[en] Sickle cell disease (SCD) is a neglected tropical disease (NTD) associated with severe health consequences, including death. Hibiscus tiliaceus L., from the Malvaceae family, is used traditionally in Kisangani, Democratic Republic of the Congo (DRC), to alleviate symptoms of SCD. However, the specific phytochemicals responsible for the observed therapeutic effects remain unclear. This study aims to characterize the aqueous leaf extract of H. tiliaceus and assess its biological activity against sickle cell disease, including its antisickling, antioxidant, and anti-inflammatory effects. Using techniques such as TLC, HPLC-UV/DAD, LC-MS, and NMR, we identified kaempferol 3-O-rutinoside and rutin in the aqueous extract of H. tiliaceus leaves. Rutin exhibited potent antioxidant and anti-inflammatory activities, with IC50 values of 5 µg/mL and 2.5 µg/mL, respectively. Conversely, kaempferol 3-O-rutinoside demonstrated superior antisickling activity, normalizing sickled red blood cells with an IC50 < 12.5 µg/mL. Due to the pathophysiology of SCD, which involves the polymerization of red blood cells, which induces oxidative stress and an inflammatory response, this study suggests the importance of H. tiliaceus for the management of SCD. Additionally, the combined effect of molecules in H. tiliaceus will help in normalizing erythrocytes, inhibiting free radicals generated by early hemolysis, thus contributing to inflammatory processes reduction. This finding provides evidence and validates the traditional use of H. tiliaceus aqueous extract for the management of SCD.
Research Center/Unit :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Borive Amani, Marguerite ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Kisangani, Kisangani 2012, Democratic Republic of the Congo
Frederich, Michel ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Jansen, Olivia ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Bonnet, Olivier ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Ledoux, Allison ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Memvanga, Patrick, B ; Centre de Recherche et d'Innovation Technologique en Environnement et en Sciences de la Santé (CRITESS), Faculty of Pharmaceutical Sciences, University of Kinshasa, Kinshasa XI 212, Democratic Republic of the Congo
Batina Agasa, Salomon; Department of Internal Medicine, Faculty of Medicine and Pharmacy, University of Kisangani, Kisangani 2012, Democratic Republic of the Congo
Mouithys-Mickalad, Ange ; Université de Liège - ULiège > Centres généraux > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Marini Djang'Eing'A, Roland ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Language :
English
Title :
Phytochemical Characterization of Hibiscus tiliaceus L. Leaves and Evaluation of Their Antisickling, Antioxidant, and Anti-Inflammatory Activities.
World Health Organization Available online: https://www.who.int/news-room/questions-and-answers/item/neglected-tropical-diseases (accessed on 15 November 2024)
Hotez P.J. Aksoy S. Brindley P.J. Kamhawi S. What constitutes a neglected tropical disease? PLoS Negl. Trop. Dis. 2020 14 e0008001 10.1371/journal.pntd.0008001 31999732
Ware R.E. Is Sickle Cell Anemia a Neglected Tropical Disease? PLoS Negl. Trop. Dis. 2013 7 e2120 10.1371/journal.pntd.0002120
Tshilolo L. Gonzalez J.P. Stigmatization of sickle cell disease across the Democratic Republic of Congo: A presentation of two cases Int. Health Trends Perspect. 2024 4 181 186 10.32920/ihtp.v4i2.2104
World Health Organization Available online: https://www.afro.who.int/health-topics/sickle-cell-disease (accessed on 8 April 2025)
Williams T.N. Sickle Cell Disease in Sub-Saharan Africa Hematol. Oncol. Clin. N. Am. 2016 30 343 358 10.1016/j.hoc.2015.11.005 27040958
Tshilolo L. Aissi L.M. Lukusa D. Kinsiama C. Wembonyama S. Gulbis B. Vertongen F. Neonatal screening for sickle cell anaemia in the Democratic Republic of the Congo: Experience from a pioneer project on 31 204 newborns J. Clin. Pathol. 2009 62 35 38 10.1136/jcp.2008.058958 19103857
Katawandja A.L. Kingwengwe A.A. Shindano E.M. Knowledge and Practices of Health Providers on the Diagnosis and Biological Monitoring of Sickle Cell Disease in the City of Kindu, in the East of the Democratic Republic of Congo OALibrary 2020 7 1 11 10.4236/oalib.1106757
Kasai E.T. Boemer F. Marini R.D. Kadima J.N. Batina S.A. Ngbonda N.D. Alworong’a J.P.O. Systematic Screening of Neonatal Sickle Cell Disease with HemoType Sickle cell Kit-Test: Case Study and Literature Review Open J. Blood Dis. 2020 10 12 21 10.4236/ojbd.2020.101002
Shongo Y.P.M. Sickle cell disease in the Democratic Republic of Congo/DRC: Burden of a heavier price J. Med. Public Health 2022 1 30 33
Akinyemi O.D.O. Oguche S. Kehinde A. Edache S.O. Tolulope O.A. Ijeoma N.D. Ayuba I.Z. Atiene S.S. Effectiveness and Safety of Hydroxyurea in the Treatment of Sickle Cell Anaemia Children in Jos, North Central Nigeria J. Trop. Pediatr. 2020 66 290 298 10.1093/tropej/fmz070
Wambebe C.O. Bamgboye E.A. Bidemi O.B. Hadiza K. Jafaru A.M. Ekpeyong M. Benedict S.A. Njoku S.O. Nasipuri N.R. Olubayo O.K. et al. Efficacy of Niprisan in the prophylactic management of patients with sickle cell disease Curr. Ther. Res. 2001 62 26 34 10.1016/S0011-393X(01)80039-4
Cordeiro N.J.V. Oniyangi O. Phytomedicines (medicines derived from plants) for sickle cell disease Cochrane Database Syst. Rev. 2004 3 CD004448 10.1002/14651858.CD004448
Tshilolo L. Tomlinson G. Williams T.N. Brígida S. Olupot-Olupot P. Lane A. Banu A. Susan E.S. Latham T.S. Ware R.E. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa N. Engl. J. Med. 2019 380 121 131 10.1056/NEJMoa1813598
Mukinayi B.M. Cibeyibeyi G.K. Disashi G.T. Gulbis B. Sickle cell disease in the Democratic Republic of Congo: What are the obstacles to treatment with hydroxyurea? Pan. Afr. Med. J. 2021 38 41 10.11604/pamj.2021.38.41.18718 33854670
Bernaudin F. Why, Who, When, and How? Rationale for Considering Allogeneic Stem Cell Transplantation in Children with Sickle Cell Disease J. Clin. Med. 2019 8 1523 10.3390/jcm8101523 31546720
Nurain I.O. Bewaji C.O. Jarrett S.J. Robertson D.D. Zhang Y. Potential of Three Ethnomedicinal Plants as Antisickling Agents Mol. Pharm. 2017 14 172 182 10.1021/acs.molpharmaceut.6b00767
Ibrahim S. Ukwuani-Kwaja A.N. Maimuna H. Ethnobotanical Survey and In vitro Antisickling Effect of Some Selected Medicinal Plants Asian J. Res. Biochem. 2021 9 1 14 10.9734/ajrb/2021/v9i130190
Yembeau N.L. Biapa Nya P.N. Pieme C.A. Tchouane K.D. Kengne Fotsing C.B. Nya Nkwikeu K.J. Feudjio A.F. Telefo P.B. Ethnopharmacological Study of the Medicinal Plants Used in the Treatment of Sickle Cell Anemia in the West Region of Cameroon Evid.-Based Complement. Altern. Med. 2022 2022 5098428 10.1155/2022/5098428
Jeffery T.D. Matthew L.R. A review of the effectiveness of hibiscus for treatment of metabolic syndrome J. Ethnopharmacol. 2021 270 113762 10.1016/j.jep.2020.113762
Abdul-Azeez Z.M. Shihab H.M. Possible Protective Anticancer effect of Ethanol Fraction of Iraqi Hibiscus tiliaceus L. Leaves Extract on Diethylnitrosamine-induced Hepatocarcinogenesis in Male Rats Iraqi J. Pharm. Sci. 2023 32 145 155 10.31351/vol32issSuppl.pp145-155
Rosa R.M. Melecchi M.I. Halmenschlager R.C. Abad F.C. Simoni C.R. Carama E.B. Gashenriques J.T. Affi J.S. Ramos A. Antioxidant and Antimutagenic Properties of Hibiscus tiliaceus L. Methanolic Extract. J. Agric Food Chem. 2006 54 7324 7330 10.1021/jf061407b
Vanzella C. Bianchetti P. Sbaraini S. Vanzin S.I. Melecchi M.I.S. Caramão E.B. Siqueira I.R. Antidepressant-like effects of methanol extract of Hibiscus tiliaceus flowers in mice BMC Complement. Altern. Med. 2012 12 41 10.1186/1472-6882-12-41 22494845
Andriani Y. Hanifah W. Kholieqoh A.H. Majid F.A.A. Hermansyah H. Amir H. Muhammad T.S.T. Antibacterial activity of hexane and methanol fractions of some selected plants against Klebsiella pneumoniae J. Adv. Pharm. Technol. Res. 2023 14 220 10.4103/JAPTR.JAPTR_183_23 37692002
Trung V.T. Linh K.T.P. Thu Trang D. Thanh Binh P. The Cuong N. Thanh N.V. Thao N.P. Antimicrobial constituents from the leaves of Hibiscus tiliaceus L. Nat. Prod. Res. 2023 1 1050 1057 10.1080/14786419.2023.2293137
Surana A.R. Kumbhare M.R. Gunjal A.R. Goswami S.S. Ghuge D.M. Chemical characterization, thrombolytic and antioxidant activity of Hibiscus tiliaceus L. leaves Nat. Prod. Res. 2022 36 6106 6110 10.1080/14786419.2022.2051705 35306945
Abdul-Awal S.M. Nazmir S. Nasrin S. Nurunnabi S.R. Uddin S.J. Evaluation of pharmacological activity of Hibiscus tiliaceus Springer Plus 2016 5 1209 10.1186/s40064-016-2891-0
Vinh L.B. Nguyet N.T.M. Thanh C.D. Huong T.T. Tram L.H. Van Thong N. Kim Y.H. Chemical constituents of Vietnamese mangrove Hibiscus tiliaceus with antioxidant and alpha-glucosidase inhibitory activity Nat. Prod. Res. 2021 35 2899 2904 10.1080/14786419.2019.1672065
Hidayati D.N. Maghfiroh H.R. Safitri A. Antibacterial activity of ethanol extracts of Hibiscus tiliaceus L. leaves from different extraction methods against Escherichia coli and Staphylococcus aureus Pharmaciana 2023 13 137 10.12928/pharmaciana.v13i1.24671
Chen J.J. Huang S.Y. Duh C.Y. Chen I.S. Wang T.C. Fang H.Y. A New Cytotoxic Amide from the Stem Wood of Hibiscus tiliaceus Planta Med. 2006 72 935 938 10.1055/s-2006-931604
Bassant M.M.I. Marawan A.E. Doha H.A.B. Emad N.Z. Souad E.G. Mouchira A.S. A pharmacological and toxicological biochemical study of cardiovascular regulatory effects of hibiscus, corn silk, marjoram, and chamomile Heliyon 2024 10 22659 10.1016/j.heliyon.2023.e22659
Lê Huyền T. Trần T.H. Nguyễn V.T. Nguyễn H.M. Flavonoid Glycoside Constituents from the Leaves of Hibiscus tiliaceus JST Eng. Technol. Sustain. Dev. 2021 31 7 11 10.51316/jst.151.etsd.2021.31.3.2
Bamba Fall A. Vanhaelen-Fastré R. Vanhaelen M. Lo I. Toppet M. Ferster A. Fondu P. In Vitro Antisickling Activity of a Rearranged Limonoid Isolated from Khaya senegalensis Planta Med. 1999 65 209 212 10.1055/s-1999-14083 10232063
Govaerts R. Nic Lughadha E. Black N. The World Checklist of Vascular Plants, a continuously updated resource for exploring global plant diversity Sci. Data 2021 8 215 10.1038/s41597-021-00997-6
Chaouqi S. Moratalla-López N. Alonso G.L. Lorenzo C. Zouahri A. Asserar N. Haidar E.M. Guedira T. Effect of Soil Composition on Secondary Metabolites of Moroccan Saffron (Crocus sativus L.) Plants 2023 12 711 10.3390/plants12040711
Mudau H.S. Mokoboki H.K. Ravhuhali K.E. Mkhize Z. Effect of Soil Type: Qualitative and Quantitative Analysis of Phytochemicals in Some Browse Species Leaves Found in Savannah Biome of South Africa Molecules 2022 27 1462 10.3390/molecules27051462 35268563
Pant P. Pandey S. Dall’Acqua S. The Influence of Environmental Conditions on Secondary Metabolites in Medicinal Plants: A Literature Review Chem. Biodivers. 2021 18 2100345 10.1002/cbdv.202100345
Ramani S. Basak S. Puneeth S. Karthick M. Malathi R. Anti Hemolytic Activity of Rutin in case of Phenyl Hydrazine induced Hemolysis Curr. Trends Biotechnol. Pharm. 2021 15 467 470 10.5530/ctbp.2021.3s.41
Muhammad A. Waziri A.D. Forcados G.E. Sanusi B. Sani H. Malami I. Abubakar I.B. Oluwatoyin H.Y. Adinoyi O.A. Mohammed H.A. Sickling-preventive effects of rutin is associated with modulation of deoxygenated haemoglobin, 2,3-bisphosphoglycerate mutase, redox status and alteration of functional chemistry in sickle erythrocytes Heliyon 2019 5 01905 10.1016/j.heliyon.2019.e01905 31297461
Gbolo B.Z. Ngbolua K.N. Ciala B.N. Semay I. Mpiana P.T. Gerbaux P. Duez P. LC-MS/MS Analysis of crude Flavonoid Compounds from Justicia secunda from Democratic Republic of the Congo and evaluation of their antisickling Activity Nat. Resour. Hum. Health 2024 4 387 397 10.53365/nrfhh/192594
Ekutsu G.E. Kitete E.M. Masengo C.A. Gbolo B.Z. Iteku J.B. Mavakala B.K. Mpiana P.T. Mudogo V. Ngbolua K.N. Molecular Docking Simulation of the antisickling activity of Naringenin-7-O-glucoside and Kaempferol-3-O-glucoside from Uapaca heudelotii Baill. (Phyllanthaceae) and their ADMET profile J. Oral Public Health 2024 5 2 10.4314/orapj.v5i2.11
Igbinumwen O. Osaro I. Ebengho M.I. Edema M.O. Oviawe A.P. Momoh S.M. Eduwuirofo L.O. Iyekekpolor R. Oghomwen T.M. Oghomwen R.O. et al. Chemical characterizations and anti-sickling potential of methanol extract of Justicia carnea (flamingo plant) Zenodo 2024 4 65 75 10.5281/zenodo.13759785
Hu X. Wang M. Pan Y. Xie Y. Han J. Zhang X. Niayale N. He H. Li Q. Zhao T. et al. Anti-inflammatory Effect of Astragalin and Chlorogenic Acid on Escherichia coli-Induced Inflammation of Sheep Endometrial Epithelium Cells Front. Vet. Sci. 2020 7 201 10.3389/fvets.2020.00201 32426380
Park H.M. Lee J.Y. Kim M.Y. Kang C.-H. Hwang H.S. Anti-Oxidative and Anti-Inflammatory Activities of Astragalus membranaceus Fermented by Lactiplantibacillus plantarum on LPS-Induced RAW 264.7 Cells Fermentation 2021 7 252 10.3390/fermentation7040252
Choi S.-S. Park H.-R. Lee K.-A. A Comparative Study of Rutin and Rutin Glycoside: Antioxidant Activity, Anti-Inflammatory Effect, Effect on Platelet Aggregation and Blood Coagulation Antioxidants 2021 10 1696 10.3390/antiox10111696
Poret M. Tran T. Villotte M. Nüsse O. Myeloperoxidase: An ingenious defense mechanism against pathogen infections in medicine and science Med. Sci. 2017 33 741 743 10.1051/medsci/20173308018
Nur E. Biemond B.J. Otten H.M. Brandjes D.P. Schnog J.J.B. Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management Am. J. Hematol. 2011 86 484 489 10.1002/ajh.22012
Queiroz R.F. Lima E.S. Oxidative stress in sickle cell disease Rev. Bras. Hematol. E Hemoter. 2013 35 16 17 10.5581/1516-8484.20130008 23580878
Cavalcante J.E. Machado R.P. Laurentino M.R. Dos Santos T.E. Bandeira I.C. Maia Filho P.A. Figueiredo M.F. Martins A.M. Lemes R.P. Clinical events and their relation to the tumor necrosis factor-alpha and interleukin-10 genotypes in Sickle-Cell-Anemia patients Hematol. Oncol. Stem Cell Ther. 2016 9 14 19 10.1016/j.hemonc.2015.11.002
Domingos I.F. Pereira-Martins D.A. Sobreira M.J.V.C. High levels of proinflammatory cytokines IL-6 and IL-8 are associated with a poor clinical outcome in sickle cell anemia Ann. Hematol. 2020 99 947 953 10.1007/s00277-020-03978-8
Zhang H. Xu H. Weihrauch D. Jones W.D. Jing X. Shi Y. Gourlay D. Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice J. Lipid Res. 2013 54 3009 3015 10.1194/jlr.M038281
Zheng W. Wang H. Wang X. Li X. Hu J. Zi X. Zhou Y. Pan D. Fu Y. Kaempferol 3-O-Rutinoside, a Flavone Derived from Tetrastigma hemsleyanum Diels et Gilg, Reduces Body Temperature through Accelerating the Elimination of IL-6 and TNF-α in a Mouse Fever Model Molecules 2024 29 1641 10.3390/molecules29071641
Wadah O. Mona S.M. Hassan S.K. Abdelkhalig M. Shantier S.W. Bashier O. Abdoon I. HPTLC Fingerprint Profile and Identification of Antidiabetic and Antioxidant Leads from Bauhinia rufescens L. Adv. Pharmacol. Pharm. Sci. 2020 2020 3201463 10.1155/2020/3201463
Hounkpe B.W. Chenou F. Domingos I.F. Cardoso E.C. Costa Sobreira M.J.V. Araujo A.S. Lucena-Araújo A.R. da Silva Neto P.V. Malheiro A. Fraiji N.A. et al. Neutrophil extracellular trap regulators in sickle cell disease: Modulation of gene expression of PADI4, neutrophil elastase, and myeloperoxidase during vaso-occlusive crisis Res. Pract. Thromb. Haemost. 2021 5 204 210 10.1002/rth2.12463 33537545
Yahfoufi N. Alsadi N. Jambi M. Matar C. The Immunomodulatory and Anti-Inflammatory Role of Polyphenols Nutrients 2018 10 1618 10.3390/nu10111618 30400131
Borive A.M. Mavar M.H. Memvanga B.P. Ndezu A.R. Nsasi B.E. Mouithys M.A. Batina A.S. Marini D.R. Evidence-based Sickle Cell management: From Traditional remedies use to laboratory assessment Phytomed. Plus 2025 Under review
Souleymane H.D. Djibo A.K. Seyni S.H. Zakaria O. Botezatu A.V. Dinica R.M. Ibrahim Maman Laouali A. Kouakou N.D.V. Phytochemical Characterization and In Vitro Evaluation of the Anti-Sickle Cell Activity of Aqueous and Ethanolic Extracts of Two Medicinal Plants from Niger: Flueggea virosa (Roxb. ex Willd.) Royle and Kigelia africana (Lam.) Benth Plants 2023 12 3522 10.3390/plants12203522
Re R. Pellegrini N. Proteggente A. Pannala A. Yang M. Rice-evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay Free Radic. Biol. Med. 1999 26 1231 1237 10.1016/S0891-5849(98)00315-3
Brand-Williams W. Cuvelier M.E. Berset C. Use of a free radical method to evaluate antioxidant activity LWT Food Sci. Technol. 1995 28 25 30 10.1016/S0023-6438(95)80008-5
Nyssen P. Mouithys-Mickalad A. Minguet G. Sauvage E. Wouters J. Franck T. Hoebeke M. Morphine, a potential inhibitor of myeloperoxidase activity Biochim. Et Biophys. Acta (BBA) Gen. Subj. 2018 1862 2236 2244 10.1016/j.bbagen.2018.07.007