Chestnut (Castanea crenata) Inner-Shell Extract Attenuates Barium-Chloride-Induced Injury and Denervation-Induced Atrophy in Skeletal Muscle of Mice.

Background/Objectives: Chestnut inner shells, traditionally used in Korean and Chinese herbal medicine, contain antioxidant and anti-inflammatory compounds that contribute to complementary medicine. This study aimed to explore the therapeutic effects of chestnut inner-shell extract (CIE) on skeletal muscle injury and atrophy using both in vivo and in vitro models. Methods: We used three experimental models representing distinct pathological mechanisms: (1) barium chloride (BaCl(2))-induced muscle injury to model acute myofiber damage, (2) sciatic nerve transection to model chronic neurogenic muscle atrophy, and (3) H(2)O(2)-treated C2C12 myoblasts to model oxidative-stress-related myogenic impairment. Histological analyses (e.g., hematoxylin and eosin staining and cross-sectional area measurement) and molecular analyses were performed to evaluate the effects of CIE on muscle structure, apoptosis, and oxidative stress. Results: In the BaCl(2) injury model, CIE treatment significantly restored the muscle fiber structure, with muscle protein levels returning to near-normal levels. In the denervation-induced muscle atrophy model, CIE treatment led to a dose-dependent decrease in apoptosis-related factors (especially cleaved caspase-3) and mitigated the Akt/mTOR signaling pathway. In the in vitro oxidative stress model, CIE suppressed the expression of NRF2 and HO-1, which are key oxidative stress response regulators. Conclusions: These findings suggest that CIE may offer therapeutic potential for mitigating skeletal muscle damage, atrophy, and oxidative stress.