Nymphoides peltata is widely used pharmacologically in Traditional Chinese Medicine and Ayurvedic medicine as a diuretic, antipyretic, or choleretic and to treat ulcers, snakebites, and edema. Previous studies have shown that phytochemicals from N. peltata have physiological activities such as anti-inflammatory, anti-tumor, and anti-wrinkle properties. Nevertheless, research on the anti-atopic dermatitis (AD) effect of N. peltata extract is limited. This study was undertaken to assess the in vitro and in vivo anti-atopic and antioxidant activities of a 95% EtOH extract of N. peltata roots (NPR). PI-induced RBL-2H3 cells and two typical hapten mice (oxazolone-induced BALB/c mice and 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice) were used to investigate the effect of NPR extract on AD. The expressions of AD-related inflammatory cytokines, skin-related genes, and antioxidant enzymes were analyzed by ELISA, immunoblotting, and immunofluorescence, and skin hydration was measured using Aquaflux AF103 and SKIN-O-MAT instruments. The chemical composition of NPR extract was analyzed using an HPLC-PDA system. In this study, NPR extracts were shown to most efficiently inhibit IL-4 in PI-induced RBL-2H3 cells and AD-like skin symptoms in oxazolone-BALB/c mice compared to its whole and aerial extracts. NPR extract markedly reduced DNCB-induced increases in mast cells, epidermal thickness, IL-4 and IgE expressions, and atopic-like symptoms in SKH-1 hairless mice. In addition, NPR extract suppressed DNCB-induced changes in the expressions of skin-related genes and skin hydration and activated the Nrf2/HO-1 pathway. Three phenolic acids (chlorogenic acid, 3,5-dicaffeoylquinic acid, and 3,4-dicaffeoylquinic acid) were identified by HPLC-PDA in NPR extract. The study shows that NPR extract exhibits anti-atopic activities by inhibiting inflammatory and oxidative stress and improving skin barrier functions, and indicates that NPR extract has potential therapeutic use for the prevention and treatment of AD.

The skin acts as a mechanical barrier that protects the body from the exterior environment, and skin barrier function is attributed to the stratum corneum (SC), which is composed of keratinocytes and skin lipids. Skin barrier homeostasis is maintained by a delicate balance between the differentiation and exfoliation of keratinocytes, and keratinocyte desquamation is regulated by members of the serine protease kalikrein (KLK) family and their endogenous inhibitor SPINK5/LEKTI (serine protease inhibitor Kazal type 5/lympho-epithelial Kazal-type-related inhibitor). Furthermore, SPINK5/LEKTI deficiency is involved in impaired skin barrier function caused by KLK over-activation. We sought to determine whether increased SPINK5/LEKTI expression ameliorates atopic dermatitis (AD) by strengthening skin barrier function using the ethanol extract of Lobelia chinensis (LCE) and its active compound, diosmetin, by treating human keratinocytes with UVB and using a DNCB-induced murine model of atopic dermatitis. LCE or diosmetin dose-dependently increased the transcriptional activation of SPINK5 promoter and prevented DNCB-induced skin barrier damage by modulating events downstream of SPINK5, that is, KLK, PAR2 (protease activated receptor 2), and TSLP (thymic stromal lymphopoietin). LCE or diosmetin normalized immune response in DNCB treated SKH-1 hairless mice as determined by reductions in serum immunoglobulin E and interleukin-4 levels and numbers of lesion-infiltrating mast cells. Our results suggest that LCE and diosmetin are good candidates for the treatment of skin barrier-disrupting diseases such as Netherton syndrome or AD, and that they do so by regulating SPINK5/LEKTI.

The activation and degranulation of immune cells play a pivotal role in allergic inflammation, a pathological condition that includes anaphylaxis, pruritus, and allergic march-related diseases. In this study, trifuhalol A, a phlorotannin isolated from Agarum cribrosum, inhibited the degranulation of immune cells and the biosynthesis of IL-33 and IgE in differentiated B cells and keratinocytes, respectively. Additionally, trifuhalol A suppressed the IL-33 and IgE-mediated activation of RBL-2H3 cells through the regulation of the TAK1 and MK2 pathways. Hence, the effect of trifuhalol A on allergic inflammation was evaluated using a Compound 48/80-induced systemic anaphylaxis mouse model and a house dust mite (HDM)-induced atopic dermatitis (AD) mouse model. Trifuhalol A alleviated anaphylactic death and pruritus, which appeared as an early-phase reaction to allergic inflammation in the Compound 48/80-induced systemic anaphylaxis model. In addition, trifuhalol A improved symptoms such as itching, edema, erythema, and hyperkeratinization in HDM-induced AD mice as a late-phase reaction. Moreover, the expression of IL-33 and thymic stromal lymphopoietin, inflammatory cytokines secreted from activated keratinocytes, was significantly reduced by trifuhalol A administration, resulting in the reduced infiltration of immune cells into the skin and a reduction in the blood levels of IgE and IL-4. In summarizing the above results, these results confirm that trifuhalol A is a potential therapeutic candidate for the regulation of allergic inflammation.

Nymphoides peltata has been widely used pharmacologically in traditional Chinese medicine to treat heat strangury and polyuria. The aim of this study was to isolate the bioactive components from N. peltata and evaluate their potential use as antioxidant and anti-wrinkle agents. Phytochemical investigation of the methanolic extract of N. peltata roots led to the isolation of 15 compounds (1–15), which were structurally determined as α-spinasterol (1), 3-O-β-D-glucopyranosyl-oleanolic acid 28-O-β-D-glucuronopyranoside (2), 4-hydroxybenzoic acid (3), protocatechuic acid (4), vanillic acid (5), p-coumaric acid (6), caffeic acid (7), ferulic acid (8), neochlorogenic acid (neo-CQA) (9), chlorogenic acid (CQA) (10), cryptochlorogenic acid (crypto-CQA) (11), isochlorogenic acid B (3,4-DCQA) (12), isochlorogenic acid A (3,5-DCQA) (13), isochlorogenic acid C (4,5-DCQA) (14), and 3,4,5-tri-O-caffeoylquinic acid (TCQA) (15). Of these 15 compounds, compound 2 was a new oleanane saponin, the chemical structure of which was characterized by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data and high-resolution electrospray ionization mass spectrometry (HRESIMS), as well as chemical reaction. Biological evaluation of the isolated compounds revealed that 3,4,5-tri-O-caffeoylquinic acid (TCQA) significantly improved Nrf2 levels in an Nrf2–ARE reporter HaCaT cell screening assay. TCQA was found to potently inhibit the Nrf2/HO-1 pathway and to possess strong anti-wrinkle activity by modulating the MAPK/NF-κB/AP-1 signaling pathway and thus inhibiting MMP-1 synthesis in HaCaT cells exposed to UVB. Our results suggest that TCQA isolated from N. peltata might be useful for developing effective antioxidant and anti-wrinkle agents.

7-O-methylluteolin (7-ML) is a flavonoid isolated from the aerial parts of Wikstroemia ganpi (W. ganpi). We describe the anti–atopic dermatitis (AD) effects of 7-ML in tert-butyl hydroperoxide (tBHP)-induced HepG2 cells and 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice. Results demonstrated that 7-ML dose-dependently inhibited the activation of Nrf2 (nuclear factor-erythroid 2-related factor 2) in tBHP-induced HepG2 cells. 7-ML applied topically to our DNCB-induced mouse model upregulated the antioxidant protein expression (phosphorylated Nrf2 (pNrf2), Nrf2, and heme oxygenase-1 (HO-1)) in skin tissues, improved epidermal thickness, and reduced mast cell infiltration into the skin. In addition, 7-ML reduced the serum levels of immunoglobulin E (IgE) and interleukin-4 (IL-4) and improved skin barrier functions. These results suggest that 7-ML should be considered a novel antioxidant and anti-AD agent.

The genus Daphnopsis has been traditionally used as a purgative, diuretic, stimulant, and psoriasis treatment. In this study, the anti-AD (atopic dermatitis) activities of the Daphnopsis costaricensis EtOH extract (DCE) were investigated in an oxazolone (OX)-induced mouse model of AD, and the anti-inflammatory effects of its active compounds were confirmed in PI-sensitized or IgE/DNP-BSA-sensitized RBL-2H3 cells. DCE improved the symptoms of OX-induced inflammatory dermatitis (swelling, erythema, and increased ear thickening) in OX-induced BALB/c mice ears and reduced epidermal thickness and mast cell infiltration. Eleven flavonoid compounds were isolated from DCE, and two compounds (7,8-dimethoxyflavone and 7,2’-dimethoxyflavone) significantly inhibited IL-4 overexpression in PI-induced RBL-2H3 cells and mast cell degranulation in IgE + DNP-BSA-induced RBL-2H3 cells. Our study indicates that DCE and two compounds (7,8-dimethoxyflavone and 7,2’-dimethoxyflavone) might effectively improve inflammatory and atopic skin symptoms.