Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Meta-Analysis

Efficacy of Curcumin for Wound Repair in Diabetic Rats/Mice: A Systematic Review and Meta-analysis of Preclinical Studies

Author(s): Yuan Li, Sheng Zhao, Leanne Van der Merwe, Wentong Dai and Cai Lin*

Volume 28, Issue 3, 2022

Published on: 17 June, 2021

Page: [187 - 197] Pages: 11

DOI: 10.2174/1381612827666210617122026

Price: $65

conference banner
Abstract

Background: Curcumin possesses multiple bioactivities that have beneficial effects on diabetic foot ulcers. Herein, we aimed to conduct a preclinical systematic review of 9 studies, including a total of 262 animals, to assess the possible mechanisms of curcumin for wound healing in diabetic animals.

Methods: Five databases were searched from inception to May 12, 2020; Rev-Man 5.3 software was applied for data analyses. Cochrane Collaboration’s tool 10-item checklist was used to evaluate the methodological quality, and data revealed scores of risk of bias ranging from 2 to 5.

Results: Meta-analysis indicated that curcumin had significant effects on wound healing rate and blood vessel density when compared with control (P < 0.05). The wound regeneration properties of curcumin for diabetic wounds are thought to mainly work through the possible mechanisms of antioxidation, enhanced cell proliferation, increased collagen formation, and angiogenesis. However, the anti-inflammatory effect on wounds in diabetic animals remain controversial.

Conclusion: The findings indicate that more randomized controlled trials should be pursued to obtain more reliable results regarding inflammatory response. Overall, curcumin might be a probable candidate for diabetic foot ulcers and may contribute to future clinical trials.

Keywords: Angiogenesis, curcumin, diabetic foot ulcers, meta-analysis, preclinical evidence, wound healing, systematic review.

« Previous Next »
[1]
Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011; 94(3): 311-21.
[http://dx.doi.org/10.1016/j.diabres.2011.10.029] [PMID: 22079683]
[2]
Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet 2005; 366(9498): 1719-24.
[http://dx.doi.org/10.1016/S0140-6736(05)67698-2] [PMID: 16291066]
[3]
Papatheodorou K, Banach M, Bekiari E, Rizzo M, Edmonds M. Complications of diabetes 2017. J Diabetes Res 2018; 2018: 3086167.
[http://dx.doi.org/10.1155/2018/3086167] [PMID: 29713648]
[4]
Kostev K, Jockwig A, Hallwachs A, Rathmann W. Prevalence and risk factors of neuropathy in newly diagnosed type 2 diabetes in primary care practices: A retrospective database analysis in Germany and U.K. Prim Care Diabetes 2014; 8(3): 250-5.
[http://dx.doi.org/10.1016/j.pcd.2014.01.011] [PMID: 24530101]
[5]
Armstrong DG, Boulton AJM, Bus SA. Diabetic foot ulcers and their recurrence. N Engl J Med 2017; 376(24): 2367-75.
[http://dx.doi.org/10.1056/NEJMra1615439] [PMID: 28614678]
[6]
Martins-Mendes D, Monteiro-Soares M, Boyko EJ, et al. The independent contribution of diabetic foot ulcer on lower extremity amputation and mortality risk. J Diabetes Complications 2014; 28(5): 632-8.
[http://dx.doi.org/10.1016/j.jdiacomp.2014.04.011] [PMID: 24877985]
[7]
Jupiter DC, Thorud JC, Buckley CJ, Shibuya N. The impact of foot ulceration and amputation on mortality in diabetic patients. I: From ulceration to death, a systematic review. Int Wound J 2016; 13(5): 892-903.
[http://dx.doi.org/10.1111/iwj.12404] [PMID: 25601358]
[8]
Forsythe RO, Brownrigg J, Hinchliffe RJ. Peripheral arterial disease and revascularization of the diabetic foot. Diabetes Obes Metab 2015; 17(5): 435-44.
[http://dx.doi.org/10.1111/dom.12422] [PMID: 25469642]
[9]
Dorresteijn JA, Kriegsman DM, Assendelft WJ, Valk GD. Patient education for preventing diabetic foot ulceration. Cochrane Database Syst Rev 2014; (12): CD001488.
[http://dx.doi.org/10.1002/14651858.CD001488.pub5] [PMID: 25514250]
[10]
Yazdanpanah L, Nasiri M, Adarvishi S. Literature review on the management of diabetic foot ulcer. World J Diabetes 2015; 6(1): 37-53.
[http://dx.doi.org/10.4239/wjd.v6.i1.37] [PMID: 25685277]
[11]
Baker LL, Chambers R, DeMuth SK, Villar F. Effects of electrical stimulation on wound healing in patients with diabetic ulcers. Diabetes Care 1997; 20(3): 405-12.
[http://dx.doi.org/10.2337/diacare.20.3.405] [PMID: 9051395]
[12]
Kessler L, Bilbault P, Ortéga F, et al. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: A prospective randomized study. Diabetes Care 2003; 26(8): 2378-82.
[http://dx.doi.org/10.2337/diacare.26.8.2378] [PMID: 12882865]
[13]
Wan Mohd Tajuddin WNB, Lajis NH, Abas F, Othman I, Naidu R. Mechanistic understanding of curcumin’s therapeutic effects in lung cancer. Nutrients 2019; 11(12): 11.
[http://dx.doi.org/10.3390/nu11122989] [PMID: 31817718]
[14]
Epstein J, Sanderson IR, Macdonald TT. Curcumin as a therapeutic agent: The evidence from in vitro, animal and human studies. Br J Nutr 2010; 103(11): 1545-57.
[http://dx.doi.org/10.1017/S0007114509993667] [PMID: 20100380]
[15]
Mohammadi A, Sahebkar A, Iranshahi M, et al. Effects of supplementation with curcuminoids on dyslipidemia in obese patients: A randomized crossover trial. Phytother Res 2013; 27(3): 374-9.
[http://dx.doi.org/10.1002/ptr.4715] [PMID: 22610853]
[16]
Panahi Y, Sahebkar A, Parvin S, Saadat A. A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications. Ann Clin Biochem 2012; 49(Pt 6): 580-8.
[http://dx.doi.org/10.1258/acb.2012.012040] [PMID: 23038702]
[17]
Sahebkar A, Mohammadi A, Atabati A, et al. Curcuminoids modulate pro-oxidant-antioxidant balance but not the immune response to heat shock protein 27 and oxidized LDL in obese individuals. Phytother Res 2013; 27(12): 1883-8.
[http://dx.doi.org/10.1002/ptr.4952] [PMID: 23494802]
[18]
Alizadeh F, Javadi M, Karami AA, Gholaminejad F, Kavianpour M, Haghighian HK. Curcumin nanomicelle improves semen parameters, oxidative stress, inflammatory biomarkers, and reproductive hormones in infertile men: A randomized clinical trial. Phytother Res 2018; 32(3): 514-21.
[http://dx.doi.org/10.1002/ptr.5998] [PMID: 29193350]
[19]
Kant V, Gopal A, Pathak NN, Kumar P, Tandan SK, Kumar D. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats. Int Immunopharmacol 2014; 20(2): 322-30.
[http://dx.doi.org/10.1016/j.intimp.2014.03.009] [PMID: 24675438]
[20]
Negi PS, Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK. Antibacterial activity of turmeric oil: A byproduct from curcumin manufacture. J Agric Food Chem 1999; 47(10): 4297-300.
[http://dx.doi.org/10.1021/jf990308d] [PMID: 10552805]
[21]
Asteriou E, Gkoutzourelas A, Mavropoulos A, Katsiari C, Sakkas LI, Bogdanos DP. Curcumin for the management of periodontitis and early acpa-positive rheumatoid arthritis: Killing two birds with one stone. Nutrients 2018; 10(7): 10.
[http://dx.doi.org/10.3390/nu10070908] [PMID: 30012973]
[22]
Kurien BT, Harris VM, Quadri SM, et al. Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: Increased survival with curcumin treatment. Lupus Sci Med 2015; 2(1): e000114.
[http://dx.doi.org/10.1136/lupus-2015-000114] [PMID: 26380101]
[23]
Santos-Parker JR, Strahler TR, Bassett CJ, Bispham NZ, Chonchol MB, Seals DR. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress. Aging 2017; 9(1): 187-208.
[http://dx.doi.org/10.18632/aging.101149] [PMID: 28070018]
[24]
Kant V, Gopal A, Kumar D, et al. Curcumin-induced angiogenesis hastens wound healing in diabetic rats. J Surg Res 2015; 193(2): 978-88.
[http://dx.doi.org/10.1016/j.jss.2014.10.019] [PMID: 25454972]
[25]
Dehghani S, Dalirfardouei R, Jafari Najaf Abadi MH, Ebrahimi Nik M, Jaafari MR, Mahdipour E. Topical application of curcumin regulates the angiogenesis in diabetic-impaired cutaneous wound. Cell Biochem Funct 2020; 38(5): 558-66.
[http://dx.doi.org/10.1002/cbf.3500] [PMID: 32030812]
[26]
Moher D, Liberati A, Tetzlaff J, Altman D. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Int J Surg 2010; 8: 336-41.
[http://dx.doi.org/10.1016/j.ijsu.2010.02.007]
[27]
Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 2014; 14: 43.
[http://dx.doi.org/10.1186/1471-2288-14-43] [PMID: 24667063]
[28]
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557-60.
[http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]
[29]
Sidhu G, Mani H, Gaddipati J, et al. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice. Wound Repair and Regeneration. 1999; 7(5): pp. 362-74.
[http://dx.doi.org/10.1046/j.1524-475X.1999.00362.x]
[30]
Liu J, Chen Z, Wang J, et al. Encapsulation of curcumin nanoparticles with mmp9-responsive and thermos-sensitive hydrogel improves diabetic wound healing. ACS Appl Mater Interfaces 2018; 10(19): 16315-26.
[http://dx.doi.org/10.1021/acsami.8b03868] [PMID: 29687718]
[31]
Amini A, Soleimani H, Abdollhifar MA, et al. Stereological and gene expression examinations on the combined effects of photobiomodulation and curcumin on wound healing in type one diabetic rats. J Cell Biochem 2019; 120(10): 17994-8004.
[http://dx.doi.org/10.1002/jcb.29102] [PMID: 31148250]
[32]
Kamar SS, Abdel-Kader DH, Rashed LA. Beneficial effect of curcumin nanoparticles-hydrogel on excisional skin wound healing in type-i diabetic rat: Histological and immunohistochemical studies. Ann Anat 2019; 222: 94-102.
[http://dx.doi.org/10.1016/j.aanat.2018.11.005] [PMID: 30521949]
[33]
Li F, Shi Y, Liang J, Zhao L. Curcumin-loaded chitosan nanoparticles promote diabetic wound healing via attenuating inflammation in a diabetic rat model. J Biomater Appl 2019; 34(4): 476-86.
[http://dx.doi.org/10.1177/0885328219860929] [PMID: 31280635]
[34]
Sharma M, Sahu K, Singh SP, Jain B. Wound healing activity of curcumin conjugated to hyaluronic acid: In vitro and in vivo evaluation. Artif Cells Nanomed Biotechnol 2018; 46(5): 1009-17.
[http://dx.doi.org/10.1080/21691401.2017.1358731] [PMID: 28754055]
[35]
Leung V, Rousseau-Blass F, Beauchamp G, Pang DSJ. Arrive has not arrived: Support for the arrive (Animal research: Reporting of in vivo experiments) guidelines does not improve the reporting quality of papers in animal welfare, analgesia or anesthesia. PLoS One 2018; 13(5): e0197882.
[http://dx.doi.org/10.1371/journal.pone.0197882] [PMID: 29795636]
[36]
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. Osteoarthritis Cartilage 2012; 20(4): 256-60.
[http://dx.doi.org/10.1016/j.joca.2012.02.010] [PMID: 22424462]
[37]
Lecour S, Bøtker HE, Condorelli G, et al. ESC working group cellular biology of the heart: Position paper: Improving the preclinical assessment of novel cardioprotective therapies. Cardiovasc Res 2014; 104(3): 399-411.
[http://dx.doi.org/10.1093/cvr/cvu225] [PMID: 25344369]
[38]
Martin P, Nunan R. Cellular and molecular mechanisms of repair in acute and chronic wound healing. Br J Dermatol 2015; 173(2): 370-8.
[http://dx.doi.org/10.1111/bjd.13954] [PMID: 26175283]
[39]
Mast BA, Schultz GS. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen 1996; 4(4): 411-20.
[http://dx.doi.org/10.1046/j.1524-475X.1996.40404.x] [PMID: 17309691]
[40]
Falanga V. Wound healing and its impairment in the diabetic foot. Lancet 2005; 366(9498): 1736-43.
[http://dx.doi.org/10.1016/S0140-6736(05)67700-8] [PMID: 16291068]
[41]
Cavanagh PR, Bus SA. Off-loading the diabetic foot for ulcer prevention and healing. Plast Reconstr Surg 2011; 127(Suppl. 1): 248S-56S.
[http://dx.doi.org/10.1097/PRS.0b013e3182024864] [PMID: 21200298]
[42]
Cavanagh PR, Lipsky BA, Bradbury AW, Botek G. Treatment for diabetic foot ulcers. Lancet 2005; 366(9498): 1725-35.
[http://dx.doi.org/10.1016/S0140-6736(05)67699-4] [PMID: 16291067]
[43]
Graziani L. Comprehensive approach to management of critical limb ischemia. Curr Treat Options Cardiovasc Med 2014; 16(9): 332.
[http://dx.doi.org/10.1007/s11936-014-0332-3] [PMID: 25080031]
[44]
Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Med Res Rev 2003; 23(2): 117-45.
[http://dx.doi.org/10.1002/med.10024] [PMID: 12500286]
[45]
Bhandarkar SS, Arbiser JL. Curcumin as an inhibitor of angiogenesis. Adv Exp Med Biol 2007; 595: 185-95.
[http://dx.doi.org/10.1007/978-0-387-46401-5_7] [PMID: 17569211]
[46]
ten Dijke P, Arthur HM. Extracellular control of TGFbeta signalling in vascular development and disease. Nat Rev Mol Cell Biol 2007; 8(11): 857-69.
[http://dx.doi.org/10.1038/nrm2262] [PMID: 17895899]
[47]
Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 2001; 280(6): C1358-66.
[http://dx.doi.org/10.1152/ajpcell.2001.280.6.C1358] [PMID: 11350730]
[48]
Mani H, Sidhu GS, Kumari R, Gaddipati JP, Seth P, Maheshwari RK. Curcumin differentially regulates TGF-beta1, its receptors and nitric oxide synthase during impaired wound healing. Biofactors 2002; 16(1-2): 29-43.
[http://dx.doi.org/10.1002/biof.5520160104] [PMID: 12515914]
[49]
Milovanova TN, Bhopale VM, Sorokina EM, et al. Lactate stimulates vasculogenic stem cells via the thioredoxin system and engages an autocrine activation loop involving hypoxia-inducible factor 1. Mol Cell Biol 2008; 28(20): 6248-61.
[http://dx.doi.org/10.1128/MCB.00795-08] [PMID: 18710947]
[50]
Milovanova T, Bhopale V, Sorokina E, et al. Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo. J Appl Physiol (Bethesda, Md : 1985) 2009; 106(2): 711-28.
[http://dx.doi.org/10.1152/japplphysiol.91054.2008]
[51]
Mohammadian Haftcheshmeh S, Karimzadeh M, Azhdari S, Vahedi P, Abdollahi E, Momtazi-Borojeni A. Modulatory effects of curcumin on the atherogenic activities of inflammatory monocytes: Evidence from in vitro and animal models of human atherosclerosis. BioFactors 2019; 34(50): 1123-33.
[52]
Sadeghi N, Mansoori A, Shayesteh A, Hashemi S. The effect of curcumin supplementation on clinical outcomes and inflammatory markers in patients with ulcerative colitis. Phytotherapy research : PTR 2020; 34(5): 1123-33.
[53]
Wang Q, Ye C, Sun S, et al. Curcumin attenuates collagen-induced rat arthritis via anti-inflammatory and apoptotic effects. Int Immunopharmacol 2019; 72: 292-300.
[http://dx.doi.org/10.1016/j.intimp.2019.04.027] [PMID: 31005039]
[54]
Mohanty C, Das M, Sahoo SK. Sustained wound healing activity of curcumin loaded oleic acid based polymeric bandage in a rat model. Mol Pharm 2012; 9(10): 2801-11.
[http://dx.doi.org/10.1021/mp300075u] [PMID: 22946786]
[55]
White CM, Pasupuleti V, Roman YM, Li Y, Hernandez AV. Oral turmeric/curcumin effects on inflammatory markers in chronic inflammatory diseases: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2019; 146: 104280.
[http://dx.doi.org/10.1016/j.phrs.2019.104280] [PMID: 31121255]
[56]
Nguyen MH, Lee SE, Tran TT, et al. A simple strategy to enhance the in vivo wound-healing activity of curcumin in the form of self-assembled nanoparticle complex of curcumin and oligochitosan. Mater Sci Eng C 2019; 98: 54-64.
[http://dx.doi.org/10.1016/j.msec.2018.12.091] [PMID: 30813056]
[57]
Zahiri M, Khanmohammadi M, Goodarzi A, et al. Encapsulation of curcumin loaded chitosan nanoparticle within poly (ε-caprolactone) and gelatin fiber mat for wound healing and layered dermal reconstitution. Int J Biol Macromol 2020; 153: 1241-50.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.10.255] [PMID: 31759002]
[58]
Macleod MR, Lawson McLean A, Kyriakopoulou A, et al. Risk of bias in reports of in vivo research: A focus for improvement. PLoS Biol 2015; 13(10): e1002273.
[http://dx.doi.org/10.1371/journal.pbio.1002273] [PMID: 26460723]

Rights & Permissions Print Cite
Article Metrics
33
1
© 2024 Bentham Science Publishers | Privacy Policy