Tannic Acid Accelerates Cutaneous Wound Healing in Rats Via Activation of the ERK 1/2 Signaling Pathways

Adv Wound Care (New Rochelle). 2019 Jul 1;8(7):341-354. doi: 10.1089/wound.2018.0853. Epub 2019 Jul 2.

Abstract

Objective: This study was aimed to evaluate the effect of tannic acid (TA), a natural plant polyphenol astringent, on wound healing in vitro and in vivo, and to elucidate the underlying molecular signaling pathway in the wound healing. Approach: Cutaneous skin wounds were created in rats and then treated until closure with purified TA, serum or tissue samples were collected to test the concentration of factors by enzyme-linked immunosorbent assay (ELISA), and the expression in gene or protein was measured by quantitative real-time polymerase chain reaction or Western blot. We explored the cell-/dose-specific responses of TA (0.1-0.4 μg/mL) on proliferation and gene and protein expression of fibroblast NIH 3T3 cells. Results: The wounds on rats treated by TA got healed faster than those in the untreated group. The histopathology study showed that TA accelerated re-epithelialization and increase in hair follicles could be detected. The levels of growth factors including basic fibroblast growth factor (bFGF), transforming growth factor-beta, and vascular endothelial growth factor in TA-treated groups were all increased, and the content of interleukin-1 (IL-1) and IL-6 was decreased significantly when compared with that of the untreated group. The NIH 3T3 cells grow faster in 6 h at concentration of 0.1 μg/mL, and the expression of bFGF in gene and protein was increased significantly in the 0.1 μg/mL TA group. Further study revealed that the protein levels of bFGF, extracellular signal regulated kinase (Erk) 1/2, and P-Erk 1/2 in Erk 1/2 pathway were increased after TA treatment. Innovation: The role of TA in wound healing efficacy is unclear; this study, therefore, assesses the effects of TA on wound healing in different periods and the underlying molecular mechanisms. Conclusion: These results suggested that TA could accelerate wound healing through modulation of inflammatory cytokines and growth factors and activate Erk 1/2 pathway. In conclusion, TA may be a potential agent in promoting wound healing.

Keywords: growth factors; pathway; rats; tannic acid; wound healing.