Spirulina maxima derived marine pectin promotes the in vitro and in vivo regeneration and wound healing in zebrafish

Abstract

Purified bioactive components of marine algae have shown great pharmaceutical and biomedical potential, including wound healing activity. However, the activity of Spirulina maxima is the least documented with regard to wound healing potential. In the present study, we investigated the regenerative and wound healing activities of a Spirulina (Arthrospira) maxima based pectin (SmP) using in vitro human dermal fibroblasts (HDFs) and in vivo zebrafish model. SmP treated (12.5–50 μg/mL) HDFs showed increased cell proliferation by 20–40% compared to the untreated HDFs. Moreover, in vitro wound healing results in HDFs demonstrated that SmP decreased the open wound area % in concentration-dependent manner at 12.5 (32%) and 25 μg/mL (12%) compared to the control (44%). Further, zebrafish larvae displayed a greater fin regenerated area in the SmP exposed group at 25 (0.48 mm2) and 50 μg/mL (0.51 mm2), whereas the untreated group had the lowest regenerated area (0.40 mm2) at 3 days post amputation. However, fin regeneration was significantly (P < 0.001) higher only in the SmP treated group at 50 μg/mL. Furthermore, the open skin wound healing % in adult zebrafish was significantly higher (P < 0.05) after topical application (600 μg/fish) of SmP (46%) compared to the control (38%). Upregulation of genes such as tgfβ1, timp2b, mmp9, tnf-α, and il-1β, and chemokines such as cxcl18b, ccl34a.4, and ccl34b.4, in the muscle and kidney tissues of SmP treated fish compared to the respective control group was demonstrated using qRT-PCR. Histological analysis results further supported the rapid epidermal growth and tissue remodeling in SmP treated fish, suggesting that SmP exerts positive effects associated with wound healing. Therefore, SmP can be considered a potential regenerative and wound healing agent.