Protective effects of Trifuhalol A, a Phlorotannin derived from edible Brown seaweed Agarum cribrosum, on dexamethasone-induced muscle atrophy in muscle cells and zebrafish models.

Muscle atrophy, characterized by declines in muscle mass and functionality, currently lacks effective therapeutic options, highlighting an urgent need for further research. This research aimed to elucidate the protective effects of Trifuhalol A (TFA), a phlorotannin derived from Agarum cribrosum, against dexamethasone (Dexa)-induced muscle atrophy in zebrafish and C2C12 cells. TFA enhanced differentiation of myoblasts and myotube formation by upregulating MyHC, myogenin, MyoD, p-Akt, and p-mTOR, as well as activation of key downstream effectors of the mTOR pathway, enhancing protein synthesis. It also inhibited key markers associated with muscle atrophy, such as FoxO3a, MuRF-1, and MAFbx. In vivo, TFA treatment prevented the Dexa-induced reduction in myofiber diameter and cross-sectional area (CSA). Zebrafish exploratory behavior tests revealed that TFA improved swimming patterns and food-tracking velocity, indicating improved swimming performance and responsiveness. In conclusion, TFA mitigates Dexa-triggered muscle atrophy, and these effects are associated with improvements in muscle morphology and swimming performance. While the underlying mechanisms remain to be fully elucidated, the observed effects may involve modulation of the Akt/mTOR/FoxO3a signaling pathway. These findings suggest that TFA holds promise as a potential functional ingredient for supporting muscle health and mitigating muscle atrophy.