Cutaneous wound healing is accelerated by mechanical stretching, and treatment with
hyperforin, a major component of a traditional herbal medicine and a known
TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of
ATP-Ca2+ signaling in keratinocytes by
hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of
hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-
cyclodextrin- (HP-β-CD-) tetracapped
hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of
hyperforin/HP-β-CD on wound healing in HaCaT keratinocytes using live imaging to observe the
ATP release and the intracellular Ca2+ increase. In response to stretching (20%),
ATP was released only from the foremost cells at the
wound edge; it then diffused to the cells behind the
wound edge and activated the P2Y receptors, which caused propagating Ca2+ waves via
TRPC6. This process might facilitate
wound closure, because the Ca2+ response and wound healing were inhibited in parallel by various inhibitors of
ATP-Ca2+ signaling. We also applied
hyperforin/HP-β-CD on an ex vivo skin model of
atopic dermatitis and found that
hyperforin/HP-β-CD treatment for 24 h improved the stretch-induced Ca2+ responses and oscillations which failed in atopic skin.