Abstract
Introduction: Nigeria has the largest burden of Sickle Cell Disease (SCD) with estimated 100,000 new born affected annually. SCD is a Hemoglobin (Hb) disorder with the major form resulting from the substitution of a polar glutamate (Glu) by non-polar Valine (Val) in an invariant region of Hbβ chain-subunit. Species of Hb found in the sickle cell trait are HbA and HbS in a 60:40 proportion, in SCD only HbS, in the HbC disease only HbC, and in the SC disease it's HbS and HbC in a 50:50 equal proportion.
Objective: This paper reviews herbal medicines usage in sub-Saharan Africa (sSA) to ameliorate the crisis associated with SCD. The model Hb tetramer suggests a higher membrane affinity of HbS and HbC, promoting dehydration of RBCs, with concomitant in vivo crystallization. Some drawbacks using these herbal drugs include; poor bioavailability and the lack of proper pharmacovigilance monitoring procedures arising from weak governance structure combined with under reporting of herbal usage to physicians were discussed. Probable epigenetic loci that could be targeted using phytomedicines for effective SCD management were also discussed.
Methods: Using search engines, several databases including Google scholar, PubMed, Academic Resource Index were utilized as a source for relevant publications/ literature. The protein coordinates for the Hb tetramer were obtained from the Protein Data Bank (PDB).
Conclusion: Manipulation of epigenetics to achieve better SCD management involves careful thinking. Herein, we discuss some epigenetic interactions that could be putatively tweaked with a view of enhancing soluble bioactive small molecular components with the potential to reactivate γ -globin genes, thereby boosting immune response in patient with SCD.
Keywords: SCD, hemoglobinopathies, phytomedicines, epigenetics, pharmacokinetics, sickle cell disease.
Graphical Abstract
[1]
World Health Organization. Geneva: World Health Organization; 2011. Sickle cell disease and other haemoglobin disorders. [Online] Available from:
http://www.who.int/mediacentre/factsheets/fs308/en/
[3]
Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008; 86: 480-7.
[4]
Abere TA, Okoye CJ, Agoreyo FO, et al. Antisickling and toxicological evaluation of the leaves of Scoparia dulcis Linn (Scrophulariaceae). BMC Complement Altern Med 2015; 15: 414.
[5]
Word Health Organization. Sickle-cell disease: A strategy for the WHO African region, WHO 2010,
www.afro.who.int/ publications.
[6]
Piel FB, Patil AP, Rosalind E, et al. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat Commun 2010; 2(1): 104-12.
[7]
Nagel RL, Fabry ME, Steinberg MH. The paradox of hemoglobin SC disease. Blood Rev 2003; 17: 167-78.
[8]
Nagel RL, Lin MJ, Witkowska HE, Fabry ME, Bestak M, Hirsch RE. Compound heterozygosity for hemoglobin C and Korle-Bu: Moderate microcytic hemolytic anemia and acceleration of crystal formation. Corrected Blood 1993; 82(6): 1907-12.
[9]
Hirsch RE, Lin MJ, Nagel RL. The inhibition of hemoglobin C crystallization by hemoglobin F. J Biol Chem 1988; 263: 5936-9.
[10]
Hirsch RE, Rybicki AC, Fataliev NA, Lin MJ, Friedman JM, Nagel RL. A potential determinant of enhanced crystallization of Hbc: spectroscopic and functional evidence of an alteration in the central cavity of oxy HbC. Br J Haematol 1997; 98: 583-8.
[11]
Hirsch RE, Rybicki AC, Fataliev NA, Lin MJ, Friedman JM, Nagel RL. A potential determinant of enhanced crystallization of Hbc: Spectroscopic and functional evidence of an alteration in the central cavity of oxyHbC. Br J Haematol 1997; 98: 583-8.
[12]
Hirsch RE, Raventos-Suarez C, Olson JA, Nagel RL. Ligand state of intraerythrocytic circulating HbC crystals in homozygous CC patients. Blood 1985; 66: 775-7.
[13]
Kaul DK, Fabry ME, Nagel RL. Microvascular sites and characteristics of sickle cell adhesion to vascular endothelium in shear flow conditions: Pathophysiological implications. Proc Natl Acad Sci USA 1989; 86: 3356-60.
[14]
Fabry ME, Kaul DK, Raventos-Suarez C, Chang H, Nagel RL. SC cells have an abnormally high intracellular hemoglobin concentration: Pathophysiological consequences. J Clin Invest 1982; 70: 1315-20.
[15]
Park SY, Yokoyama T, Shibayama N, Shiro Y, Tame JR. 1.25 Å resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms. J Mol Biol 2006; 360: 690-701.
[16]
Berman HM, Westbrook J, Feng Z, et al. The Protein Data Bank. Nucleic Acids Res 2000; 28: 235-42.
[17]
Pettersen EF, Goddard TD, Huang CC, et al. UCSF Chimera--a visualization system for exploratory research and analy sis. J Comput Chem 2004; 25: 1605-12.
[18]
Ghatge MS, Ahmed MH, Omar AS, et al. Crystal structure of carbonmonoxy sickle hemoglobin in R-state conformation. J Struct Biol 2016; 194: 446-50.
[19]
Imaga NA. Phytomedicines and Nutraceuticals: Alternative therapeutics for sickle cell anaemia. Sci World J 2013; 2013269659
[20]
Abere TA, Egharevba CO, Chukwurah IO. Pharmacognostic evaluation and antisickling activity of the leaves of Securinega virosa Roxb. ex Willd (Euphorbiaceae). Afr J Biotechnol 2014; 13(40): 4040-5.
[21]
Morris CR. Alterations of the arginine metabolome in sickle cell disease: a growing 247 rationale for arginine therapy. Hematol Oncol Clin North Am 2014; 28(2): 301-21.
[22]
Erhabor O, Ibrahim BA, Abdulrahaman Y, et al. L arginine and no levels are diminished in Children of African Descent with Acute Vaso-Occlusive Sickle Cell Crisis in Sokoto, Nigeria. J Intern Med 2016; 2(2): 22-7.
[23]
Kato GJ, Hebbel RP, Stenberg MH, Gladwin MT. Vasculopathy in Sickle Cell Disease: Biology, Pathophysiology, Genetics, Translational Medicine and New Research Directions. Am J Hematol 2009; 84(9): 618-25.
[24]
Ameh SJ, Tarfa FD, Ebeshi BU. Traditional herbal management of Sickle Cell Anemia: Lessons from Nigeria. Anaemia 2012; 2012: 9-14.
[25]
Freire SM, Torres LM, Rogue NF, Souccar C, Lapa AJ. Analgesic activity of a triterpenes isolated from Scoparia dulcis Linn (Vassourinha). Mem Inst Oswaldo Cruz 1991; 86: 149-51.
[26]
Sulaiman CT, Gopalakrishnan VK. Radical scavenging and in-vitro Hemolytic Activity of Aqueous Extracts of Selected Acacia Species. J Appl Pharmaceutical Sci 2013; 3(03): 109-11.
[27]
Malviya S, Rawat S, Kharia A, Verma M. Medicinal attributes of Acacia nilotica Linn. - A comprehensive review on ethnopharmacological claims. Int J Pharm Life Sci 2011; 2(6): 830-7.
[28]
Li X, Wang H, Liu C, Chen R. Chemical constituents of Acacia catechu. Zhongguo Zhongyao Zazhi 2010; 35(11): 1425-7.
[29]
Sofowora A. Medicinal plants and traditional medicine in Africa. Spectrum books limited Ibadan. 2008; p. 356-374.
[30]
Sahu M, Singh V, Yadav S, Harris KK. Plant extracts with antisickling propensities: a feasible succor towards sickle cell disease management- a mini review. J Phytol 2012; 4(3): 24-9.
[31]
Agnihotri S, Wakode S, Agnihotri A. An overview on anti-inflammatory properties and chemo-profiles of plants used in traditional medicine. Indian J Nat Prod Resour 2010; 1(2): 150-67.
[32]
Okwu DE, Ukanwa N. Isolation, characterization and antibacterial activity screening of anthocyanidine glycosides from Alchornea cordifolia (Schumach. And Thonn.) Mull Arg leaves E-. J Chem 2010; 7(1): 41-8.
[33]
Mpiana PT, Tshibangu DST, Shehonde OM, Ngbolua KN. In-vitro antidrepanocytary activity (antisickle cell anaemia) of some Congolese plants. Phytomedicine 2007; 14(2-3): 192-5.
[34]
Otunola GO, Oloyede OB, Oladiji AT, Afolayan AJ. Comparative analysis of the chemical composition of three spices – Allium sativum L., Zingiber officinale Rosc. and Capsicum frutescens L. commonly consumed in Nigieria. Afr J Biotechnol 2010; 9(41): 6927-31.
[35]
Yisa J, Egila JN, Darlinton AO. Chemical composition of Annona senegalensis from Nupe land, Nigeria. Afr J Biotechnol 2010; 9(26): 4106-9.
[36]
Fadeyi OE, Fabiyi OA, Olatunji GA, Ahmed A. Comparative in Vitro and Screenhouse Response of Abelmoschus esculentus Infected with Meloidogyne Incognita to Anacardium. University of Mauritius Research Journal 2016; p. 22.
[37]
Mpiana PT, Ngbolua KTNN, Bokota MT, et al. In vitro effects of anthocyanin extracts from Justicia secunda Vahl on the solubility of Haeemoglobin S and membrane stability of sickle erythrocytes. Blood Transfus 2010; 8(4): 248-54.
[38]
Pal D, Mishra P, Sachan N, Ghosh AK. Biological activities and medicinal properties of Cajanus cajan (L) Millsp. J Adv Pharm Technol Res 2011; 2(4): 207-14.
[39]
Zu YG, Liu XL, Fu YJ, et al. Chemical composition of the SPE-CO extracts from Cajanus cajan (L.) Huth and their antimicrobial activity in vitro and in vivo. Phytomed 2010; 17: 1095-101.
[40]
Foster S. Green Tea (Camellia sinensis). Alternative Medicine Review Monographs Thorne Inc 2002; 200-204.
[41]
Ohnishi ST, Ohnishi T, Ogunmola GB. Green tea extract and aged garlic extract inhibit anion transport and sickle cell dehydration in-vitro. Blood Cells Mol Dis 2001; 27: 148-57.
[42]
Afolabi IS, Osikoya IO, Fajimi OD, Usoroh PI. zeylanica and Uvaria. Afr J Biotechnol 2012; 9(53): 9032-6.
[43]
Oduola T, Adeniyi FAA, Ogunyemi EO, Bello IS, Idowu TO. Antisickling agent in an extract of unripe pawpaw (Csarica papaya). Afr J Biotechnol 2006; 5(20): 1947-9.
[44]
Elumalai A, Mathangi N, Didala A, Kasarla R, Venkatesh Y. A Review on Ceiba pentandra and its medicinal features. Asian J Pharm Technol 2012; 2(3): 83-6.
[45]
Soladoye MO, Chukwuma EC. Phytochemical analysis of the stem and root of Cissus populnea (Vitaceae) – an important medicinal plant in Central Nigeria. Phytol Balcanica 2012; 18(2): 149-53.
[46]
Simeone EI, Tufon EN, Victor ON, Noel NN. Antisickling potential of the ethanol seed extracts of Vigna unguiculata and Vigna subterranean. Int J Biochem Biotechnol 2012; 1(9): 226-9.
[47]
Moody JO, Ojo O, Omotade OO, Adeyemo AA, Olusese PE, Ogundipe A. Anti-sickling potential of a Nigerian herbal formular and the major plant component Cissus populnea L. CPK. Phytother Res 2003; 10: 1137-76. a
[48]
Ejele AE, Akpan IO, Ogukwe CE, Onyeocha VO, Ukiwe LN. Bioassay-guided isolation and partial characterization of an antisickling compound from Enantia chlorantha. Intern Res J Biochem Bioinform 2012; 2(7): 149-54.
[49]
Singh J, Baghotia A, Goel SP. Eugenia caryophyllata Thunberg (Family Myrtaceae): A Review. IJRPBS 2012; 3(4): 1469-75.
[50]
Chaieb K, Hajlaoui H, Zmantar T, et al. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): A short review. Phytother Res 2007; 21(6): 501-6.
[51]
Wambebe C, Khamofu H, Momoh JA, et al. Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with sickle cell disorder. Phytomedicine 2001; 8(4): 252-61.
[52]
Mpiana PT, Mudogo V, Kabangu YF. Antisickling activity and thermostability of anthocyanins extract from a congolese plant, Hymenocardia acida Tul. (Hymenocardiaceae). Int J Pharmacol 2009; 5: 65-70.
[53]
Correa GM, Alcântara AFC. Chemical constituents and biological activities of species of Justicia - a review. Braz J Pharmacogn 2012; 22(1): 220-38.
[54]
Tshilanda DD, Mpiana PT, Onyamboko DNV, et al. Antisickling activity of butyl stearate isolated from Ocimum basilicum (Lamiaceae). Asian Pac J Trop Biomed 2014; 4(5): 393-8.
[55]
Gbadamosi IT, Adeyemi SB, Adeyemi AA, Moody JO. In vitro antisickling activities of two indigenous plant recipes in Ibadan, Nigeria. Int J Phytochem 2013; 4(2): 205-11.
[56]
Ohnishi ST, Ohnishi T, Ogunmola GB. Green tea extract and aged -garlic extract inhibit anion transport and sickle cell dehydration in vitro. Blood Cells Molecules, and Diseases 2001; 27: 148-57.
[57]
Ekanem AP, Udoh FV, Oku EE. Effects of ethanol extract of Piper guineense seeds (Schum. and Thonn) on the conception of mice (Mus musculus). Afr J Pharm Pharmacol 2010; 4(6): 362-7.
[58]
Tzeng SH, Ko WC, Ko FN, Teng CM. Inhibition of platelet aggregation by some flavonoids. Thromb Res 1991; 64: 91-100.
[59]
Kokkalou E, Souleles C. Flavonoid constituents of Pelergonium xasperum Enrh. Ex Willd. Geraniaceae. Plantes Med Phytother 1988; 22: 247-53.
[60]
Arukwe U, Amadi BA, Duru MKC, et al. Chemical composition of Persea americana leaf, fruit and seed. IJRRAS 2012; 11(2): 346-9.
[61]
Owolabi MA, Coker HAB, Jaja SI. Bioactivity of the phytoconstituents of the leaves of Persea Americana. J Med Plants Res 2010; 4(12): 1130-5.
[62]
Kubec R, Kim S, Musah RA. S-Substituted cysteine derivatives and thiosulfinate formation in Petiveria alliacea-Part II. Phytochemistry 2002; 61: 675-80.
[63]
Kubec R, Musah RA. Cysteine sulfoxide derivatives in Petiveria alliacea. Phytochemistry 2001; 58: 981-5.
[64]
Gosmann G, Gattuso S, Gattuso M, et al. Botanical (morphological, micrographic), chemical and pharmacological characteristics of Pfaffia species (Amaranthaceae) native to South Brazil. Braz J Pharm Sci 2003; 39(2): 142-7.
[65]
Mazzanti G, Braghiroli L. Analgesic, anti-inflammatory action of Pfaffia paniculata (Martius) Kuntze. Phytother Res 1994; 8: 413-6.
[66]
Adejumo COE, Kolapo AL, Roleola OP, Kasim LS. In vitro antisickling activities and phytochemical evaluation of Plumbago. Altern Med 2010; 2(3): 282-301.
[67]
Vijayakumar R, Senthilvelan M, Ravindran R, Devi RS. Plumbago zeylanica action on blood coagulation profile with and without blood volume reduction. Vascul Pharmacol 2006; 45(2): 86-90.
[68]
Iyamu EW, Turner EA, Asakura T. Niprisan (Nix-0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions. Br J Haematol 2003; 122(6): 1001-8.
[69]
Iyamu EW, Turner EA, Asakura T. In vitro effects of Niprisan (Nix 0699). A natural occurring potent antisickling agent. Br J Haematol 2002; 118(1): 337-43.
[70]
Anowi CF, Umeokoli BO, Onyegbule AF, Okonkwo C, Chibeze I. Analgesic, phytochemical and acute toxicity evaluation of the methanol extract of the leaves of Pterocarpus santalinoides- Family Fabacea. IJPSR 2012; 3(7): 2018-23.
[71]
Okpuzor J, Adebesin O, Ogbunugafor H, Amadi I. The potential of medicinal plants in sickle cell disease control: A review. Int J Biomed Health Sci 2008; 4(2): 47-55.
[72]
Abugri DA, Tiimob BJ, Apalangya VA, Pritchett G, McElhenney WH. Bioactive and nutritive compounds in Sorghum bicolor (Guinea corn) red leaves and their health implication. Food Chem 2013; 138(1): 718-23.
[73]
Mpiana PT, Ngbolua KN, Mudogo V, et al. Anti Sickle Erythrocytes Haemolysis Properties and Inhibitory Effect of Anthocyanins Extracts of Trema orientalis (Ulmaceae) on the Aggregation of Human Deoxyhemoglobin S in vitro. J Med Sci 2011; 11: 129-37.
[74]
Elekwa I, Monanu MO, Anosike EO. In vitro effects of aqueous extracts of Zanthxylum macrophyla roots on adenosine triphosphatases from human erythrocytes of different genotypes. Biokemistri 2005; 17(1): 19-25.
[75]
Adesina SK. The Nigerian Xanthoxylum; Chemical and Biological Values. Afr J Trad Compl Alternat Med 2005; 2(3): 282-301.
[76]
Ameh SJ, Obodozie OO, Chindo BA, Babalola PC, Gamaniel KS. Herbal clinical trials-historical development and application in the 21st Century. Pharmacologia 2012; 3: 121-31.
[77]
Meena S, Varsha S, Somnath Y, Harris KK. Plant extracts with antisickling propensities: A feasible succour towards sickle cell disease management- a mini review. J Phytol 2012; 4(3): 24-9.
[78]
Ameh SJ, Tarfa FD, Ebeshi BU. Traditional Herbal Management of Sickle Cell Anemia: Lessons from Nigeria. Anemia 2012; 2012607436
[79]
Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12: 413-20.
[80]
Gupta S, Kesarla R, Omri A. Formulation Strategies to Improve the Bioavailability of Poorly Absorbed Drugs with Special Emphasis on Self-Emulsifying Systems. ISRN Pharm 2013; 2013848043
[81]
Ang HH. Analysis of lead content in herbal preparations in Malaysia. Hum Exp Toxicol 2003; 22: 445-51.
[82]
Ang HH, Lee EL, Cheang HS. Determination of mercury by cold vapor atomic absorption spectrophotometer in tongkat ali preparations obtained in Malaysia. Int J Toxicol 2004; 23: 65-71.
[83]
Parab S, Kulkarni RA, Thatte U. Heavy metals in herbal medicines. Indian J Gastroenterol 2003; 22: 111-2.
[84]
Busari AA, Mufutau MA. High prevalence of complementary and alternative medicine use among patients with sickle cell disease in a tertiary hospital in Lagos, South West, Nigeria. BMC Complement Altern Med 2017; 17: 299.
[85]
Oshikoya KA, Senbanjo IO, Njokanma OF, Soipe A. Use of complementary and alternative medicines for children with chronic health conditions in Lagos. BMC Complement 2008; 8: 66.
[86]
Phua DH, Zosel A, Heard K. Dietary supplements and herbal medicine toxicities-when to anticipate them and how to manage them. Int J Emerg Med 2009; 2(2): 69-76.
[87]
Adeyeye M, Gbadero D, Farayola L, Olalere N. Evaluation of an Undocumented Polyherbal (Faradin®) Used for the Treatment of Sickle Cell Disease in West Africa. Part I: Phytochemistry and Ex-vivo Anti-sickling Study. BJPR 2017; 17(1): 1-14.
[88]
Wanwimolruk S, Prachayasittikul V. Cytochrome P450 mediated herbal drug interactions (Part 1). EXCLI J 2014; 13: 347-91.
[89]
Hermann R, von Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012; 78: 1458-77.
[90]
Verma A, Gupta AK, Kumar A, Khan PK. Cytogenetic toxicity of Aloe vera (a medicinal plant). Drug Chem Toxicol 2012; 35(1): 32-25.
[91]
Wang BQ. Salvia miltiorrhiza: Chemical and pharmacological review of a medicinal plant. J Med Plants Res 2010; 4(25): 2813-20.
[92]
Barbosa-Ferreira M, Dagli ML, Maiorka PC, Gorniak SL. Sub-acute intoxication by Senna occidentalis seeds in rats. Food Chem Toxicol 2005; 43(4): 497-503.
[93]
Lanski SL, Greenwald M, Perkins A, Simon HK. Herbal therapy use in a paediatric emergency department population: expect the unexpected. Paediatrics 2003; 111: 981-5.
[94]
Awang DV, Fugh-Berman A. Herbal interactions with cardiovascular drugs. J Cardiovasc Nurs 2002; 16(4): 64-70.
[96]
Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs 2001; 61: 2163-75.
[97]
Akinleye MO, Amaeze OU, Opeodu OT, Okubanjo OO. Effect of Ciklavitβ - a Nigerian Poly-herbal Formulation on the Dissolution Profile of Proguanil Tablets: Potential for Herb-drug Interaction. BJPR 2016; 12(6): 1-9.
[98]
Thorne S, Paterson B, Russell C, Schultz A. Complementary/alternative medicine in chronic illness as informed self-care decision making. Int J Nurs Stud 2002; 39(7): 671-83.
[99]
Nayyar GM, Attaran A, Clark JP, et al. Responding to the pandemic of falsified medicines. Am J Trop Med Hyg 2015; 92(6)(Suppl.): 113-8.
[100]
Falodun A. Herbal Medicine in Africa-Distribution, Standardization and Prospects. Res J Phytochem 2010; 4: 154-61.
[101]
Falodun A, Qadir MI, Choudhary MI. Isolation and characterization of xanthine oxidase inhibitory constituents of Pyrenacantha staudtii. Yao Xue Xue Bao 2009; 44: 390-4.
[102]
Idoko OT, Kochhar S, Agbenyega TE, Ogutu B, Ota MO. Impact, challenges, and future projections of vaccine trials in Africa. Am J Trop Med Hyg 2013; 88(3): 414-9.
[103]
Puppalwar G, Mourya M, Kadhe G, Mane A. Conducting clinical trials in emerging markets of sub-Saharan Africa: Review of guidelines and resources for foreign sponsors. Open Access J Clin Trials 2015; 7: 23-34.
[104]
Ndomondo-Sigonda M, Miot J, Naidoo S, Dodoo A, Kaale E. Medicines Regulation in Africa: Current State and Opportunities. Pharmaceut Med 2017; 31: 383-97.
[105]
Chikowe I, Osei-Safo D, Harrison JJ, et al. Post-marketing surveillance of anti-malarial medicines used in Malawi. Malar J 2015; 14: 127.
[106]
Njeri M, Ouma C, Kibiego P, et al. Post market survey of antiretroviral medicines in Kenya. NASCOP, Nairobi. 2012.
[107]
WHO. Survey of the quality of selected antimalarial medicines circulating in six countries of sub-Saharan Africa. WHO Press, Geneva. 2011.
[108]
Ray PD, Yosim A, Fry RC. Incorporating epigenetic data into the risk assessment process for the toxic metals arsenic, cadmium, chromium, lead, and mercury: Strategies and challenges. Frontiers in Genetics 2014; 5: 201.
[109]
Lettre G, Sankaran VJ, Bezerra MAC, et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and -globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci USA 2008; 105(33): 11869-74.
[110]
Sebastiani P, Solovieffi N, Hartley SW, et al. Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study. Am J Hematol 2010; 85(1): 29-35.
[111]
Alsultan A, Ngo DA, Farrell JJ, et al. A functional promoter polymorphism of the δ-globin gene is a specific marker of the Arab-Indian haplotype. Amer Jnl Hematol 2012; 87: 824-6.
[112]
Hammer C, Begemann M, McLaren PJ, et al. Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses. Am J Hum Genet 2015; 97(5): 738-43.
[113]
Bauer DE, Kamran SC, Lessard S, et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 2013; 342: 253-.
[114]
Guillaume L, Vijay GS, Bezerra MAC, et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and_-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci USA 2008; 105(33): 11869-74.
[115]
Bogdanović O, Veenstra GJC. DNA methylation and methyl-CpG binding proteins: Developmental requirements and function. Chromosoma 2009; 118(5): 549-65.
[116]
Umesh K, Ujjawal S, Garima R. Reversal of hypermethylation and reactivation of glutathione S-transferase pi 1 gene by curcumin in breast cancer cell line. Tumour Biol 2017; 39(2)1010428317692258
[117]
Khor TO, Huang Y, Wu TY. Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem Pharmacol 2011; 82: 1073-8.
[118]
Axelsson AS, Tubbs E, Mecham B, et al. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Sci Transl Med 2017; 9(394): 4477.
[119]
Alli LA, Okoh MP. Phyto-Medicine in Gene(s) Targeting Future Direction for Sickle Cell Disease Management. Hereditary Genet 2016; 5: 2.
[120]
Arango D, Morohashi K, Yilmaz A, et al. Molecular basis for the action of a dietary flavonoid revealed by the comprehensive identification of apigenin human targets. Proc Natl Acad Sci USA 2013; 110(24): E2153-62.
[121]
Busch C, Burkard M, Leischner C, Lauer UM, Frank J, Venturelli S. Epigenetic activities of flavonoids in the prevention and treatment of cancer. Clin Epigenetics 2015; 7: 64.
[122]
Gilbert ER, Liu D. Flavonoids influence epigenetic-modifying enzyme activity:structure - function relationships and the therapeutic potential for cancer. Curr Med Chem 2010; 17(17): 1756-68.
[123]
Delcuve GP, Khan DH, Davie JR. Roles of histone deacetylases in epigenetic regulation: Emerging paradigms from studies with inhibitors. Clin Epigenetics 2012; 4(1): 5.
[124]
Ginzburg Y, Rivella S. beta-thalassemia: A model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. Blood 2011; 118: 4321-30.
[125]
Bassett SA, Barnett MPG. The Role of Dietary Histone Deacetylases (HDACs) Inhibitors in Health and Disease. Nutrients 2014; 6(10): 4273-301.
[126]
Kinnersley B, Labussiere M, Holroyd A, et al. Genome-wide association study identifies multiple susceptibility loci for glioma. Nat Commun 2015; 6: Article number: 8559.
Article Metrics
27
6