In vitro assessment of the anti-inflammatory and skin-moisturizing effects of Filipendula palmata (Pall.) Maxim. On human keratinocytes and identification of its bioactive phytochemicals.

The meadowsweet family (genus Filipendula) includes about 30 species, which have been traditionally used in folk medicine to treat various inflammatory diseases. Particularily, F. palmata (Pall.) Maxim. (Siberian meadowsweet) were traditionally and widely used as an ethnic herb in the Oroqen application. Limited studies have been documented on most species, except for two main species, F. ulmaria (L.) Maxim. and F. vulgaris Moench. Thus, this study aimed to investigate the anti-inflammatory and skin-moisturizing effects of 70% ethanolic extract (FPE) of F. palmata on human epidermal keratinocytes. HaCaT keratinocytes were treated with FPE under different conditions. Quantitative real time-PCR, enzyme-linked immunosorbent assay, western blotting methods were used to evaluate the effect and molecular mechanism of the cells treated with FPE. The bioactive compounds in FPE, which are responsible for biological activities, was explored using mass spectrometric analysis. FPE did not show a cytotoxic effect on the cells at concentrations below 200 μg/mL. FPE significantly suppressed the intracellular reactive oxygen species and mitochondrial superoxide of inflamed HaCaT cells induced by tumor necrosis factor-α and interferon-γ (T + I) and inflammatory chemokine genes and proteins, such as CC chemokine ligands (CCL5, CCL17, and CCL27) and CXC chemokine ligand (CXCL8). These anti-inflammatory activities of FPE were mediated by the downregulation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. In normal HaCaT cells, FPE significantly promoted the production of hyaluronic acid (HA) via the downregulation of hyaluronidase (HYAL1 and HYAL2) and upregulation of hyaluronic acid synthase (HAS1, HAS2, and HAS3) genes, and these effects seemed to be associated with the PI3K/Akt/NF-κB signaling. Ultraperformance liquid chromatography-tandem mass spectrometry indicated that FPE contains four flavonoids, including (+)-catechin, miquelianin, scutellarin, and quercitrin, as its major phytochemicals. Finally, we demonstrated that miquelianin and quercitrin contribute partially to the anti-inflammatory and HA-producing activity of FPE without cytotoxic effects on HaCaT cells. Our findings suggest that topical applications of FPE can be utilized as an alternative therapy for treating skin inflammation. Additionally, our findings serve as a reference in applying FPE as a functional ingredient to treat inflammatory skin diseases and promote skin health.

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