Phytochemical Composition, Antihyperglycaemic Activity, and Acute Oral Toxicity of Aqueous and Ethanolic Gossypium herbaceum Leaf Extracts in Diabetic Wistar Rats

Abstract

Gossypium herbaceum L. (Malvaceae) has a history of medicinal use for the management of various ailments, but experimental evidence supporting the antidiabetic potential and safety of its leaves remains limited. Aim of the study: This study evaluated the phytochemical composition, antihyperglycaemic activity, and acute oral toxicity of aqueous and 70% ethanolic leaf extracts of G. herbaceum using complementary in vitro and in vivo approaches. Materials and Methods: Mature G. herbaceum leaves were collected, authenticated, and extracted separately with distilled water and 70% ethanol by maceration. Qualitative phytochemical screening was performed using standard procedures. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (40 mg/kg). Thirty rats were randomly allocated to five groups (n = 6): normal control, diabetic control, glibenclamide (5 mg/kg), aqueous extract (400 mg/kg), and 70% ethanolic extract (400 mg/kg). Treatments were administered orally once daily for 28 days. Fasting blood glucose (FBG) and body weight were monitored during treatment. Acute oral toxicity was evaluated in female rats according to OECD Test Guideline 423 at a limit dose of 2000 mg/kg, with mortality, clinical signs, and body-weight changes recorded over 14 days. Results: Both extracts contained flavonoids, alkaloids, tannins, saponins, and phenolic constituents, with comparatively stronger qualitative reactions observed for several phytochemical classes in the ethanolic extract. Streptozotocin administration produced pronounced hyperglycaemia and body-weight loss relative to the normal control. Following 28 days of treatment, FBG decreased significantly to 180 ± 15 mg/dL and 140 ± 12 mg/dL in the aqueous and ethanolic extract groups, respectively, from 350 ± 25 mg/dL in diabetic controls (p < 0.05), representing reductions of 48.6% and 60.0%. Glibenclamide reduced FBG to 101 ± 14 mg/dL, corresponding to a 71.1% reduction. Both extracts significantly attenuated diabetes-associated weight loss, with final body weights of 214 ± 16 g and 220 ± 18 g for the aqueous and ethanolic extracts, respectively, compared with 200 ± 15 g in diabetic controls (p < 0.05). At the acute toxicity limit dose of 2000 mg/kg, neither extract caused mortality nor overt treatment-related clinical abnormalities, and the body-weight progression remained normal throughout the 14-day observation period. The acute LD₅₀ was therefore considered >2000 mg/kg under the experimental conditions. Conclusion: Aqueous and 70% ethanolic G. herbaceum leaf extracts exhibited significant antihyperglycaemic activity in streptozotocin-induced diabetic rats, with the ethanolic extract showing greater efficacy. The enhanced activity of the ethanolic preparation may reflect more efficient extraction of pharmacologically relevant constituents, although quantitative phytochemical profiling and mechanistic studies are needed to confirm this hypothesis. Both extracts demonstrated a favourable acute oral safety profile at 2000 mg/kg. These findings support further investigation of G. herbaceum leaves as a potential source of antidiabetic bioactive compounds, particularly through bioactivity-guided fractionation, compound identification, mechanistic validation, and longer-term toxicological studies.