In vitro and In vivo Models for Anti-inflammation: An Evaluative Review
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Keywords

Anti-inflammatory activity
In vitro models
In vivo models
Inflammation
Prostaglandins
Arthritis

Abstract

Anti-inflammatory activity study involves developing a model that mimics, or provokes the production or release of, the biochemical mediators of inflammation, and monitoring the response of these biochemicals to the test drugs. This report constitutes an updated review of the in vitro and in vivo study models for assessing anti-inflammatory activity in plant extracts and synthetic drugs. The materials, instrumentation, and methods involved, as well as the mechanism of anti-inflammatory activity tested in each model, are extensively described. The merits and limitations of each method have also been discussed. A comparative assessment of the in vivo animal models vis-à-vis, the in vitro enzyme models have been made to assist scientists and researchers in the choice of assay method in terms of sensitivity, reliability, duration of test, ethical, and cost considerations.

References

da Silva, D.M.; Langer, H.; Graf, T. Inflammatory and Molecular Pathways in Heart Failure-Ischemia, HFpEF and Transthyretin Cardiac Amyloidosis. Int. J. Mol. Sci., 2019, 20(9), E2322.

Zhang, X.; Wu, X.; Hu, Q.; Wu, J.; Wang, G.; Hong, Z.; Ren, J. Lab for Trauma and Surgical Infections. Mitochondrial DNA in Liver Inflammation and Oxidative Stress. Life Sci., 2019, 223, 116464.

Fritsch, J.; Abreu, M.T. The Microbiota and the Immune Response: What Is the Chicken and What Is the Egg? Gastrointest. Endosc. Clin. N. Am., 2019, 29(3), 381-93.

Pahwa, R.; Jialal, I. Chronic Inflammation. Treasure Island (FL): StatPearls Publishing; 2019.

Chen, L.; Deng, H.; Cui, H.; Fang, J.; Zuo, Z.; Junliang, D.; Li, Y.; Wang, X.; Zhao, L. Inflammatory Responses and Inflammation-associated Diseases in Organs. Oncotarget, 2018, 9(6), 7204-18.

Zhou, Y.; Hong, Y.; Huang, H. Triptolide Attenuates Inflammatory Response in Membranous Glomerulo-nephritis Rat via Downregulation of NF-κB Signaling Pathway. Kidney Blood Press. Res., 2016, 41, 901-10.

Abdulkhaleq, L.A.; Assi, M.A.; Abdullah, M.R.; Zamri- Saad, Y.H.; Taufiq-Yap, M.; Hezmee, M.N. The Crucial Roles of Inflammatory Mediators in Inflammation: A Review. Vet. World, 2018, 11(5), 627-35.

Branco, A.C.C.; Yoshikawa, F.S.Y.; Pietrobon, A.J.; Sato, M.N. Role of Histamine in Modulating the Immune Response and Inflammation. Mediators Inflamm., 2018, 2018, 9524075.

Oguntibeju, O.O. Medicinal Plants with Anti-inflammatory Activities from Selected Countries and Regions of Africa. J. Inflamm. Res., 2018, 11, 307-17.

Kabir, I.; Ansari, I. A Review on In Vivo and In Vitro Experimental Models to Investigate the Anti-inflammatory Activity of Herbal Extracts. Asian J. Pharm. Clin. Res., 2018, 11(11), 9-35.

Phanse, M.A.; Patil, M.J.; Abbulu, K.; Chaudhari, P.D.; Patel, B. In-Vivo and In-Vitro Screening of Medicinal Plants for their Anti-inflammatory Activity: An Overview. J. Appl. Pharm. Sci., 2012, 2(7), 19-33.

Umar, M.I.; Altaf, R.; Iqbal, M.A.; Sadiq, M.B. In Vivo Experimental Models to Investigate the Anti-inflammatory Activity of Herbal Extracts (Review). Sci. Int. (Lahore), 2010, 22(3), 199-203.

Murakami, M.; Nakatani, Y.; Atsumi, G.; Inoue, K.; Kudo, I. Regulatory Functions of Phospholipase A2. Crit. Rev. Immunol., 2017, 37(2-6), 121-79.

Uzuazokaro, M.A.; Nwodo, O.F.C.; Ozah, I.R. Inhibition of Phospholipase A2 and Prostaglandin Synthase Activities as Possible Mechanisms for the Anti-Inflammatory Effect of Cucumis sativus Fruit Homogenate. Acta Sci. Pharm. Sci., 2019, 3(7), 68-73.

Aguilar, J.L.; Rojas, P.; Marcelo, A.; Plaza, A.; Bauer, R.; Reininger, E.; Klaas, C.A.; Merfort, I. Anti-inflammatory Activity of Two Different Extracts of Uncaria tomentosa (Rubiaceae). J. Ethnopharmacol., 2002, 81, 271-6.

Man, K.H.; Man-Deuk, H. Inhibitory Effect of Hyaluronidase and DPPH Radical Scavening Activity Using Extraction of Equisetum arvense. Eur. J. Adv. Res. Biol. Life Sci., 2015, 3(2), 47-53.

Anosike, C.A.; Obidoa, O.; Ezeanyika, L.U.S. Membrane Stabilization as a Mechanism of the Anti-inflammatory Activity of Methanol Extract of Garden Egg (Solanum aethiopicum). DARU J. Pharm. Sci., 2012, 20, 76.

Zhou, J.; Sun, Y.Y.; Sun, M.Y.; Mao, W.A.; Wang, L.; Zhang, J.; Zhang, H. Prim-O-glucosylcimifugin Attenuates Lipopolysaccharide Induced Inflammatory Response in RAW 264.7 Macrophages. Pharmcogn. Mag., 2017, 13, 378-84.

Chakraborty, A.; Devi, R.; Rita, S.; Sharatchandra, K.; Singh, T.I. Preliminary Studies on Anti-inflammatory and Analgesic Activities of Spilanthes acmella in Experimental Animal Models. Indian J. Pharmacol., 2006, 36, 148-50.

Eze, F.I.; Siwe-Noundou, X.; Osadebe, P.O.; Krause, R.W.M. Phytochemical, Anti-inflammatory and Anti-trypanosomal Properties of Anthocleista vogelii Planch (Loganiaceae) Stem Bark. J. Ethnopharmacol., 2019, 238, 111851.

Ueno, A.; Naraba, H.; Ikeda, Y.; Ushikubi, F.; Murata, T.; Naramiya, S.; Ohishi, S. Intrinsic Prostacyclin Contributes to Exudation Induced by Bradikinin or Carrageenan: A study on the Paw Edema Induced in IP-receptor Deficient Mice. Life Sci., 2000, 66, 155-60.

Mondal, A.; Maity, T.K.; Bishayee, A. Analgesic and Anti- Inflammatory Activities of Quercetin-3-methoxy-40 -glucosyl- 7-glucoside Isolated from Indian Medicinal Plant Melothria heterophylla. Medicines, 2019, 6(59), 1-11.

Ojewole, J.A. Analgesic, Antiinflammatory and Hypoglycaemic Effects of Ethanol Extract of Zingiber officinale (Roscoe) Rhizomes (Zingiberaceae) in Mice and Rats. Phytother. Res., 2006, 20(9), 764-72.

Osadebe, P.O.; Okoye, F.B.C. Anti-inflammatory Effects of Crude Methanolic Extract and Fractions of Alchornea cordifolia Leaves. J. Ethnopharmacol., 2003, 89, 19-24.

Akindele, A.J.; Ibe, I.F.; Adeyemi, O.O. Analgesic and Antipyretic Activities of Drymaria cordata (Linn.) Willd (Caryophyllaceae) Extract. Afr. J. Tradit. Complement. Alternat. Med., 2012, 9(1), 25-35.

Mihai, D.P.; Seremet, O.C.; Nitulescu, G.; Ivopol, M.; Sevastre, A.; Negres, S.; Ivopol, G.; Nitulescu, M.G.; Olaru, O.T. Evaluation of Natural Extracts in Animal Models of Pain and Inflammation for a Potential Therapy of Hemorrhoidal Disease. Sci. Pharm., 2019, 87, 14.

Sur, B.; Kang, S.; Kim, M.; Oh, S. Inhibition of Carrageenan/ Kaolin-Induced Arthritis in Rats and of Inflammatory Cytokine Expressions in Human IL-1β-Stimulated Fibroblast-like Synoviocytes by a Benzylideneacetophenone Derivative. Inflammation, 2018, 42, 928-36.

Sarkar, D.; Dutta, A.; Das, M.; Sarkar, K.; Mandal, C.; Chatterjee M. Effect of Aloe vera on Nitric Oxide Production by Macrophages during Inflammation. Indian J. Pharmacol., 2005, 37, 371-5.

Anosike, C.A.; Obidoa, O.; Ezeanyika, L.U.S. The Anti-inflammatory Activity of Garden Egg (Solanum aethiopicum) on Egg Albumin-induced Oedema and Granuloma Tissue Formation in Rats. Asian Pac. J. Trop. Med., 2012, 5, 62-6.

Hisamuddin, N.; Mossadeq, W.M.S.; Sulaiman, M.R.; Abas, F.; Leong, S.W.; Kamarudin, N.; Ong, H.M.; Azmi, A.F.A.; Ayumi, R.R.; Talib, M. Anti-Edematogenic and Anti- Granuloma Activity of a Synthetic Curcuminoid Analog, 5-(3,4-Dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta- 2,4-dien-1-one, in Mouse Models of Inflammation. Molecules, 2019, 24(2614), 1-14.

Nair, V.G.; Prajapati, P.K.; Nishteswar, K.; Unnikrishnan, V.; Nariya, M.B. Analgesic and Anti-inflammatory Activities of Bulbophyllum neilgherrense Wight. Pseudobulb: A Folklore Plant. Ayu Pharmacol. Study, 2018, 39, 76-80.

Okoli, C.O.; Akah, P.A.; Onuoha, N.J.; Okoye, T.C; Nwoye, A.C.; Nworu, C.S. Acanthus montanus: An Experimental Evaluation of the Antimicrobial, Anti-inflammatory and Immunological Properties of a Traditional Remedy for Furuncles. BMC Complement. Alternat. Med., 2008, 8, 27.

Falcão, T.R.; Rodrigues, C.A.; de Araújo, A.A.; de Medeiros, C.A.C.; Soares, L.A.L.; Ferreira, M.R.A.; Vasconcelos, R.C.; de Araújo Júnior, R.F.; de Lopes, M.L.D.; Guerra, G.C.B. Crude Extract from Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz Leaves Decreased Intra-articular Inflammation Induced by Zymosan in Rats. BMC Complement. Alternat. Med., 2019, 19, 47.

Wang, Y.; Chen, P.; Tang, C.; Li, Y.; Zhang, H. Antinociceptive and Anti-inflammatory Activities of Extract and Two Isolated Flavonoids of Carthamus tinctorius L. J. Ethnopharmacol., 2014, 151, 944-50.

Karim, N.; Khan, I.; Khan, W.; Khan, A.; Halim, S.A.; Khan, H.; Hussain, J.; Al-Harrasi, A. Anti-nociceptive and Anti-inflammatory Activities of Asparacosin a Involve Selective Cyclooxygenase 2 and Inflammatory Cytokines Inhibition: An In Vitro, In Vivo, and In Silico Approach. Front. Immunol., 2019, 10, 581.

Natália, R.P.; de Castro, C.P.N.; Josiane M.; de Freitas, M.R.; da Jde, C.C.; Aragão, D.M.; Castañon, M.C.; Scio, E. Cecropia pachystachya: A Species with Expressive In Vivo topical Anti- Inflammatory and In Vitro Antioxidant Effects. Biomed. Res. Int., 2014, 2014, 10.

Yin, Z.Z.; Jin, H.L.; Yin, X.Z.; Li, T.Z.; Quan, J.S.; Jin, Z.N. Effect of Boschniakia rossica on Expression of GSTP, p53 and p21(ras) Proteins in Early Stage of Chemical Hepatocarcinogenesis and its Anti-inflammatory Activities in Rats. World J. Gastroenterol., 2000, 6, 812-8.

Kuhns, D.B.; DeCarlo, E.; Hawk, D.M.; Gallin, J.I. Dynamics of the Cellular and Humoral Components of the Inflammatory Response Elicited in Skin Blisters in Humans. J. Clin. Invest., 1992, 89, 1734-40.

Chondrex. Protocol for the Successful Induction of Collagen- Induced Arthritis in Rats. Redmond: Chondrex, Inc.; 2015, p. 1-5.

Jitta, S.R.; Daram, P.; Gourishetti, K.; Misra, C.S.; Polu, P.R.; Shah, A.; Shreedhara, C.S.; Nampoothiri, M.; Lobo, R. Terminalia tomentosa Bark Ameliorates Inflammation and Arthritis in Carrageenan Induced Inflammatory Model and Freund’s Adjuvant- Induced Arthritis Model in Rats. J. Toxicol., 2019, 2019, 11.

Duarte, D.B.; Vasko, M.R.; Fehrenbacher, J.C. Models of Inflammation: Carrageenan Air Pouch. Curr. Protoc. Pharmacol., 2012, 5, 5-6.

Pinheiro, M.M.G.; Miltojević, A.B.; Radulović, NS.; Abdul- Wahab, I.R.; Boylan, F.; Fernandes, P.D. Anti-Inflammatory Activity of Choisya ternata Kunth Essential Oil, Ternanthranin, and Its Two Synthetic Analogs (Methyl and Propyl N-Methylanthranilates). PLoS One, 2015, 10, e0121063.

Suleiman, M.M.; Mamman, M.; Naidoo, V.; Tauheed, M.; Eloff, J.N. Anti-inflammatory and Antinociceptive Activities of Loxostylis alata A. Spreng. (Anacardiaceae). Am. J. Res. Commun., 2014, 2(7), 227-46.

Ghule, B.V.; Ghante, M.H.; Upaganlawar, A.B.; Yeole, P.G. Analgesic and Anti-inflammatory Activities of Lagenaria siceraria Stand. Fruit Juice Extract in Rats and Mice. Pharmacogn. Mag., 2006, 2, 232-6.

Brown, J.; Roberts, J. Histamine, bradykinin, and their antagonists. In: Gilman, A.; Hardman, J.; Limbird, L., editors. Goodman and Gilman’s, The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw Hill; 2001. p. 645-67.

Okoli, C.O.; Akah, P.A.; Nwafor, S.V.; Anisiobi, A.I.; Ibegbunam, I.N.; Erojiekwe, O. Anti-inflammatory Activity of Hexane Leaf Extract of Aspila africana C.D. Adams. J. Ethnopharmacol., 2007, 109, 219-25.

Suleiman, M.; Mamman, M.; Elayoni, E.I.; Ya’u, M.; Abdullahi, A.; Ahmad, M.T. Evaluation of Analgesic and Anti-inflammatory Effects of the Crude Methanol Extract of the Stem-Bark of Annona senegalensis Pers. Int. J. Med. Arom. Plants, 2014, 2, 88-96.

Olajide, O.A.; Echianu, C.A.; Adedapo, A.D.A.; Makinde, J.M. Anti-inflammatory Studies on Adenanthera pavonina Seed Extract. Inflammopharmacology, 2004, 12(2), 196-201.

Agbaje, E.O.; Fageyinbo, M.S. Evaluating Anti-inflammatory Activity of Aqueous Root Extract of Strophanthus hispidus DC. (Apocynaceae). Int. J. Applied Res. Nat. Prod., 2012, 4(4), 7-14.

Badilla, B.; Arias, Y.; Mora, G.A.; Poveda, L.J. Anti inflammatory and Antinociceptive Activities of Loasa speciosa in Rats and Mice. Fitoterapia, 2003, 74, 45-51.

Rogero, S.O.; Lugao, A.B.; Ikeda, T.I.; Cruz, A.S. Teste In Vitro de Citotoxicidade: Estudo Comparativo Entre Duas Metodologias. Mater. Res., 2003, 6, 317-20.

DzoyemL, J.P.; McGaw, J.; Kuete, V.; Bakowsky, U. Anti-inflammatory and Anti-nociceptive Activities of African Medicinal Spices and Vegetables Medicinal Spices and Vegetables from Africa. In: Medicinal Spices and Vegetables from Africa, Therapeutic Potential against Metabolic, Inflammatory, Infectious and Systemic Diseases. Amsterdam: Elsevier Inc.; 2017. p. 239-70.

Patil, K.R.; Mahajan, U.B.; Unger, B.S.; Goyal, S.N.; Belemkar, S.; Surana, S.J.; Ojha, S.; Patil, C.R. 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.

Zhao, J.; Maitituersun, A.; Li, C.; Li, Q.; Xu, F.; Liu, T. Evaluation on Analgesic and Anti-Inflammatory Activities of Total Flavonoids from Juniperus sabina. Evid. Based Complement. Alternat. Med., 2018, 2018, 1-9.

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