Abdalla HB, Napimoga MH, Lopes AH, de Macedo Maganin AG, Cunha TM, Van Dyke TE, Clemente Napimoga JT (2020) Activation of PPAR-gamma induces macrophage polarization and reduces neutrophil migration mediated by heme oxygenase 1. Int Immunopharmacol 84:106565. https://doi.org/10.1016/j.intimp.2020.106565

Article  CAS  Google Scholar 

Allhorn M, Lundqvist K, Schmidtchen A, Akerstrom B (2003) Heme-scavenging role of alpha1-microglobulin in chronic ulcers. J Invest Dermatol 121(3):640–646. https://doi.org/10.1046/j.1523-1747.2003.12409.x

Article  CAS  Google Scholar 

Cada DJ, Levien TL, Baker DE (2013) Dimethyl fumarate. Hosp Pharm 48(8):668–679. https://doi.org/10.1310/hpj4808-668

Article  CAS  Google Scholar 

Chamberlain LM, Godek ML, Gonzalez-Juarrero M, Grainger DW (2009) Phenotypic non-equivalence of murine (monocyte-) macrophage cells in biomaterial and inflammatory models. J Biomed Mater Res A 88(4):858–871. https://doi.org/10.1002/jbm.a.31930

Article  CAS  Google Scholar 

Chen QY, Wang GG, Li W, Jiang YX, Lu XH, Zhou PP (2016) Heme oxygenase-1 promotes delayed wound healing in diabetic rats. J Diabetes Res 2016:9726503. https://doi.org/10.1155/2016/9726503

Article  CAS  Google Scholar 

Choi KM, Kashyap PC, Dutta N, Stoltz GJ, Ordog T, Shea Donohue T et al (2010) CD206-positive M2 macrophages that express heme oxygenase-1 protect against diabetic gastroparesis in mice. Gastroenterology 138(7):2399-2409 e2391. https://doi.org/10.1053/j.gastro.2010.02.014

Article  CAS  Google Scholar 

Corna G, Campana L, Pignatti E, Castiglioni A, Tagliafico E, Bosurgi L et al (2010) Polarization dictates iron handling by inflammatory and alternatively activated macrophages. Haematologica 95(11):1814–1822. https://doi.org/10.3324/haematol.2010.023879

Article  CAS  Google Scholar 

Dinh T, Tecilazich F, Kafanas A, Doupis J, Gnardellis C, Leal E et al (2012) Mechanisms involved in the development and healing of diabetic foot ulceration. Diabetes 61(11):2937–2947. https://doi.org/10.2337/db12-0227

Article  CAS  Google Scholar 

Dornadula S, Thiruppathi S, Palanisamy R, Umapathy D, Suzuki T, Ramkumar KM (2019) Differential proteomic profiling identifies novel molecular targets of pterostilbene against experimental diabetes. J Cell Physiol 234(3):1996–2012. https://doi.org/10.1002/jcp.26835

Article  CAS  Google Scholar 

Ganesh GV, Ramkumar KM (2021) Dysregulation of Nrf2 redox pathway in macrophages under diabetic microenvironment. Exp Gerontol 152:111479. https://doi.org/10.1016/j.exger.2021.111479

Article  CAS  Google Scholar 

Hozzein WN, Badr G, Badr BM, Allam A, Ghamdi AA, Al-Wadaan MA, Al-Waili NS (2018) Bee venom improves diabetic wound healing by protecting functional macrophages from apoptosis and enhancing Nrf2, Ang-1 and Tie-2 signaling. Mol Immunol 103:322–335. https://doi.org/10.1016/j.molimm.2018.10.016

Article  CAS  Google Scholar 

Imoto S, Kono M, Suzuki T, Shibuya Y, Sawamura T, Mizokoshi Y et al (2018) Haemin-induced cell death in human monocytic cells is consistent with ferroptosis. Transfus Apher Sci 57(4):524–531. https://doi.org/10.1016/j.transci.2018.05.028

Article  Google Scholar 

Joshi N, Werner S (2017) Nrf2 is highly expressed in neutrophils, but myeloid cell-derived Nrf2 is dispensable for wound healing in mice. PLoS ONE 12(10):e0187162. https://doi.org/10.1371/journal.pone.0187162

Article  CAS  Google Scholar 

Kallenborn-Gerhardt W, Moser CV, Lorenz JE, Steger M, Heidler J, Scheving R et al (2017) Rab7-a novel redox target that modulates inflammatory pain processing. Pain 158(7):1354–1365. https://doi.org/10.1097/j.pain.0000000000000920

Article  CAS  Google Scholar 

Kumar D, Jena GR, Ram M, Lingaraju MC, Singh V, Prasad R et al (2019) Hemin attenuated oxidative stress and inflammation to improve wound healing in diabetic rats. Naunyn Schmiedebergs Arch Pharmacol 392(11):1435–1445. https://doi.org/10.1007/s00210-019-01682-7

Article  CAS  Google Scholar 

Lee YJ, Kwon SB, An JM, Kim CH, Lee SH, Choi CY et al (2015) Increased protein oxidation and decreased expression of nuclear factor E2-related factor 2 protein in skin tissue of patients with diabetes. Clin Exp Dermatol 40(2):192–200. https://doi.org/10.1111/ced.12487

Article  CAS  Google Scholar 

Li Y, Ma F, Li H, Song Y, Zhang H, Jiang Z, Wu H (2018) Dimethyl fumarate accelerates wound healing under diabetic condition. J Mol Endocrinol 61(4):163–172. https://doi.org/10.1530/JME-18-0102

Article  CAS  Google Scholar 

Li M, Yu H, Pan H, Zhou X, Ruan Q, Kong D et al (2019) Nrf2 suppression delays diabetic wound healing through sustained oxidative stress and inflammation. Front Pharmacol 10:1099. https://doi.org/10.3389/fphar.2019.01099

Article  CAS  Google Scholar 

Lu J, Xie L, Liu C, Zhang Q, Sun S (2017) PTEN/PI3k/AKT regulates macrophage polarization in emphysematous mice. Scand J Immunol 85(6):395–405. https://doi.org/10.1111/sji.12545

Article  CAS  Google Scholar 

Marro S, Chiabrando D, Messana E, Stolte J, Turco E, Tolosano E, Muckenthaler MU (2010) Heme controls ferroportin1 (FPN1) transcription involving Bach1, Nrf2 and a MARE/ARE sequence motif at position -7007 of the FPN1 promoter. Haematologica 95(8):1261–1268. https://doi.org/10.3324/haematol.2009.020123

Article  CAS  Google Scholar 

Nakaso K, Yano H, Fukuhara Y, Takeshima T, Wada-Isoe K, Nakashima K (2003) PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells. FEBS Lett 546(2–3):181–184. https://doi.org/10.1016/s0014-5793(03)00517-9

Article  CAS  Google Scholar 

Qiu-Yi Choo SCMY, Ho PC, Tanaka Y, Lin H-S (2014) Pterostilbene surpassed resveratrol for anti-inflammatory application: potency consideration and pharmacokinetics perspective. J Funct Foods 11:352–362. https://doi.org/10.1016/j.jff.2014.10.018

Article  CAS  Google Scholar 

Ram M, Singh V, Kumawat S, Kumar D, Lingaraju MC, Uttam Singh T et al (2015) Deferoxamine modulates cytokines and growth factors to accelerate cutaneous wound healing in diabetic rats. Eur J Pharmacol 764:9–21. https://doi.org/10.1016/j.ejphar.2015.06.029

Article  CAS  Google Scholar 

Ramkumar KM, Sekar TV, Foygel K, Elango B, Paulmurugan R (2013) Reporter protein complementation imaging assay to screen and study Nrf2 activators in cells and living animals. Anal Chem 85(15):7542–7549. https://doi.org/10.1021/ac401569j

Article  CAS  Google Scholar 

Safety and Efficacy of ActiGraft Compared to Standard of Care in DFUs (2019) Clinical Trials. Retrieved 30 November 2021, from https://clinicaltrials.gov/ct2/show/NCT04185558

Schaer CA, Schoedon G, Imhof A, Kurrer MO, Schaer DJ (2006) Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines the noninflammatory and protective transcriptional response of macrophages to hemoglobin. Circ Res 99(9):943–950. https://doi.org/10.1161/01.RES.0000247067.34173.1b

Article  CAS  Google Scholar 

Sindrilaru A, Peters T, Wieschalka S, Baican C, Baican A, Peter H et al (2011) An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Invest 121(3):985–997. https://doi.org/10.1172/JCI44490

Article  CAS  Google Scholar 

Sireesh D, Ganesh MR, Dhamodharan U, Sakthivadivel M, Sivasubramanian S, Gunasekaran P, Ramkumar KM (2017) Role of pterostilbene in attenuating immune mediated devastation of pancreatic beta cells via Nrf2 signaling cascade. J Nutr Biochem 44:11–21. https://doi.org/10.1016/j.jnutbio.2017.02.015

Article  CAS  Google Scholar 

Soares MA, Cohen OD, Low YC, Sartor RA, Ellison T, Anil U et al (2016) Restoration of Nrf2 signaling normalizes the regenerative niche. Diabetes 65(3):633–646. https://doi.org/10.2337/db15-0453

Article  CAS  Google Scholar 

Song L, Lee C, Schindler C (2011) Deletion of the murine scavenger receptor CD68. J Lipid Res 52(8):1542–1550. https://doi.org/10.1194/jlr.M015412

Article  CAS  Google Scholar 

Suganya N, Bhakkiyalakshmi E, Subin TS, Krishnamurthi K, Devi SS, Lau K et al (2014) Proteomic identification of pterostilbene-mediated anticancer activities in HepG2 cells. Chem Res Toxicol 27(7):1243–1252. https://doi.org/10.1021/tx5001392

Article  CAS  Google Scholar 

Takahashi Y, Kobayashi T, D’Alessandro-Gabazza CN, Toda M, Fujiwara K, Okano T et al (2019) Protective role of matrix metalloproteinase-2 in allergic bronchial asthma. Front Immunol 10:1795. https://doi.org/10.3389/fimmu.2019.01795

Article  CAS  Google Scholar 

Tchanque-Fossuo C, Dahle SE, Buchman S, Isseroff R (2016) 737 Deferoxamine in wound healing. J Investig Dermatol 136:S130. https://doi.org/10.1016/j.jid.2016.02.780

Article  Google Scholar 

Toby Richards SH, Wright J, Loukogeorgakis S, Khanbhai M (2012) Anaemia, inflammation, renal function, and the diabetic foot: What are the relationships? Diabetic Foot J 15(4):150–158

Google Scholar 

Vella L, Gatt A, Formosa C (2017) Does baseline hemoglobin a1c level predict diabetic foot ulcer outcome or wound healing time? J Am Podiatr Med Assoc 107(4):272–279. https://doi.org/10.7547/15-176

Article  Google Scholar 

Vijayan V, Wagener F, Immenschuh S (2018) The macrophage heme-heme oxygenase-1 system and its role in inflammation. Biochem Pharmacol 153:159–167. https://doi.org/10.1016/j.bcp.2018.02.010

Article  CAS  Google Scholar 

Wang WT, Sun L, Sun CH (2019) PDIA3-regulated inflammation and oxidative stress contribute to the traumatic brain injury (TBI) in mice. Biochem Biophys Res Commun 518(4):657–663. https://doi.org/10.1016/j.bbrc.2019.08.100

Article  CAS  Google Scholar 

Zhang F, Fan D, Mo XN (2018) Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS-induced acute injury. Mol Med Rep 17(6):7769–7773. https://doi.org/10.3892/mmr.2018.8808

Article  CAS  Google Scholar 

Zhao S, Ghosh A, Lo CS, Chenier I, Scholey JW, Filep JG et al (2018) Nrf2 deficiency upregulates intrarenal angiotensin-converting enzyme-2 and angiotensin 1–7 receptor expression and attenuates hypertension and nephropathy in diabetic mice. Endocrinology 159(2):836–852. https://doi.org/10.1210/en.2017-00752

Article  CAS  Google Scholar 

Zhou J, Ci X, Ma X, Yu Q, Cui Y, Zhen Y, Li S (2019) Pterostilbene activates the Nrf2-dependent antioxidant response to ameliorate arsenic-induced intracellular damage and apoptosis in human keratinocytes. Front Pharmacol 10:497. https://doi.org/10.3389/fphar.2019.00497

Article  CAS  Google Scholar