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The juice of  Ageratum houstonianum  is used in folk medicine as an external wound healing aid for skin injuries. However, the active component of  A. houstonianum  and its mode of action in skin wound healing has not been investigated. This study was conducted to investigate the effect of  A. houstonianum  ethanolnolic extract (AHE) on the expression of aquaporin-3 (AQP3), an integral membrane protein for water and glycerol transport in keratinocytes, and to identify the structure of the  A. houstonianum  bioactive compound. Here, we show that AHE increased  AQP3  gene expression at the transcriptional level through the p38 MAPK pathway in HaCaT cells. Furthermore, AHE ameliorated suppression of  AQP3  expression caused by ultraviolet B (UVB) irradiation. Agerarin (6,7-dimethoxy-2,2-dimethyl-2 H -chromene) was identified as the bioactive compound responsible for the up-regulation of  AQP3  expression by enhancing the expression of the transcription factor circadian locomotor output cycles kaput ( CLOCK ). In conclusion, agerarin is a bioactive compound in AHE responsible for CLOCK-mediated  AQP3  expression in keratinocytes.

Agerarin, identified from Ageratum houstonianum, stimulates circadian CLOCK-mediated aquaporin-3 gene expression in HaCaT keratinocytes