Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Restores Redox Homeostasis and Modulates Myogenesis, Myostatin, and Muscle Atrophy Markers in Hypobaric Hypoxia Induced Muscle Loss in Rats

The present study aimed to see the pharmacological effects of the aqueous extract of Ganoderma lucidum in amelioration of hypobaric hypoxia (HH) mediated muscle wastage. Male Sprague-Dawley rats (200-220 g) were allocated into five groups (25 total, n = 5 in each group): unexposed control (Group 1), 7-d HH exposed (Group 2), and 7-d HH administered with G. lucidum orally at 50 mg/kg BW (Group 3), 100 mg/kg BW (Group 4), and 200 mg/kg BW (Group 5). All groups were kept in a simulated decompression chamber (maintained at 282 mmHg pressure, nearly 7620 m altitude, and 8% oxygen) except Group 1. After completion of HH exposure, the gastrocnemius muscle was collected for studying regulatory mechanism of muscle homeostasis at morphological, biochemical, and molecular level. HH-induced oxidative stress deteriorated physical parameters and dysregulated regulatory proteins of muscle mass. Treatment with G. lucidum improved physical parameters (bodyweight, muscle mass weight, and its relative change with tibia length), restored oxidative stress (ROS, MDA, and reduced GSH), AOPP levels, and LDH activity at an intended dose of 100 mg/kg BW. Furthermore, muscle mass regulatory proteins P-Akt, GSK-3β, Caspase3, Murf-1 and Atrogin1 were restored in the treatment groups. G. lucidum also elevated the Myf5, MyoD, MyoG, MRF and MHC expression, and restored the expression of myostatin and its canonical mediators' proteins. Histological assessment of myofibers showed polygonal shape, intact sarcoplasm, and peripheral nuclei. The present study indicates that G. lucidum extract showed pharmacological potential to modulate the regulatory mechanism of muscle homeostasis in HH environment.