Safety assessment of crude aqueous methanol extract of Annona senegalensis stem bark: acute and sub-chronic toxicity studies

Abstract

Annona senegalensis Pers., (wild custard apple), is a shrub used traditionally to treat respiratory and skin diseases. Previous studies have demonstrated its anti-malaria, anti-snake envenomation and anti-cancer activities. However, its toxicological profile remains limited, particularly in male and female animals. This study aims to evaluate the safety of crude aqueous methanol extract of Annona senegalensis stem bark (AMEAS) through acute and sub-chronic toxicity studies. The stem bark of A. senegalensis was collected, air-dried, pulverized, and extracted using 70% methanol. Phytochemical screening, elemental analysis, and acute toxicity evaluation were carried out on AMEAS. Sub-chronic toxicity study was conducted on Wistar rats of both sexes at different doses administered orally for 28 days. Elemental analysis revealed the presence of heavy metals and essential mineral elements with the highest contents being calcium (59.88%) and potassium (25.39%). Acute toxicity testing showed no mortality up to 5000 mg/kg, suggesting an LD₅₀ greater than 5000 mg/kg. In the sub-chronic toxicity study, no mortality or significant harmful effects were observed. The blood glucose decreased from 13.68 mMol/L at 250 mg/kg to 10.71 mMol/L at 1000 mg/kg, much lower than the distilled water group (17.06 mMol/L). In conclusion, the extract appeared to be well-tolerated, with no obvious adverse effects. AMEAS is rich in Calcium (Ca) and potassium (K). It has been shown to have LD₅₀ greater than 5000 mg/kg and is assumed to be safe. On repeated use, AMEAS may cause hypoglycemia and weight loss which may be useful in managing diabetes and obesity respectively.

Graphical Abstract

Keywords:

• Annona senegalensis
• elemental analysis
• acute toxicity
• sub-chronic toxicity
• blood glucose level
• splenomegaly

Acknowledgments

The authors would like to thank mal Hamza, Mal Ngaski and Mal Abdulmalik Yabo, who are Technical Staff of the Usmanu Danfodiyo University, Sokoto as well as Dr Umar Mohammed, head of the Histopathology Department of the Usmanu Danfodiyo University Teaching Hospital, Sokoto, all for the technical assistance and invaluable services.

Authors’ contributions

MSN and HEM: study protocol/designed and coordination of the entire project. CJU and IYA: pharmacology, heamatology and biochemical studies. MSN, ML and HEM: extraction, elemental analysis and phytochemical study. AAB and CJU: statistical analysis. AHA, MSN and ML: plant collection, identification and preparation. AM and MSN: Manuscript proof reading.

Disclosure statement

The authors declare none.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This research was funded by the Tertiary Education Trust Fund (Tetfund), under the National Research Fund (NRF) Grant Award Scheme, with reference TETF/ES/DR&D-CE/NRF2020/SETI/110/VOL.1