Nutraceutical with Anti-Inflammatory Activity for the Management of Airway Remodeling in Bronchial Asthma: Kalanchoe integra Var. Crenata (Andr.) Cuf Leaf Extract
Asiedu-Gyekye Isaac Julius, Awortwe Charles, Nyamekye Effah Samuel, Antwi Daniel Ansong, Seidu Mahmood, Adjei Samuel, Banga N’guessan Benoit Kwame, Amoateng Patrick, Nkansah Edwin
Department of Animal Experimentation, Noguchi Memorial Institute for Medical Research, College of Health Sciences, Legon, Ghana.
Department of Chemical Pathology, School of Allied Health Sciences, College of Health Sciences, Korle-Bu, Ghana.
Department of Pharmacology and Toxicology, University of Ghana School of Pharmacy, College of Health Sciences, Legon, Ghana.
Department of Physiology, University of Ghana Medical School, Col-lege of Health Sciences, Korle-Bu, Ghana.
Division of Pharmacology, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa.
DOI: 10.4236/pp.2014.53032   PDF    HTML   XML   4,534 Downloads   7,821 Views   Citations

Abstract

Background: Kalanchoe integra is widely used in folklore medicine as an antiasthmatic agent. Previous studies have shown the ameliorating effect of Kalanchoe integra leaf extract [KILE] on bronchial hyperesponsiveness and inflammation. Further, the stabilizing effect of Kalanchoe sp on mast cell degranulation, suggests that Kalanchoe species are suitable candidates for allergic asthma therapy. This study is designed to investigate the anti-asthmatic potential of KILE and monitor the accompanying histopathological and immunobiochemical changes that occur in an animal model of bronchial asthma using ovalbumin sensitized guinea pigs. Method: Thirty male guinea pigs were divided into five groups of six animals each. Bronchial asthma was simulated in guinea pigs using ovalbumin. Both low dose (300 mg/kg) and high dose extract (900 mg/kg) were administered daily for 42 days. Prednisolone (2.5 mg/kg) was the standard drug used. Results: Guinea pigs in all KILE treated groups maintained the integrity of their airway structures: bronchial folds and walls, alveoli, alveolar ducts and sacs. KILE and prednisolone caused a reduction in immune parameters (p < 0.001), extent of bronchoconstriction, bronchial wall thickness and goblet cell accumulation in the sensitized guinea pigs. Conclusion: This study demonstrates the anti-asthmatic potential of KILE during prolonged administration by the oral route.

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Julius, A. , Charles, A. , Samuel, N. , Ansong, A. , Mahmood, S. , Samuel, A. , Benoit Kwame, B. , Patrick, A. and Edwin, N. (2014) Nutraceutical with Anti-Inflammatory Activity for the Management of Airway Remodeling in Bronchial Asthma: Kalanchoe integra Var. Crenata (Andr.) Cuf Leaf Extract. Pharmacology & Pharmacy, 5, 250-261. doi: 10.4236/pp.2014.53032.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Pandey, M., Debnath, M., Gupta, S. and Chikara, S.K. (2011) Phytomedicine: An Ancient Approach Turning into Future Potential Source of Therapeutics. Journal of Pharmacology and Phytotherapy, 3, 27-37.
[2] Dymock, W., Warden, C.J.H. and Hooper, D. (1890) Pharmacographica Indica. Trubner & Co. London, Educational Society’s Press, Calcutta, 1, 590.
[3] Dokosi, O.B. (1998) Herbs of Ghana. 32-33.
[4] Biswas, S.K., Chowdhury, A., Das, J., Hosen, S.Z., Uddin, R. and Rahaman, M.S. (2011) Literature Review on Pharmacological Potentials of Kalanchoe pinnata (Crassulaceae). African Journal Pharmarcy and Pharmacology, 5, 1258-1262. http://dx.doi.org/10.5897/AJPP11.273
[5] Ghasi, S., Egwuib, C., Achukwu, P. and Onyeanusi, J. (2011) Assessment of the Medical Benefit in the Folkloric Use of Bryophyllum Pinnatum Leaf among the Igbos of Nigeria for the Treatment of Hypertension. African Journal Pharmarcy and Pharmacology, 5, 83-92. http://dx.doi.org/10.5897/AJPP10.309
[6] Cruz, E., Da-silva, S., Muzitano, M., Silva, P., Costa, S. and Rossi-Bergmann, B. (2008) Immunomodulatory Pretreatment with Kalanchoe pinnata Extract and Its Quercitrin Flavonoid Effectively Protects Mice against Fatal Anaphylactic Shock. International Immunopharmacology, 8, 1616-1621.
http://dx.doi.org/10.1016/j.intimp.2008.07.006
[7] Harlalka, G.V., Patil, C.R. and Patil, M.R. (2007) Protective Effect of Kalanchoe pinnata pers. (Crassulaceae) on Gentamicin-Induced Nephrotoxicity in Rats. Indian Journal of Pharmacology, 39, 201.
http://dx.doi.org/10.4103/0253-7613.36540
[8] Ojewole, J.A. (2005) Antinociceptive, Anti-Inflammatory and Antidiabetic Effects of Bryophyllum pinnatum (Crassulaceae) Leaf Aqueous Extract. Journal of Ethnopharmacology, 99, 13-19.
http://dx.doi.org/10.1016/j.jep.2005.01.025
[9] Cruz, E., Reuter, S., Martin, H., Dehzad, N., Muzitano, M., Costa, S., Rossi-Bergmann, B., Buhl, R., Stassen, M. and Taube, C. (2012) Kalanchoe pinnata Inhibits Mast Cell Activation and Prevents Allergic Airway Disease. Phytomedicine, 19, 115-121. http://dx.doi.org/10.1016/j.phymed.2011.06.030
[10] Okwu D.E. and Nnamdi F.U. (2011) Two Novel Flavonoids from Bryophyllum pinnatum and Their Antimicrobial Activity. Pharmacy and Respiratory Journal, 3, 1-10.
[11] Theide, J. and Eggli, U. (2007) Crassulaceae. Flowering Plants. Eudicots, Springer.
[12] Barnes, P.J. (1996) Pathophysiology of Asthma. British Journal of Clinical Pharmacology, 42, 3-10.
http://dx.doi.org/10.1046/j.1365-2125.1996.03721.x
[13] Broide, D.H., Gleich, G.J., Cuomo, A.J., Coburn, D.A., Federman, E.C., Schwartz, L.B. and Wasserman, S.I. (1991) Evidence of ongoing Mast Cell and Eosinophil Degranulation in Symptomatic Asthma Airway. Journal of Allergy and Clinical Immunology, 88, 637-648. http://dx.doi.org/10.1016/0091-6749(91)90158-K
[14] Larzarus, S.S., Boushey, H., Fahy, J., Chinchili, V., Lemanske, R., Sorkness, C., Kraft, M., Fish, J., Peters, S. and Craig, T. (2001) Long-Acting Beta2-Agonist Monotherapy vs Continued Therapy with Inhaled Corticosteroids in Patients with Persistent Asthma: A Randomized Controlled Trial. The Journal of the American Medicine Association, 285, 2583-2593. http://dx.doi.org/10.1001/jama.285.20.2583
[15] Minic, P. and Sovtic, A. (2008) The Use of Corticosteroids in Pediatric Respiratory Disease. Arhiv za Farmaciju, 58, 172-184.
[16] Johansson, M.W., Han, S.T., Gunderson, K.A., Busse, W.W., Jarjour, N.N. and Mosher, D.F. (2012) Platelet Activation, P-Selectin and Eosinophil β1-Integrin Activation in Asthma. American Journal of Respiratory Cell and Molecular Biology, 185, 498-507.
[17] Bloemen, K., Ver straelen, S., Van Den Heuvel, R., Witters, H., Nelissen, I. and Schoeters, G. (2007) The Allergic Cascade: Review of the Most Important Molecules in the Asthmatic Lung. Immunology Letters, 113, 6-18.
http://dx.doi.org/10.1016/j.imlet.2007.07.010
[18] Fahy, J.V., Corry, D.B. and Boushey, H.A. (2000) Airway Inflammation and Remodeling in Asthma. Current Opinion in Pulmonary Medicine, 6, 15-20. http://dx.doi.org/10.1097/00063198-200001000-00004
[19] Durham, S.R., Till, S.J. and Corrigan, C.J. (2000) T Lymphocytes in Asthma: Bronchial versus Peripheral Responses. Journal of Allergy and Clinical Immunology, 106, S221-S226. http://dx.doi.org/10.1067/mai.2000.110154
[20] Di-Stefano, A., Diane, M.C., Schick, C.M. and McKelvy, J.F. (2001) Decreased T Lymphocyte Infiltration in Bronchial Biopsies of Subjects with Severe Chronic Obstructive Pulmonary Disease. Clinical & Experimental Allergy, 31, 893-902. http://dx.doi.org/10.1046/j.1365-2222.2001.01098.x
[21] Park, H.J., Lee, C.M., Jung, I.D., Lee, J.S., Jeong, Y.I., Chang, J.H., Chun, S.H., Kim, M.J., Choi, I.W., Ahn, S.C., Shin, Y.K., Yeom, S.R. and Park, Y.M. (2009) Quercetin Regulates Th1/Th2 Balance in a Murine Model of Asthma. International Immunopharmacology, 9, 261-267. http://dx.doi.org/10.1016/j.intimp.2008.10.021
[22] Joskova, M., Franova, S. and Sadlonova, V. (2011) Acute Bronchodilator Effect of Quercetin in Experimental Allergic Asthma. Bratislavské Lekárske Listy, 112, 9-12.
[23] Fortunato, L.R., de Freitas Alves, C., Teixeira, M.M. and Rogerio, A.P. (2012) Quercetin: A Flavonoid with the Potential to Treat Asthma. Brazilian Journal of Pharmaceutical Sciences, 48, 4.
http://dx.doi.org/10.1590/S1984-82502012000400002
[24] Asiedu-Gyekye, I.J., Awortwe, C., Antwi, D., et al. (2013) Comparative Study of Two kalanchoe Species: Total Flavonoid, Phenolic Contents and Antioxidant Properties. African Journal of Pure and Applied Chemistry, 6, 65-73.
[25] Pattewar, S.V. (2012) Kalanchoe pinnata: Phytochemical and Pharmacological Profile. International Journal of Phytopharmarcy, 2, 1-8.
[26] Asiedu-Gyekye, I.J., Awortwe, C., Tagoe, B.N.A., Antwi, D.A., Adjei, S., Edusei, I.D., N’guessan, B.B., Amoateng, P. and Nkansah, E. (2014) Preliminary Investigation into the Antiasthmatic Potential of Kalanchoe Integra Leaf Extract Using a Model of Allergic Airway Inflammation. European Journal of Medicinal Plants, 4, 542-562.
[27] Organization for Economic Cooperation and Development (OECD) (2001) Guidelines. Guidelines for Testing of Chemicals.
[28] WHO (2000) General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine. Geneva, 80.
[29] Awortwe, C., Sackeyfio, A., Osei-safo, D., Bugyei, K. and Asiedu-Gyekye, I. (2011) Dual Effect of Taraxacum Officinale Leaves Anticholinergic and Inhibitory Effect on Inflammatory Cells in Ovalbumin-Sensitized Guinea-Pigs. African Journal of Pharmacy and Pharmacology, 5, 2613-2619. http://dx.doi.org/10.5897/AJPP11.616
[30] Droste, J.H., Kerhof, M., Monchy, J.G. de, Schouten, J.P. and Rijcken, B. (1996) Association of Skin Test Reactivity, Specific IgE, Total IgE, and Eosinophils with Nasal Symptoms in a Community-Based Population Study. Journal Allergy Clinical Immunology, 97, 922-932. http://dx.doi.org/10.1016/S0091-6749(96)80066-2
[31] Koh, H.S., Lee, K.S., Han, D.H., Rha, Y.H. and Choi, S.H. (2013) Relationship between Serum Total IgE, Specific IgE, and Peripheral Blood Eosinophil Count According to Specific Allergic Diseases. Allergy Asthma & Respiratory Disease, 1, 123-128. http://dx.doi.org/10.4168/aard.2013.1.2.123
[32] Krieger, S.M., Poole, A., Wienskinki, C.M. and Woolshier, M.R. (2008) Respiratory Sensitization and Allergy: Current Research Approaches and Needs. Toxicology & Applied Pharmacology, 226, 1-13.
http://dx.doi.org/10.1016/j.taap.2007.10.008
[33] Parmar, S.K., Gangwal, A.P., Prajapati, T.R., Pandya, K.B., Ranpariya, V.L. and Sheth, N.R. (2010) Evaluation of Antiasthmatic Activity of a Polyherbal Formulation Containing Four Plant Extracts. Journal of Current Pharmaceutical Respiration, 2, 40-44.
[34] Pandit, P., Singh, A., Bafna, A.R., Kadam, P.V. and Patil, M.J. (2008) Evaluation of Antiasthmatic Activity of Curculigo orchioides Gaertn. rhizomes. Indian Journal of Pharmaceutical Science, 70, 440.
http://dx.doi.org/10.4103/0250-474X.44590
[35] Bousquet, J., Jeffery, P.K., Busse, W.W., Johnson, M. and Vignola, A.M. (2000) Asthma from Bronchoconstriction to Airways Inflammation and Remodeling. American Journal of Respiration and critical care Medicine, 161, 1720-1745. http://dx.doi.org/10.1164/ajrccm.161.5.9903102
[36] Minai-Fleminger, Y. and Levi-Schaffer, F. (2009) Mast Cells and Eosinophils: The Two Key Effector Cells in Allergic Inflammation. Inflammation Research, 58, 631-638. http://dx.doi.org/10.1007/s00011-009-0042-6
[37] Schall, T.J. and Bacon, K.B. (994) Chemokines, Leukocyte Trafficking, and Inflammation. Current Opinion in Immunology, 6, 865-873. http://dx.doi.org/10.1016/0952-7915(94)90006-X
[38] Gundel, R.H., Wegner, C.D. and Letts, L.G. (1992) The Onset and Recovery from Airway Hyperresponsiveness: Relationship with Inflammatory Cell Infiltrates and Release of Cytotoxic Granule Proteins. Clinical & Experimental Allergy, 22, 303-308. http://dx.doi.org/10.1111/j.1365-2222.1992.tb03087.x
[39] Montefort, S., Herbert, C.A., Robinson, C. and Holgate, S.T. (1992) The Bronchial Epithelium as a Target for Inflammatory Attack in Asthma. Clinical & Experimental Allergy, 22, 511-520.
http://dx.doi.org/10.1111/j.1365-2222.1992.tb00159.x
[40] Merwat, S.N. and Spechler, S.J. (2009) Might the Use of Acid-Suppressive Medications Predispose to the Development of Eosinophilic Esophagitis? A Matter of Opinion. The American Journal of Gastroenterology, 104, 1897-1902.
http://dx.doi.org/10.1038/ajg.2009.87
[41] Robinson, D.S., Hamid, Q., Ying, S., Tsicopoulos, A., Barkans, J., Bentley, A.M., Corrigan, C., Durham, S.R. and Kay, A.B. (1992) Predominant TH2-Like Bronchoalveolar T-Lymphocyte Population in Atopic Asthma. New England Journal of Medicine, 326, 298-304. http://dx.doi.org/10.1056/NEJM199201303260504
[42] Rakh, M.S., Khedkar, A.N., Aghav, N.N. and Chaudhari, S.R. (2012) Antiallergic and Analgesic Activity of Momordica dioica Roxb. Willd Fruit Seed. Asian Pacific Journal of Tropical Biomedicine, 2, S192-S196.
http://dx.doi.org/10.1016/S2221-1691(12)60157-9
[43] Gomes, D., Muzitano, M., Costa, S. and Rossi-Bergmann, B. (2010) Effectiveness of the Immunomodulatory Extract of Kalanchoe pinnata against Murine Visceral Leishmaniasis. Parasitology, 137, 613-618.
http://dx.doi.org/10.1017/S0031182009991405
[44] Bousquet, J., Chanez, P., Lacoste, J.Y., Barnéon, G., Ghavanian, N., Enander, I., Venge, P. and Ahlstedt, S. (1990) Eosinophilic Inflammation in Asthma. New England Journal of Medicine, 323, 1033-1039.
http://dx.doi.org/10.1056/NEJM199010113231505
[45] Desai, S.N., Van, G., Robson, J., Letts, L.G., Gundel, R.H., Gleich, G.J., Piper, P.J. and Noonan, T.C. (1993) Human Eosinophil Major Basic Protein Augments Bronchoconstriction Induced by Intravenous Agonists in Guinea Pigs. Agents and Actions, 39, C132-C135. http://dx.doi.org/10.1007/BF01972744
[46] Gundel, R.H., Letts, L.G. and Gleich, G.J. (1991) Human Eosinophil Major Basic Protein Induces Airway Constriction and Airway Hyperresponsiveness in Primates. Journal of Clinical Investigation, 87, 1470-1473.
http://dx.doi.org/10.1172/JCI115155
[47] Durham, S.R., Loegering, D.A., Dunnette, S., Gleich, G.J. and Kay, A.B. (1989) Blood Eosinophils and Eosinophil-Derived Proteins in Allergic Asthma. Journal of Allergy and Clinical Immunology, 84, 931-936.
http://dx.doi.org/10.1016/0091-6749(89)90391-6
[48] Mahajan, S.G. and Mehta, A.A. (2011) Suppression of Ovalbumin-Induced Th2-Driven Airway Inflammation by β-Sitosterol in a Guinea Pig Model of Asthma. European Journal of Pharmcology, 650, 458-464.
http://dx.doi.org/10.1016/j.ejphar.2010.09.075
[49] Hamid, A.A., Aiyelaagbe, O.O., Usman, L.A., Ameen, O.M. and Lawal, A. (2010) Antioxidants: Its Medicinal and Pharmacological Applications. African Journal of Pure and Applied Chemistry, 4, 142-151.
[50] Bhatti, M., Kamboj, A., Saluja, A.K. and Jain, U.K. (2012) In Vitro Evaluation and Comparison of Antioxidant Activities of Various Extracts of Leaves and Stems of Kalanchoe pinnatum. International Journal of Green Pharmarcy, 6, 340-347. http://dx.doi.org/10.4103/0973-8258.108255
[51] Khakzad, M.R., Mirsadraee, M., Mohammadpour, A., Ghafarzadegan, K., Hadi, R., Saghari, M. and Meshkat, M. (2012) Effect of Verapamil on Bronchial Goblet Cells of Asthma: An Experimental Study on Sensitized Animals. Pulmonary Pharmacology & Therapeutics, 25, 163-168. http://dx.doi.org/10.1016/j.pupt.2011.11.001
[52] Kondo, M., Nakata, J., Arai, N., Izumo, T., Tagaya, E., Takeyama, K., Tamaoki, J. and Nagai, A. (2012) Niflumic Acid Inhibits Goblet Cell Degranulation in a Guinea Pig Asthma Model. Allergology International, 61, 133-142.
http://dx.doi.org/10.2332/allergolint.11-OA-0307
[53] Mushaben, E.M., Kramer, E.L., Brandt, E.B., Khurana Hershey, G.K. and Cras, T.D. (2011) Rapamycin Attenuates Airway Hyperreactivity, Goblet Cells, and IgE in Experimental Allergic Asthma. Journal of Immunology, 187, 5756-5763. http://dx.doi.org/10.4049/jimmunol.1102133
[54] Hays, S.R., Woodruff, P.G., Khashayar, R., Ferrando, R.E., Liu, J., Fung, P., Zhao, C.Q., Wong, H.H. and Fahy, J.V. (2001) Allergen Challenge Causes Inflammation but Not Goblet Cell Degranulation in Asthmatic Subjects. Journal of Allergy and Clinical Immunology, 108, 784-790. http://dx.doi.org/10.1067/mai.2001.119162
[55] Kanani, A., Schellenberg, R. and Warrington, R. (2011) Urticaria and Angioedema. Allergy, Asthma & Clinical Immunology, 7, S9. http://dx.doi.org/10.1186/1710-1492-7-S1-S9
[56] Papiris, S.A., Manali, E.D., Kolileas, L., Traintafillido, C. and Tsangaris, I. (2009) Acute Severe Asthma: New Approaches to Assessment and Treatment. Drugs, 69, 2363-2391.
[57] Bochner, B.S. and Busse, W. (2005) Allergy and Asthma. Journal of Allergy and Clinical Immunology, 115, 953-959. http://dx.doi.org/10.1016/j.jaci.2005.02.032
[58] Bajoriūniene, I., Malakauskas, K., Lavinskiene, S., Jeroch, J., Vitkauskiene, A. and Sakalauskas, R. (2012) Peripheral Blood Th17 Cells and Neutrophils in Dermatophagoides Pteronyssinus-Induced Early- and Late-Phase Asthmatic Response. Medicina, 48, 442-451.
[59] Pradalier, A. (1993) Late-Phase Reaction in Asthma: Basic Mechanisms. International Archives of Allergy and Immunology, 101, 322-325. http://dx.doi.org/10.1159/000236471
[60] Arvidsson, M.B., Löwhagen, O. and Rak, S. (2007) Early and Late Phase Asthmatic Response in Lower Airways of Cat-Allergic Asthmatic Patients—A Comparison between Experimental and Environmental Allergen Challenge. Allergy, 62, 488-494. http://dx.doi.org/10.1111/j.1398-9995.2007.01278.x

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