Topical Application of Cha-Koji, Green Tea Leaves Fermented with Aspergillus Luchuensis var Kawachii Kitahara, Promotes Acute Cutaneous Wound Healing in Mice

“Koji” is one of the most well-known probiotic microorganisms in Japan that contribute to the maintenance of human health. Although the beneficial effects of some probiotics on ulcer healing have been demonstrated, there have been no reports on the wound healing effects of koji to date. In the present study, we investigated the effects of “cha-koji”, green tea leaves fermented with Aspergillus luchuensis, on cutaneous wound healing, using a linear incision wound mouse model. Topical application of autoclave-sterilized cha-koji suspension on the dorsal incision wound area healed the wound significantly faster and, notably, with less scarring than did the green tea or the control distilled water treatment. Further in vitro experiments revealed that the accelerated effects of cha-koji could be attributed to its increased anti-bacterial activity, enhanced epidermal cell proliferation and migration, augmented expression of the anti-inflammatory cytokine transforming growth factor-β1, reduced expression of inflammatory cytokine interleukin-6 in macrophages, and decreased endoplasmic reticulum stress. In addition, we conducted a skin sensitizing potential test, which revealed that cha-koji had no adverse effects that posed a sensitizing risk. Thus, cha-koji may have a potent therapeutic effect on cutaneous wound healing, opening up a new avenue for its clinical application as a medical aid.