PMID- 37926050
OWN - NLM
STAT- MEDLINE
DCOM- 20240112
LR  - 20240112
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 164
DP  - 2023 Dec
TI  - Pterostilbene accelerates wound healing response in diabetic mice through Nrf2 
      regulation.
PG  - 17-27
LID - S0161-5890(23)00208-0 [pii]
LID - 10.1016/j.molimm.2023.10.010 [doi]
AB  - Pterostilbene (PTS), known for its diverse beneficial effects via Nuclear factor 
      erythroid-2 related factor (Nrf2) activation, holds potential for Diabetic Foot 
      Ulcer (DFU) treatment. However, PTS-mediated Nrf2 regulation in diabetic wounds 
      has yet to be elucidated. We used IC21 macrophage-conditioned media to simulate 
      complex events that can influence the fibroblast phenotype using L929 cells 
      during the wound healing process under a hyperglycemic microenvironment. We found 
      that PTS attenuated fibroblast migration and alpha-smooth muscle actin (alpha-SMA) 
      levels and hypoxia-inducible factor- 1 alpha (HIF1alpha). Furthermore, we 
      demonstrated that wounds in diabetic mice characterized by impaired wound closure 
      in a heightened inflammatory milieu, such as the NOD-like receptor P3 (NLRP3) and 
      intercellular adhesion molecule 1 (ICAM1), and deficient Nrf2 response 
      accompanying lowered Akt signaling and heme oxygenase1 (HO1) expression along 
      with the impaired macrophage M2 marker CD206 expression, was rescued by 
      administration of PTS. Such an elicited response was also compared favorably with 
      the standard treatment using Regranex, a commercially available topical 
      formulation for treating DFUs. Our findings suggest that PTS regulates Nrf2 in 
      diabetic wounds, triggering a pro-wound healing response mediated by macrophages. 
      This insight holds the potential for developing targeted therapies to heal 
      chronic wounds, including DFUs.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Ganesh, Goutham V
AU  - Ganesh GV
AD  - Department of Biotechnology, School of Bioengineering, SRM Institute of Science 
      and Technology, Kattankulathur 603 203, Tamil Nadu, India.
FAU - Ramkumar, Kunka Mohanram
AU  - Ramkumar KM
AD  - Department of Biotechnology, School of Bioengineering, SRM Institute of Science 
      and Technology, Kattankulathur 603 203, Tamil Nadu, India. Electronic address: 
      ramkumak@srmist.edu.in.
LA  - eng
PT  - Journal Article
DEP - 20231103
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (NF-E2-Related Factor 2)
RN  - 26R60S6A5I (pterostilbene)
RN  - 0 (Stilbenes)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Diabetes Mellitus, Experimental/complications
MH  - Macrophages/metabolism
MH  - *NF-E2-Related Factor 2/metabolism
MH  - Signal Transduction
MH  - *Wound Healing/drug effects
MH  - *Stilbenes/pharmacology/therapeutic use
MH  - *Diabetic Foot/drug therapy
OTO - NOTNLM
OT  - Diabetic Foot Ulcers
OT  - Fibroblast migration
OT  - Macrophage M2 response
OT  - Nuclear factor erythroid-2 related factor
OT  - Pterostilbene
OT  - Targeted therapies
COIS- Declaration of Competing Interest The authors have no relevant financial or 
      non-financial interests to disclose.
EDAT- 2023/11/06 00:41
MHDA- 2023/12/17 09:43
CRDT- 2023/11/05 18:13
PHST- 2023/06/29 00:00 [received]
PHST- 2023/08/31 00:00 [revised]
PHST- 2023/10/16 00:00 [accepted]
PHST- 2023/12/17 09:43 [medline]
PHST- 2023/11/06 00:41 [pubmed]
PHST- 2023/11/05 18:13 [entrez]
AID - S0161-5890(23)00208-0 [pii]
AID - 10.1016/j.molimm.2023.10.010 [doi]
PST - ppublish
SO  - Mol Immunol. 2023 Dec;164:17-27. doi: 10.1016/j.molimm.2023.10.010. Epub 2023 Nov 
      3.