Momordica charantia L. improves airway hyperresponsiveness and suppresses inflammation in a murine model of allergic asthma
Main Article Content
Keywords
allergy, Cucurbitaceae, herbal medicine, inflammation, ovalbumin
Abstract
Objective: To evaluate the effect of a hydroethanolic extract of Momordica charantia L. (“bitter melon”, Cucurbitaceae) leaves (MCHA) on ovalbumin (OVA)-induced asthma model. Balb/c mice were sensitized twice and challenged for 4 alternate days with OVA and then treated with MCHA (500 mg/kg) for 7 consecutive days.
Methods: Control groups received treatment with normal saline or dexamethasone (2 mg/kg) on the same day. We assessed in vivo bronchial hyperresponsiveness and ex-vivo inflammation and mucus production in bronchoalveolar lavage (BAL), lung homogenates, and lung tissue.
Results: MCHA significantly improved airway hyperresponsiveness near baseline levels. MCHA administration significantly improved airway and lung inflammation, demonstrated by decreased total and inflammatory cells in BAL, lower levels of IL-5 and IL-13 in lung homogenate, and fewer inflammatory cells in lung tissue. Additionally, MCHA significantly diminished goblet cells in lung tissue.
Conclusions: Administration of a hydroethanolic extract of M. charantia leaves was effective in treating OVA-induced asthma in an animal model.
References
1. Global Initiative for Asthma. Global strategy for asthma management and prevention. [cited 2020]. Availavle from: http://www.ginasthma.org
2. Cruz AA, Pizzichini ALGFE, Fiterman J, Jones LFFPMMMPM, Lima MA, Stirbulo PAMCR. Diretrizes da sociedade brasileira de pneumologia e tisiologia para o manejo da asma-2012. J Bras Pneumol Tisiol. 2012;38:S1-46.
3. The Plant List. [cited 2021]. Available from: http://www.theplantlist.org
4. Dandawate PR, Subramaniam D, Padhye SB, Anant S. Bitter melon: a panacea for inflammation and cancer. Chin J Nat Med. 2016;14(2):81–100. 10.1016/S1875-5364(16) 60002-X
5. Bortolotti M, Mercatelli D, Polito L. Momordica charantia, a nutraceutical approach for inflammatory related diseases. Front Pharmacol. 2019;10:1–9. 10.3389/fphar.2019.00486
6. Zhang J, Huang Y, Kikuchi T, Tokuda H, Suzuki N, Inafuku K, et al. Cucurbitane triterpenoids from the leaves of momordica charantia, and their cancer chemopreventive effects and cytotoxicities. Chem Biodivers. 2012;9(2):428–40. http://doi.wiley.com/10.1002/cbdv.201100142
7. Ma J, Krynitsky AJ, Grundel E, Rader JI. Quantitative determination of cucurbitane-type triterpenes and Triterpene Glycosides in dietary supplements containing bitter melon (Momordica charantia) by HPLC-MS/MS. J AOAC Int. 2012;95 (6):1597–1608. https://academic.oup.com/jaoac/article/95/6/1597-1608/5655273
8. Chanda J, Mukherjee PK, Biswas R, Malakar D, Pillai M. Study of pancreatic lipase inhibition kinetics and LC-QTOF-MS based identification of bioactive constituents of Momordica charantia fruits. Biomed Chromatogr. 2018;e4463. https://onlinelibrary.wiley.com/doi/abs/10.1002/bmc.4463
9. Azevedo BC, Morel LJF, Carmona F, Cunha TM, Contini SHT, Delprete PG, et al. Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma. J Ethnopharmacol. 2018;218:76–89. http://linkinghub.elsevier.com/retrieve/pii/S0378874117334566
10. de Freitas Morel LJ, de Azevedo BC, Carmona F, Contini SHT, Teles AM, Ramalho FS, et al. A standardized methanol extract of Eclipta prostrata (L.) L. (Asteraceae) reduces bronchial hyperresponsiveness and production of Th2 cytokines in a murine model of asthma. J Ethnopharmacol. 2017;198:226–34. http://linkinghub.elsevier.com/retrieve/pii/S0378874116323121
11. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277–85. https://pubmed.ncbi.nlm.nih.gov/15003729/
12. Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol. 1999;162(10):6284–93. https://www.jimmunol.org/content/162/10/6284.short
13. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282(5397):2258–61. https://www.science.org/doi/abs/10.1126/science.282.5397.2258
14. Krawinkel MB, Keding GB. Bitter gourd (Momordica charantia): a dietary approach to hyperglycemia. Nutr Rev. 2006;64:331–7. http://www.ncbi.nlm.nih.gov/pubmed/16910221
15. El Batran SAES, El-Gengaihi SE, El Shabrawy OA. Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats. J Ethnopharmacol. 2006;108(2):236–42. http://www.ncbi.nlm.nih.gov/pubmed/16815658
16. Yang SJ, Choi JM, Park SE, Rhee EJ, Lee WY, Oh KW, et al. Preventive effects of bitter melon (Momordica charantia) against insulin resistance and diabetes are associated with the inhibition of NF-κB and JNK pathways in high-fat-fed OLETF rats. J Nutr Biochem. 2015;26(3):234–40. http://www.sciencedirect.com/science/article/pii/S095528631400237X
17. Rahman IU, Khan RU, Rahman KU, Bashir M. Lower hypoglycemic but higher antiatherogenic effects of bitter melon than glibenclamide in type 2 diabetic patients. Nutr J. 2015;14(1): 13. http://ezproxy.think.edu.au/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=25504465&site=ehost-live&scope=site&custid=s8454151
18. Kim SK, Jung J, Jung JH, Yoon N, Kang SS, Roh GS, et al. Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus. Complement Ther Med. 2020;52:102524. https://linkinghub.elsevier.com/retrieve/pii/S0965229920302491
19. Cortez-Navarrete M, Martínez-Abundis E, Pérez-Rubio KG, González-Ortiz M, Méndez-del Villar M. Momordica charantia administration improves insulin secretion in type 2 diabetes mellitus. J Med Food. 2018;21(7):672–77. http://www.liebertpub.com/doi/10.1089/jmf.2017.0114
20. Peter EL, Kasali FM, Deyno S, Mtewa A, Nagendrappa PB, Tolo CU, et al. Momordica charantia L. lowers elevated glycaemia in type 2 diabetes mellitus patients: systematic review and meta-analysis. J Ethnopharmacol. 2019;231:311–24. 10.1016/j.jep.2018.10.033
21. Jia S, Shen M, Zhang F, Xie J. Recent advances in momordica charantia: functional components and biological activities. Int J Mol Sci. 2017;18(12). 2555 https://www.mdpi.com/1422-0067/18/12/2555
22. Soo May L, Sanip Z, Ahmed Shokri A, Abdul Kadir A, Md Lazin MR. The effects of Momordica charantia (bitter melon) supplementation in patients with primary knee osteoarthritis: a single-blinded, randomized controlled trial. Complement Ther Clin Pract. 2018;32:181–6. https://linkinghub.elsevier.com/retrieve/pii/S1744388118301701
23. Liaw C, Huang H, Hsiao P, Zhang L, Lin Z, Hwang S, et al. 5β,19-Epoxycucurbitane Triterpenoids from Momordica charantia and their anti-inflammatory and cytotoxic activity. Planta Med. 2015;81(1):62–70. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1383307
24. Chao C-Y, Sung P-J, Wang W-H, Kuo Y-H. Anti-inflammatory effect of momordica charantia in sepsis Mice. Molecules. 2014; 19:12777–88. http://www.mdpi.com/1420-3049/19/8/12777/
25. Shivanagoudra SR, Perera WH, Perez JL, Athrey G, Sun Y, Wu CS, et al. In vitro and in silico elucidation of antidiabetic and anti-inflammatory activities of bioactive compounds from Momordica charantia L. Bioorganic Med Chem. 2019;27(14):3097–109. 10.1016/j.bmc.2019.05.035
26. Kobori M, Nakayama H, Fukushima K, Ohnishi-Kameyama M, Ono H, Fukushima T, et al. Bitter gourd suppresses lipopolysaccharide-induced inflammatory responses. J Agric Food Chem. 2008;56(11):4004–11. http://www.ncbi.nlm.nih.gov/pubmed/18489106
27. Lii C-K, Chen H-W, Yun W-T, Liu K-L. Suppressive effects of wild bitter gourd (Momordica charantia Linn. var. abbreviata ser.) fruit extracts on inflammatory responses in RAW 264.7 macrophages. J Ethnopharmacol. 2009;122(2):227–3. http://www.ncbi.nlm.nih.gov/pubmed/19330915
28. Nhiem NX, Yen PH, Ngan NTT, Quang TH, Kiem P Van, Minh C Van, et al. Inhibition of nuclear transcription factor-κB and activation of peroxisome proliferator-activated receptors in HepG2 cells by cucurbitane-type triterpene glycosides from Momordica charantia. J Med Food. 2012;15(4):369–377. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3308713&tool=pmcentrez&rendertype=abstract
29. Hogan SP. Recent advances in eosinophil biology. Int Arch Allergy Immunol. 2007;143:3–14. https://www.karger.com/Article/Abstract/101398
30. van Rensen ELJ, Evertse CE, van Schadewijk WAAM, van Wijngaarden S, Ayre G, Mauad T, et al. Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment. Allergy. 2009;64(1):72–80. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1398-9995.2008.01881.x
31. Davoine F, Lacy P. Eosinophil cytokines, chemokines, and growth factors: emerging roles in immunity. Front Immunol. 2014;5:1–17. 10.3389/fimmu.2014.00570
2. Cruz AA, Pizzichini ALGFE, Fiterman J, Jones LFFPMMMPM, Lima MA, Stirbulo PAMCR. Diretrizes da sociedade brasileira de pneumologia e tisiologia para o manejo da asma-2012. J Bras Pneumol Tisiol. 2012;38:S1-46.
3. The Plant List. [cited 2021]. Available from: http://www.theplantlist.org
4. Dandawate PR, Subramaniam D, Padhye SB, Anant S. Bitter melon: a panacea for inflammation and cancer. Chin J Nat Med. 2016;14(2):81–100. 10.1016/S1875-5364(16) 60002-X
5. Bortolotti M, Mercatelli D, Polito L. Momordica charantia, a nutraceutical approach for inflammatory related diseases. Front Pharmacol. 2019;10:1–9. 10.3389/fphar.2019.00486
6. Zhang J, Huang Y, Kikuchi T, Tokuda H, Suzuki N, Inafuku K, et al. Cucurbitane triterpenoids from the leaves of momordica charantia, and their cancer chemopreventive effects and cytotoxicities. Chem Biodivers. 2012;9(2):428–40. http://doi.wiley.com/10.1002/cbdv.201100142
7. Ma J, Krynitsky AJ, Grundel E, Rader JI. Quantitative determination of cucurbitane-type triterpenes and Triterpene Glycosides in dietary supplements containing bitter melon (Momordica charantia) by HPLC-MS/MS. J AOAC Int. 2012;95 (6):1597–1608. https://academic.oup.com/jaoac/article/95/6/1597-1608/5655273
8. Chanda J, Mukherjee PK, Biswas R, Malakar D, Pillai M. Study of pancreatic lipase inhibition kinetics and LC-QTOF-MS based identification of bioactive constituents of Momordica charantia fruits. Biomed Chromatogr. 2018;e4463. https://onlinelibrary.wiley.com/doi/abs/10.1002/bmc.4463
9. Azevedo BC, Morel LJF, Carmona F, Cunha TM, Contini SHT, Delprete PG, et al. Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma. J Ethnopharmacol. 2018;218:76–89. http://linkinghub.elsevier.com/retrieve/pii/S0378874117334566
10. de Freitas Morel LJ, de Azevedo BC, Carmona F, Contini SHT, Teles AM, Ramalho FS, et al. A standardized methanol extract of Eclipta prostrata (L.) L. (Asteraceae) reduces bronchial hyperresponsiveness and production of Th2 cytokines in a murine model of asthma. J Ethnopharmacol. 2017;198:226–34. http://linkinghub.elsevier.com/retrieve/pii/S0378874116323121
11. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277–85. https://pubmed.ncbi.nlm.nih.gov/15003729/
12. Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol. 1999;162(10):6284–93. https://www.jimmunol.org/content/162/10/6284.short
13. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282(5397):2258–61. https://www.science.org/doi/abs/10.1126/science.282.5397.2258
14. Krawinkel MB, Keding GB. Bitter gourd (Momordica charantia): a dietary approach to hyperglycemia. Nutr Rev. 2006;64:331–7. http://www.ncbi.nlm.nih.gov/pubmed/16910221
15. El Batran SAES, El-Gengaihi SE, El Shabrawy OA. Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats. J Ethnopharmacol. 2006;108(2):236–42. http://www.ncbi.nlm.nih.gov/pubmed/16815658
16. Yang SJ, Choi JM, Park SE, Rhee EJ, Lee WY, Oh KW, et al. Preventive effects of bitter melon (Momordica charantia) against insulin resistance and diabetes are associated with the inhibition of NF-κB and JNK pathways in high-fat-fed OLETF rats. J Nutr Biochem. 2015;26(3):234–40. http://www.sciencedirect.com/science/article/pii/S095528631400237X
17. Rahman IU, Khan RU, Rahman KU, Bashir M. Lower hypoglycemic but higher antiatherogenic effects of bitter melon than glibenclamide in type 2 diabetic patients. Nutr J. 2015;14(1): 13. http://ezproxy.think.edu.au/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=25504465&site=ehost-live&scope=site&custid=s8454151
18. Kim SK, Jung J, Jung JH, Yoon N, Kang SS, Roh GS, et al. Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus. Complement Ther Med. 2020;52:102524. https://linkinghub.elsevier.com/retrieve/pii/S0965229920302491
19. Cortez-Navarrete M, Martínez-Abundis E, Pérez-Rubio KG, González-Ortiz M, Méndez-del Villar M. Momordica charantia administration improves insulin secretion in type 2 diabetes mellitus. J Med Food. 2018;21(7):672–77. http://www.liebertpub.com/doi/10.1089/jmf.2017.0114
20. Peter EL, Kasali FM, Deyno S, Mtewa A, Nagendrappa PB, Tolo CU, et al. Momordica charantia L. lowers elevated glycaemia in type 2 diabetes mellitus patients: systematic review and meta-analysis. J Ethnopharmacol. 2019;231:311–24. 10.1016/j.jep.2018.10.033
21. Jia S, Shen M, Zhang F, Xie J. Recent advances in momordica charantia: functional components and biological activities. Int J Mol Sci. 2017;18(12). 2555 https://www.mdpi.com/1422-0067/18/12/2555
22. Soo May L, Sanip Z, Ahmed Shokri A, Abdul Kadir A, Md Lazin MR. The effects of Momordica charantia (bitter melon) supplementation in patients with primary knee osteoarthritis: a single-blinded, randomized controlled trial. Complement Ther Clin Pract. 2018;32:181–6. https://linkinghub.elsevier.com/retrieve/pii/S1744388118301701
23. Liaw C, Huang H, Hsiao P, Zhang L, Lin Z, Hwang S, et al. 5β,19-Epoxycucurbitane Triterpenoids from Momordica charantia and their anti-inflammatory and cytotoxic activity. Planta Med. 2015;81(1):62–70. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1383307
24. Chao C-Y, Sung P-J, Wang W-H, Kuo Y-H. Anti-inflammatory effect of momordica charantia in sepsis Mice. Molecules. 2014; 19:12777–88. http://www.mdpi.com/1420-3049/19/8/12777/
25. Shivanagoudra SR, Perera WH, Perez JL, Athrey G, Sun Y, Wu CS, et al. In vitro and in silico elucidation of antidiabetic and anti-inflammatory activities of bioactive compounds from Momordica charantia L. Bioorganic Med Chem. 2019;27(14):3097–109. 10.1016/j.bmc.2019.05.035
26. Kobori M, Nakayama H, Fukushima K, Ohnishi-Kameyama M, Ono H, Fukushima T, et al. Bitter gourd suppresses lipopolysaccharide-induced inflammatory responses. J Agric Food Chem. 2008;56(11):4004–11. http://www.ncbi.nlm.nih.gov/pubmed/18489106
27. Lii C-K, Chen H-W, Yun W-T, Liu K-L. Suppressive effects of wild bitter gourd (Momordica charantia Linn. var. abbreviata ser.) fruit extracts on inflammatory responses in RAW 264.7 macrophages. J Ethnopharmacol. 2009;122(2):227–3. http://www.ncbi.nlm.nih.gov/pubmed/19330915
28. Nhiem NX, Yen PH, Ngan NTT, Quang TH, Kiem P Van, Minh C Van, et al. Inhibition of nuclear transcription factor-κB and activation of peroxisome proliferator-activated receptors in HepG2 cells by cucurbitane-type triterpene glycosides from Momordica charantia. J Med Food. 2012;15(4):369–377. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3308713&tool=pmcentrez&rendertype=abstract
29. Hogan SP. Recent advances in eosinophil biology. Int Arch Allergy Immunol. 2007;143:3–14. https://www.karger.com/Article/Abstract/101398
30. van Rensen ELJ, Evertse CE, van Schadewijk WAAM, van Wijngaarden S, Ayre G, Mauad T, et al. Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment. Allergy. 2009;64(1):72–80. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1398-9995.2008.01881.x
31. Davoine F, Lacy P. Eosinophil cytokines, chemokines, and growth factors: emerging roles in immunity. Front Immunol. 2014;5:1–17. 10.3389/fimmu.2014.00570
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Mar 1, 2022
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Lopes Frota, C. do P., Castro Ribeiro, A., Alvarenga Calil Filho, M. T., de Freitas Morel, L. J., Zambelli Ramalho, L. N., Amaral, J. C., Taleb Contini, S. H., Braulio da Fonseca, V. M., Carvalho Borges, M. de, Soares Pereira, A. M., & Carmona, F. (2022). Momordica charantia L. improves airway hyperresponsiveness and suppresses inflammation in a murine model of allergic asthma. Allergologia Et Immunopathologia, 50(2), 115-123. https://doi.org/10.15586/aei.v50i2.577
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How to Cite
Lopes Frota, C. do P., Castro Ribeiro, A., Alvarenga Calil Filho, M. T., de Freitas Morel, L. J., Zambelli Ramalho, L. N., Amaral, J. C., Taleb Contini, S. H., Braulio da Fonseca, V. M., Carvalho Borges, M. de, Soares Pereira, A. M., & Carmona, F. (2022). Momordica charantia L. improves airway hyperresponsiveness and suppresses inflammation in a murine model of allergic asthma. Allergologia Et Immunopathologia, 50(2), 115-123. https://doi.org/10.15586/aei.v50i2.577