Ethnobotanical Survey and In vitro Antisickling Effect of Some Selected Medicinal Plants

Background: Sickle cell disease is a genetic disorder in which an individual inherits the sickle cell allele from both parents. The modern disease modifying therapies are quite expensive and often come with side effects, hence, there is need to search for natural alternatives from medicinal plants. This research was aimed at evaluating the antisickling effects of some selected medicinal plants. Materials and Methods: Ethnobotanical survey was conducted on the medicinal plants used in Zuru Local Government Area of Kebbi State, Nigeria for the treatment/management of sickle cell disease. Five (5) most cited plants; Carica papaya leaf, Prosopis africana stem-bark, Guiera senegalensis leaf, Syzygium aromaticum seed and Boswellia dalzielli stem bark were selected and their methanol extracts were subjected to in vitro antisickling activity using sodium metabisulphite. Phytochemical screening on the most active plant extracts was conducted using standard methods. Results: The plant extracts and their combinations exhibited antisickling activities with varying degrees of efficacy. C. papaya leaf extract, P. africana stem bark extract and G. senegalensis leaf extract were the most potent that caused reduction in the percentage sickling to 3.87±2.73, 8.38±1.06 and 28.35±2.07% respectively. Phytochemical screening revealed the presence of alkaloids and Tannins in all the three (3) plant extracts. Anthraquinones and glycosides were present only C. papaya and G. senegalensis leaf extracts, while Flavonoids and Saponins were only present in G. senegalensis leaf extract and P. africana stem bark extracts. Phenols were present in C. papaya leaf extract and P. africana stem bark extracts, while phlobatannins was only in C. papaya leaf extract. Conclusion: The medicinal plant extracts were able to reduce the percentage of sickled cells. This may be due to the presence of some of the phytochemicals. Hence, these medicinal plants may be used as alternative to hydroxyurea in ameliorating the sickling in human HbS containing RBCs.

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Survey of Medicinal Plants Used in the Management of Sickle Cell Disease by Traditional Medical Practitioners of Gbonyin Local Government Area of Ekiti State, Nigeria

Nigerian Journal of Natural Products and Medicine ◽

10.4314/njnpm.v19i0.8 ◽

2015 ◽

Vol 19 ◽

pp. 78-84

Author(s):

TI Famojuro ◽

JO Moody

Keyword(s):

Sickle Cell Disease ◽

Local Government ◽

Medicinal Plants ◽

Plant Species ◽

Sickle Cell ◽

Mangifera Indica ◽

Local Government Area ◽

Herbal Remedies ◽

Cell Disease ◽

Ethnobotanical Survey

Ethnobotanical survey was conducted on plants used traditionally for the management of sickle cell disease (SCD) in Gbonyin Local Government Area (LGA) of Ekiti State, South Western Nigeria. The study was conducted to document some of the medicinal plants used in the management of SCD with the aim of identifying possible drug leads from the phytomedicine of the area. A semi-structured questionnaire was used to obtain information on the use of herbal remedies for the management of SCD. A total of 32 respondents were interviewed in this study. twenty of them were males while twelve were females with the age range of 25 to 70 years. A total of 44 plant species belonging to 44 genera and 30 families were identified to be useful for the management of SCD. The most prominent among these plant families (genera) are Anacardiaceae (Anacardium occidentalis, Mangifera indica, Spondias mombin), Euphorbiaceae (Croton lobatus, Jatropha gossypifolia, Plukeneta conophora) and Fabaceae (Cajanus cajan, Pterocarpus osun, Cassia siamea) with three species each. Eighty percent (80%) of the 32 respondents interviewed said that their clients did not report any side effect and that the herbs were either collected from the forest (where available) or purchased from the herb markets. In all, the commonest plant species among the recipes given by the respondents according to their Use Mention Index (UMI) include: Elaeis guineense Jacq., Arecaceae (0.124); Khaya grandifoliola C.DC., Meliaceae (0.094); Carica papaya L., Caricaceae(0.094); Hymenocardia acida Tul., Phyllanthaceae (0.094); Mangifera indica L., Anacardiaceae (0.094); Parquetina nigrescens (Afzel.) Bullock, Asclepiadaceae (0.094) and Xylopia aethiopica (Dunal) A. Rich., Annonaceae (0.094).The main method of preparation is by decoction and in most cases, the preparation is taken orally twice to thrice daily. All the plants identified in this work have been used by most of the herbalists and adjudged to be efficacious in SCD management. The study concluded that the medicinal folklore of the Ekiti State LGA covered by this survey indicated high potential for drug discovery for the management of sickle cell disease.Keywords: Ethnobotany, Sickle Cell Disease, Traditional Medicine, Gbonyin LGA, Medicinal Plants

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Antisickling Activity of the Fresh and Dried Roots of Cissus populnea Guill. Et Perr (Vitaceae)

Nigerian Journal of Natural Products and Medicine ◽

10.4314/njnpm.v19i0.16 ◽

2015 ◽

Vol 19 ◽

pp. 134-138

Author(s):

EM Adebayo ◽

AA Adeyemi ◽

OO Omotade ◽

FA Fasola ◽

TO Ajayi ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Maximum Activity ◽

Research Strategy ◽

Powdered Sample ◽

Phytochemical Screening ◽

Cell Disease ◽

Traditional Use ◽

Standard Drug

Research into plants with claimed traditional use in the management of sickle cell anaemia constitutes a useful research strategy in the search for new antisickling drugs and templates. The root of Cissus populnea has been used traditionally in the management of sickle cell disease (SCD). Phytochemical screening of the fresh and powdered sample of the root of C. populnea (CP) was done using standard methods followed by in vitro antisickling evaluation of extracts, solvent-partitioned fraction (ethylacetate) and the vacuum liquid chromatographic fractions (VLC) of the fresh and dried roots of C. populnea with sodium metabisulphite induced sickling of HbSS erythrocytes. p-hydroxybenzoic acid and normal saline were used as positive and negative controls respectively. Phytochemical screening revealed the presence of tannins, saponins and cardiac glycosides. The result of this study showed that the extracts and solvent partitioned fraction (ethylacetate) from the root of CP have antisickling property with a higher activity for the ethylacetate partitioned fraction of the dried roots compared to that of the fresh roots. The VLC fractions exhibited higher activity than the crude extracts; fraction 3 (FR3) had the maximum activity of 96.4% while 88.6% activity was demonstrated for the standard drug (PABA) at an incubation time of 45 min. This study has thus provided scientific evidence for the traditional use of CP in the management of SCD.Keywords: Sickle Cell Disease, Cissus populnea, Antisickling Activity

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Hypoxia-induced acute lung injury in murine models of sickle cell disease

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00288.2002 ◽

2004 ◽

Vol 286 (4) ◽

pp. L705-L714 ◽

Cited By ~ 57

Author(s):

Kirkwood A. Pritchard ◽

Jingsong Ou ◽

Zhijun Ou ◽

Yang Shi ◽

James P. Franciosi ◽

...

Keyword(s):

Sickle Cell Disease ◽

Lung Injury ◽

Sickle Cell ◽

Globin Gene ◽

Heat Shock Protein 90 ◽

Cell Disease ◽

Vascular Congestion ◽

Nitrite Nitrate ◽

Endothelial Nitric Oxide

Vaso-occlusive events are the major source of morbidity and mortality in sickle cell disease (SCD); however, the pathogenic mechanisms driving these events remain unclear. Using hypoxia to induce pulmonary injury, we investigated mechanisms by which sickle hemoglobin increases susceptibility to lung injury in a murine model of SCD, where mice either exclusively express the human α/sickle β-globin (hαβS) transgene (SCD mice) or are heterozygous for the normal murine β-globin gene and express the hαβStransgene (mβ+/-, hαβS+/-; heterozygote SCD mice). Under normoxia, lungs from the SCD mice contained higher levels of xanthine oxidase (XO), nitrotyrosine, and cGMP than controls (C57BL/6 mice). Hypoxia increased XO and nitrotyrosine and decreased cGMP content in the lungs of all mice. After hypoxia, vascular congestion was increased in lungs with a greater content of XO and nitrotyrosine. Under normoxia, the association of heat shock protein 90 (HSP90) with endothelial nitric oxide synthase (eNOS) in lungs of SCD and heterozygote SCD mice was decreased compared with the levels of association in lungs of controls. Hypoxia further decreased association of HSP90 with eNOS in lungs of SCD and heterozygote SCD mice, but not in the control lungs. Pretreatment of rat pulmonary microvascular endothelial cells in vitro with xanthine/XO decreased A-23187-stimulated nitrite + nitrate production and HSP90 interactions with eNOS. These data support the hypotheses that hypoxia increases XO release from ischemic tissues and that the local increase in XO-induced oxidative stress can then inhibit HSP90 interactions with eNOS, decreasing ·NO generation and predisposing the lung to vaso-occlusion.

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Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients

Frontiers in Immunology ◽

10.3389/fimmu.2020.535147 ◽

2020 ◽

Vol 11 ◽

Author(s):

Vanessa Araujo Gomes Santaterra ◽

Maiara Marx Luz Fiusa ◽

Bidossessi Wilfried Hounkpe ◽

Francine Chenou ◽

Wouitchekpo Vincent Tonasse ◽

...

Keyword(s):

Sickle Cell Disease ◽

Healthy Volunteers ◽

Sickle Cell ◽

Endothelial Barrier ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Experimental Conditions ◽

Cell Monolayers ◽

Junction Protein

Free extracellular heme has been shown to activate several compartments of innate immunity, acting as a danger-associated molecular pattern (DAMP) in hemolytic diseases. Although localized endothelial barrier (EB) disruption is an important part of inflammation that allows circulating leukocytes to reach inflamed tissues, non-localized/deregulated disruption of the EB can lead to widespread microvascular hyperpermeability and secondary tissue damage. In mouse models of sickle cell disease (SCD), EB disruption has been associated with the development of a form of acute lung injury that closely resembles acute chest syndrome (ACS), and that can be elicited by acute heme infusion. Here we explored the effect of heme on EB integrity using human endothelial cell monolayers, in experimental conditions that include elements that more closely resemble in vivo conditions. EB integrity was assessed by electric cell-substrate impedance sensing in the presence of varying concentrations of heme and sera from SCD patients or healthy volunteers. Heme caused a dose-dependent decrease of the electrical resistance of cell monolayers, consistent with EB disruption, which was confirmed by staining of junction protein VE-cadherin. In addition, sera from SCD patients, but not from healthy volunteers, were also capable to induce EB disruption. Interestingly, these effects were not associated with total heme levels in serum. However, when heme was added to sera from SCD patients, but not from healthy volunteers, EB disruption could be elicited, and this effect was associated with hemopexin serum levels. Together our in vitro studies provide additional support to the concept of heme as a DAMP in hemolytic conditions.

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Mineral Content and Antisickling Activity of Annona senegalensis, Alchornea cordifolia and Vigna unguiculata Used in the Management of Sickle Cell Disease in the Kwilu Province (Congo, DR)

International Blood Research & Reviews ◽

10.9734/ibrr/2020/v11i330131 ◽

2020 ◽

pp. 18-27

Author(s):

Jules M. Kitadi ◽

Clément L. Inkoto ◽

Emmanuel M. Lengbiye ◽

Damien S. T. Tshibangu ◽

Dorothée D. Tshilanda ◽

...

Keyword(s):

Sickle Cell Disease ◽

Mineral Composition ◽

Sickle Cell ◽

Mineral Elements ◽

Spectrometric Method ◽

Spectrometric Analysis ◽

Composition Analysis ◽

Cell Disease ◽

Republic Of The Congo

Aims: To determine the mineral composition of some plants (Annona senegalensis Pers., Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. and Vigna unguiculate (L.) Walp.) used in the management of sickle cell disease by traditional practitioners in Kwilu province and to evaluate their antisickling activity in vitro. Study Design: Plant collection in the Kwilu province, sample preparation, antisickling tests and fluorescence spectrometric analysis. Place and Duration of Study: This work was performed at the Faculty of Science, University of Kinshasa, Congo DR, from October 2016 to January 2018. Methodology: These three plants were harvested in the province of Kwilu in Democratic Republic of the Congo. The mineral composition analysis was carried out using the fluorescence spectrometric method while the in vitro antisickling activity was evaluate using Emmel and hemolysis tests. Results: Twenty three mineral elements were identified in each of these three plants: Potassium (K), Phosphorus (P), Calcium (Ca), Sodium (Na), Magnesium (Mg), Sulphur (S), Chlorine (Cl) and trace elements as: Aluminum (Al), Silicon (Si), Vanadium (V), Chromium (Cr), Manganese (Mn), Iron (Fe), Nickel (Ni), Copper (Cu), Zinc (Zn), Selenium (Se), Brome (Br), Molybdenum (Mo), Tin (Sn), Iodine (I), Barium (Ba) and Lead (Pb). Annona senegalensis Pers., Alchornea cordifolia (Schumach. & Thonn.) Müll.Arg. and Vigna unguiculate (L.) Walp. aqueous extracts showed the capacity to prevent the sickling and the hemolysis of red blood cells. Conclusion: The obtained results confirm the antisickling activity thus justifying the use of these plants in Traditional Medicine for the management of sickle cell disease. The presence of some mineral elements like Fe, Zn, Mg and Se are useful for sickle cell disease patients.

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In vivo survival studies of 51Cr-labeled methyl acetimidate treated erythrocytes in patients with sickle cell disease

Blood ◽

10.1182/blood.v56.6.1041.1041 ◽

1980 ◽

Vol 56 (6) ◽

pp. 1041-1047 ◽

Cited By ~ 5

Author(s):

TG Gabuzda ◽

TL Chao ◽

MR Berenfeld ◽

T Gelbart

Keyword(s):

Sickle Cell Disease ◽

Survival Time ◽

Sickle Cell ◽

Clinical Testing ◽

Cell Disease ◽

Show Evidence ◽

Survival Studies ◽

Circulating Antibody

Abstract Studies of the survival time of 51Cr labeled erythrocytes treated in vitro with methyl acetimidate (MAI) were conducted in 13 patients with sickle cell disease in order to assess the suitability of this antisickling agent for more extensive clinical testing. In comparison with previously measured control values (average t1/2 8.4 +/- 1.1 days a), the survival time of the treated erythrocytes in 10 of the patients who were not transfused was initially prolonged (average t1/2 24.4 +/- 4.6 days). However, 5 of the 13 patients studied developed circulating antibody against the MAI treated erythrocytes, markedly reducing the survival time of MAI treated erythrocytes in subsequent studies. Two patients, each challenged 3 times with infused MAI treated erythrocytes, failed to show evidence of antibody production, suggesting that not all subjects become immunized even after repeated exposure. In spite of many other promising properties of MAI as an antisickling agent of potential value, consideration of its use in further clinical testing must depend on successful avoidance of immunization in patients receiving infusions of treated erythrocytes.

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Placenta growth factor in sickle cell disease: association with hemolysis and inflammation

Blood ◽

10.1182/blood-2009-04-217950 ◽

2010 ◽

Vol 115 (10) ◽

pp. 2014-2020 ◽

Cited By ~ 35

Author(s):

Julia E. Brittain ◽

Ben Hulkower ◽

Susan K. Jones ◽

Dell Strayhorn ◽

Laura De Castro ◽

...

Keyword(s):

Growth Factor ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Predictive Accuracy ◽

Cross Sectional Study ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Placenta Growth Factor ◽

Cross Sectional

Abstract Placenta growth factor (PlGF) is released by immature erythrocytes and is elevated in sickle cell disease (SCD). Previous data generated in vitro suggest that PlGF may play a role in the pathophysiology of SCD-associated pulmonary hypertension (PHT) by inducing the release of the vasoconstrictor, endothelin-1. In this cross-sectional study of 74 patients with SCD, we confirm that PlGF is significantly elevated in SCD compared with healthy control subjects. We found significantly higher levels of PlGF in SCD patients with PHT but observed no association of PlGF with the frequency of acute pain episodes or history of acute chest syndrome. The observed correlation between PlGF and various measures of red cell destruction suggests that hemolysis, and the resultant erythropoietic response, results in the up-regulation of PlGF. Although relatively specific, PlGF, as well as N-terminal pro-brain natriuretic peptide and soluble vascular cell adhesion molecule, has low predictive accuracy for the presence of PHT. Prospective studies are required to conclusively define the contribution of PlGF to the pathogenesis of PHT and other hemolytic complications in SCD.

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Voxelotor Treatment Interferes With Quantitative and Qualitative Hemoglobin Variant Analysis in Multiple Sickle Cell Disease Genotypes

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa067 ◽

2020 ◽

Vol 154 (5) ◽

pp. 627-634

Author(s):

Nicola J Rutherford-Parker ◽

Sean T Campbell ◽

Jennifer M Colby ◽

Zahra Shajani-Yi

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

High Performance ◽

Clinical Laboratory ◽

The United States ◽

Cell Disease ◽

Hemoglobin Variant ◽

Hbd Punjab ◽

The Impact

Abstract Objectives Voxelotor was recently approved for use in the United States as a treatment for sickle cell disease (SCD) and has been shown to interfere with the quantitation of hemoglobin (Hb) S percentage. This study aimed to determine the effect of voxelotor on the quantitation of hemoglobin variant levels in patients with multiple SCD genotypes. Methods In vitro experiments were performed to assess the impact of voxelotor treatment on hemoglobin variant testing. Whole blood samples were incubated with voxelotor and then analyzed by routinely used quantitative and qualitative clinical laboratory methods (high-performance liquid chromatography [HPLC], capillary zone electrophoresis [CZE], and acid and alkaline electrophoresis). Results Voxelotor modified the α-globin chain of multiple hemoglobins, including HbA, HbS, HbC, HbD-Punjab, HbE, HbA2, and HbF. These voxelotor-hemoglobin complexes prevented accurate quantitation of multiple hemoglobin species, including HbS, by HPLC and CZE. Conclusions Technical limitations in quantifying HbS percentage may preclude the use of HPLC or CZE for monitoring patients treated with voxelotor. Furthermore, it is unclear whether HbS-voxelotor complexes are clinically equivalent to HbS. Consensus guidelines for reporting hemoglobin variant percentages for patients taking voxelotor are needed, as these values are necessary for determining the number of RBC units to exchange in acute situations.

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