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Vernonia amygdalina Delile (bitter leaf) and Spondias mombin Linn (hog plum) are medicinal plants widely used in traditional medicine for treating various ailments. This study aimed to evaluate the safety profile, phytochemical constituents and toxicological effects of these extracts in Female Wistar rats. Ethanol extract of both plants were collected, authenticated and prepared. Qualitative phytochemical screening was conducted revealing the presence of alkaloids, anthraquinones, phenolic compounds, steroids/triterpenes, saponins and cardiac glycosides, with a notable absence of cyanogenic glycosides. Sub-acute assessment on Female Wistar rats were carried out following oral gavage of the extracts at 100mg/kg and 200mg/kg doses for 28 days. The V. amygdalina extract demonstrated high systemic tolerance, with all doses maintaining stable blood, liver, and kidney functions. It exhibited beneficial immunomodulatory effects, specifically activating the spleen and mobilizing lung defense mechanisms. Meanwhile, a mild liver inflammation (portal hepatitis) was observed exclusively at the 200 mg dose. Conversely, S. mombin extract presented a safety paradox: standard blood tests suggested it was systemically protective (reduced AST/ALT and Urea), yet histopathology study revealed toxicity. This toxicity manifested as destructive localized damage, including ulceration of the coronary arteries and bronchioles, making the extract critically unsafe for internal consumption. This research validates V. amygdalina as a safe, systemic immunomodulator within the tested dose range. While S. mombin presented a safety paradox. The findings strongly necessitate the mandatory integration of detailed histopathology into regulatory safety screening protocols for traditional plant medicines to detect latent, life-threatening organ toxicity that standard blood tests can miss
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