ETHNOPHARMACOLOGICAL RELEVANCE: Sphenocentrum jollyanum (Pierre) is a medicinal plant native to West African countries, especially Nigeria and Ghana. The leaf of S. jollyanum is a traditional therapy for diabetes, erectile dysfunction, gastrointestinal disorders, and malaria. However, there is a paucity of information on the mitochondrial-restorative and apoptotic-modulating properties of S. jollyanum leaf. AIM OF THE STUDY: The anti-inflammatory, apoptotic-modulating, and mitochondrial-restorative effects of S. jollyanum were studied using diabetic Wistar albino rats induced with streptozotocin. METHODS: A high-fat diet (HFD) and a single dose injection of 10 mg/kg of streptozotocin (STZ) were used to induce type-2 diabetes model. Thirty-six (36) rats were randomly assigned into six groups as follows: Group 1 (normal diet + normal saline), Group 2 (HFD + 50 mg/kg STZ), Group 3 (HFD + 50 mg/kg STZ + 10 mg/kg glibenclamide), Group 4 (HFD + 50 mg/kg STZ + 50 mg/kg of S. jollyanum extract), Group 5 (HFD + 50 mg/kg STZ + 100 mg/kg of S. jollyanum extract), Group 6 (HFD + 50 mg/kg STZ + 200 mg/kg of S. jollyanum extract). Glucose levels (fasting) were monitored in the rats at a 48-h interval. After experimental treatment for 28 days, blood was collected via cardiac puncture into plain bottles. After differential centrifugation, serum was extracted into plain bottles for assessment of insulin, caspases 3 and 9 activity, as well as IL-1β, IL-6, CRP, and TNF-α levels. Liver mitochondria were isolated for mitochondrial ATPase activity, lipid peroxidation and mitochondrial permeability while liver and pancreatic tissues were prepared for histopathology using standard laboratory procedures. RESULTS: Induction of the Wistar rats with 50 mg/kg of streptozotocin increased fasting glucose, caspase 3, caspase 9, IL-1β, IL-6, TNF-α, CRP, troponin I, as well as increased mitochondrial permeability, mitochondrial lipid peroxidation, and mitochondrial ATPase activity significantly compared to the normoglycemic group and glibenclamide-treated group. This was also accompanied by pathological lesions in the liver and pancreas. Administration of S. jollyanum aqueous leaf extract significantly decreased mitochondrial ATPase activity, mitochondrial lipid peroxidation, caspase 3 and caspase 9 activity, and mitochondrial permeability, fasting blood glucose, IL-1β, IL-6, TNF-α, CRP, and troponin I levels in the diabetic rats, while significantly boosting serum insulin content (p <
0.0001). CONCLUSION: S. jollyanum aqueous leaf demonstrates anti-inflammatory, mitochondrial-protective and apoptotic-modulating influences while reversing hepatic and pancreatic damage in diabetic Wistar rats.