Mollugin Supports Zebrafish Tail Regeneration in Association with Altered Inflammatory and Oxidative Responses

Mollugin is a natural naphthoquinone compound with reported anti-inflammatory and antioxidant activities, yet its role in tissue regeneration remains incompletely understood. In this study, a zebrafish tail amputation model was used to investigate the effects of Mollugin on wound repair and associated immune and redox responses. Zebrafish embryos were treated with Mollugin at concentrations of 22 µg/mL, 66 µg/mL, and 200 µg/mL following tail injury. Mollugin treatment was associated with improved tail-area recovery in a dose-dependent manner, accompanied by reduced expression of apoptosis-related genes and suppression of pro-inflammatory mediators, including IL-1β, IL-6, TNF-α, TLR4, and NF-κB1. In parallel, Mollugin restored antioxidant enzyme activities of superoxide dismutase and catalase. Fluorescence imaging in Tg(mpeg1:GFP) zebrafish showed a time-dependent effect of Mollugin on macrophage accumulation, with no obvious reduction at 24 h, but decreased macrophage-positive area at 48 h in the 66 and 200 µg/mL groups compared with the injured model group. qRT-PCR analysis further showed reduced expression of the M1-associated marker iNOS and increased expression of the M2-associated marker arginase-1. Collectively, these findings suggest that Mollugin may support zebrafish tail regeneration in association with changes in inflammatory, oxidative stress, apoptosis-related, and macrophage-associated markers. Further studies are needed to define the underlying cellular and molecular mechanisms.