Yahaya Gavamukulya

Green synthesized Polyscias fulva silver nanoparticles ameliorate uterine fibroids in female Wistar Albino rats

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.

Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis

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 μg/ml and PC3 cells with an IC50 of 48.17 μg/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.