Nano-curcumin mitigates muscle impairment in hypoxic hindlimb-unloaded mice

Skeletal muscle atrophy due to hindlimb unloading (HU) is worsened under hypoxic conditions, mimicking clinical scenarios such as prolonged bed rest and chronic cardiopulmonary disease. Curcumin has therapeutic potential but suffers from poor bioavailability. This study evaluated the efficacy of curcumin encapsulated in zein-casein nanoparticles (Cur Z-CS NP) in mitigating muscle deterioration in HU mice under hypoxia.

Cur Z-CS NP were synthesized and characterized for physicochemical properties and drug release. Male C57BL/6 J mice were divided into normoxic and hypoxic groups, each further split into ground control and HU subgroups, and treated with placebo, free curcumin, or Cur Z-CS NP. Muscle function, histology, and gene expression were assessed in gastrocnemius muscles.

Cur Z-CS NP exhibited favorable size, charge, and sustained curcumin release. HU and hypoxia significantly reduced body and muscle weights, as well as grip strength and fiber cross-sectional area (p < 0.05). Cur Z-CS NP treatment reversed these effects, increasing muscle mass and fiber size, and significantly improving grip strength. Myonuclear counts were preserved or elevated in treated HU mice, particularly under hypoxia. Cur Z-CS NP also reduced expression of caspase-1, spliced XBP-1, and MLKL, indicating suppression of apoptosis, ER stress, and necroptosis. Although MND size was decreased in HU hypoxic mice, Cur Z-CS NP partially restored it. Wire hanging time remained unaffected.

Cur Z-CS NP mitigates muscle atrophy and cellular stress in HU hypoxic mice, offering a promising therapeutic strategy for muscle wasting under conditions of disuse and hypoxia.