T2MC- A poly-herbal that inhibits polymerization of intracellular sickle hemoglobin and regulates the expression of erythrocyte Ca2+ activated K+ channel

Document Type : Original article

Authors

1 Drug Research and Production Unit, Obafemi Awolowo University

2 Department of Hematology and immunology, College of medicne, Obafemi Awolowo University, Ile-Ife. Nigeria

3 Drug Research and Production Unit, faculty of Pharmacy Obafemi Awolowo University

Abstract

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 Kchannel, thereby preventing cell dehydration.
Recommended applications/industries: T2MC is a potent antisickling nutraceutical and could be used in the management of sickle cell disease.

Keywords


Article Title [فارسی]

T2MC- پلی گیاهی که از پلیمریزاسیون هموگلوبین داسی داخل سلولی جلوگیری کرده و بیان کانال های K + فعال شده توسط گلبول قرمز + Ca را تنظیم می کند

Authors [فارسی]

  • 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
Abstract [فارسی]

< 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 Kchannel, thereby preventing cell dehydration.
< Recommended applications/industries: T2MC is a potent antisickling nutraceutical and could be used in the management of sickle cell disease.

Keywords [فارسی]

  • Telfairia occidentalis
  • Moringa oleifera
  • Cnidoscolus aconitifolius
  • Sickle cell anemia
  • Red cell density
  • Gardos channel
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