Therapeutic Potential of DPHC, A Brown Seaweed Polyphenol, Against TNF-α-Induced Inflammatory Muscle Loss

Inflammatory muscle loss results from excessive inflammatory responses, causing muscle damage and weakness. In the current investigation, we evaluated the protective effects of diphlorethohydroxycarmalol (DPHC) against tumor necrosis factor-alpha (TNF-α)-induced skeletal muscle inflammation and muscle loss and elucidated the underlying mechanisms. Furthermore, the effect of DPHC on swimming performance was confirmed under TNF-α-induced inflammatory muscle loss-conditioned zebrafish by assessing the swimming number, distance moved, time spent swimming, frequency of swimming zebrafishes in an upstream swim track (Zone A). In vivo behavioral endurance test results indicated that TNF-α treatment significantly decreased the number of swimming zebrafish and swimming distance in Zone A compared with the Control. Meanwhile, the DPHC treatment significantly increased the number of swimming zebrafish and swimming distance in Zone A compared to TNF-α-induced zebrafish. These findings indicate that DPHC treatment effectively improved the swimming performance of TNF-α-induced zebrafish. In an additional study, TNF-α significantly induced inflammatory muscle loss by upregulating nuclear factor kappa light chain enhancer of activated B cells (NF-κB) mitogen activated protein kinase (MAPK) associated proteins and MuRF-1 in the skeletal muscle tissues of TNF-α-induced zebrafish. However, DPHC administration significantly counteracted TNF-α-induced inflammation and muscle loss by downregulating NF-Κb and MAPK-associated proteins, as well as the muscle degradation-related proteins MuRF-1 and MAFbx, in the skeletal muscle tissues of TNF-α-induced zebrafish. In summary, our research findings demonstrated that DPHC from <i>Ishige okamurae</i> could be used for the development of nutraceuticals or functional foods targeting inflammatory muscle loss.