Affiliations: Department of Pathology, Uniformed Services University
of the Health Sciences, Bethesda, MD 20814, USA | Armed Forces Medical College, Pune, India
Note: [] Corresponding author: Radha K. Maheshwari, Ph.D., Department of
Pathology, Uniformed Services University of the Health Sciences, 4301 Jones
Bridge Road, Bethesda, MD 20814, USA. Tel.: +1 301 295 3394/3497; Fax: +1 301
295 1640; E-mail: rmaheshwari@usuhs.mil
Abstract: Wound healing is a highly ordered process, requiring complex and
coordinated interactions involving peptide growth factors of which transforming
growth factor-beta (TGF-β) is one of the most important.
Nitric oxide is also an important factor in healing and its production is
regulated by inducible nitric oxide synthase (iNOS). We have earlier shown that
curcumin (diferuloylmethane), a natural product obtained from the plant
Curcuma longa, enhances cutaneous wound healing in normal and diabetic rats.
In this study, we have investigated the effect of curcumin treatment by topical
application in dexamethasone-impaired cutaneous healing in a full thickness
punch wound model in rats. We assessed healing in terms of histology,
morphometry, and collagenization on the fourth and seventh days post-wounding
and analyzed the regulation of TGF-β1, its receptors
type I (tIrc) and type II (tIIrc) and iNOS. Curcumin significantly accelerated
healing of wounds with or without dexamethasone treatment as revealed by a
reduction in the wound width and gap length compared to controls. Curcumin
treatment resulted in the enhanced expression of TGF-β1
and TGF-β tIIrc in both normal and impaired healing
wounds as revealed by immunohistochemistry. Macrophages in the wound bed showed
an enhanced expression of TGF-β1 mRNA in curcumin
treated wounds as evidenced by in situ hybridization. However, enhanced
expression of TGF-β tIrc by curcumin treatment observed
only in dexamethasone-impaired wounds at the 7th day post-wounding. iNOS levels
were increased following curcumin treatment in unimpaired wounds, but not so in
the dexamethasone-impaired wounds. The study indicates an enhancement in
dexamethasone impaired wound repair by topical curcumin and its differential
regulatory effect on TGF-β1, it's receptors and iNOS in
this cutaneous wound-healing model.
