Effect of Topical Application of Chlorogenic Acid on Excision Wound Healing in Rats

Abstract

This study was undertaken to evaluate the therapeutic effects of topical chlorogenic acid on excision wounds in Wistar rats. A 1 % (w/w) chlorogenic acid or silver sulfadiazine ointment was applied topically once a day for 15 days on full-thickness excision wounds created on rats. The 1 % (w/w) chlorogenic acid ointment had potent wound healing capacity as evident from the wound contraction on the 15th post-surgery day, which was similar to that produced by 1 % (w/w) silver sulfadiazine ointment. Increased rates of epithelialization were observed in the treated rats. It also improved cellular proliferation, increased tumor necrosis factor-α levels during the inflammatory phase (12 h, 24 h, 48 h, and 72 h post-wounding) of wound healing, upregulated transforming growth factor-β1 and elevated collagen IV synthesis in the chlorogenic acid-treated group. The results also indicated that chlorogenic acid possesses potent antioxidant activity by increasing superoxide dismutase, catalase, and glutathione, and decreasing lipid peroxidation. In conclusion, these results demonstrate that topical application of chlorogenic acid can accelerate the process of excision wound healing by its ability to increase collagen synthesis through upregulation of key players such as tumor necrosis factor-α and transforming growth factor-β1 in different phases of wound healing as well as by its antioxidant potential.

Key words

chlorogenic acid - collagen - TGF-β1 - TNF-α - wound healing

• References

• 1 Gantwerker EA, Hom DB. Skin: histology and physiology of wound healing. Facial Plast Surg Clin North Am 2011; 19: 441-453
• 2 Clark RA. Biology of dermal wound repair. Dermatol Clin 1993; 11: 647-666
• 3 Lamme EN, Van Leeuwen RTJ, Brandsma K, Van Marle J, Middelkoop E. Higher numbers of autologous fibroblasts in an artificial dermal substitute improve tissue regeneration and modulate scar tissue formation. J Pathol 2000; 190: 595-603
• 4 Gupta A, Singh RL, Raghubir R. Antioxidant status during cutaneous wound healing in immunocompromised rats. Mol Cell Biochem 2002; 241: 1-7
• 5 Russo A, Longo R, Vanella A. Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia 2002; 73: 21-29
• 6 James TJ, Hughes MA, Hofman D, Cherry GW, Taylor RP. Antioxidant characteristics chronic wound fluid. Br J Dermatol 2001; 145: 185-186
• 7 Clifford MN. Diet-derived phenols in plasma and tissues and their implications for health. Planta Med 2004; 70: 1103-1114
• 8 Sies H, Stahl W, Sevanian A. Nutritional, dietary and postprandial oxidative stress. J Nutr 2005; 135: 969-972
• 9 Wang Y, Ho CT. Polyphenolic chemistry of tea and coffee: a century of progress. J Agric Food Chem 2009; 57: 8109-8114
• 10 Huang X. Current status and prospect of the study of Lonicera japonica Thunb. Zhongguo Zhong Yao Za Zhi 1997; 22: 247-249
• 11 Xu JG, Hu QP, Liu Y. Antioxidant and DNA-protective activities of chlorogenic acid isomers. J Agric Food Chem 2012; 60: 11625-11630
• 12 Lee AR, Moon HK. Effect of topically applied silver sulphadiazine on fibroblast cell proliferation and biochemical properties of wound. Arch Pharm Res 2003; 26: 855-860
• 13 Romero-Cerecero O, Zamilpa-Álvarez A, Ramos-Mora A, Alonso-Cortés D, Jiménez-Ferrer JE, Huerta-Reyes ME, Tortoriello J. Effect on the wound healing process and in vitro cell proliferation by the medicinal Mexican plant Ageratina pichinchensis . Planta Med 2011; 77: 979-983
• 14 Niehaus WG, Samuelsson B. Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968; 6: 126-130
• 15 Ellman GL. Tissue sulphydryl groups. Arch Biochem Biophys 1959; 82: 70-77
• 16 Kuthan H, Haussmann HJ, Werringloer J. A spectrophotometric assay for superoxide dismutase activities in crude tissue fractions. Biochem J 1986; 237: 175-180
• 17 Sinha KA. Colorimetric assay of catalase. Anal Biochem 1972; 47: 389-394
• 18 Adams PD. Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol Cell 2009; 36: 2-14
• 19 Wong T, McGrath JA, Navsaria H. The role of fibroblasts in tissue engineering and regeneration. Br J Dermatol 2007; 156: 1149-1155
• 20 Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 2009; 17: 153-162
• 21 Abreu-Velez AM, Howard MS. Collagen IV in normal skin and in pathological processes. N Am J Med Sci 2012; 4: 1-8
• 22 Lim Y, Levya MA, Bray TM. Dietary supplementation of N-acetylcysteine enhances early inflammatory responses during cutaneous wound healing in protein malnourished mice B. J Nutr Biochem 2006; 17: 328-336
• 23 Lawrence WT, Diegelmann RF. Growth factors in wound healing. Clin Dermatol 1994; 12: 157-169
• 24 Caiado F, Carvalho T, Silva F, Castro C, Clode N, Dye JF, Dias S. The role of fibrin E on the modulation of endothelial progenitors adhesion, differentiation and angiogenic growth factor production and the promotion of wound healing. Biomaterials 2011; 32: 7096-7105
• 25 Atiba A, Nishimura M, Kakinuma S, Hiraoka T, Goryo M, Shimada Y, Ueno H, Uzuka Y. Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production. Am J Surg 2011; 201: 809-818
• 26 Jiang F, Zhang Y, Dusting GJ. NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol Rev 2011; 63: 218-242
• 27 Gouthamchandra K, Mahmood R, Manjunatha H. Free radical scavenging, antioxidant enzymes and wound healing activities of leaves extracts from Clerodendrum infortunatum L. Environ Toxicol Pharmacol 2010; 30: 11-18