Opio, MosesKiyimba, KenedyNabitandikwa, CatherineMaseruka, RichardWotoyitidde, Tony LukwagoAndima, MosesChebijira, MercyEdeya, Sharon TracyNabatanzi, AliceGavamukulya, YahayaKibuule, DanWaako, PaulOwor, Richard OrikoObakiro, Samuel Baker2026-07-172026-07-172025Opio, M., Kiyimba, K., Nabitandikwa, C., Maseruka, R., Wotoyitidde, T. L., Andima, M., Chebijira, M., Edeya, S. T., Nabatanzi, A., Gavamukulya, Y., Kibuule, D., Waako, P., Owor, R. O., & Obakiro, S. B. (2025). Unraveling the therapeutic potential of Tephrosia linearis: Anti-inflammatory, analgesic activity, and molecular docking approaches. Pharmacological Research - Natural Products, 9, 100389. https://doi.org/10.1016/j.prenap.2025.100389https://bdears.busitema.ac.ug/handle/123456789/8021ArticleBackground Inflammatory diseases such as arthritis affect over 300 million people globally. The current treatment mainly involves the use of Non-Steroidal Anti-inflammatory drugs (NSAIDS) which possess several adverse drug reactions that are sometimes life threatening. This has prompted many patients to gain interest in plant-based remedies. Tephrosia linearis (Willd.) Pers (Fabaceae) is widely used in Uganda to manage symptoms of inflammation. However, there was a paucity of information concerning its analgesic and anti-inflammatory activities. This study investigated the anti-inflammatory, analgesic, and acute toxicity effects of ethanolic extracts from the aerial parts of Tephrosia linearis in Wistar albino rats. Methods Plant samples were collected from Katakwi District, Eastern Uganda and extracted using 70 % ethanol. Quantitative phytochemical analysis was conducted using UV/Vis spectroscopy. Acute toxicity was assessed using Lorke’s method, while analgesic and anti-inflammatory activities were evaluated through Complete Freud’s Adjuvant-induced arthritis model. Three doses of T. linearis (200, 400, and 800 mg/kg) were compared with a control group receiving 20 mg/kg of diclofenac. Three marker compounds were assessed using in silico modeling to predict their pharmacokinetic properties, organ toxicity, and binding energy against selected protein targets involved in inflammation. Results The ethanolic extract contained significant concentrations of flavonoids (82.9 ± 0.1 mg/g), tannins (140.2 ± 0.9 mg/g), alkaloids (93.4 ± 1.0 mg/g), and triterpenoids (76.1 ± 1.5 mg/g). No toxic effects were observed at doses below 2000 mg/kg, with an estimated LD50 of 2692 mg/kg. The extract exhibited a non-dose dependent analgesic and anti-inflammatory activities that were significantly lower than that of diclofenac (p < 0.05). Molecular docking revealed strong binding affinities for apigenin, luteolin, and velutin with COX2, PLA2, and TNFα. Conclusion This study supports T. linearis as a safe herbal remedy for managing inflammation, suggesting further optimization through active ingredient isolation for enhanced therapeutic outcomes.enArticle