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Purpose: To investigate the ameliorative effects of Vitellaria paradoxa (VP) nut extract for an anterior cruciate ligament transection with medial meniscectomy (ACLT+MMx)-induced osteoarthritis (OA) in high-fat diet (HFD)-induced obese rats. Methods: The rats were fed by HFD for 5 weeks before surgery-induced OA. Rats were treated orally with three different doses of VP nut extract (111.6, 223.2, and 446.4 mg/kg) for 8 weeks. Results: The VP nut triterpene-rich extract decreased the level of triglycerides and increased high-density lipoprotein-cholesterol. The level of nitric oxide, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α decreased after treatment with VP nut triterpene-rich extract, especially in high-doses. The VP nut triterpene-rich extracts also alleviated swelling in the knee OA, weight-bearing difference, and suppressed cartilage degradation. Conclusion: The Vitellaria paradoxa nut triterpene-rich extract suppressed proinflammatory mediators and attenuated the cartilage degradation and pain in osteoarthritis with an obesity rat model. As such, Vitellaria paradoxa nut triterpene-rich extract can be used as an alternative for osteoarthritis treatment. [ABSTRACT FROM AUTHOR]