Anti-Allergic and Anti-Inflammatory Effects of Kuwanon G and Morusin on MC/9 Mast Cells and HaCaT Keratinocytes

Abstract

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. The use of immunomodulatory corticosteroids in AD treatment causes adverse side effects. Therefore, novel natural anti-inflammatory therapeutics are needed. The aim of the present study was to investigate the anti-allergic and anti-inflammatory activities of kuwanon G and morusin. To investigate the effect of kuwanon G and morusin on skin inflammation, enzyme-linked immunosorbent assays (ELISA) to quantitate secreted (RANTES/CCL5), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were performed, followed by Western blotting to measure the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and nuclear transcription factor-κB (NF-κB) p65 in tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-stimulated HaCaT keratinocytes. In order to evaluate the anti-allergic effects, ELISA to quantify histamine and leukotriene C4 (LTC4) production and Western blotting to measure 5-lipoxygenase (5-LO) activation were performed using PMA and A23187-stimulated MC/9 mast cells. Kuwanon G reduced the release of RANTES/CCL5, TARC/CCL17, and MDC/CCL22 via down-regulation of STAT1 and NF-κB p65 signaling in TNF-α and IFN-γ-stimulated HaCaT keratinocytes. Kuwanon G also inhibited histamine production and 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Morusin inhibited RANTES/CCL5 and TARC/CCL17 secretion via the suppression of STAT1 and NF-κB p65 phosphorylation in TNF-α and IFN-γ-stimulated HaCaT keratinocytes, and the release of histamine and LTC4 by suppressing 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Kuwanon G and morusin are potential anti-inflammatory mediators for the treatment of allergic and inflammatory skin diseases such as AD.

Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G

“…to 3.71 µM; kuwanon G: ≤ 3.13 µg/mL equiv. to 4.52 µM) are lower than the ones found to be cytotoxic in human normal cells (morusin: IC 50 = 9.48 µg/mL in human normal mammary epithelial cells (MCF-10A), IC 50 = 12.45 µg/mL in human normal liver cells (LO2), no alteration in viability of HaCaT keratinocytes and MC/9 mast cells at concentrations of up to 5 µM; kuwanon G: no alteration in viability of HaCaT keratinocytes and MC/9 mast cells at concentrations up to 20 and 10 µM, respectively) ( Gao et al, 2017 , Jin et al, 2019 , Li et al, 2015 ). Unfortunately, the isolation of pure phytochemicals from plant material is a complex, time-consuming, costly and low-yield process.…”

The Beneficial Effects of Morusin, an Isoprene Flavonoid Isolated from the Root Bark of Morus

“…Many studies have confirmed the anti-inflammatory capacity of morusin in different in vivo and in vitro contexts—(1) Morusin treatment inhibits secretion of cytokines such as CCL5 and CCL17 in TNFα- and IFN-γ-stimulated keratinocytes and also inhibits the release of histamine and LTC 4 in A23187-stimulated MC/9 mast cells [ 24 ]. (2) Morusin treatment inhibits PMA-induced MUC5AC production in a human pulmonary mucoepidermoid cell line NCI-H292, showing prominent anti-inflammatory effects in vitro [ 25 ].…”

“…Although the mechanism underlying iNOS regulation by morusin has not been directly addressed yet, it may be recapitulated by the NF-κB pathway, a key intracellular pathway that governs pro-inflammatory signaling in multiple ways including reactive oxygen species (ROS) production, cytokine production and immune cell activation [ 32 , 33 ]. Furthermore, morusin suppressed STAT1-mediated cytokine secretion in TNF-α- and IFN-γ-stimulated keratinocytes [ 24 ]. Indeed, many studies have already emphasized that the versatile effects of morusin may be associated with downregulation of the NF-κB pathway and its crosstalk with STAT1, STAT3 and Wnt/β-catenin signaling [ 24 , 25 , 26 , 29 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

<p>Morusin Ameliorates IL-1β-Induced Chondrocyte Inflammation and Osteoarthritis via NF-κB Signal Pathway</p>

“…In fact, Morusin was believed to reduce the inflammatory reaction in several diseases. 17,36,37 We, therefore, explored whether it possessed anti-inflammatory properties in osteoarthritis. Our data demonstrate that Morusin significantly inhibits the IL-1β-induced inflammatory reaction in chondrocytes; potentially via suppression of the NF-κB signaling pathway.…”

“…15 This compound has been found to engage in a myriad of biological functions, including anti-inflammatory, antioxidative and antitumor activities. [16][17][18] For instance, Morusin was reported to attenuate LPS-induced proinflammatory responses in RAW264.7 cells. 19 Additionally, an in vivo study revealed that Morusin ameliorates 2, 4, 6-trinitrobenzene sulfonic acid sodium salt (TNBS)induced colitis in rats.…”