Gardenia Fruit and Its Active Compound Crocin Protect Against Dexamethasone‐Induced Muscle Atrophy via Nrf2 Activation

Background: Muscle mass gradually declines with age and the development of an effective strategy to prevent this is important. Gardenia fruit ( Gardenia jasminoides ; GJ), commonly used as a natural food colorant and in traditional herbal medicines, possesses antiinflammatory, antidiabetic, and antiangiogenic properties. However, its effects on muscle atrophy remain unexplored. Purpose: In this study, we investigated the potential of GJ extract to mitigate dexamethasone (DEX)‐induced muscle atrophy. Methods: Cell experiments used C2C12 cells and myotube atrophy was induced with 50 μM DEX. Animal experiments used 7 week‐old C57BL/6 mice and fed GJ at 0.05% or 0.1% in the diet for 8 weeks. DEX was injected intraperitoneally at 15 mg/kg per day for 18 days before dissection to induce muscle atrophy and the effects were evaluated. Results: GJ enhanced myogenic differentiation by upregulating myogenic regulatory factors like Myf5 and MyoD and inhibited DEX‐induced myotube atrophy. Additionally, GJ reduced DEX‐induced ROS production and mitochondrial dysfunction via Nrf2 activation. In mice, GJ protected the loss of muscle mass and decrease in muscle function by DEX. DEX‐induced oxidative stress was reduced by GJ via the activation of Nrf2, followed by the transcription of antioxidant genes. HPLC analysis identified geniposide (GP) and crocin (CC) as the main constituents of GJ. However, only CC was found to exert antioxidant effects and effectively reduce DEX‐induced oxidative stress and muscle atrophy via Nrf2 activation. Conclusion: These findings suggest that GJ, particularly its bioactive component CC, may serve as a potential therapeutic agent for muscle atrophy.