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Currently, highly active antiretroviral therapy is unable to cure HIV/AIDS because of HIV latency. This study aimed at documenting medicinal plants used in the management of HIV/AIDS in Eastern Uganda so as to identify phytochemicals with HIV latency reversing potential. An ethnobotanical survey was conducted across eight districts in Eastern Uganda. Traditional medicine practitioners were interviewed using semi-structured questionnaires. Qualitative and quantitative phytochemical tests were respectively, performed to determine the presence and quantity of phytochemicals in frequently mentioned plant species. Data were analysed and presented using descriptive statistics and Informant Consensus Factor (ICF). Twenty-one plant species from fourteen plant families were reported to be used in the management of HIV/AIDS. Six plant species with the highest frequency of mention were: Zanthoxylum chalybeum, Gymnosporia senegalensis, Warbugia ugandensis, Leonatis nepetifolia, Croton macrostachyus and Rhoicissus tridentata. Qualitative phytochemical analysis of all the six most frequently mentioned plant species revealed the presence of flavonoids, tannins, terpenoids, alkaloids and phenolics. Quantitative analysis revealed the highest content of flavonoids in L. nepetifolia (20.4 mg/g of dry extract) while the lowest content was determined in C. macrostachyus (7.1 mg/g of dry extract). On the other hand, the highest content of tannins was observed in L. nepetifolia. (199.9 mg/g of dry extract) while the lowest content was found in R. tridentata. (42.6 mg/g of dry extract). Medicinal plants used by traditional medicine practitioners in Eastern Uganda to manage HIV/AIDS are rich in phytochemicals including flavonoids and tannins. Further studies to evaluate the HIV-1 latency reversing ability of these phytochemicals are recommended to discover novel molecules against HIV/AIDS.
Albizia coriaria (Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting information regarding its toxicity. We therefore evaluated the acute and subacute toxicity of the ethanolic stem bark extract of A. coriaria in mature healthy Wistar albino rats following Lorke's method and OECD guidelines 407. The LD50 of the ethanolic stem bark extract of A. coriaria was 2000 mg/kg. The acute toxicity signs observed included piloerection, hyperventilation, lethargy, and loss of righting reflex. There was a significant increase in aspartate aminotransferase, alkaline phosphatase, red blood cells and haemoglobin in rats after 28 days at the dose of 500 mg/kg. Histological analyses revealed multifocal random parenchymal necrosis and scattered periportal mononuclear inflammatory cells infiltration in the liver, interstitial nephritis in the kidney and multifocal lymphoid accumulation in the peribronchiolar and perivascular lung tissue at 500 mg/kg. The ethanolic stem bark of A. coriaria was therefore moderately toxic to the rats when administered in a single high oral dose within 24 h. The extract caused a dose dependent toxicity with significant damage to the kidney, liver and lung tissues at a dose of 500 mg/kg after 28 days. Herbal medicines containing A. coriaria extracts should be consumed cautiously due to likelihood of toxicity particularly at higher doses greater than 500 mg/kg.
Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic β-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor β1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1β), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.
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.
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.
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 non-curative, 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 425 nm 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 25 nm while scanning electron microscopy (SEM) showed a spherical shape with an average size of 35 nm. The PFAgNPs caused lethargy, hyperventilation, and hyperactivity at a dose of 300 mg/kg BW, whereas 2000 mg/kg caused severe toxicity, resulting in death in acute toxicity testing. The no observed adverse effect level was 50 mg/kgBW, the lowest observed adverse effect level was 100 mg/kgBW, and median lethal dose (LD50) was 1000 mg/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.
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.
This study explored the perception of medical and nursing students and clinical instructors Objective Structured Clinical Examination (OSCE) in five sub-Saharan African health training institutions (Uganda, Malawi, Nigeria, Ghana, Zambia). We used questionnaires among 686 students and 46 clinical instructors, focused group discussions, and key informant interviews to find out their perception. Both students and clinical instructors mostly preferred OSCE because it is fair, organized, and tests real healthcare skills more than the conventional methods like long case. But students said the time on some stations was too short, stressful, and noted challenges during OSCE such as lack of some materials on some stations. Teachers agreed that OSCE is helpful but hard to do due to insufficient staffing and space. Both suggested more practice sessions through Pre OSCE, better training for teachers, and feedback to help students improve. The study confirms that OSCE is the most efficient way to evaluate nursing and medical students, however the study also highlights that a mixed method evaluation would be the best option for evaluation of clinical competence.
Currently, highly active antiretroviral therapy is unable to cure HIV/AIDS because of HIV latency. This study aimed at documenting medicinal plants used in the management of HIV/AIDS in Eastern Uganda so as to identify phytochemicals with HIV latency reversing potential. An ethnobotanical survey was conducted across eight districts in Eastern Uganda. Traditional medicine practitioners were interviewed using semi-structured questionnaires. Qualitative and quantitative phytochemical tests were respectively, performed to determine the presence and quantity of phytochemicals in frequently mentioned plant species. Data were analysed and presented using descriptive statistics and Informant Consensus Factor (ICF). Twenty-one plant species from fourteen plant families were reported to be used in the management of HIV/AIDS. Six plant species with the highest frequency of mention were: Zanthoxylum chalybeum, Gymnosporia senegalensis, Warbugia ugandensis, Leonatis nepetifolia, Croton macrostachyus and Rhoicissus tridentata. Qualitative phytochemical analysis of all the six most frequently mentioned plant species revealed the presence of flavonoids, tannins, terpenoids, alkaloids and phenolics. Quantitative analysis revealed the highest content of flavonoids in L. nepetifolia (20.4 mg/g of dry extract) while the lowest content was determined in C. macrostachyus (7.1 mg/g of dry extract). On the other hand, the highest content of tannins was observed in L. nepetifolia. (199.9 mg/g of dry extract) while the lowest content was found in R. tridentata. (42.6 mg/g of dry extract). Medicinal plants used by traditional medicine practitioners in Eastern Uganda to manage HIV/AIDS are rich in phytochemicals including flavonoids and tannins. Further studies to evaluate the HIV-1 latency reversing ability of these phytochemicals are recommended to discover novel molecules against HIV/AIDS.
Diabetes mellitus (DM) is the fourth leading cause of morbidity and mortality among non-communicable diseases affecting about 422 million people worldwide and an estimated 1.5 million deaths directly attributed to diabetes each year with a prevalence of approximately 4.1% in Uganda. The disease is on an unprecedented rise in developing countries yet access to conventional diabetes medication is a huge challenge due to limited resources. Moreover, the current management and treatment options are life-long, expensive and associated with undesirable side effects. Consequently, there is widespread use of complementary and alternative medicines, mostly herbal medicines in the management of DM in Uganda.