RESUMO
Introduction: Dr Iguedo Goko Cleanser® is a herbal formulation (HF) widely marketed in southern Nigeria and purported to be very efficacious for the management of various diseases including giardiasis, toilet infections, hypertension, diabetes, ulcer, impotence, low libido, low sperm count amongst others. Medicinal plants reportedly produce an array of adverse reactions capable of inducing harmful conditions, including death. Aim: This study evaluated the subchronic toxicity concern of HF on testicular function and gonadal histoarchitecture in Wistar rats. Methods: Thirty Wistar rats of both sexes were randomly divided into six groups (5/group) and were orally administered HF for 60 days. The control groups received 5 mL/kg of distilled water; the treatment groups were administered 476.24 and 158.75 mg/kg body weight of HF each for both male and female rats. Using standard procedures, semen analysis was done for all male rats. Animals were anaesthetised and sacrificed on the 62nd day; the gonads were eviscerated, weighed and fixed in 10% buffered formalin for histopathological examinations. Results: Significant (p < 0.05) increase in sperm count relative to control as well as spermatotoxic effects were observed in male rats. Histologically, the ovary presented some degrees of pathologies: cloggy appearing ovarian cortex with a display of a tumour-like cortical area, scantily displayed primordial follicles, haemorrhagic blood vessels, atretic secondary follicle, and eroding granulosa cells amongst others. Testicular histopathology showed abnormal seminiferous tubules' histoarchitecture, degenerated spermatids, distorted spermatogenic cells' orientation, and displaced spermatids into the luminal space. Conclusion: Herbal drugs are usually regarded to be completely safe due to their natural sources, however, this study discovered exposure-related toxic effects of Dr Iguedo Goko Cleanser® on testicular function and gonadal histomorphology. The findings recommend extreme caution with chronic use and avoidance whenever possible.
RESUMO
BACKGROUND: Previous folkloric and experimental reports have demonstrated the antimalarial efficacy of Azadirachta indica (AZA) extracts. However, one of the major challenges facing its application for the clinical treatment of malaria is the design of an acceptable dosage form. OBJECTIVE: Consequently, we developed AZA extract-loaded nanostructured lipid carriers (NLC) for the formulation of suppositories, denoted as nanosuppositories, for intrarectal treatment of malaria. METHODS: Various batches of NLC-bearing AZA extract were formulated based on lipid matrices prepared using graded concentrations of Softisan®154 and Tetracarpidium conophorum or walnut oil. NLC was investigated by size and differential scanning calorimetry (DSC). Suppository bearing AZA extract-loaded NLC was developed using cocoa butter or theobroma oil, and their physicochemical properties were profiled. In vitro drug release and in vivo antimalarial activity (using Plasmodium berghei-infected mice) were investigated. RESULTS: NLCs exhibited sizes in nanometers ranging from 329.5 - 806.0 nm, and were amorphized as shown by DSC thermograms. Nanosuppositories were torpedo- or bullet- shaped, weighing 138 - 368 mg, softened/liquefied between 4.10 - 6.92 min, and had controlled release behaviour. In vivo antimalarial study revealed excellent antimalarial efficacy of the nanosuppositories comparable with a commercial brand (Plasmotrim®) and better than the placebo (unloaded nanosuppository), and without toxic alterations of hepatic and renal biochemical factors. CONCLUSION: Thus, AZA extract could be rationally loaded in nanostructured lipid carriers (NLC) for further development as nanosuppository and deployed as an effective alternative with optimum convenience for intrarectal treatment of malaria.
