T2MC- A poly-herbal that inhibits polymerization of intracellular sickle hemoglobin and regulates the expression of erythrocyte Ca2+ activated K+ channel
محورهای موضوعی : مجله گیاهان دارویی
موجیسولا کریل-اولوتای
1
,
نوراح آکینولا
2
,
جوسف ابدانسی
3
1 - واحد تحقیق و تولید دارو ، دانشگاه اوبافمی اوولوو
2 - گروه هماتولوژی و ایمونولوژی ، دانشکده پزشکی ، دانشگاه اوبافمی اوولوو ، ایل-ایفه. نیجریه
3 - واحد تحقیق و تولید دارو ، دانشکده داروسازی دانشگاه اوبافمی اوولوو
کلید واژه: Moringa oleifera, Telfairia occidentalis, Cnidoscolus aconitifolius, Sickle cell anemia, Red cell density, Gardos channel,
چکیده مقاله :
Background & Aim:Telfairia occidentalis, Moringa oleifera and Cnidoscolus aconitifolius are nutritious vegetables used individually, or in different combinations as blood boosters in managing sickle cell anemia in South-Western Nigeria. Inthis study, we evaluated the antisickling properties of the polyherbal combination, as well as the mode(s) of action, using molecular biology techniques.Experimental: T. occidentalis, M. oleifera and C. aconitifolius leaves were extracted separately in ethanol after identification by a taxonomist. The extracts were combined in different ratios (TMC, T2MC, TM2C, TMC2) and evaluated at 4 mg/mL concentration for antisickling properties. Ciklavit®, an antisickling nutraceutical, was utilized as the positive control. We evaluated the combination (T2MC) for the rate of inhibition of polymerization of sickle hemoglobin (HbS), erythrocyte membrane stabilization, and rehydration of dense sickle red cells in vitro. The regulation of the Gardos channel, erythropoietin (EPO), mitogenesis, and antioxidant genes was assessed in vivo by harvesting and analyzing the bone marrows, kidneys, livers of Wistar rats administered with T2MC orally at 50 and 100 mg/kg body weight for 28 days. Folic acid was employed as the positive control.Results: The T2MC treated samples showed significantly higher (p <0.05) antisickling activities (95.4 ± 0.15% inhibition and 95.6 ± 0.28% reversal), and cell membrane stabilization (76.8 ± 0.05%) than the positive controls. Additionally, T2MC reduced the density of sickle red cells by 18.2 ± 0.86%, and showed inhibition of polymerization of HBS comparable to positive controls. Finally, T2MC down-regulated the expression of the Gardos-channel and the erythropoietin genes suggesting that T2MC works by inhibiting the activation of Ca2+activated K+channel, thereby preventing cell dehydration.Recommended applications/industries: T2MC is a potent antisickling nutraceutical and could be used in the management of sickle cell disease.
< Background & Aim:Telfairia occidentalis, Moringa oleifera and Cnidoscolus aconitifolius are nutritious vegetables used individually, or in different combinations as blood boosters in managing sickle cell anemia in South-Western Nigeria. Inthis study, we evaluated the antisickling properties of the polyherbal combination, as well as the mode(s) of action, using molecular biology techniques. < Experimental: T. occidentalis, M. oleifera and C. aconitifolius leaves were extracted separately in ethanol after identification by a taxonomist. The extracts were combined in different ratios (TMC, T2MC, TM2C, TMC2) and evaluated at 4 mg/mL concentration for antisickling properties. Ciklavit®, an antisickling nutraceutical, was utilized as the positive control. We evaluated the combination (T2MC) for the rate of inhibition of polymerization of sickle hemoglobin (HbS), erythrocyte membrane stabilization, and rehydration of dense sickle red cells in vitro. The regulation of the Gardos channel, erythropoietin (EPO), mitogenesis, and antioxidant genes was assessed in vivo by harvesting and analyzing the bone marrows, kidneys, livers of Wistar rats administered with T2MC orally at 50 and 100 mg/kg body weight for 28 days. Folic acid was employed as the positive control. < Results: The T2MC treated samples showed significantly higher (p < 0.05) antisickling activities (95.4 ± 0.15% inhibition and 95.6 ± 0.28% reversal), and cell membrane stabilization (76.8 ± 0.05%) than the positive controls. Additionally, T2MC reduced the density of sickle red cells by 18.2 ± 0.86%, and showed inhibition of polymerization of HBS comparable to positive controls. Finally, T2MC down-regulated the expression of the Gardos-channel and the erythropoietin genes suggesting that T2MC works by inhibiting the activation of Ca2+activated K+ channel, thereby preventing cell dehydration. < Recommended applications/industries: T2MC is a potent antisickling nutraceutical and could be used in the management of sickle cell disease.
Adejumo, O.E., Kolapo, A.L. and Akintomiwa, A.O. 2012. Moringa oleifera Lam. (Moringaceae) grown in Nigeria: In vitro antisickling activity on deoxygenated erythrocyte cells. Journal of Pharmacy and Bioallied Sciences, 4:118-22.
Akinola, N.O., Stevens, S.M.E., Franklin, I.M., Nash, B. and Stuart, J. 1992. Subclinical ischaemic episodes during the steady state of sickle cell anaemia. Journal of Clinical Pathology, 45:902-906.
Alada, A.R.A. 2000. The haematological effect of Telfeiria occidentalis diet preparation. African Journal of Biomedial Research, 3: 185-186.
Atabo, S., Umar, I.A., James, D.B. and Mamman, A.I. 2016. Sickled erythrocytes reversal and membrane stabilizing compounds in Telfairia occidentalis. Scientifica, 2016 :1568061.
Athanassiou, G., Moutzouri, A., Kourakli, A. and Zoumbos, N. 2006. Effect of hydroxyurea on the deformability of the red blood cell membrane in patients with sickle cell anemia. Clinical Hemorheology and Microcirculation, 35: 291–295.
Au, S.W., Gover, S., Lam, V.M. and Adams, M.J. 2000. Human glucose-6-phosphate dehydrogenase: The crystal structure reveals a structural NADP (+) molecule and provides insights into enzyme deficiency. Structure, 8: 293–303.
Awoyinka, O.A. and Balogun, I.O. 2007. Phytochemical screening and in vitro bioactivity of Cnidoscolus aconitifolius (Euphorbiaceae). Journal of Medicinal. Plant Research, 1: 63- 65.
Benkerrou, M.C., Alberti, N., Couque, Z., Haouari, A., Ba, F., Missud, P., Boizeau, L, et al. 2013. Impact of glucose-6-phosphate dehydrogenase deficiency on sickle cell anaemia expression in infancy and early childhood: a prospective study. British Journal of Haematology, 163: 646-654.
Brugnara, C., De Franceshi, L. and Alper, S.L. 1993. Inhibition of Ca2+ dependent K+ transport and cell dehydration in sickle erythrocytes by CLT and other imidazole derivatives. Journal of Clinical Investigation, 92: 520-526.
Brugnara, C., Gee, B., Armsby, C.C., Kurth, S., Sakamoto, M. and Rifai, N. 1996. Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. Journal of Clinical Investigation, 97: 1227-1234.
Brugnara, C., De Franceschi, L., Bennekou, P., Alper, S.L. and Christophersen, P. 2001. Novel therapies for prevention of erythrocyte dehydration in sickle cell anemia. Drug News Perspective, 14: 208-220.
Charache, S., Terrin, M.L., Moore, R.D., Dover, G.J., Barton, F.B., Eckert, S.V. et al. 1995. Effect of hydroxyurea on the frequency of painful crises in sickle cell Anemia: Investigators of the multicenter study of hydroxyurea in sickle cell anemia. The New England Journal of Medicine, 332: 1317–1322.
Chikezie, P.C., Chikezie, C.M. and Amaragbulem, P.I. 2011. Polymerization of human sickle cell hemoglobin (HbS) in the presence of three antimalarial drugs. African Journal of Biochemistry Research, 5: 39-42.
Cyril-Olutayo, C.M. and Agbedahunsi, J.M. 2015. Effects of the ethanolic extract of Cnidoscolus aconitifolius (Mill.) I.M. Johnst. on HbS red blood cells In Vitro. Nigerian Journal of Natural Products Medicine, 19:115-121.
Cyril-Olutayo, M.C., Agbedahunsi, J.M. and Akinola, N.O. 2018. The Mechanism of action of Moringa oleifera leaf extract used in managing sickle cell patients in South West Nigeria. Nigerian Journal Pharmacy Research, 14: 69-79.
Cyril-Olutayo, M.C., Agbedahunsi, J.M. and Akinola, N.O. 2019. Studies on the effect of a nutritious vegetable, Telfairia occidentalis, on HbSS blood. Journal of Traditional and Complementary Medicine, 9:156-162.
Dash, B.P., Archana, Y., Satapathy, N. and Naik, S.K. 2013. Search for antisickling agents from plants. Pharmacognosy Review, 7: 53–60.
Dedeken, L., Lê, P.Q., Azzi, N., Brachet, C., Heijmans, C., Huybrechts, S., Devalck. C., Rozen, L., Ngalula, M. and Ferster, A. 2014. Hematopoietic stem cell transplantation for severe sickle cell disease in childhood: a single center experience of 50 patients. British Journal of Haematology, 165:402-408.
Delaunay, J. 2007. The molecular basis of hereditary red cell membrane disorders. Blood Reviews, 21:1–20.
Eaton, W.A. and Hofrichter, J. 1990. Sickle cell hemoglobin polymerization. Advances in Protein Chemistry, 40: 263-279.
Egunyomi, A., Moody, J.O. and Eletu, O.M. 2009. Antisickling activities of two ethnomedicinal plant recipes used for the management of sickle cell anaemia in Ibadan, Nigeria. African Journal of Biotechnology, 8: 020-825.
El-Shabrany, O.A., El-Gindi, O.D., Melek, F.R., Abdel-Khalk, S.M. and Haggig, M.M. 1997. Biological properties of saponin mixtures of Fagonia creticaand Fagonia mollis. Fitoterapia, LXVIII, 219-222.
Eseyin, O.A., Sattar, M.A. and Rathore, H.A. 2014. A review of the pharmacological and biological activities of the aerial parts of Telfairia occidentalis Hook.f. (Cucurbitaceae). Tropical Journal of Pharmaceutical Research, 13:1761-1769.
Fasuyi, A.O. 2006. Nutritional potentials of some tropical vegetable leaf meals: Chemical characterization and functional properties. African Journal of Biotechnology, 5:49-53.
Ferrone, F.A. 2004. Polymerization and sickle cell disease: a molecular view. Microcirculation, 11:115-128.
Gillete, P.N., Misra, R., Wambebe, C., Asakura, T. and Pandey, R.C. 2004. Development of Niprisan, an antisickling phytopharmaceutical from traditional medicine: Lessons learned and challenges for the future. Fourth International Healthcare and Herbal Expo and Seminar, Source Book, New Delhi, India; 141-149.
Hartwell, L.H., Hood, L., Golgery, M.L., Reynolds, A.E., Silver, L.M. and Veres, R.C. 2000. Genetics: From genes to genomes 1st Ed. McGraw-Hill, New York, pp. 514-521.
Hulbert, M.L. and Shenoy, S. 2018. Hematopoietic stem cell transplantation for sickle cell disease: Progress and challenges. Pediatric Blood and Cancer, 65:e27263.
Imaga, N.A. 2013. Phytomedicines and nutraceuticals: alternative therapeutics for sickle cell anemia. The Scietific World Journal, 269659.
Iwu, M.M., Igboko, A.O., Onwubiko, H. and Ndu, U.E. 1988. Effect of cajaminose from Cajanus cajan on gelation and oxygen affinity of sickle cell hemoglobin. Journal of Ethnopharmacology, 20: 99-104.
Iyamu, E.W., Turner, E.A. and Asakura, T. 2002. In vitro effects of NIPRISAN (Nix-0699): A naturally occurring, potent anti-sickling agent. British Journal of Haematology, 118:337-343.
Mackie, L.H., Frank, R.S. and Hochmuth, R.M. 1987. Erythrocyte density separation on discontinuous Percoll gradients. Biorheology, 24: 227-230.
Messmann, R., Gannon, S., Sarnaik, S. and Johnson, R.M. 1990. Mechanical properties of sickle cell membranes. Blood, 75: 1711-1717.
Mordi, J.C. and Akanji, M.A. 2012. Phytochemical screening of the dried leaf extract of Cnidoscolus aconitifolius and associated changes in liver enzymes induced by its administration in Wistar rats. Current Research Journal of Biological Sciences, 4:153-158.
Moura, L.F.W.G., Netoc, J.X., Lopesc, T.D.P., Benjamin, S.R., Brito, F.C.R., Magalhães, F.E.A. et al. 2019. Ethnobotanic, phytochemical uses and ethnopharmacological profile of genus Cnidoscolus spp. (Euphorbiaceae): A comprehensive overview. Biomedicine Pharmacotherapy, 109:1670-1679.
Mpiana, P.T., Ngbolua, K.N., Bokota, M.T., Kasonga, T.K., Atibu, E.K. and Mudogo, V. 2010“In Vitro Effects of Anthocyanins Extracts from Justicia secunda Vahl on the Solubility of Hemoglobin S and Membrane Stability of Sickle Erythrocytes,” Blood Transfusion, 8: 248-254.
Ojiako, E.N. 2014. Phytochemical analysis and antimicrobial screening of Moringa oleifera leaves extract. The International Journal of Engineering and Science (IJES), 3(3): 32-35.
Osuntokun, O.T., Oluduro, A.O., Idowu, T.O. and Omotuyi AO. 2017. Assessment of Nephrotoxicity, Anti-Inflammatory and Antioxidant Properties of Epigallocatechin, Epicatechin and Stigmasterol Phytosterol (Synergy) Derived from Ethyl Acetate Stem Bark Extract of Spondias Mombin on Wistar Rats Using Molecular Method of Analysis. Journal of Molecular Microbiology, 1:5.
Oyewole, O.I., Malomo, S.O. and Adebayo, J.O. 2008. Comparative studies on antisickling properties of thiocyanate, tellurite and hydroxyurea. Pakistan Journal of Medical Sciences, 24:18–22.
Pathak, D., Pathal, K. and Singla, A.K. 1991. Flavonoids as medicinal agents: Recent Advances. Fitoterapia, LXII, 371-376.
Sadique, J., Al-Rqodah, W.A., Baghhath, M.F. and El-Ginay, R.R. 1989. The bioactivity of certain medicinal plants on the stabilization of the RBC system. Fitoterapia, LXVI: 525-532.
Salman, T.M., Olayaki, L.A. and Oyeyemi, W.A. 2008. Aqueous extract of Telfairia occidentalis leaves reduces blood sugar and increases haematological and reproductive indices in male rats. African Journal of Biotechnology, 7: 2299-2303.
Saturnin, H.B.V., Mamatchi, M., Eunice, K.N., Balbine, F.A., Lumo, A.K., Paul, A., Bonaventure, A.C. and Amouzou Kou’santa, A. 2018. Pharmacological effects of Moringa oleifera(Lam.) leaves powder in the treatment of anaemia in children aged from 6 to 30 months in Lissezoun in Central Benin. Biochemistry and Physiology, 7: 244. Doi: 10.4172/2168-9652.1000244.
World Health Organization, 2001. Updated estimates of the frequency of the hemoglobin disorders in each country. www.who.ch/programmes/ncd/hgm/haemogl.htm.
World Health Organization, 2017. Sickle cell disease, Report by the Regional Office for Africa.
