Hispidin‐enriched Sanghuangporus sanghuang mycelia SS‐MN4 ameliorate disuse atrophy while improving muscle endurance

Abstract Background Disuse atrophy is a frequent cause of muscle atrophy, which can occur in individuals of any age who have been inactive for a prolonged period or immobilization. Additionally, acute diseases such as COVID‐19 can cause frequent sequelae and exacerbate muscle wasting, leading to additional fatigue symptoms. It is necessary to investigate potent functional nutrients for muscle reinforcement in both disuse atrophy and fatigue to ensure better physical performance. Methods The effects of Sanghuangporus sanghuang SS‐MN4 mycelia were tested on two groups of 6‐week‐old male mice—one with disuse atrophy and the other with fatigue. The disuse atrophy group was divided into three sub‐groups: a control group, a group that underwent hind limb casting for 7 days and then recovered for 7 days and a group that was administered with SS‐MN4 orally for 14 days, underwent hind limb casting for 7 days and then recovered for 7 days. The fatigue group was divided into two sub‐groups: a control group that received no SS‐MN4 intervention and an experimental group that was administered with SS‐MN4 orally for 39 days and tested for exhaustive swimming and running on Day 31 and Day 33, respectively. RNA sequencing (RNA‐seq) and western blot analysis were conducted on C2C12 cell lines to identify the therapeutic effects of SS‐MN4 treatment. Results In a disuse atrophy model induced by hind limb casting, supplementing with 250 mg/kg of SS‐MN4 for 14 days led to 111.2% gastrocnemius muscle mass recovery and an 89.1% improvement in motor function on a treadmill ( P < 0.05). In a fatigue animal model, equivalent SS‐MN4 dosage improved swimming (178.7%) and running (162.4%) activities ( P < 0.05) and reduced blood urea nitrogen levels by 18% ( P < 0.05). SS‐MN4 treatment also increased liver and muscle glycogen storage by 34.36% and 55.6%, respectively, suggesting a higher energy reserve for exercise. RNA‐seq and western blot studies from the C2C12 myotube showed that SS‐MN4 extract upregulates Myh4 and helps sustain myotube integrity against dexamethasone damage. Conclusions Supplementation of SS‐MN4 (250‐mg/kg body weight) with hispidin as active compound revealed a potential usage as a muscle nutritional supplement enhancing muscle recovery, fast‐twitch fibre regrowth and fatigue resistance.