Browsing by Author "Gavamukulya, Yahaya"

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    Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis
    (IOS Press, 2021) Gavamukulya, Yahaya; Mainab, Esther N.; El-Shemy, Hany A.; Merokac, Amos M.; Kangogo, Geoffrey K.; Magomab, Gabriel; Wamunyokoli, Fred
    BACKGROUND: Green synthesized nanoparticles have been earmarked for use in nanomedicine including for the development of better anticancer drugs. OBJECTIVE: The aim of this study was to undertake biochemical evaluation of anticancer activities of green synthesized silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata. METHODS: Previously synthesized silver nanoparticles were used for the study. The effects of the AgNPs and 5-Fluorouracil were studied on PC3, HeLa and PNT1A cells. The resazurin, migration and colonogenic assays as well as qRT-PCR were employed. RESULTS: The AgNPs-F displayed significant antiproliferative effects against HeLa cells with an IC50 of 38.58 g/ml and PC3 cells with an IC50 of 48.17 g/ml but selectively spared normal PNT1A cells (selectivity index of 7.8), in comparison with first line drug 5FU and AgNPs-L whose selectivity index were 3.56 and 2.26 respectively. The migration assay revealed potential inhibition of the metastatic activity of the cells by the AgNPs-F while the colonogenic assay indicated the permanent effect of the AgNPs-F on the cancer cells yet being reversible on the normal cells in contrast with 5FU and AgNPs-L. CASP9 was significantly over expressed in all HeLa cells treated with the AgNPs-F (1.53-fold), AgNPs-L (1.52-fold) and 5FU (4.30-fold). CXCL1 was under expressed in HeLa cells treated with AgNPs-F (0.69-fold) and AgNPs-L (0.58-fold) and over expressed in cells treated with 5FU (4.95-fold), but the difference was not statistically significant. CXCR2 was significantly over expressed in HeLa cells treated with 5FU (8.66-fold) and AgNPs-F (1.12-fold) but under expressed in cells treated with AgNPs-L (0.76-fold). CONCLUSIONS: Here we show that biosynthesized AgNPs especially AgNPs-F can be used in the development of novel and better anticancer drugs. The mechanism of action of the AgNPs involves activation of the intrinsic apoptosis pathway through upregulation of CASP9 and concerted down regulation of the CXCL1/ CXCR2 gene axis. Keywords: Silver nanoparticles, HeLa, PC3, PNT1A, CASP9, CXCL1/CXCR2
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    Deciphering the molecular mechanism of aloe-emodin in managing type II diabetes mellitus using network pharmacology, molecular docking, and molecular dynamics simulation approaches.
    (Springer Nature, 2025) Obakiro, Samuel Baker; Kiyimba, Kenedy; Gavamukulya, Yahaya; Maseruka, Richard; Nabitandikwa, Catherine; Kibuuka, Ronald; Lulenzi, Jalia; Lukwago, Tonny Wotoyitide; Chebijira, Mercy; Opio, Moses; Tracy, Edeya Sharon; Kibuule, Dan; Oriko, Richard Owor; Waako, Paul; Makaye, Angela; Shadrack, Daniel M.; Andima, Moses
    Aloe-emodin (AE) has drawn interest due to its potential activity against type II diabetes mellitus (T2DM). However, the mechanisms underlying its antidiabetic activity are not well explored. Using network pharmacology, molecular docking and molecular dynamics simulation studies, we investigated its molecular mechanisms in the management of T2DM. Potential target genes of AE were predicted using the Swiss Target Prediction (http://www.swisstargetprediction.ch/) database. The GeneCards, OMIM and DisGeNET databases were used to compile a comprehensive list of genes associated with T2DM. A compound-disease-target network was constructed, and protein–protein interaction networks were analysed to identify hub genes. Finally, molecular docking and interaction analysis between AE and the identified proteins were performed using AutoDock tools. Investigation of AE targets and genes associated with T2DM identified 32 overlapping genes. Gene ontology studies revealed that AE may exert its anti-diabetic effects by modulating glucose metabolism and enhancing cellular response to glucose. Furthermore, KEGG pathway analysis suggested that AE influences these processes by targeting pathways related to apoptosis, insulin resistance, and T2DM signaling. The core target proteins identified were TNF, ALB, TP53, PPARG, BCL2, CASP3, and EGFR. AE interaction with each of these proteins exhibited a binding energy of>−5 kcal/mol, with TNF showing the lowest binding energy (−7.75 kcal/mol). Molecular dynamics simulation further validated the molecular docking results with TNF and EGFR exhibiting a strong affinity for AE and forming stable interactions. AE exerts its antidiabetic activity through multiple mechanisms, with the most significant being the amelioration of pancreatic β-cell apoptosis by binding to and inhibiting the actions of TNFα. Further cellular and molecular studies are needed to validate these findings. Keywords Aloe emodin · Type II diabetes mellitus · Network pharmacology · Molecular docking In Silico Pharmacology (2025) 13:45
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    Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology
    (Nature, 2025) Akurut, Eva; Gavamukulya, Yahaya; Mulindwa, Julius; Isiagi, Moses; Galiwango, Ronald; Bbuye, Mudarshiru; Lujumba, Ibra; Kiberu, Davis; Nabisubi, Patricia; Kebirungi, Grace; Kambugu, Andrew; Castelnuovo, Barbara; Nkurunungi, Gyaviira; Jjingo, Daudi; Oketch, Brenda; Kateete, David Patrick; Mboowa, Gerald
    The global burden of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis), the rise of drug-resistant strains, necessitates an urgent need for developing more effective vaccines. This study employed an in-silico approach to design a multi-epitope vaccine targeting the PE_PGRS16 protein, a conserved virulence factor found across both species, including drug-resistant strains. PE_PGRS16 was chosen due to its extracellular localization, adhesion properties, and virulence characteristics, making it a promising vaccine target. Epitopes for B-cells, Cytotoxic T Lymphocytes, and Helper T Lymphocytes were selected based on antigenicity, non-toxicity, and immune response potential. The vaccine construct demonstrated favorable properties, including high antigenicity, solubility, and stability, with a low instability index (-31.31) and binding energy (-44.566) when docked to TLR4, suggesting its potential for immune activation. Griselimycin was incorporated as an adjuvant to enhance immunogenicity, as predicted by C-ImmSim simulations. Population coverage analysis for East Africa revealed high applicability, with 98.35% coverage for Class I epitopes, 100% coverage for Class II epitopes, and 100% combined coverage, with average hit values of 8.4, 12.26, and 20.66, respectively. These results suggest broad potential for global vaccine deployment. This study presents a novel multi-epitope vaccine targeting PE_PGRS16, with the potential to combat Mycobacterium tuberculosis and Mycobacterium bovis infections, including drug-resistant forms. Further experimental validation is necessary to confirm its efficacy and safety. Keywords Mycobacterium tuberculosis, Mycobacterium bovis, Vaccines, BCG, Reverse vaccinology, Molecular Docking, Tuberculosis, Drug resistance
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    Drug likeliness, pharmacokinetics profiling and efficacy of polyscias fulva bioactive compounds in the management of uterine fibroids; an integrative in silico and in vivo approach.
    (Elsevier Ltd., 2025) Kiyimba, Kenedy; Munyendo, Lincoln; Obakiro, Samuel Baker; Gavamukulya, Yahaya; Ahmed, Ayaz; Choudhary, Muhammad Iqbal; Shafiq, Muhammad; Ul-Haq, Zaheer; Guantai, Eric
    Polyscias fulva is traditionally used in Uganda for the management of Uterine fibroids (UF). However, there is paucity of data regarding its efficacy, biological targets and potential mechanisms of action hence prompting scientific validation process through insilico and invivo approaches. In this study, we utilized network pharmacology, molecular docking, molecular dynamic simulations and invivo assays to investigate the drug likeliness, pharmacokinetics and efficacy of Polyscias fulva against Uterine fibroids. Four Polyscias fulva bioactive compounds; pinoresinol, lichexanthone, methyl atarate, β-sitosterol exhibited drug likeness properties with moderate safety profiles. Forty-eight (48) uterine fibroid targets were identified as potential targets for the eleven Polyscias fulva compounds. Protein-protein interaction (PPI) analysis revealed four key targets (HIF1A, ESR1, EGFR, and CASP3). The KEGG pathway and GO enrichment analyses revealed that these key targets play significant roles in regulating the positive regulation of cyclin-dependent protein serine/threonine kinase activity, positive regulation of nitric-oxide synthase activity and positive regulation of transcription, DNA-templated. β-sitosterol demonstrated the strongest binding affinity with the four targets, showing particularly strong affinities for EGFR (−9.75 kcal/mol) and HIF1A (−9.21 kcal/mol). Molecular dynamics (MD) simulations revealed high stability in these protein-ligand complexes, with CASP3 displaying the lowest deviation and most consistent RMSD (0.14 nm) of the protein, followed by EGFR (0.25), HIF1A (0.29), and ESR1 (0.79). In-vivo evaluation on female Wistar rats with Polyscias fulva ethanolic extract showed an ameliorative effect of the extracts against monosodium glutamate-induced (MSG) UF. Treated animals exhibited a decrease in serum proteins, cholesterol, estrogen, and progesterone levels (P < 0.05) and the extract preserved uterine tissue histoachitecture as compared to controls. In conclusion, Polyscias fulva demonstrates potential ameliorative activity against UF with promising pharmacokinetic properties and safety profiles.
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    Factors affecting lifestyle modification among adults with type II diabetes mellitus attending care at Mbale regional referral hospital in Mbale city, Eastern Uganda: a mixed methods study.
    (Sage, 2025) Gidudu, Mariam; Nandutu, Lornah; Ankunda, Ronnet; Epuitai, Joshua; Lulenzi, Jalia; Ssenyonga, Lydia V. N.; Gavamukulya, Yahaya; Nabirye, Rose Chalo
    Background: Globally diabetes affects over 530million adults with Type II Diabetes (T2DM) accounting for approximately 98% of patients. T2DM is preventable, and its onset can be markedly postponed by increasing physical activity, reducing weight, and changing dietary habits, poor adherence to lifestyle modification was attributed to a number of factors such as poverty, and diet education. The main objective of this study was to explore factors affecting lifestyle modification among adults with type II diabetes mellitus at Mbale Regional Referral Hospital (MRRH)-Mbale City, Eastern Uganda. Design and methods: A descriptive cross-sectional study involving 262 participants was conducted in MRRH among T2DM patients attending the diabetic clinic. Quantitative data was collected through structured administered questionnaires. Simple random sampling was used to recruit respondents for the study. Quantitative data was analyzed at univariate, and bivariate levels using SPSS version 25. Qualitative data was analyzed using thematic analysis. Statistical significance was set at p-value of <0.05. Results: About 70.1% of the participants were females, 63.4% were above 50years, and 29.7% of participants had high knowledge on T2DM. Most participants engaged in health practices like recommended diet, regular physical activity, body weight monitoring, blood sugar monitoring, and health checkups. Gender, religion, occupation, physical exercise, smoking, and weight management significantly affected lifestyle modifications. Qualitative results revealed three main themes namely, social support, health education, and having a conducive environment as promoters to lifestyle modification, while two main themes namely lack of social support and religious and cultural beliefs were the main barriers. Conclusion: Generally, participants had good knowledge on the lifestyle modifications of T2DM. Gender, religion, occupation, physical exercise, smoking, and weight management significantly affected lifestyle modifications. Social support, health education, and having a conducive environment were reported as promoters to lifestyle modification, while lack of social support and religious and cultural beliefs were the main barriers. It is recommended that health care workers should continuously educate the patients on the lifestyle modifications considering their financial status, and all other limiting factors. A holistic approach to lifestyle modifications needs to be taken in order to help reduce the complications associated with the condition. Keywords: type II diabetes mellitus (T2DM), glycemic control, dietary management, physical exercise, social support, health education
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    Green synthesized polyscias fulva silver nanoparticles ameliorate uterine fibroids in female wistar albino rats.
    (PLOS One, 2025) Kiyimba, Kenedy; Ahmed, Ayaz; Choudhary, Muhammad Iqbal; Rehman, Khadija; Hasan, Syed Mehmood; Jabbar, Abdul; Obakiro, Samuel Baker; Shah, Muhammad Raza; Munyendo, Were Lincoln; Guantai, Eric M.; Gavamukulya, Yahaya
    Uterine fibroids affect a substantial proportion of women in their reproductive age. Despite their effectiveness, surgical options such as hysterectomy are invasive, costly, and associated with recurrences. Pharmacological treatments are noncurative, only alleviate symptoms, and associated with adverse effects. Polyscias fulva (Araliaceae) is traditionally used to manage uterine fibroids in East Africa. In this study we synthesized Polyscias fulva silver nanoparticles (PFAgNPs), evaluated their toxicity and activity against monosodium glutamate (MSG)-induced uterine fibroids in Wistar albino rats. The UV-visible spectroscopy showed maximal absorbance at 425nm with adequate stability at varying temperatures, pH and storage conditions. Dynamic light scattering (DLS) analysis revealed an average hydrodynamic size of 107.4 d.nm, polydispersity index of 0.264, and zeta potential of -18.3 mV. X-ray diffraction (XRD) confirmed the crystalline nature of PFAgNPs with an average size of 25nm while scanning electron microscopy (SEM) showed a spherical shape with an average size of 35nm. The PFAgNPs caused lethargy, hyperventilation, and hyperactivity at a dose of 300mg/kg BW, whereas 2000mg/kg caused severe toxicity, resulting in death in acute toxicity testing. The no observed adverse effect level was 50mg/kgBW, the lowest observed adverse effect level was 100mg/kgBW, and median lethal dose (LD50) was 1000mg/kg. The PFAgNPs significantly decreased (P<0.05) serum proteins, cholesterol, estrogen and progesterone alongside preservation of the histoarchitecture of the uterus. Further research is needed to investigate the clinical safety of PFAgNPs in managing uterine fibroids.
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    In vitro antiplasmodial activity, acute toxicity and phytochemical quantification of selected medicinal plants used for the management of uncomplicated malaria in eastern Uganda.
    (Elsevier Ltd., 2025) Obakiro, Samuel Baker; Nabitandikwa, Catherine; Kiyimba, Kenedy; Ocan, Moses; Gavamukulya, Yahaya; Andima, Moses; Lukwago, Tonny Wotoyitide; Maseruka, Richard; Chebijira, Mercy; Opio, Moses; Hokello, Joseph Francis; Kibuule, Dan; Nabatanzi, Alice; Orena, Stephen; Waako, Paul; Owor, Richard Oriko
    Ethnopharmacological relevance The emergence of artemisinin resistance and limited antimalarial drug access in Uganda has increased reliance on herbal medicines as complementary and alternative therapies. Indigenous use of Albizia coriaria, Zanthoxylum chalybeum, Entada abyssinica, Maytenus senegalensis, and Kigelia Africana for malaria treatment is widespread but scientific evidence of their efficacy and safety was limited. Aim of the study This study aimed to validate the traditional antimalarial use of the five medicinal plants by evaluating their phytochemical composition, acute toxicity, and in vitro antiplasmodial activity against chloroquine-sensitive (3D7), chloroquine-resistant (Dd2) and clinical P. falciparum isolates. Materials and methods Phytochemical screening and quantification was conducted on 70 % hydroethanolic extracts from dried plant samples using UV–Vis spectrophotometry. The acute oral toxicity testing was conducted in Wistar albino rats using OECD 423 limit dose test. The antiplasmodial efficacy was evaluated using a 72-h SYBR Green assay on Plasmodium falciparum laboratory strains (3D7, Dd2) and clinical isolates. Results Alkaloids, flavonoids, tannins, and terpenoids were present in all the plant samples in varying quantities. Z. chalybeum was the most potent extract (IC50 0.81–1.28 μg/ml), followed by A. coriaria and E. abyssinica (IC50 10–50 μg/ml). M. senegalensis showed weak activity while K. africana was largely inactive (IC50 > 100 μg/ml). A. coriaria and M. senegalensis showed moderate acute toxicity (LD50 < 2000 mg/kg), while the other extracts showed no severe signs of acute toxicity in Wistar albino rats (LD50 > 2000 mg/kg). Conclusion Zanthoxylum chalybeum, Albizia coriaria and Entada abyssinica demonstrated promising antiplasmodial activity that supports their traditional use in management of malaria. However, more efficacy studies using in vivo models, sub-chronic and chronic toxicity studies particularly on A. coriaria and advanced phytochemical profiling are needed to delineate their therapeutic potential before being prioritized for development of standardized herbal remedies and novel antimalarial drugs.
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    In vitro antiplasmodial activity, acute toxicity and phytochemical quantification of selected medicinal plants used in symptomatic management of malaria in eastern Uganda.
    (Elsevier Ltd., 2025) Obakiroa, Samuel Baker; Nabitandikwa, Catherine; Kiyimba, Kenedy; Ocan, Moses; Gavamukulya, Yahaya; Andima, Moses; Lukwago, Tonny Wotoyitide; Maseruka, Richard; Mercy, Chebijira; Opio, Moses; Hokello, Joseph; Kibuule, Dan; Nabatanzi, Alice; Orenah, Stephen; Waako, Paul; Owor, Oriko Richard
    Ethnopharmacological relevance: The emergence of artemisinin resistance alongside limited antimalarial access in Uganda has intensified the use of herbal medicines as complementary and alternative therapies. Whereas there is widespread indigenous use of Zanthoxylum chalybeum, Albizia coriaria, Entada abyssinica, Maytenus senegalensis, and Kigelia Africana in treatment of malaria, there was limited scientific evidence of efficacy and safety. Aim of the study: This study assessed the in vitro antiplasmodial activity, acute toxicity, and phytochemical composition of the five plants so as to identify alternative sources of antimalarial drugs. Materials and methods: Phytochemical screening and quantification was conducted on ethanolic extracts from dried samples using UV-Vis spectrophotometry. The acute toxicity testing was conducted in Wistar albino rats using limit dose test and the antiplasmodial efficacy evaluated using a 72-hour SYBR Green assay on Plasmodium falciparum laboratory and clinical isolates. Results: Alkaloids, flavonoids, tannins, and terpenoids were present in all the samples. Z. chalybeum was the most potent, with IC50 values as low as 0.90 and 1.54 µg/ml against both chloroquine-sensitive (3D7) and resistant (Dd2) strains respectively. Albizia coriaria and Entada abyssinica also displayed moderate activity, with IC50s ranging from 30.26 to 101.26 µg/ml. Acute toxicity studies indicated that most extracts were relatively safe in Wistar albino rats, except for A. coriaria and M. senegalensis, which were moderately toxic with median lethal less than 2000mg/kg. Conclusion: Z. chalybeum, A. coriaria and E. abyssinica are promising medicinal plants for developing novel and effective antimalarial drugs, especially against drug-resistant strains that warrant more phytochemical and pharmacological studies. Keywords: Medicinal plants, Malaria, Antiplasmodial activity, Phytochemicals, Drug resistance
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    Phytochemical analysis and toxicity evaluation of polyscias fulva stem bark extract using gas chromatography‑mass spectrometry, fourier transform infrared spectroscopy, in silico, and in vivo studies in wistar rats.
    (Discover Toxicology, 2025) Kiyimba, Kenedy; Ahmed, Ayaz; Choudhary, Muhammad Iqbal; Obakiro, Samuel Baker; Gavamukulya, Yahaya; Guantai, Eric M.; Munyendo, Were Lincoln
    Scientific research on Polyscias fulva has demonstrated the plant’s pharmacological properties, including antitumor, antibacterial, and hypoglycemic effects, but there is a paucity of data concerning the phytochemical components responsible for these effects as well as the safety of Polyscias fulva. This study aimed to profile the phytoconstituents in the different solvent fractions of the ethanolic extract of Polyscias fulva stem bark using GC–MS and FTIR analysis, and subsequently evaluate acute and sub-acute toxicity effects in Wistar albino rats. GC–MS analysis identified 19 major phytocompounds. In silico toxicity prediction revealed the potential skin sensitization, eye corrosion, and respiratory toxicity effects of some of the identified compounds. Polyscias fulva ethanolic stem bark extract showed minimum acute toxicity in Wistar albino rats, with an LD50 exceeding 5000 mg/kg. Sub-acute toxicity testing did not show any significant biochemical or hematological toxic effects. However, dose dependent histopathological toxic effects were noted in the lungs with the lower doses (200 and 400 mg/kg) causing mild bronchitis with mononuclear cell infiltration, and the highest dose (800 mg/kg) causing marked peri-bronchiolar and perivascular lymphoid cell accumulation. These findings suggest the presence of pharmacologically active phytochemicals in Polyscias fulva with no major acute toxicity, biochemical or hematological toxic effects, but with lung specific dose-dependent histopathological toxic effects, and predicted skin and eye sensitivity reactions. Further research is needed to identify the specific phytochemicals responsible for its pharmacological activities and potential toxic effects, to inform its safe use in managing human ailments. Keywords Polyscias fulva · Acute toxicity · Sub-acute toxicity · GC–MS · FTIR
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    Sero-prevalence and factors associated with helicobacter pylori infection in a rural population in eastern Uganda:
    (Primary Health Care: Open Access, 2021) Nekaka, Rebecca; Oboth, Paul; Nteziyaremye, Julius; Gavamukulya, Yahaya; Ssenyonga, Lydia VN; Iramiot, Jacob Stanley
    Background: Globally, 50% or more of the world’s population is infected with Helicobacter pylori making it the most widely spread bacteria across the world. The low developed countries are more overburdened by Helicobacter pylori infection than the developed countries. H. pylori infection is associated with duodenal ulcer, chronic atrophic gastritis (CAG), lymphomas, and adenocarcinoma. This study reports the prevalence of H. pylori and itsassociated factors in Eastern Uganda. Materials and methods: A cross-sectional study involving 275 participants was carried out in eastern Uganda. H. pylori serology was done and face to face interviewer-administered questionnaire were used for data collection. Data were entered in Microsoft Excel and imported to Stata version 14 for analysis and a P value of <0.05 was considered statistically significant. Results: The seroprevalence of H. pylori was 27.3% (75/275) with 28.4% (50/176) of the females being positive compared to 25.3% (25/99) of the males. Consumption of animal products (meat, milk, and eggs) was the only statistically significant factor associated with H. pylori seropositivity (P <0.001, 95% CI =1.934-4.209, AOR=2.85). Conclusion: The H. pylori seroprevalence is high in eastern Uganda. Consumption of animal products was a positive predictor of infectivity. Keywords: Helicobacter pylori • Animal products • Seroprevalence • Kibuku • Eastern Uganda
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    Sub-Acute toxicity effects of methanolic stem bark extract of entada abyssinica on biochemical, haematological and histopathological parameters in wistar albino rats
    (Frontiers in pharmacology, 2021) Obakiro, Samuel Baker; Kiprop, Ambrose; Kigondu, Elizabeth; K’owino, Isaac; Kiyimba, Kenedy; Kato, Charles Drago; Gavamukulya, Yahaya
    Background: Whereas the efficacy of Entada abyssinica (fabaceae) extracts against various ailments has been scientifically validated, its safety has not been established. This study was undertaken to evaluate the toxicity effects of methanolic stem bark extract of E. abyssinica on biochemical, haematological and histological parameters of Wistar albino rats following repeated oral administration. Methods: Wistar albino rats of both sexes were randomized into groups and orally administered daily with determined doses (150, 300 and 600 mg/kg) of E. abyssinica methanolic extract using 1% tween 80 in distilled water as a control for 28 days. On the 29th day, all the animals were sacrificed and dissected to collect blood and selected organs. The serum and whole blood were assayed for biochemical and haematological parameters respectively while selected organs were examined for histopathological lesions. Numerical data was analyzed using graph pad prism and expressed as mean ± standard error of mean. The differences between the treatment and control groups were tested for statistical significance using one-way analysis of variance and/or Student’s t-test. Results: In repeated daily oral doses (150, 300 and 600 mg/kg), the methanolic stem bark extract of E. abyssinica did not cause significant alteration in majority of the biochemical and hematological indices. However, the extract significantly elevated the level of uric acid (all doses), aspartate aminotransferase (300 and 600 mg/kg), low density lipoproteins (150 mg/kg) and mean corpuscular heamoglobin concentration (all doses). On the other hand, the extracts reduced high density lipoproteins (150 and 300 mg/kg), mean corpuscular volume (all doses), haematocrit (150 and 600 mg/kg), mean platelet volume (150 and 600 mg/kg) and procalcitonin (150 mg/kg). In the vital organs, therewere no significant lesions observed except at the highest dose (600 mg/kg) where there was mild evidence of lymphocyte infiltration in the liver and focal interstitial nephritis. Conclusion: The methanolic stem bark extract of E. abyssinica is relatively safe in Wistar albino rats when repetitively administered orally in small doses for a prolonged period of time. We recommend more chronic toxicity studies and clinical trials on herbal remedies containing this plant to ensure that its use is free of potential toxicity to humans. Keywords: toxicity, fabaceae, traditional medicine, Entada abyssinica, biochemical, haematological, histopathalogical, wistar albina rats
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    Unraveling the therapeutic potential of tephrosia linearis : anti-inflammatory, analgesic activity, and molecular docking approaches.
    (Elsevier Ltd, 2025) Opio, Moses; Kiyimba, Kenedy; Nabitandikwa, Catherine; Maseruka, Richard; Wotoyitidde, Tony Lukwago; Andima, Moses; Chebijira, Mercy; Edeya, Sharon Tracy; Nabatanzi, Alice; Gavamukulya, Yahaya; Kibuule, Dan; Waako, Paul; Owor, Richard Oriko; Obakiro, Samuel Baker
    Background Inflammatory diseases such as arthritis affect over 300 million people globally. The current treatment mainly involves the use of Non-Steroidal Anti-inflammatory drugs (NSAIDS) which possess several adverse drug reactions that are sometimes life threatening. This has prompted many patients to gain interest in plant-based remedies. Tephrosia linearis (Willd.) Pers (Fabaceae) is widely used in Uganda to manage symptoms of inflammation. However, there was a paucity of information concerning its analgesic and anti-inflammatory activities. This study investigated the anti-inflammatory, analgesic, and acute toxicity effects of ethanolic extracts from the aerial parts of Tephrosia linearis in Wistar albino rats. Methods Plant samples were collected from Katakwi District, Eastern Uganda and extracted using 70 % ethanol. Quantitative phytochemical analysis was conducted using UV/Vis spectroscopy. Acute toxicity was assessed using Lorke’s method, while analgesic and anti-inflammatory activities were evaluated through Complete Freud’s Adjuvant-induced arthritis model. Three doses of T. linearis (200, 400, and 800 mg/kg) were compared with a control group receiving 20 mg/kg of diclofenac. Three marker compounds were assessed using in silico modeling to predict their pharmacokinetic properties, organ toxicity, and binding energy against selected protein targets involved in inflammation. Results The ethanolic extract contained significant concentrations of flavonoids (82.9 ± 0.1 mg/g), tannins (140.2 ± 0.9 mg/g), alkaloids (93.4 ± 1.0 mg/g), and triterpenoids (76.1 ± 1.5 mg/g). No toxic effects were observed at doses below 2000 mg/kg, with an estimated LD50 of 2692 mg/kg. The extract exhibited a non-dose dependent analgesic and anti-inflammatory activities that were significantly lower than that of diclofenac (p < 0.05). Molecular docking revealed strong binding affinities for apigenin, luteolin, and velutin with COX2, PLA2, and TNFα. Conclusion This study supports T. linearis as a safe herbal remedy for managing inflammation, suggesting further optimization through active ingredient isolation for enhanced therapeutic outcomes.