Our previous report showed that Hydnocarpi Semen (HS) extract has
wound repair activity at
ulcer lesion in diabetic mice. In this study, fractions of
n-Hexane, ethylacetate (EtOAc), and
butanol (BuOH) from HS
crude extract were evaluated for their wound healing activity by using in vivo diabetic
ulcer models and in vitro acute
inflammation model. Although
n-Hexane and EtOAc fractions promote wound healing in mice with
ulcer, the BuOH fraction exhibited the most potent wound healing activity and the
wound area score significantly decreased
after treatment of BuOH fraction even at dose of 2 mg/kg. BuOH fraction stimulated macrophages to increase the production of
nitric oxide (NO) and TNF-α. The BuOH fraction also enhanced the production of TGF-β and
VEGF, which were involved in fibroblast activation and angiogenesis. The
mRNA expression and activation of MMP-9 were increased by three fractions and the activity was higher in BuOH fraction-treated group compared to the other groups. The mechanism that the HS helps to promote healing of diabetic
ulcer is possibly associated with the production of TNF-α, a proinflammatory
cytokine, as well as the secretion of
VEGF, TGF-β, and MMP-9, which were involved in proliferation of capillaries and fibroblasts. These results suggest that HS can be a new candidate material for the treatment of
wound in
skin ulcer.