A., Winkler, J.W. and Chiang, N. (2015) Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome. Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids, 1851: 397-413. [Crossref] [PubMed] [PMC]

4. Uttara, B., Singh, A.V., Zamboni, P. and Mahajan, R.T. (2009) Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 7: 65-74. [Crossref]

5. Huether, S.E. and McCance, K.L. (2015) Understanding Pathophysiology. Elsevier Health Sciences, Forlag.

6. Anwikar, S. and Bhitre, M. (2010) Study of the synergistic anti-inflammatory activity of Solanum xanthocarpum Schrader and Wendl and Cassia fistula Linn. Int. J. Ayurveda Res., 1(3): 167. [Crossref] [PubMed] [PMC]

7. Nguyen, T.T. (2012) Systems Biology Approaches to Corticosteroid Pharmacogenomics and Systemic Inflammation (Doctoral dissertation, Rutgers University-Graduate School-New Brunswick).

8. Porter, S. (2013) Tidy's Physiotherapy. Elsevier Health Sciences, Amsterdam.

9. Goljan, E.F. (2014) Rapid Review Pathology: With Student Consult Online Access. Elsevier Health Sciences, Philadelphia, PA.

10. Kumar, V., Abbas, A.K. and Aster, J.C. (2013) Robbins Basic Pathology. Elsevier Health Sciences, Philadephia, United States.

11. Kumar, V., Abbas, A.K., Aster, J.C. and Robbins, S.L. (2012) Inflammation and repair. Robbins Basic Pathology. Saunders, Philadelphia, London. p29-74.

12. Bitencourt, C.S., Bessi, V.L., Huynh, D.N., Menard, L., Lefebvre, J.S., Levesque, T. and Marleau, S. (2013) Cooperative role of endogenous leucotrienes and platelet-activating factor in ischaemia-reperfusion-mediated tissue injury. J. Cell Mol. Med., 17: 1554-1565. [Crossref] [PubMed] [PMC]

13. Curcic, S., Holzer, M., Frei, R., Pasterk, L., Schicho, R., Heinemann, A. and Marsche, G. (2015) Neutrophil effector responses are suppressed by secretory phospholipase A 2 modified HDL. Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids, 1851: 184-193. [Crossref] [PubMed] [PMC]

14. McDonald, B. and Kubes, P. (2012) Leukocyte Trafficking. Inflammatory Diseases of Blood Vessels. Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Canada. p28. [Crossref]

15. Nourshargh, S., Hordijk, P.L. and Sixt, M. (2010) Breaching multiple barriers: Leukocyte motility through venular walls and the interstitium. Nat. Rev. Mol. Cell Biol., 11: 366-378. [Crossref] [PubMed]

16. Springer, T.A., Anderson, D.C., Rosenthal, A.S. and Rothlein, R., editors. (2012) Leukocyte Adhesion Molecules: Proceedings of the First International Conference on: Structure, Function and Regulation of Molecules Involved in Leukocyte Adhesion, Held in Titisee, West Germany, September 28-October 2, 1988. Springer Science and Business Media.

17. Ogra, P.L., Mestecky, J., Lamm, M.E., Strober, W., McGhee, J.R. and Bienenstock, J. (2012) Handbook of Mucosal Immunology. Academic Press, San Diego.

18. Sies, H., editor. (2013), Oxidative Stress. Elsevier, London.

19. Gleeson, M., Bishop, N.C., Stensel, D.J., Lindley, M.R., Mastana, S.S. and Nimmo, M.A. (2011) The anti-inflammatory effects of exercise: Mechanisms and implications for the prevention and treatment of disease. Nat. Rev. Immunol., 11: 607. [Crossref] [PubMed]

20. Murakami, M. (2012) The Molecular Mechanisms of Chronic Inflammation Development. Frontiers E-Books, Tokyo.

21. Ogrunc, M., Di Micco, R., Liontos, M., Bombardelli, L., Mione, M., Fumagalli, M., and di Fagagna, F.D.A. (2014) Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation. Cell Death Differ., 21: 998-1012. [Crossref] [PubMed] [PMC]

22. Kong, A.N.T. (2013) Inflammation, Oxidative Stress, and Cancer: Dietary Approaches for Cancer Prevention. CRC Press, London, New York. [Crossref]

23. Niederhuber, J.E. (2014) Abeloff's Clinical Oncology. Churchill Livingstone Elsevier, Philadelphia, PA.

24. Halliwell, B. and Gutteridge, J.M. (2015) Free Radicals in Biology and Medicine. Oxford University Press, USA. [Crossref]

25. Gilfillan, A.M. and Metcalfe, D., editors. (2011) Mast Cell Biology: Contemporary and Emerging Topics. Vol. 716. Springer Science and Business Media, New York. [Crossref] [PubMed] [PMC]

26. Platko, S. (2015) Mast Cells Shape Early Life Programming of Social Behavior (Doctoral Dissertation, The Ohio State University).

27. Weissmann, G., editor. (2013) Mediators of Inflammation. Springer Science and Business Media, New York.

28. Baumann, M.H., Williams, Z., Zolkowska, D. and Rothman, R.B. (2011) Serotonin (5-HT) precursor loading with 5-hydroxyl-tryptophan (5-HTP) reduces locomotor activation produced by (+)-amphetamine in the rat. Drug Alcohol. Depend., 114: 147-152. [PubMed]

29. Raskin, R. E., & Meyer, D. (2015) Canine and Feline Cytology: A Color Atlas and Interpretation Guide. Elsevier Health Sciences, Philadelphia, PA.

30. Hsieh, F.H. (2014) Primer to the immune response. Ann Allergy, Asthma Immunol., 113: 333. [Crossref]

31. Mak, T.W., Saunders, M.E. and Jett, B.D. (2013) Primer to the Immune Response. Newnes.

32. Piomelli, D. (2013) Arachidonic Acid in Cell Signaling. Springer Science and Business Media, New York.

33. Lieberman, M., Marks, A.D. and Peet, A. (2013), Marks basic medical biochemistry. Wolters Kluwer Health/Lippincott Williams & Wilkins.

34. Drazen, J., editor. (2016) Five-Lipoxygenase Products in Asthma. CRC Press.

35. Inoki, R., Kudo, T. and Olgart, L.M. (2012), Dynamic Aspects of Dental Pulp: Molecular Biology, Pharmacology and Pathophysiology. Springer Science and Business Media.

36. Lands, W.E., editor. (2012) Biochemistry of Arachidonic Acid Metabolism. Vol. 1. Springer Science and Business Media.

37. Nigam, S. and Pace-Asciak, C.R., editors. (2012) Lipoxygenases and their Metabolites: Biological Functions. Vol. 447. Springer Science and Business Media.

38. Bailey, J.M., editor. (2013) Prostaglandins, Leukotrienes, Lipoxins, and PAF: Mechanism of Action, Molecular Biology, and Clinical Applications. Springer Science and Business Media.

39. Zhong, B., Shen, H., Sun, X., Wang, H., Zhang, Y. and Sun, Z. (2012) Additive effects of ulinastatin and docetaxel on growth of breast cancer xenograft in nude mice and expression of PGE2, IL-10, and IL-2 in primary breast cancer cells. Cancer Biother. Radiopharm., 27: 252-258. [Crossref]

40. Engelhardt, N. (2014) Synthese und Charakterisierung von Oberflachen-Funktionalisierten Polymeren Nanopartikeln auf Poly (2-oxazolin)-Basis (Doctoral Dissertation).

41. Honn, K.V., Marnett, L.J., Nigam, S., Jones, R.L. and Wong, P.Y., editors. (2013) Eicosanoids and other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury. Vol. 3. Springer Science and Business Media, New York.

42. Nigam, S., Honn, K.V., Marnett, L.J. and Walden, T. Jr., editors. (2012) Eicosanoids and other Bioactive Lipids in Cancer, Inflammation and Radiation Injury: Proceedings of the 2nd International Conference September 17-21, 1991 Berlin, FRG. Vol. 71. Springer Science and Business Media.

43. Wang, D. and DuBois, R.N. (2010) The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene, 29: 781-788. [Crossref] [PubMed] [PMC]

44. Andreucci, V.E., editor. (2012), Acute Renal Failure: Pathophysiology, Prevention, and Treatment. Springer Science and Business Media, New York.

45. Dunn, M., editor. (2013), Prostaglandins and the Kidney: Biochemistry, Physiology, Pharmacology, and Clinical Applications. Springer Science and Business Media, Holder.

46. Bazan, N.G., Murphy, M.G. and Toffano, G., editors. (2012), Neurobiology of Essential Fatty Acids. Vol. 318. Springer Science and Business Media, Australia.

47. Johnson, M.H. (2012), Essential Reproduction. John Wiley & Sons, Chichester, West Sussex.

48. Newton, R.F. and Roberts, S.M., editors. (2016) Prostaglandins and Thromboxanes: Butterworths Monographs in Chemistry. Butterworth-Heinemann, London, Boston.

49. Kosaka, M., Sugahara, T., Schmidt, K.L. and Simon, E., editors. (2013) Thermotherapy for Neoplasia, Inflammation, and Pain. Springer Science and Business Media, Tokyo.

50. Jordan, J.M. (2008) Osteoarthritis: Diagnosis and Medical/Surgical Management. JAMA, 299: 1840-1841. [Crossref]

51. Marks, F. and Furstenberger, G., editors. (2008) Prostaglandins, Leukotrienes, and Other Eicosanoids: From Biogenesis to Clinical Application. John Wiley & Sons, New York.

52. Seta, F. and Bachschmid, M. (2012) Cyclooxygenase Pathway of the Arachidonate Cascade. eLS. Francesca Seta, Boston University School of Medicine, Boston, Massachusetts, USA.

53. Rubin, E. and Reisner, H.M., editors. (2009) Essentials of Rubin's Pathology. Lippincott Williams & Wilkins, Philadelphia, United States.

54. Heegaard, P.M., Dedieu, L., Johnson, N., Le Potier, M.F., Mockey, M., Mutinelli, F. and Sorensen, N.S. (2011) Adjuvants and delivery systems in veterinary vaccinology: Current state and future developments. Arch. Virol., 156: 183-202. [Crossref]

55. Guo, B., Lager, K.M., Henningson, J.N., Miller, L.C., Schlink, S.N., Kappes, M.A. and Faaberg, K.S. (2013) Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. Virology, 435: 372-384. [Crossref] [PubMed]

56. Marza, A.D., Abdullah, F.F.J., Ahmed, I.M., Chung, E.L.T., Ibrahim, H.H., Zamri-Saad, M. and Lila, M.A.M. (2015) Involvement of nervous system in cattle and buffaloes due to Pasteurella multocida B: 2 infection: A review of clinicopathological and pathophysiological changes. J. Adv. Vet. Anim. Res., 2: 252-262. [Crossref]

57. Moreland, L.W., editor. (2004) Rheumatology and Immunology Therapy: A to Z Essentials. Springer Science and Business Media, Goed.

58. Horadagoda, N.U., Hodgson, J.C., Moon, G.M., Wijewardana, T.G. and Eckersall, P.D. (2002) Development of a clinical syndrome resembling haemorrhagic septicaemia in the buffalo following intravenous inoculation of Pasteurella multocida serotype B: 2 endotoxin and the role of tumour necrosis factor-a. Res. Vet. Sci., 72: 194-200. [Crossref]

59. Opriessnig, T., Gimenez-Lirola, L.G. and Halbur, P.G. (2011) Polymicrobial respiratory disease in pigs. Anim. Health Res. Rev., 12: 133-148. [Crossref] [PubMed]

60. Shivachandra, S.B., Viswas, K.N. and Kumar, A.A. (2011) A review of hemorrhagic septicemia in cattle and buffalo. Anim. Health Res. Rev., 12: 67-82. [Crossref] [PubMed]

61. Praveena, P.E., Periasamy, S., Kumar, A.A. and Singh, N. (2010) Cytokine profiles, apoptosis and pathology of experimental Pasteurella multocida serotype A1 infection in mice. Res. Vet. Sci., 89: 332-339. [Crossref] [PubMed]

62. Jiang, D., Liang, J. and Noble, P.W. (2011) Hyaluronan as an immune regulator in human diseases. Physiol. Rev., 91: 221-264. [Crossref] [PubMed] [PMC]

63. Wilkie, I.W., Harper, M., Boyce, J.D. and Adler, B. (2012) Pasteurella multocida: Diseases and pathogenesis. In: Pasteurella multocida. Springer Berlin Heidelberg, Berlin, Heidelberg. p1-22. [Crossref]

64. Gebhardt, C., Hirschberger, J., Rau, S., Arndt, G., Krainer, K., Schweigert, F.J. and Kohn, B. (2009) Use of C-reactive protein to predict outcome in dogs with systemic inflammatory response syndrome or sepsis. J. Vet. Emerg. Crit. Care, 19: 450-458. [Crossref] [PubMed]

65. Mackiewicz, A., Kushner, I. and Baumann, H. (1993) Acute Phase Proteins Molecular Biology, Biochemistry, and Clinical Applications. CRC Press, Boca Raton.

66. Pepys, M.B., editor. (2012) Acute Phase Proteins in the Acute Phase Response. Springer Science and Business Media, New York.

67. Lotze, M.T. and Thomson, A.W., editors. (2011) Measuring Immunity: Basic Science and Clinical Practice. Academic Press, Amsterdam.

68. Biswas, S.K. and Mantovani, A., editors. (2014) Macrophages: Biology and Role in the Pathology of Diseases. Springer, New York.

69. Cocco, E., Bellone, S., El-Sahwi, K., Cargnelutti, M., Buza, N., Tavassoli, F.A. and Santin, A.D. (2010) Serum amyloid A. Cancer, 116: 843-851. [Crossref] [PubMed] [PMC]

70. Du Clos, T.W. and Mold, C. (2004) C-reactive protein. Immunol. Res., 30: 261-277. [Crossref]

71. Nishimoto, N., Yoshizaki, K., Tagoh, H., Monden, M., Kishimoto, S., Hirano, T. and Kishimoto, T. (1989) Elevation of serum interleukin 6 prior to acute phase proteins on the inflammation by surgical operation. Clin. Immunol. Immunopathol., 50: 399-401. [Crossref]

72. Cheng, Y., Li, M., Wang, S., Peng, H., Reid, S., Ni, N. and Wang, B. (2010) Carbohydrate biomarkers for future disease detection and treatment. Sci. China Chem., 53: 3-20. [Crossref]

73. Khaleel, M.M., Abdullah, F.F.J., Adamu, L., Osman, A.Y., Haron, A.W., Saad, M.Z. and Omar, A.R. (2013) Acute phase protein responses in mice infected with river water contaminated by Pasteurella multocida type B: 2. Am J. Anim. Vet. Sci., 8: 159. [Crossref]

74. Lacy, P. (2015) Editorial: Secretion of cytokines and chemokines by innate immune cells. Front Immunol., 6: 190. [Crossref] [PubMed] [PMC]

75. Nelson, D.S. (2014) Immunobiology of the Macrophage Ed. Academic Press, New York.

76. Gordon, S. and Martinez, F.O. (2010) Alternative activation of macrophages: Mechanism and functions. Immunity, 32: 593-604. [Crossref] [PubMed]

77. Murray, P.J. and Wynn, T.A. (2011) Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol., 11: 723-737. [Crossref] [PubMed] [PMC]

78. Wynn, T.A., Chawla, A. and Pollard, J.W. (2013) Macrophage biology in development, homeostasis and disease. Nature, 496: 445-455. [Crossref] [PubMed]

79. Winkler, I.G., Sims, N.A., Pettit, A.R., Barbier, V., Nowlan, B., Helwani, F. and Levesque, J.P. (2010) Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood, 116: 4815-4828. [Crossref] [PubMed]

80. Abbas, A.K., Lichtman, A.H. and Pillai, S. (2014) Basic Immunology: Functions and Disorders of the Immune System. Elsevier Health Sciences, Philadelphia, PA.

81. Murphy, K. and Weaver, C. (2016), Janeway's Immunobiology. Garland Science, New York.

82. Delavary, B.M., van der Veer, W.M., van Egmond, M., Niessen, F.B, and Beelen, R.H. (2011) Macrophages in skin injury and repair. Immunobiology, 216: 753-762. [Crossref] [PubMed]

83. Smith, P.D., MacDonald, T.T. and Blumberg, R.S., editors. (2013) Principles of Mucosal Immunology. Garland Science, New York.

84. Rabson, A., Roitt, I.M. and Delves, P.J. (2005) Really Essential Medical Immunology. Blackwell Pub, Malden, Mass.

85. Kao, J.Y. (2013) Principles of mucosal immunology. Gastroenterology, 145: 483. [Crossref]

86. Felippe, M.J.B., editor. (2015) Equine Clinical Immunology. John Wiley & Sons, Ames, Iowa, Chichester, West Sussex, UK.

87. Graves, D.B. (2012) The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology. J. Phys. D: Appl. Phys., 45: 263001. [Crossref]

88. Zanoni, I., Ostuni, R., Marek, L.R., Barresi, S., Barbalat, R., Barton, G.M. and Kagan, J.C. (2011) CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell, 147: 868-880. [Crossref] [PubMed] [PMC]

89. O'Connell, R.M., Taganov, K.D., Boldin, M.P., Cheng, G. and Baltimore, D. (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc. Natl. Acad. Sci., 104: 1604-1609. [Crossref] [PubMed] [PMC]

90. del Fresno, C., Garcia-Rio, F., Gomez-Pi-a, V., Soares-Schanoski, A., Fernandez-Ruiz, I., Jurado, T. and Prados, C. (2009) Potent phagocytic activity with impaired antigen presentation identifying lipopolysaccharide-tolerant human monocytes: Demonstration in isolated monocytes from cystic fibrosis patients. J. Immunol., 182: 6494-6507. [Crossref] [PubMed]

91. Khan, F.H. (2009) The Elements of Immunology. Pearson Education India, New Delhi.

92. DeFranco, A.L., Locksley, R.M. and Robertson, M. (2007) Immunity: The Immune Response in Infectious and Inflammatory Disease. New Science Press, London.

93. van Furth, R., editor. (2012), Mononuclear Phagocytes: Characteristics, Physiology and Function. Springer Science and Business Media, New York.

94. Vanhaesebroeck, B., Vogt, P.K. and Rommel, C. (2010) PI3K: From the bench to the clinic and back. In: Phosphoinositide 3-Kinase in Health and Disease. Springer, Berlin Heidelberg. p1-19. [Crossref] [PubMed] [PMC]

95. Netea, M.G. and Mantovani, A. (2014) Adaptive characteristics of innate immune responses in macrophages. In: Macrophages: Biology and Role in the Pathology of Diseases. Springer, New York. p339-348. [Crossref]

96. Liener, I., editor. (2012) The Lectins: Properties, Functions, and Applications in Biology and Medicine. Elsevier, California, USA.

97. Male, D., Brostoff, J., Roth, D. and Roitt, I. (2012) Immunology: With STUDENT CONSULT Online Access. Elsevier Health Sciences, Philadelphia, United States.

98. Kumar, H., Kawai, T. and Akira, S. (2011) Pathogen recognition by the innate immune system. Int. Rev. Immunol., 30: 16-34. [Crossref] [PubMed]

99. Kawai, T. and Akira, S. (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol., 11: 373-384. [Crossref]

100. Kawai, T. and Akira, S. (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity, 34: 637-650. [Crossref] [PubMed]

101. van Furth, R., editor. (2013) Mononuclear Phagocytes: Functional Aspects. Springer Science and Business Media, New York.

102. Forman, H.J., Fukuto, J.M. and Torres, M. (2004) Redox signaling: Thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers. Am. J. Physiol. Cell Physiol., 287: C246-C256. [Crossref]

103. Phalitakul, S., Okada, M., Hara, Y. and Yamawaki, H. (2011) Vaspin prevents TNF-a-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-?B and PKC? activation in cultured rat vascular smooth muscle cells. Pharmacol. Res., 64: 493-500. [Crossref]

104. Craig, C.R. and Stitzel, R.E., editors. (2004) Modern Pharmacology with Clinical Applications. Lippincott Williams & Wilkins, Philadelphia, PA.

105. Burchum, J. and Rosenthal, L. (2014) Lehne's Pharmacology for Nursing Care. Elsevier Health Sciences, St. Louis.

106. Izuhara, K., Holgate, S.T. and Wills-Karp, M., editors. (2011) Inflammation and Allergy Drug Design. John Wiley & Sons, Chichester. [Crossref]

107. Vane, J.R., Botting, J. and Botting, R.M., editors. (2012) Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors. Springer Science and Business Media, New York, United States.

108. Van Arman, C.G. (2013) Anti-inflammatory Drugs. Vol. 50. Springer Science and Business Media, Dordrecht, The Netherlands.

109. Levin, J.I. and Laufer, S., editors. (2012) Anti-inflammatory Drug Discovery (No. 26). Royal Society of Chemistry, London. [Crossref]

110. Dhami, N. (2013) Trends in pharmacognosy: A modern science of natural medicines. J. Herb. Med., 3: 123-131. [Crossref]

111. Benzie, I.F. and Wachtel-Galor, S., editors. (2011) Herbal Medicine: Biomolecular and Clinical Aspects. CRC Press, Boca Raton (FL).

112. Wee, J.J., Mee, P.K. and Chung, A.S. (2011) Herbal Medicine: Biomolecular and Clinical Aspects. CRC Press, Boca Raton (FL).

113. Zhang, A.L., Xue, C.C. and Fong, H.H. (2011) Integration of Herbal Medicine into Evidence-Based Clinical Practice. Taylor & Francis Group, LLC, Boca Raton FL.

114. Wachtel-Galor, S. and Benzie, I.F. (2012) Herbal Medicine: An Introduction to its History, Usage, Regulation, Current Trends, and Research Needs. CRC Press, Boca Raton, Fla, USA.

115. Li, W., Wei, H., Li, H., Gao, J., Feng, S.S. and Guo, Y. (2014) Cancer nanoimmunotherapy using advanced pharmaceutical nanotechnology. Nanomedicine, 9: 2587-2605. [Crossref] [PubMed]

116. Maity, P., Hansda, D., Bandyopadhyay, U. and Mishra, D.K. (2009) Biological activities of crude extracts and chemical constituents of Bael, Aegle marmelos (L.) Corr. Indian J. Exp. Biol., 47: 849-861. [PubMed]

117. Cseke, L.J., Kirakosyan, A., Kaufman, P.B., Warber, S., Duke, J.A. and Brielmann, H.L. (2016) Natural Products from Plants. CRC Press, Boca. Raton, Florida.

118. Ramzan, I., editor. (2015) Phytotherapies: Efficacy, Safety, and Regulation. John Wiley & Sons, Hoboken, NJ. [Crossref]

119. Dias, D.A., Urban, S. and Roessner, U. (2012) A historical overview of natural products in drug discovery. Metabolites, 2: 303-336. [Crossref] [PubMed] [PMC]

120. Saad, B. and Said, O. (2011) Greco-Arab and Islamic Herbal Medicine: Traditional System, Ethics, Safety, Efficacy, and Regulatory Issues. John Wiley & Sons, Hoboken. [Crossref]

121. Qi, Z. and Kelley, E. (2014) The WHO traditional medicine strategy 2014-2023: A perspective. Science, 346: S5-S6.

122. World Health Organization. (2014). WHO Traditional Medicine Strategy 2014-2023. World Health Organization, Geneva; 2013.

123. Murray, M.T. and Pizzorno, J.E. (2013) Textbook of Natural Medicine. Elsevier, St Louis.

124. Khan, I.A. and Abourashed, E.A. (2011) Leung's Encyclopedia of Common Natural Ingredients: Used in Food, Drugs and Cosmetics. John Wiley & Sons, New York.

125. Subramoniam, A. (2014) Present scenario, challenges and future perspectives in plant-based medicine development. Ann. Phytomed., 3: 31-36.

126. Adams, J., Andrews, G., Barnes, J., Broom, A. and Magin, P., editors. (2012) Traditional, Complementary and Integrative Medicine: An International Reader. Palgrave Macmillan, London.

127. Kotsirilos, V., Vitetta, L. and Sali, A. (2011) A Guide to Evidence-Based Integrative and Complementary Medicine. Elsevier. Australia.