Hydrangea serrata Hot Water Extract and Its Major Ingredient Hydrangenol Improve Skin Moisturization and Wrinkle Conditions via AP-1 and Akt/PI3K Pathway Upregulation

Hydrangea serrata is a plant grown in Korea and Japan with a particular natural compound, hydrangenol. H. serrata has been researched for its anti-fungal properties, and ability to attenuate allergies and promote muscle growth. Its ability to reduce skin dryness is poorly understood. For that reason, we investigated whether H. serrata hot water extracts (Hs-WE) can moisturize keratinocytes. In clinical studies (Approval Code: GIRB-21929-NY and approval Date: 5 October 2021), skin wrinkles and skin moisturizing levels were improved in subjects applying 0.5% Hs-WE compared to the placebo group. We confirmed the components of Hs-WE from the LC/MS-MS analysis. Hs-WE and hydrangenol did not show cytotoxicity in HaCaT cells at all concentrations. Cell growth was also promoted by Hs-WE (5–20 µg/mL) and hydrangenol (15–60 µM) in a wound healing assay. Skin moisturizing factors were upregulated by the presence of Hs-WE or hydrangenol, and the hyaluronidases (HYAL) were inhibited at the mRNA level. Meanwhile, COL1A1 was increased by the presence of Hs-WE or hydrangenol. MAPK, AP-1, and Akt/PI3k signaling proteins, which are associated with cell proliferation and moisturizing factors, were increased by the administration of Hs-WE and hydrangenol. Has-1, 2, and 3 levels were enhanced via JNK when using the inhibitors of MAPK proteins and Hs-WE and hydrangenol, respectively. Taken together, Hs-WE could be used as cosmeceutical materials for improving skin conditions.