Topical anti-inflammatory activity of palmitoleic acid improves wound healing

Eleine Weimann, Maysa Braga Barros Silva, Gilson Masahiro Murata, Jose Ricardo Bortolon, Alexandre Dermargos, Rui Curi, Elaine Hatanaka, Eleine Weimann, Maysa Braga Barros Silva, Gilson Masahiro Murata, Jose Ricardo Bortolon, Alexandre Dermargos, Rui Curi, Elaine Hatanaka

Abstract

This study investigated the effects of palmitoleic acid on different phases of the healing process. Macroscopic analyses were performed on wounds in rats with or without palmitoleic acid treatment, and the results showed that palmitoleic acid directly hastened wound closure. The topical treatment of wounds with palmitoleic acid resulted in smaller wounds than those observed in the control group. The anti-inflammatory activity of palmitoleic acid may be responsible for healing, especially in the stages of granulation tissue formation and remodelling. Palmitoleic acid modified TNF-α, IL-1β, IL-6, CINC-2α/β, MIP-3α and VEGF-α profiles at the wound site 24, 48, 120, 216 and 288 hours post-wounding. Assays assessing neutrophil migration and exudate formation in sterile inflammatory air pouches revealed that palmitoleic acid had potent anti-inflammatory activity, inhibiting the LPS-induced release of TNF-α (73.14%, p≤0.05), IL-1β (66.19%, p≤0.001), IL-6 (75.19%, p≤0.001), MIP-3α (70.38%, p≤0.05), and l-selectin (16%, p≤0.05). Palmitoleic acid also inhibited LPS-stimulated neutrophil migration. We concluded that palmitoleic acid accelerates wound healing via an anti-inflammatory effect.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Wound closure velocity.
Fig 1. Wound closure velocity.
Macroscopic wound closure in the control rats (A) and the rats treated daily with palmitoleic acid (B). Representative photos and wound area values recorded over a 12-day period. (C) Wound closure velocity (mm2/day) and (D) ratios of integrated wound closure area with or without palmitoleic treatment. Values are expressed as the mean±SEM of at least 10 animals per group. *p≤0.05 versus control, as indicated by analysis of variance (ANOVA) and post hoc Tukey’s test.
Fig 2. Neutrophils migration.
Fig 2. Neutrophils migration.
Neutrophil influx into air pouches after palmitoleic acid (100 mM) injection. LPS (5 μg/mL) was used as a positive control. Values are presented as the means±SEM of eight animals per group. **p

Fig 3. Air pouch cytokines release.

Cytokine…

Fig 3. Air pouch cytokines release.

Cytokine release into air pouches after palmitoleic acid (100…

Fig 3. Air pouch cytokines release.
Cytokine release into air pouches after palmitoleic acid (100 mM) injection. LPS (5 μg/mL) was used as a positive control. Values are presented as the means±SEM of eight animals per group. *p

Fig 4. Cytokines concentration in wound.

Kinetic…

Fig 4. Cytokines concentration in wound.

Kinetic profiles of cytokine concentrations in the control (PBS)…

Fig 4. Cytokines concentration in wound.
Kinetic profiles of cytokine concentrations in the control (PBS) and treated rats (PALM) measured before (0), 4 hours (4), 24 hours (24), 48 hours (48), 72 hours (72) and 120 hours (120) after wound induction. Values are presented as the mean±SE of at least 8 animals per group.
Similar articles
Cited by
References
    1. Kolouchová I, Sigler K, Schreiberová O, Masák J, Řezanka T. New yeast-based approaches in production of palmitoleic acid. Bioresour Technol. 2015;192: 726–34. 10.1016/j.biortech.2015.06.048 - DOI - PubMed
    1. Yoon WJ, Kim MJ, Moon HJ, Kim GO, Lee NH, Hyun CG. Effect of palmitoleic acid on melanogenic protein expression in murine b16 melanoma. J Oleo Sci 59:315–319, 2010. - PubMed
    1. Fischer CL, Drake DR, Dawson DV, Blanchette DR, Brogden KA, Wertz PW. Antibacterial activity of sphingoid bases and fatty acods against Gram-positive and Gram-negative bacteria. Antimicrob Agents Chemother 56:1157–1161, 2012. 10.1128/AAC.05151-11 - DOI - PMC - PubMed
    1. Wille JJ, Kydonieus A. Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective againstgram-positive bacteria. Skin Pharmacol Appl Skin Physiol. 2003;16:176–187. 10.1159/000069757 - DOI - PubMed
    1. Gao ZL, Gu XH, Cheng FT, Jiang FH Sea buckthorn may be a hopeful drug for prevention and treatment of liver fibrosis. Effect of Sea buckthorn on liver fibrosis: A clinical study. World J Gastroenterol. 2003; 9: 1615–1617. 10.3748/wjg.v9.i7.1615 - DOI - PMC - PubMed
Show all 31 references
Publication types
MeSH terms
Grant support
This research was supported by the Brazilian research funding agencies FAPESP (São Paulo Research Foundation, #14/03947-1 and #11/15360-7) and CNPq (National Council for Scientific and Technological Development (#307769/2014-3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Fig 3. Air pouch cytokines release.
Fig 3. Air pouch cytokines release.
Cytokine release into air pouches after palmitoleic acid (100 mM) injection. LPS (5 μg/mL) was used as a positive control. Values are presented as the means±SEM of eight animals per group. *p

Fig 4. Cytokines concentration in wound.

Kinetic…

Fig 4. Cytokines concentration in wound.

Kinetic profiles of cytokine concentrations in the control (PBS)…

Fig 4. Cytokines concentration in wound.
Kinetic profiles of cytokine concentrations in the control (PBS) and treated rats (PALM) measured before (0), 4 hours (4), 24 hours (24), 48 hours (48), 72 hours (72) and 120 hours (120) after wound induction. Values are presented as the mean±SE of at least 8 animals per group.
Fig 4. Cytokines concentration in wound.
Fig 4. Cytokines concentration in wound.
Kinetic profiles of cytokine concentrations in the control (PBS) and treated rats (PALM) measured before (0), 4 hours (4), 24 hours (24), 48 hours (48), 72 hours (72) and 120 hours (120) after wound induction. Values are presented as the mean±SE of at least 8 animals per group.

References

    1. Kolouchová I, Sigler K, Schreiberová O, Masák J, Řezanka T. New yeast-based approaches in production of palmitoleic acid. Bioresour Technol. 2015;192: 726–34. 10.1016/j.biortech.2015.06.048
    1. Yoon WJ, Kim MJ, Moon HJ, Kim GO, Lee NH, Hyun CG. Effect of palmitoleic acid on melanogenic protein expression in murine b16 melanoma. J Oleo Sci 59:315–319, 2010.
    1. Fischer CL, Drake DR, Dawson DV, Blanchette DR, Brogden KA, Wertz PW. Antibacterial activity of sphingoid bases and fatty acods against Gram-positive and Gram-negative bacteria. Antimicrob Agents Chemother 56:1157–1161, 2012. 10.1128/AAC.05151-11
    1. Wille JJ, Kydonieus A. Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective againstgram-positive bacteria. Skin Pharmacol Appl Skin Physiol. 2003;16:176–187. 10.1159/000069757
    1. Gao ZL, Gu XH, Cheng FT, Jiang FH Sea buckthorn may be a hopeful drug for prevention and treatment of liver fibrosis. Effect of Sea buckthorn on liver fibrosis: A clinical study. World J Gastroenterol. 2003; 9: 1615–1617. 10.3748/wjg.v9.i7.1615
    1. Akamatsu H, Oguchi M, Nishijima S, Asada Y, Takahashi M, Ushijima T, Niwa Y. The inhibition of free radical generation by human neutrophils through the synergistic effects of metronidazole with palmitoleic acid: a possible mechanism of action of metronidazole in rosacea and acne. Arch Dermatol Res. 1990;282: 449–454.
    1. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453: 314–321. 10.1038/nature07039
    1. Cardoso CR, Souza MA, Ferro EA, Favoreto S Jr, Pena JD. Influence of topicaladministration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds. Wound Repair Regen. 2004;12: 235–243. 10.1111/j.1067-1927.2004.012216.x
    1. Cardoso CR, Favoreto S Jr, Oliveira LL, Vancim JO, Barban GB, Ferraz DB, Silva JS. Oleic acid modulation of the immune response in wound healing: a new approach for skin repair. Immunobiology. 2011; 216: 409–415. 10.1016/j.imbio.2010.06.007
    1. Pereira LM, Hatanaka E, Martins EF, Oliveira F, Liberti EA, Farsky SH, Curi R, Pithon-Curi TC. Effect of oleic and linoleic acids on the inflammatory phase of wound healing in rats. Cell Biochem Funct. 2008;26:197–204. 10.1002/cbf.1432
    1. Rodrigues HG, Vinolo MA, Magdalon J, Fujiwara H, Cavalcanti DM, Farsky SH, Calder PC, Hatanaka E, Curi R. Dietary free oleic and linoleic acid enhances neutrophil function and modulates the inflammatory response in rats. Lipids. 2010;45: 809–819. 10.1007/s11745-010-3461-9
    1. Rodrigues HG, Vinolo MA, Magdalon J, Vitzel K, Nachbar RT, Pessoa AF, dos Santos MF, Hatanaka E, Calder PC, Curi R. Oral administration of oleic or linoleic acid accelerates the inflammatory phase of wound healing. J Invest Dermatol. 2012;132:208–215. 10.1038/jid.2011.265
    1. Farsky SH, Walber J, Costa-Cruz M, Cury Y, Teixeira CF, Curry Y. Leukocyte response induced by Bothrops jararaca crude venom: in vivo and in vitro studies. Toxicon 1997;35: 185–193.
    1. Hatanaka E, Levada-Pires AC, Pithon-Curi TC, Curi R. Systematic study on ROS production induced by oleic, linoleic, and gamma-linolenic acids in human and rat neutrophils. Free Radic Biol Med. 2006;41:1124–1132. 10.1016/j.freeradbiomed.2006.06.014
    1. Martins de Lima T, Gorjão R, Hatanaka E, Cury-Boaventura MF, Portioli Silva EP, Procopio J, Curi R. Mechanisms by which fatty acids regulate leucocyte function. Clin Sci. 2007;113(2):65–77. 10.1042/CS20070006
    1. Vinolo MA, Hatanaka E, Lambertucci RH, Newsholme P, Curi R. Effects of short chain fatty acids on effector mechanisms of neutrophils. Cell Biochem Funct. 2009;27: 48–55. 10.1002/cbf.1533
    1. Vinolo MA, Rodrigues HG, Hatanaka E, Hebeda CB, Farsky SH, Curi R. Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites. Clin Sci. 2009;117:331–338. 10.1042/CS20080642
    1. Vinolo MA, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem. 2011;22:849–855. 10.1016/j.jnutbio.2010.07.009
    1. Magdalon J, Hatanaka E, Romanatto T, Rodrigues HG, Kuwabara WM, Scaife C, Newsholme P, Curi R. A proteomic analysis of the functional effects of fatty acids in NIH 3T3 fibroblasts. Lipids Health Dis. 2011. 24;10:218 10.1186/1476-511X-10-218
    1. Magdalon J, Vinolo MA, Rodrigues HG, Paschoal VA, Torres RP, Mancini-Filho J, Calder PC, Hatanaka E, Curi R. Oral administration of oleic or linoleic acids modulates the production of inflammatory mediators by rat macrophages. Lipids. 2012;47:803–812. 10.1007/s11745-012-3687-9
    1. Hatanaka E, Dermargos A, Hirata AE, Vinolo MA, Carpinelli AR, Newsholme P, Armelin HA, Curi R. Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation. PLoS One. 2013. April 8;8(4):e58626 10.1371/journal.pone.0058626
    1. Ruthig DJ, Meckling-Gill KA. Both (n-3) and (n-6) fatty acids stimulate wound healing in the rat intestinal epithelial cell line, IEC-6. J Nutr. 1999;129:1791–1798. 10.1093/jn/129.10.1791
    1. Calder PC. n-3 fatty acids, inflammation, and immunity-relevance to postsurgical and critically ill patients. Lipids. 2004;39: 1147–1161.
    1. Calder PC. Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients. Brasilian Journal of Medical and Biological Research 2003; 36: 433–446.
    1. Ziboh VA, Miller CC, Cho Y. Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites. Am J Clin Nutr 71:361S–6S, 2000. 10.1093/ajcn/71.1.361s
    1. Nakatsuji T, Kao MC, Zhang L, Zouboulis CC, Gallo RL, Huang CM. Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating beta-defensin-2 expression. J Invest Dermatol. 2010;130:985–994. 10.1038/jid.2009.384
    1. Pieper B, Caliri MH. Nontraditional wound care: A review of the evidence for the use of sugar, papaya/papain, and fatty acids. J Wound Ostomy Continence Nurs. 2003; 30:175–183. 10.1067/mjw.2003.131
    1. Svensjö T, Pomahac B, Yao F, Slama J, Eriksson E. Accelerated healing of full-thickness skin wounds in a wet environment. Plast Reconstr Surg. 2000;106:602–614.
    1. Mária J, Ingrid Ž. Effects of bioactive compounds on senescence and components of senescence associated secretory phenotypes in vitro. Food Funct. 2017;8:2394–2418. 10.1039/c7fo00161d
    1. Gwak Jae Ha, Sohn So Young. Identifying the trends in wound-healing patents for successful investment strategies PLoS One. 2017; 12(3): e0174203 10.1371/journal.pone.0174203
    1. Lima MHM, Caricilli AM, Abreu LL, Araújo EP, Pelegrinelli FF, Thirone ACP, Tsukumo DM, Pessoa AFM, dos Santos MF, de Moraes M A, Carvalheira JBC, Velloso LA, Saad MJA. Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial. PLoS One. 2012; 7(5): e36974 10.1371/journal.pone.0036974

Source: PubMed

3
Suscribir