Browsing by Author "Ahmed, Ayaz"

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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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    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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    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