OBJECTIVE To investigate the effect and preliminary mechanism of astaxanthin-nano-emulsion on the healing and post-healing scar hyperplasia of full-thickness skin defect wounds in SD rats. METHODS Twenty-four male SD rats were divided into blank control group, model group, cumene cream ointment positive control group and astaxanthin-nano-emulsion experimental group using the random number table method. Animal models were made using the whole skin defect method, in which the blank control group was treated with fasting and anesthetic shaving only, without the actual modeling procedure. In the positive control group and experimental group, 500 mg of cumene cream ointment and equal amount of astaxanthin-nano-emulsion were applied to each wound twice daily on the next postoperative day, and the wound or scar area was measured on the 1st, 3rd, 6th, 7th, 9th, 11th, 14th, 18th, 21st, and 28th postoperative days. At weeks 2, 3, and 4, the whole skin layer was taken slightly larger than the extent of the mold, HE and Masson staining were conducted to observe the morphology, distribution and contents of fibroblasts and collagen fibers in the skin tissues at different time; and the alpha-smooth muscle actin (α-SMA), interleukin 6 (IL-6), apoptotic and autophagy-related factors in the skin tissues at week 4 were detected by protein immunoblotting (Western blot, WB). One-way ANOVA was performed on the data. RESULTS During the whole experiment, the administration group was observed to have faster healing and higher quality of scar healing than the model group. At week 4, the number of fibroblasts in the astaxanthin-nano-emulsion group was significantly lower than that in the cumene cream group (P<0.05), the collagen fiber area density was also significantly lower than that in the cumene cream group (P<0.01). The results of WB experiments showed that the α-SMA in the astaxanthin and cumene cream groups were not significantly different at week 4, but both were significantly lower than the model group (P<0.01). The IL-6 protein expression in the astaxanthin group was lower than the model group (P<0.01), but the IL-6 protein expression level in the cumene cream group was significantly higher than the other two groups (P<0.001). The expressions of pro-apoptotic factors Bcl-2-associated X protein (Bax) and phosphatidylinositol 3 kinase/serine/threonine protein kinase/rapamycin (PI3K/Akt/mTOR) pathway-related proteins were significantly increased in the astaxanthin group (P<0.05). CONCLUSION Astaxanthin-nano-emulsion can promote skin wound healing, reduce fibroblast proliferation and collagen production, inhibit fibrosis, reduce inflammation, and inhibit scar contracture in rats, thus improving the development of hypertrophic scars on skin wounds after healing, and the mechanism may be related to the induction of apoptosis and the activation of PI3K/Akt/mTOR pathway down-regulates autophagy.
Key words
astaxanthin /
wound healing /
hypertrophic scar /
apoptosis /
autophagy
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References
[1] XIAO F L, TAN J. Advances in drug treatment for hypertrophic scar[J]. Chin J Aesthet Med(中国美容医学), 2021, 30(4):181-184.
[2] HU D H, LIU J Q. A long way to go in scar research-further enhancement of basic and clinical research of the scar[J]. Chin J Burns(中华烧伤杂志), 2011, 27(6):407-410.
[3] SATISH L, LYONS-WEILER J, HEBDA P A, et al. Gene expression patterns in isolated keloid fibroblasts[J]. Wound Repair Regen, 2006, 14(4):463-470.
[4] OGAWA R. The most current algorithms for the treatment and prevention of hypertrophic scars and keloids[J]. Plast Reconstr Surg, 2010, 125(2):557-568.
[5] DAVINELLI S, NIELSEN M E. Astaxanthin in skin health, repair, and disease: a comprehensive review[J]. Nutrients, 2018, 10(4):522. Doi: 10.3390/nu10040522.
[6] RITTO D, TANASAWET S, SINGKHORN S, et al. Astaxanthin induces migration in human skin keratinocytes via Rac1 activation and RhoA inhibition[J]. Nutr Res Pract, 2017, 11(4):2752-80.
[7] SUGANYA V, ANURADHA V. In silico molecular docking of astaxanthin and sorafenib with different apoptotic proteins involved in hepatocellular carcinoma[J]. Biocatal Agric Biotechnol, 2019, 19(5):101076. Doi:10.1016/j.bcab.2019.101076.
[8] FANG Q, GUO S, ZHOU H, et al. Astaxanthin protects against early burn-wound progression in rats by attenuating oxidative stress-induced inflammation and mitochondria-related apoptosis[J]. Sci Rep, 2017, 7(1):41440. Doi:10.1038/srep41440.
[9] MAEZAWA T, TANAKA M, KANAZASHI M, et al. Astaxanthin supplementation attenuates immobilization-induced skeletal muscle fibrosis via suppression of oxidative stress[J]. J Physiol Sci, 2017, 67(5):603-611.
[10] SHEN M, CHEN K, LU J, et al. Protective effect of astaxanthin on liver fibrosis through modulation of TGF-β1 expression and autophagy[J]. Mediat Inflamm, 2014, 2014(4):954502. Doi:10.1155/2014/954502.
[11] WAKABAYASHI K, HAMADA C, KANDA R, et al. Oral astaxanthin supplementation prevents peritoneal fibrosis in rats[J]. Perit Dial Int, 2015, 35(5):506-516.
[12] XIE X, CHEN Q, TAO J. Astaxanthin promotes Nrf2/ARE signaling to inhibit HG-induced renal fibrosis in GMCs[J]. Mar Drugs, 2018, 16(4):117. Doi:10.3390/md16040117.
[13] ZHANG J, WANG Q Z, Zhao S H, et al. Astaxanthin attenuated pressure overload-induced cardiac dysfunction and myocardial fibrosis: Partially by activating SIRT1[J]. Biochim Biophys Acta Gen Subj, 2017, 1861(7):1715-1728.
[14] GE H H, CHEN Z P, LI Q, et al. The study on effect and mechanisms of astaxanthin in hypertrophic scar fibroblast[J]. Chin J Aesthet Med(中国美容医学), 2019, 28(1):97-99.
[15] ZHANG D D, ZHANG H, ZHAO J F, et al. Treatment of chronic ulcer in diabetic rats with asiaticosides [J]. Chin Pharm J(中国药学杂志), 2017, 52(8):643-648.
[16] HUANG J W, WANG J, AN L F, et al. Effect of sanchinoside R1 hydrogel on the repairment of hypertrophic scar of rabbit ear skin and on the expression of bFGF and TGF-β1[J]. Mod J Integr Tradit Chin West Med(现代中西医结合杂志), 2020, 29(12):1269-1274.
[17] CHEN Y, CHEN J J. Holistic diagnosis and treatment of scar[J]. Chin J Burns(中华烧伤杂志), 2016, 32(11):641-643.
[18] HINZ B. Formation and function of the myofibroblast during tissue repair[J]. J Invest Dermatol, 2007, 127(3):526-537.
[19] ZENG J, XIONG Q, ZHANG L L, et al. Preparation of SPACE peptide modified fibroblast growth factor 21 and its inhibitory effect on skin scar formation in mice[J]. Chin J Immunol(中国免疫学杂志), 2021, 37(11):1308-1312.
[20] WOLFRAM D, TZANKOV A, PULZL P, et al. Hypertrophic scars and keloids--a review of their pathophysiology, risk factors, and therapeutic management[J]. Dermatol Surg, 2009, 35(2):171-181.
[21] SHI J, XIAO H, LI J, et al. Wild-type p53-modulated autophagy and autophagic fibroblast apoptosis inhibit hypertrophic scar formation[J]. Lab Invest, 2018, 98(11):1423-1437.
[22] LONG Y C. The expression and correlation analysis of MiR21 and autophagy related factors in human pathological scar[D]. Nanchong:North Sichuan Medical College, 2019.
[23] LEVINE B, KROEMER G. Autophagy in the pathogenesis of disease[J]. Cell, 2008, 132(1):27-42.
[24] DESMOULIERE A, BADID C, BOCHATON-PIALLAT M L, et al. Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury[J]. Int J Biochem Cell Biol, 1997, 29(1):19-30.
[25] JIANG D Y, JIA S S, WANG X L. Burn treatment and wound repair[J/OL]. Chin J Injury Repair Wound Heal(Electronic Edition), 2021, 16(4):283-288[2021-08-01]. https://www.cnki.net.
[26] NUOBU Y Z, ZUO R, JIN L, et al. Clinical research progress of platelet-rich plasma in the prevention and treatment of scar[J]. Hebei Med J(河北医药), 2022, 44(15):2375-2379.
[27] MORRIS D E, WU L, ZHAO L L, et al. Acute and chronic animal models for excessive dermal scarring: quantitative studies[J]. Plast Reconstr Surg, 1997, 100(3):674-681.
[28] LI X W, LIU H L, WU J X. Research progress of pathological scar animal models[J]. Lab Anim Sci(实验动物科学), 2009, 26(2):46-49.
[29] ZHANG Q, LIU D E. Progress on basic research of pathological scar[J]. Med Recapit(医学综述), 2010, 16(4):490-493.
[30] ZHOU S Z, LI Q F. Research progress of animal models for cutaneous wound healing and hypertrophic scar[J]. J Tissue Eng Reconstr Surg(组织工程与重建外科杂志), 2018, 14(1):48-52.
[31] AKSOY M H, VARGEL I, CANTER I H, et al. A new experimental hypertrophic scar model in guinea pigs[J]. Aesthet Plast Surg, 2002, 26(5):388-396.
[32] JIN X R, LI W W, REN Z Y, et al. Research overview of skin scar modeling[J]. Hunan J Tradit Chin Med(湖南中医杂志), 2016, 32(8):231-232.
[33] LIU M, HU J X, QIN G H, et al. Toxicological safety evaluation of astaxanthin[J]. J Toxicol(毒理学杂志), 2008(3):244-246.
[34] SI L L, HAN C, ZHAO J P, et al. Toxicological safety assessment of astaxanthin[J]. Food Nutr Chin(中国食物与营养), 2019, 25(1):31-35.
[35] RAO A R, SINDHUJA H N, DHARMESH S M, et al. Effective inhibition of skin cancer, tyrosinase, and antioxidative properties by astaxanthin and astaxanthin esters from the green alga Haematococcus pluvialis[J]. J Agric Food Chem, 2013, 61(16):3842-3851.
[36] NIU T, ZHOU J, WANG F, et al. Safety assessment of astaxanthin from Haematococcus pluvialis: Acute toxicity, genotoxicity, distribution and repeat-dose toxicity studies in gestation mice[J]. Regul Toxicol Pharmacol, 2020, 115(8):104695. Doi:10.1016/j.yrtph.2020.104695.
[37] STEWART J S, LIGNELL A, PETTERSSON A, et al. Safety assessment of astaxanthin-rich microalgae biomass: acute and subchronic toxicity studies in rats[J]. Food Chem Toxicol, 2008, 46(9):3030-3036.
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