Department of Pharmacology

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    In Vivo Investigation Of Immunomodulatory And Immunoadjuvant Activity Of Selected Medicinal Plants In Sudan In Immunized Animal Models
    (University of Khartoum, 2022) Tasnim Omer Elsammani Elshiekh Ibrahim
    Abstract Background: Immunomodulation is one of the therapeutic approaches used to manage various diseases. This study aimed to evaluate the immunomodulatory activity of ethanolic and dichloromethane extracts of stems of Tinospora bakis and Capparis decidua, leaves of Vernonia amygdalina and bark of Termenalia brownii in sheep red blood cells (SRBCs) immunized rats. And to study the immunoadjuvant activity for the immunostimulant active extracts in Ovalbumin (OVA) immunized mice. Methods: For each plant extract rats were divided into six groups (n=5): All groups were immunized with SRBCS (1X106 cells/ 0.1 ml) except group I which received normal saline (10 ml/kg, IP). Rats were treated as follows: group II received normal saline, the rest of groups were administered the extracts of selected plants at dose of 125,250 and 500 mg/kg (I.P) and levamisole (2.5mg/kg, I.P.) respectively for six consecutive days. On day 7 the humoral antibody response to SRBC was assessed by measurement of SRBCs specific antibody titer using hemagglutination reaction and cellular immune response was evaluated by Foot pad reaction test. Plants dichloromethane extracts were evaluated using same protocol except one dose was used (500 mg/kg). For immunoadjuvant activity mice were randomly divided into five groups (n=5). Group I: received normal saline (10 ml/kg, S.C),Group II – V received 100 µg of OVA dissolved in normal saline or extracts with proven immunostimulant effect at dose of 500mg/kg subcutaneously on day 0 and day 14. Blood was collected on day 0, 14 and 28 for measurement of IgG1 and IgG 2a level using indirect ELISA. Spleens were isolated on day 28 for lymphocyte immunophenotyping (CD3+, CD4+ and CD8+) and cytokines intracellular expression (Th1: IL-2, IFN-γ and TNF-α) and Th2 (IL-4) using Flowcytometry. Data were analyzed statistically A level of statistical significance was set to be ≤ 0.05. Results: Ethanolic extracts of Tinospora bakis, Capparis decidua, Vernonia amygdalina and levamisole showed significant increments in SRBCs specific antibody titer (P=0.0012, P=0.0001, P=0.0001, P=0.005 respectively). No dose dependence was observed. For cellular immunity, the mean difference in footpad thickness was significantly increased by the ethanolic extracts after 48 h of injection of antigen in rats’ paws (Capparis decidua P = 0.0003, Vernonia amygdalina P = 0.0001, Tinospora bakis P = 0.008, levamisole P=0.043, No dose dependence was observed. No significant immunomodulation was produced by treatment with dichloromethane extracts. For immunoadjuvant activity 500 mg/kg of ethanolic extract of Tinospora bakis significantly stimulate Th1 cytokines (IL-2, IFN-γ and TNF-α levels, p = 0.0056, 0.0036 and 0.0016 respectively) and Th2 cytokine (P = 0.0021) and IgG1and IgG2a (P = 0.0001 and 0.0001 respectively) production. While Vernonia amygdalina and Capparis decidua significantly increase IgG1 production (P= 0.0013 and 0.0001 respectively) and significantly suppress Th1 cytokines IL-2 0.0013, IFNγ 0.002 for V. amygdalina and IL-2 P = 0.0001, IFNγ 0.02 for C. decidua. Conclusion: Tinospora bakis, Vernonia amygdalina and Capparis decidua showed promising immunomodulatory activity. They stimulate both humoral and cellular immune responses. They exhibit promising immunoadjuvant activity, thus they can be suitable vaccines adjuvants. مستخلص الأطروحة مقدمة: يعتبر التأثير علي الجهاز المناعي احد الطرق لعلاج كثير من الامراض . الهدف من هذه الدراسة هو تقييم النشاط المحفز للمناعة للمستخلصات الايثانولية و الدايكلروميثينية لسيقان نبات عرق الحجر و الطندب و اوراق غرب الوادي و اخيرا لحاء نبات الدروت علي الفئران الملقحة بالكريات الحمراء للخراف. وايضا تهدف لدراسة امكانية استخدام المستخلص الذي اثبت انه محفز للمناعة كمساعد للقاح علي الجرذان الملقحة باوفاالبيومين. طرائق البحث: لكل مستخلص نبات تم تقسيم الفئران لست مجموعات (ن=5). المجموعات المختبرة لقحت بكريات الدم الحمراء للخراف ( 1 × 610) وتم اعطاؤها مستخلصات النباتات بجرعة (125, 250 و 500 مجم / كجم I.P ) و الليفاميثول الدواء القياسي (2.5 مجم /كجم I.P) علي التوالي لمدة ستة ايام متتالية .في اليوم السابع قيست الاجسام المضادة لكريات الدم الحمراء للخراف باستخدام تفاعل التراص الدموي و المناعة الخلوية باستخدام حجم الوذمة المستحدثة بقدم الفأر. لدراسة نشاط المستخلصات كمساعد للقاحات , قسمت الفئران لخمس مجموعات (ن=5),المجموعة 1 : اعطيت محلول الملح ,المجموعات من 2-5 اعطيت 100مايكروجرام من الاوفالبيومين او المستخلص الذي اثبت ان لديه اثر تحفيزي للمناعة بجرعة 500 مجم/كجم تحت الجلد في اليوم 0 و اليوم 14. تم جمع عينات الدم في اليوم 0 و اليوم 14 قبل اعطاء العلاج واليوم 28 لاجراء قياس مستوي الاجسام المضادة IgG1 و IgG2a ضد الاوفالبيومين باستخدام ELISA. كما تم نزع الطوحال في اليوم 28 لدراسة تاثير المستخلصات علي عدد الخلايا الليمفاوية (CD3+, CD4+ and CD8+) و قياس مستوي السايتوكينات IFN-γ IL-2: Th1) TNF-α ) و ( Th2: IL-4) باستخدام جهاز الفلوسايتوميتر. تم تحليل النتائج احصائيا النتائج: العلاج بالمستخلص الايثانولي لنباتات عرق الحجر، الطندب و غرب الوادي و اليفاميسول نتج عنه زيادة في الاجسام المضادة المنتجة ضد الكريات الحمراء للخراف ( p= 0.0012 , 0.0001, 0.0001 و 0.005 بالتوالي). بالنسبة للمناعة الخلوية هناك زيادة في متوسط الفرق في حجم انتفاخ قدم الفأر نتجت من العلاج بالمستخلص الايثانولي للنباتات ( الطندب p=0.0003, غرب الوادي p= 0.0001, عرق الحجر p=0.008 و الليفاميسول p= 0.043). المستخلص لدايكلروميثيني لم ينتج عنه اثر علي المناعة. بالنسبة لاستخدام النباتات كمساعد للقاحات ,العلاج بالمستخلص الايثانولي لنبات عرق الحجر بجرعة 500 مجم/كجم نتج عنه زيادة في السايتوكينات Th1 ( IL-2, IFNγ,TNFαp= 0.0056,p=0.0036 وp=0.0016 علي التوالي) و سايتوكينات Th2 (IL-4 p=0.0021 ) وزيادة في انتاج الاجسام المضادة ضد الاوفاالبيومين IgG1 و IgG2a (p=0.0001 وp=0.0001) . اما بالنسبة لنبات غرب الوادي و الطندب زادت نسبة انتاج الاجسام المضادة من نوع IgG1 (p= 0.0013 و p=0.0001 علي التوالي) كما لوحظ تثبيط انتاج سايتوكينات Th1 IL-2 P= 0.0013و IFNγ P= 0.002 لنبات غرب الوادي و لنبات الطندبIL-2 P=0.0001 و IFNγ P= 0.02 . الخاتمة: المستخلص الايثانولي لنبات عرق الحجر، الطندب و غرب الوادي يعمل علي تحفيز المناعة الخلوية و المناعة بالاجسام المضادة في الفئران. نبات عرق الحجر ينشط الاستجابة المناعية لخلايا Th1 و Th2 حيث يمكن ان يوفر مركبات واعدة يمكن استخدامها كمساعد للقاح مستقبلا . نبات غرب الوادي و نبات الطندب يحفزان الاستجابة المناعية لخلايا Th2 فقط حيث يمكن استخامهما كمركبات مساعدة للقاح لانتاج المناعة بالاجسام المضادة حيث انها فاعلة ضد الميكروبات التي تعيش خارج الخلايا.
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    Assessment of Pharmacovigilance System (Post-Market Surveillance of Adverse Drug Reaction) In Khartoum State, 2014
    (University of Khartoum, ) Yassin, Salma Mohamed Elhassan ; Bashier Ibrahim Osman
    Background: Adverse drug reactions (ADRs), contribute significantly to morbidity and mortality. The pharmacovigilance (PV) system safeguards the public through efficient and timely identification, collection, assessment, and dissemination of medicine-related adverse events. Assessment of PV systems over time is necessary to identify areas that need strengthening. The current study was conducted with an objective to assess PV in Khartoum state by using the Strengthening Pharmaceutical Systems (SPS) Program updated guidelines for the developing countries. Materials and Methods: This was a cross-sectional, observational, descriptive study. Data were collected from three different levels: National PV center, State PV unites and Drug Information Centers (DIC) assigned body for PV activity in hospitals. Sample size ensured total coverage of 17 sentinel site at hospitals. Data were collected by structured questionnaire and analyzed using Statistic Package for Societal Science (SPSS) version 21 and Microsoft excel. Results: The existence of all indicators at national, state levels and hospitals was found to be 56%, 60% and 4% respectively. Core indicators were shown to be at national, state levels and hospitals existed in the following sequence 69%, 61% and 6% respectively. While supplementary indicators were found to exist at national, state levels and hospitals as follow 35%, 50% and 0% respectively. According to the structural, process, and outcome classification ,the existence of structural indicators was found to be 80%, 88% and13% at the national , state levels and hospitals respectively , while process indicators existence was 44% ,46% and 0% respectively and outcome indicator`s existence was 40% ,44% and 0% respectively. The PV system was also evaluated according to five components the results of which were as follow: First component, (The Policy, Law, and Regulation) with 25% existence of indicator at national level only. The existence of indicators for the second component, (System, Structure, and Stakeholder Coordination) was found to be 93% , 90% at national and State levels respectively ,while 10% of indicators were present in 70% of hospitals. The existence of indicators for the third component, (Signal Generation and Data Management) was found to be 50% , 50% at national and State levels respectively, while 25% of indicators were present in only 20% of hospitals. The existence of indicators for the forth component, (Risk Assessment and Evaluation) was found to be 25% , 29% at national and state levels respectively, while 25% of indicators were present in only 7% of hospitals . The existence of indicators for the fifth component, ( Risk Management and Communication) was found to be 40% , 44% at national , state levels respectively ,while 75% of indicators were present in about(13-20%) hospitals respectively . Conclusion: The study concluded the existence of PV system at national and state centers and they demonstrate that PV activities were already taking place. Greater efforts are needed in hospitals to build this system and filling the gap and also to link existing activities to create a comprehensive PV system. Finally, the study recommends Country should development of strategic plans to incorporate both passive and active surveillance approaches, coordinate and work with all stakeholders, strengthen risk management and communication, and enhance the impact of PV and medicine safety systems.
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    Antitheilerial Activity of Some Medicinal Plants in Sudan
    (University of Khartoum, 2015-04-26) Mahgoub Farah Mohammed, Hayat ; Tigani Hassan Elamin ; Pharmacology and Toxicology
    This study investigates the antitheilerial activity (in vitro) of the aqueous extract of four local medicinal plants, Gardenia ternifolia(Abu Gawie), Kigelia africana(Abu shutour), Sonchus cornutus(Moleita) and Tinospora bakis(Irg al-Hagar). Preliminary screening of the aqueousextracts of the four plants for activity against Theileria lestoquardi(ovine theileriosis) was done at concentrations of 250, 500, 5000 and 10000 ppm. The antimalarial drug, Paluther (Artemether 80), was tested for antitheilerial effect. On the other hand, Butalex (buparvaquone) was used as a standard drug. Screening for antitheilerial activity revealed K. africanato be the most potent candidate among the studied plants, followed by Gardenia ternifolia, and Tinospora bakis. However, Sonchus cornutuslacks activity. The highest activity of K. africana, Gardenia ternifolia andT. bakisat 10000 ppm was 80%, 60% and 30%, respectively; Artemether 80 producing 45% activity at 10mg/L. But buparvaquone at 10mg/L produced 100% activity. LC50of K. africana, G. ternifolia andT. bakiswas 2660.28 ppm, 6745.28ppm and 184268.54 ppm, respectively. However, Artemether 80 and buparvaquone having LC50of 21.29 mg/L and 0.000015 mg/L, respectively. Plant extracts plus Artemether80 and buparvaquonecaused changes in the morphology, colour and mean number of macroschizonts. The number of cells with extra cellular macroschizonts increased, but the mean XIV number of divided cells (binucleated and multinucleated) and viable cells decreased. The four plants, Artemether 80 and buparvaquone caused partial cytotoxicity at the highest concentration resulting in changes of the morphology of lymphoblast cells and decreasing the number of viable cells.
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    Application of Derivative Spectrophotometry for Analysis of Pharmaceutical Preparations
    (University of Khartoum, 2015-04-07) Abdoun, Siham ; Kamal Eldin Eltayeb Ibrahim
    Simple, rapid, non hazardous, accurate, non expensive and precise derivative spectrophotometric method was developed and optimized for analysis of mebendazole, tinidazole, albendazole metronidazole, metronidazole benzoate and combination of hydrochlorothiazideand amiloride hydrochloride in pharmaceutical formulations as their official method either HPLC which is expensive or non aqueous titration which is hazardous and not accurate. The work included the study of the expected interference of pharmaceutical excipients, used in these formulations bychoice of different brand formulations.
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    The Antidiabetic and Hypolipidaemic Effects of Cicer arientinum, Cinnanomum verumand Citrus aurantifolinin Types I and II Diabetes Mellitus
    (University of Khartoum, 2015-04-07) Abdullah, Howeida ; Idris Babiker Eltayeb ; Pharmacology
    This research aimed to study the antidiabetic effect of the aqueous and methanolic extracts of the seeds of Cicer arientinum, the bark of Cinnanomum verumand the leaves of Citrus aurantifolinin adult Wistar Albino rats.