Chronic nonhealing wounds of the lower extremities resulting in major amputations are a major health problem worldwide.
Significance:
Diabetes and ischemia are two major etiologies of nonhealing wounds of the lower extremities. Hyperglycemia from diabetes and oxidative stress from ischemia activate polyadenosine diphosphate (ADP)-ribose polymerase-1 (PARP-1), which is a nuclear enzyme that is best known for its role in DNA repair. However, the exact function of PARP-1 in ischemic/diabetic wound healing has not been well studied.
Recent Advances:
Poly-ADP-ribose (PAR) polymer has been detected in the wound bed and many of the PARylation-related reactions (oxidative stress response, expression of inflammatory cytokines and chemokines, cell proliferation, and migration) are important in the wound healing process. However, the role of PARP-1 in wound healing and the potential of targeting PARP-1 therapeutically in wounds are only recently being elucidated, with much still unknown. This review summarizes the recent advances in this field, highlighting some of the mechanisms through which PARP-1 may affect normal wound closure.
Future Directions:
The review also presents a perspective on some of the downstream targets of PARP-1 that may be explored for their role in wound healing and discusses about the therapeutic potential of PARP inhibitors for wound healing.
Get full access to this article
View all access options for this article.
References
1.
FrykbergRG, BanksJ. Challenges in the treatment of chronic wounds. Adv Wound Care, 2015; 4:560–582.
2.
SenCK, GordilloGM, RoyS, et al.Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen, 2009; 17:763–771.
3.
BondorCI, VeresiuIA, FloreaB, VinikEJ, VinikAI, GavanNA. Epidemiology of diabetic foot ulcers and amputations in Romania: results of a cross-sectional quality of life questionnaire based survey. J Diabetes Res, 2016; 2016:5439521.
4.
ReiberGE, VileikyteL, BoykoEJ, et al.Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care, 1999; 22:157–162.
5.
LawallH, BramlageP, AmannB. Treatment of peripheral arterial disease using stem and progenitor cell therapy. J Vasc Surg, 2011; 53:445–453.
6.
AmeJC, SpenlehauerC, de MurciaG. The PARP superfamily. BioEssays News Rev Mol Cell Dev Biol, 2004; 26:882–893.
7.
D'AmoursD, DesnoyersS, D'SilvaI, PoirierGG. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J, 1999; 342:249–268.
8.
SzantoM, BrunyanszkiA, KissB, et al.: Poly(ADP-ribose) polymerase-2: emerging transcriptional roles of a DNA-repair protein. Cell Mol Life Sci, 2012; 69:4079–4092.
9.
KrausWL.Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation. Curr Opin Cell Biol, 2008; 20:294–302.
10.
KrishnakumarR, KrausWL. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol Cell, 2010; 39:8–24.
11.
LuoX, KrausWL. On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev, 2012; 26:417–432.
12.
ChatterjeeS, BergerSJ, BergerNA. Poly(ADP-ribose) polymerase: a guardian of the genome that facilitates DNA repair by protecting against DNA recombination. Mol Cell Biochem, 1999; 193:23–30.
13.
IzharL, AdamsonB, CicciaA, et al.A systematic analysis of factors localized to damaged chromatin reveals PARP-dependent recruitment of transcription factors. Cell Rep, 2015; 11:1486–1500.
14.
NirodiC, NagDasS, GygiSP, OlsonG, AebersoldR, RichmondA. A role for poly(ADP-ribose) polymerase in the transcriptional regulation of the melanoma growth stimulatory activity (CXCL1) gene expression. J Biol Chem, 2001; 276:9366–9374.
15.
PlazaS, AumercierM, BaillyM, DozierC, SauleS. Involvement of poly (ADP-ribose)-polymerase in the Pax-6 gene regulation in neuroretina. Oncogene, 1999; 18:1041–1051.
16.
ButlerAJ, OrdahlCP. Poly(ADP-ribose) polymerase binds with transcription enhancer factor 1 to MCAT1 elements to regulate muscle-specific transcription. Mol Cell Biol, 1999; 19:296–306.
17.
MeisterernstM, StelzerG, RoederRG. Poly(ADP-ribose) polymerase enhances activator-dependent transcription in vitro. Proc Natl Acad Sci U S A, 1997; 94:2261–2265.
18.
OeiSL, GriesenbeckJ, SchweigerM, BabichV, KropotovA, TomilinN. Interaction of the transcription factor YY1 with human poly(ADP-ribosyl) transferase. Biochem Biophys Res Commun, 1997; 240:108–111.
19.
HassaPO, HottigerMO. A role of poly (ADP-ribose) polymerase in NF-kappaB transcriptional activation. Biol Chem, 1999; 380:953–959.
20.
RawlingJM, Alvarez-GonzalezR. TFIIF, a basal eukaryotic transcription factor, is a substrate for poly(ADP-ribosyl)ation. Biochem J, 1997; 324:249–253.
21.
NieJ, SakamotoS, SongD, QuZ, OtaK, TaniguchiT. Interaction of Oct-1 and automodification domain of poly(ADP-ribose) synthetase. FEBS Lett, 1998; 424:27–32.
22.
KannanP, YuY, WankhadeS, TainskyMA. PolyADP-ribose polymerase is a coactivator for AP-2-mediated transcriptional activation. Nucleic Acids Res, 1999; 27:866–874.
23.
OeiSL, GriesenbeckJ, SchweigerM, ZieglerM. Regulation of RNA polymerase II-dependent transcription by poly(ADP-ribosyl)ation of transcription factors. J Biol Chem, 1998; 273:31644–31647.
24.
PoirierGG, de MurciaG, Jongstra-BilenJ, NiedergangC, MandelP. Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure. Proc Natl Acad Sci USA, 1982; 79:3423–3427.
25.
HuletskyA, de MurciaG, MullerS, et al.The effect of poly(ADP-ribosyl)ation on native and H1-depleted chromatin. A role of poly(ADP-ribosyl)ation on core nucleosome structure. J Biol Chem, 1989; 264:8878–8886.
MartinKA, CesaroniM, DennyMF, LupeyLN, TemperaI. Global transcriptome analysis reveals that poly(ADP-ribose) polymerase 1 regulates gene expression through EZH2. Mol Cell Biol, 2015; 35:3934–3944.
28.
MathisG, AlthausFR. Release of core DNA from nucleosomal core particles following (ADP-ribose)n-modification in vitro. Biochem Biophys Res Commun, 1987; 143:1049–1054.
29.
TulinA, SpradlingA. Chromatin loosening by poly(ADP)-ribose polymerase (PARP) at Drosophila puff loci. Science, 2003; 299:560–562.
30.
RealeA, MatteisGD, GalleazziG, ZampieriM, CaiafaP. Modulation of DNMT1 activity by ADP-ribose polymers. Oncogene, 2005; 24:13–19.
31.
ZampieriM, PassanantiC, CalabreseR, et al.Parp1 localizes within the Dnmt1 promoter and protects its unmethylated state by its enzymatic activity. PLoS One, 2009; 4:e4717.
32.
ClarkNJ, KramerM, MuthurajanUM, LugerK. Alternative modes of binding of poly(ADP-ribose) polymerase 1 to free DNA and nucleosomes. J Biol Chem, 2012; 287:32430–32439.
33.
KunE, KirstenE, MendeleyevJ, OrdahlCP. Regulation of the enzymatic catalysis of poly(ADP-ribose) polymerase by dsDNA, polyamines, Mg2+, Ca2+, histones H1 and H3, and ATP. Biochemistry, 2004; 43:210–216.
34.
KauppinenTM, ChanWY, SuhSW, WigginsAK, HuangEJ, SwansonRA. Direct phosphorylation and regulation of poly(ADP-ribose) polymerase-1 by extracellular signal-regulated kinases 1/2. Proc Natl Acad Sci U S A, 2006; 103:7136–7141.
35.
Dominguez-GomezG, Diaz-ChavezJ, Chavez-BlancoA, et al.Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin. Oncol Rep, 2015; 33:721–728.
36.
LonskayaI, PotamanVN, ShlyakhtenkoLS, OussatchevaEA, LyubchenkoYL, SoldatenkovVA. Regulation of poly(ADP-ribose) polymerase-1 by DNA structure-specific binding. J Biol Chem, 2005; 280:17076–17083.
37.
KimMY, ZhangT, KrausWL. Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev, 2005; 19:1951–1967.
38.
ZhangT, KrausWL. SIRT1-dependent regulation of chromatin and transcription: linking NAD(+) metabolism and signaling to the control of cellular functions. Biochim Biophys Acta, 2010; 1804:1666–1675.
39.
ZhangT, BerrocalJG, YaoJ, et al.Regulation of poly(ADP-ribose) polymerase-1-dependent gene expression through promoter-directed recruitment of a nuclear NAD+ synthase. J Biol Chem, 2012; 287:12405–12416.
40.
GagneJP, HendzelMJ, DroitA, PoirierGG. The expanding role of poly(ADP-ribose) metabolism: current challenges and new perspectives. Curr Opin Cell Biol, 2006; 18:145–151.
41.
FrizzellKM, GambleMJ, BerrocalJG, et al.Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells. J Biol Chem, 2009; 284:33926–33938.
42.
Rodriguez-VargasJM, Ruiz-MaganaMJ, Ruiz-RuizC, et al.ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy. Cell Res, 2012; 22:1181–1198.
43.
Garcia SorianoF, ViragL, JagtapP, et al.Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med, 2001; 7:108–113.
44.
LiuJ, WuY, WangB, YuanX, FangB. High levels of glucose induced the caspase-3/PARP signaling pathway, leading to apoptosis in human periodontal ligament fibroblasts. Cell Biochem Biophys, 2013; 66:229–237.
45.
SenCK.Wound healing essentials: let there be oxygen. Wound Repair Regen, 2009; 17:1–18.
46.
OkonkwoUA, DiPietroLA. Diabetes and wound angiogenesis. Int J Mol Sci, 2017; 18:1419.
47.
EndaraM, MasdenD, GoldsteinJ, GondekS, SteinbergJ, AttingerC. The role of chronic and perioperative glucose management in high-risk surgical closures: a case for tighter glycemic control. Plast Reconstr Surg, 2013; 132:996–1004.
48.
LanCC, WuCS, HuangSM, WuIH, ChenGS. High-glucose environment enhanced oxidative stress and increased interleukin-8 secretion from keratinocytes: new insights into impaired diabetic wound healing. Diabetes, 2013; 62:2530–2538.
49.
HuSC, LanCE. High-glucose environment disturbs the physiologic functions of keratinocytes: focusing on diabetic wound healing. J Dermatol Sci, 2016; 84:121–127.
50.
SchaferM, WernerS. Oxidative stress in normal and impaired wound repair. Pharmacol Res, 2008; 58:165–171.
LongCA, BoulomV, AlbadawiH, et al.Poly-ADP-ribose-polymerase inhibition ameliorates hind limb ischemia reperfusion injury in a murine model of type 2 diabetes. Ann Surg, 2013; 258:1087–1095.
53.
KassanM, ChoiSK, GalanM, et al.Enhanced NF-kappaB activity impairs vascular function through PARP-1-, SP-1-, and COX-2-dependent mechanisms in type 2 diabetes. Diabetes, 2013; 62:2078–2087.
54.
LiB, LiR, ZhangC, et al.MicroRNA-7a/b protects against cardiac myocyte injury in ischemia/reperfusion by targeting poly(ADP-ribose) polymerase. PLoS One, 2014; 9:e90096.
55.
Tas HekimogluA, ToprakG, AkkocH, et al.Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase in distant liver injury induced by renal ischemia-reperfusion in rats. Eur Rev Med Pharmacol Sci, 2014; 18:34–38.
56.
El-HamolyT, HegedusC, LakatosP, et al.Activation of poly(ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators. Mol Med, 2014; 20:363–371.
57.
BryanN, AhswinH, SmartN, BayonY, WohlertS, HuntJA. Reactive oxygen species (ROS)—a family of fate deciding molecules pivotal in constructive inflammation and wound healing. Eur Cell Mater, 2012; 24:249–265.
58.
OlahG, FinnertyCC, SbranaE, et al.Increased poly(ADP-ribosyl)ation in skeletal muscle tissue of pediatric patients with severe burn injury: prevention by propranolol treatment. Shock, 2011; 36:18–23.
59.
JagtapPG, BalogluE, SouthanGJ, et al.Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. J Med Chem, 2005; 48:5100–5103.
60.
RosadoMM, BenniciE, NovelliF, PioliC. Beyond DNA repair, the immunological role of PARP-1 and its siblings. Immunology, 2013; 139:428–437.
61.
JagtapP, SzaboC. Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov, 2005; 4:421–440.
62.
AhmadA, OlahG, HerndonDN, SzaboC. The clinically used PARP inhibitor olaparib improves organ function, suppresses inflammatory responses and accelerates wound healing in a murine model of third-degree burn injury. Br J Pharmacol, 2018; 175:232–245.
63.
El-HamolyT, El-DensharyES, SaadSM, El-GhazalyMA. 3-aminobenzamide, a poly (ADP ribose) polymerase inhibitor, enhances wound healing in whole body gamma irradiated model. Wound Repair Regen, 2015; 23:672–684.
64.
PastarI, StojadinovicO, YinNC, et al.Epithelialization in wound healing: a comprehensive review. Adv Wound Care, 2014; 3:445–464.
65.
Simbulan-RosenthalCM, RosenthalDS, HilzH, et al.The expression of poly(ADP-ribose) polymerase during differentiation-linked DNA replication reveals that it is a component of the multiprotein DNA replication complex. Biochemistry, 1996; 35:11622–11633.
66.
EkiT.Poly (ADP-ribose) polymerase inhibits DNA replication by human replicative DNA polymerase alpha, delta and epsilon in vitro. FEBS Lett, 1994; 356:261–266.
67.
PaganoA, Metrailler-RuchonnetI, Aurrand-LionsM, LucattelliM, DonatiY, ArgiroffoCB. Poly(ADP-ribose) polymerase-1 (PARP-1) controls lung cell proliferation and repair after hyperoxia-induced lung damage. Am J Physiol Lung Cell Mol Physiol, 2007; 293:L619–L629.
68.
PyriochouA, OlahG, DeitchEA, SzaboC, PapapetropoulosA. Inhibition of angiogenesis by the poly(ADP-ribose) polymerase inhibitor PJ-34. Int J Mol Med, 2008; 22:113–118.
69.
Gonzalez-FloresA, Aguilar-QuesadaR, SilesE, et al.Interaction between PARP-1 and HIF-2alpha in the hypoxic response. Oncogene, 2014; 33:891–898.
70.
MathewsMT, BerkBC. PARP-1 inhibition prevents oxidative and nitrosative stress-induced endothelial cell death via transactivation of the VEGF receptor 2. Arterioscler Thromb Vasc Biol, 2008; 28:711–717.
71.
CaldiniR, FantiE, MagnelliL, et al.Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2. Vasc Cell, 2011; 3:12.
72.
SarrasMPJr., MasonS, McAllisterG, IntineRV.Inhibition of poly-ADP ribose polymerase enzyme activity prevents hyperglycemia-induced impairment of angiogenesis during wound healing. Wound Repair Regen, 2014; 22:666–670.
73.
BinuS, SoumyaSJ, KumarVB, SudhakaranPR. Poly-ADP-ribosylation of vascular endothelial growth factor and its implications on angiogenesis. Adv Exp Med Biol, 2012; 749:269–278.
74.
ZhouX, PatelD, SenS, et al.Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis. J Vasc Surg, 2017; 65:1161–1169.
75.
ComptonCC, GillJM, BradfordDA, RegauerS, GallicoGG, O'ConnorNE. Skin regenerated from cultured epithelial autografts on full-thickness burn wounds from 6 days to 5 years after grafting. A light, electron microscopic and immunohistochemical study. Lab Invest J Tech Methods Pathol, 1989; 60:600–612.
RaiNK, TripathiK, SharmaD, ShuklaVK. Apoptosis: a basic physiologic process in wound healing. Int J Low Extrem Wounds, 2005; 4:138–144.
78.
TidballJG, St PierreBA. Apoptosis of macrophages during the resulution of muscle inflammation. J Leukoc Biol, 1996; 59:380–388.
79.
RizziN, DenegriM, ChiodiI, et al.Transcriptional activation of a constitutive heterochromatic domain of the human genome in response to heat shock. Mol Biol Cell, 2004; 15:543–551.
80.
GillSE, ParksWC. Metalloproteinases and their inhibitors: regulators of wound healing. Int J Biochem Cell Biol, 2008; 40:1334–1347.
81.
LiuY, MinD, BoltonT, et al.Increased matrix metalloproteinase-9 predicts poor wound healing in diabetic foot ulcers: response to Muller et al. Diabetes Care, 2009; 32:e137.
82.
WangY, WangL, ZhangF, et al.Inhibition of PARP prevents angiotensin II-induced aortic fibrosis in rats. Int J Cardiol, 2013; 167:2285–2293.
83.
OkadaH, InoueT, KikutaT, et al.Poly(ADP-ribose) polymerase-1 enhances transcription of the profibrotic CCN2 gene. J Am Soc Nephrol, 2008; 19:933–942.
84.
LeiP, JiangZ, ZhuH, LiX, SuN, YuX. Poly(ADP-ribose) polymerase-1 in high glucose-induced epithelial-mesenchymal transition during peritoneal fibrosis. Int J Mol Med, 2012; 29:472–478.
85.
CarterR, SykesV, LanningD. Scarless fetal mouse wound healing may initiate apoptosis through caspase 7 and cleavage of PARP. J Surg Res, 2009; 156:74–79.
LodhiN, KossenkovAV, TulinAV. Bookmarking promoters in mitotic chromatin: poly(ADP-ribose)polymerase-1 as an epigenetic mark. Nucleic Acids Res, 2014; 42:7028–7038.
88.
SultanM, SchulzMH, RichardH, et al.A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science, 2008; 321:956–960.
89.
SugaH, SugayaM, FujitaH, et al.TLR4, rather than TLR2, regulates wound healing through TGF-beta and CCL5 expression. J Dermatol Sci, 2014; 73:117–124.
90.
ChenL, GuoS, RanzerMJ, DiPietroLA. Toll-like receptor 4 has an essential role in early skin wound healing. J Invest Dermatol, 2013; 133:258–267.
91.
SinghK, SinghVK, AgrawalNK, GuptaSK, SinghK. Association of Toll-like receptor 4 polymorphisms with diabetic foot ulcers and application of artificial neural network in DFU risk assessment in type 2 diabetes patients. BioMed Res Int, 2013; 2013:318686.
92.
TeichertM, MildeL, HolmA, et al.Pericyte-expressed Tie2 controls angiogenesis and vessel maturation. Nat Commun, 2017; 8:16106.
93.
EvellinS, GalvagniF, ZippoA, et al.FOSL1 controls the assembly of endothelial cells into capillary tubes by direct repression of alphav and beta3 integrin transcription. Mol Cell Biol, 2013; 33:1198–1209.
94.
SinghNK, QuyenDV, Kundumani-SridharanV, BrooksPC, RaoGN. AP-1 (Fra-1/c-Jun)-mediated induction of expression of matrix metalloproteinase-2 is required for 15S-hydroxyeicosatetraenoic acid-induced angiogenesis. J Biol Chem, 2010; 285:16830–16843.
95.
GalvagniF, OrlandiniM, OlivieroS. Role of the AP-1 transcription factor FOSL1 in endothelial cells adhesion and migration. Cell Adh Migr, 2013; 7:408–411.
KadaukeS, UdugamaMI, PawlickiJM, et al.Tissue-specific mitotic bookmarking by hematopoietic transcription factor GATA1. Cell, 2012; 150:725–737.
98.
SchroderWA, MajorL, SuhrbierA. The role of SerpinB2 in immunity. Crit Rev Immunol, 2011; 31:15–30.
99.
LeeJA, CochranBJ, LobovS, RansonM. Forty years later and the role of plasminogen activator inhibitor type 2/SERPINB2 is still an enigma. Semin Thromb Hemost, 2011; 37:395–407.
100.
StaceyMC, MataSD. Lower levels of PAI-2 may contribute to impaired healing in venous ulcers - a preliminary study. Cardiovasc Surg, 2000; 8:381–385.
101.
KroezeKL, BoinkMA, Sampat-SardjoepersadSC, WaaijmanT, ScheperRJ, GibbsS. Autocrine regulation of re-epithelialization after wounding by chemokine receptors CCR1, CCR10, CXCR1, CXCR2, and CXCR3. J Invest Dermatol, 2012; 132:216–225.
102.
ShapiraS, Ben-AmotzO, SherO, et al.Delayed wound healing in heat stable antigen (HSA/CD24)-deficient mice. PLoS One, 2015; 10:e0139787.
UnderhillC, ToulmondeM, BonnefoiH. A review of PARP inhibitors: from bench to bedside. Ann Oncol, 2011; 22:268–279.
105.
GibsonBA, KrausWL. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat Rev Mol Cell Biol, 2012; 13:411–424.
106.
ColomboI, LheureuxS, OzaAM. Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer. Drug Des Dev Ther, 2018; 12:605–617.
107.
BixelK, HaysJL. Olaparib in the management of ovarian cancer. Pharmacogenomics Pers Med, 2015; 8:127–135.
108.
FongPC, BossDS, YapTA, et al.Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med, 2009; 361:123–134.
109.
DrewY, LedermannJ, HallG, et al.Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer. Br J Cancer, 2016; 114:e21.
110.
ShenY, RehmanFL, FengY, et al.BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res, 2013; 19:5003–5015.
111.
WahlbergE, KarlbergT, KouznetsovaE, et al.Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors. Nat Biotechnol, 2012; 30:283–288.
112.
MuraiJ, HuangSY, RenaudA, et al.Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther, 2014; 13:433–443.
113.
MooreKN, MirzaMR, MatulonisUA. The poly (ADP ribose) polymerase inhibitor niraparib: management of toxicities. Gynecol Oncol, 2018; 149:214–220.
114.
ZhuX, WangK, ZhangK, LinX, ZhuL, ZhouF. Puerarin protects human neuroblastoma SH-SY5Y cells against glutamate-induced oxidative stress and mitochondrial dysfunction. J Biochem Mol Toxicol, 2016; 30:22–28.
115.
ZhuX, XieM, WangK, et al.The effect of puerarin against IL-1beta-mediated leukostasis and apoptosis in retinal capillary endothelial cells (TR-iBRB2). Mol Vis, 2014; 20:1815–1823.
116.
ZhangZ, LamTN, ZuoZ. Radix Puerariae: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol, 2013; 53:787–811.
117.
WangS, ShiXL, FengM, et al.Puerarin protects against CCl4-induced liver fibrosis in mice: possible role of PARP-1 inhibition. Int Immunopharmacol, 2016; 38:238–245.
118.
MaedaJ, RoybalEJ, BrentsCA, UesakaM, AizawaY, KatoTA. Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells. Oncol Rep, 2014; 31:551–556.
119.
ZhouP, HuangJ, TianF. Specific noncovalent interactions at protein-ligand interface: implications for rational drug design. Curr Med Chem, 2012; 19:226–238.
120.
SouthanGJ, SzaboC. Poly(ADP-ribose) polymerase inhibitors. Curr Med Chem, 2003; 10:321–340.
