Toxicity of Antidiarrheal and Spasmolytic Herbal Mixtures Used in Neonates and Infants less than Six Months of Age in Young Rodents

Abstract

Background: Leaves of Alstonia boonei De Wild. (Apocynaceae), Aristolochia ringens Vahl. (Aristlochiaceae) [Anti-diarrhoea], Allium ascalonicum L. (Amaryllidaceae) and Calliandra haematocephala Haask. (Fabaceae) [Spasmolytic] are components of anti-diarrhoea and spasmolytic herbal mixtures commonly used to treat diarrhoea and abdominal colics in neonates and infants less than 6 months of age in Lagos, Nigeria. Objective: This study was done to evaluate the acute and sub-acute toxicity of the anti-diarrhoea (aqueous leaf extracts of A. boonei and A. ringens) and spasmolytic (aqueous leaf extracts of A. ascalonicum and C. haematocephala) herbal mixtures in young experimental rodents. Materials and Methods: Each herbal mixture contained dried leaves of the two plants in equal amounts and was extracted as used traditionally by herbal practitioners. The acute toxicity test was done using young albino mice of both sexes (average weight 15 g) and the 28 day sub-acute toxicity test was done using young albino rats (average weight 120 g) of both sexes to evaluate the safety of the herbal mixtures. Results: No mortality occurred during the oral acute toxicity study for both the anti-diarrhoea and spasmolytic herbal mixtures. The intraperitoneal acute toxicity study showed mortality at higher doses for both anti-diarrhoea (LD50:1318 mg/kg) and spasmolytic (LD50: 1175 mg/kg) herbal mixtures. In the 28 day sub-acute toxicity study, both the anti-diarrhoea and spasmolytic herbal mixtures produced no significant increase in the weight of rats, dose-dependent elevations of total cholesterol and low density lipoprotein, significant dose-dependent reductions in platelet counts (p<0.05). The histopathological analysis done after 28 days showed that unlike the spasmolytic herbal mixture, the anti-diarrhoea herbal mixture had dose-dependent fluid congestions of the liver, kidney and brain, and tubular necrosis in the kidneys. Conclusion: The results of this study show that when administered through the intraperitoneal route in the acute toxicity study, mortality occurred at the higher doses for both the anti-diarrhoea and spasmolytic herbal mixtures. After 28 days, the antidiarrhoea herbal mixture containing Alstonia boonei and Aristolochia ringens was toxic when administered to young rodents in high doses. The results of this study show evidence of toxicity and these are important safety signals. Therefore, parents, health care providers and regulatory authorities should be aware of the potential toxicity of these herbal mixtures, especially when used in the young child without scientific dose finding studies. Pharmacovigilance is essential to detect and document safety of herbal medicines.