Sangho Choi

Rhododendron album Blume extract inhibits TNF-α/IFN-γ-induced chemokine production via blockade of NF-κB and JAK/STAT activation in human epidermal keratinocytes

Rhododendron album Blume (RA) has traditionally been used as an herbal medicine and is considered to have anti‑inflammatory properties. It is a well‑known medicine for treatment of allergic or atopic diseases. In the present study, the biological effects of an RA methanol extract (RAME) on inflammation were investigated in tumor necrosis factor‑α (TNF‑α)/interferon‑γ (IFN‑γ)‑stimulated human keratinocytes. The present study aimed to investigate the potential mechanisms by which RAME inhibited TNF‑α/IFN‑γ‑induced expression of chemokines [thymus‑ and activation-regulated chemokine (TARC) and macrophage‑derived chemokine (MDC)] and cytokines [interleukin (IL)‑6 and IL‑8] through the nuclear factor‑κB (NF‑κB) pathway in human keratinocytes. The effects of RAME treatment on cell viability were investigated in TNF‑α/IFN‑γ‑stimulated HaCaT cells. The expression of TARC, MDC, IL‑6 and IL‑8 was assessed using reverse transcription‑quantitative polymerase chain reaction analysis or ELISA, and its effect on the inhibitory mitogen-activated protein kinase pathway was also studied using western blot analysis. TNF‑α/IFN‑γ induced the expression of IL‑6, IL‑8, TARC and MDC in a dose‑dependent manner through NF‑κB and Janus kinase/signal transducers and activators of transcription (JAK/STAT) activation. Notably, treatment with RAME significantly suppressed TNF-α/IFN-γ-induced expression of IL‑6, IL‑8, TARC, and MDC. In addition, RAME treatment inhibited the activation of NF‑κB and the JAK/STAT pathway in TNF‑α/IFN‑γ‑induced HaCaT cells. These results suggest that RAME decreases the production of chemokines and pro‑inflammatory cytokines by suppressing the NF‑κB and the JAK/STAT pathways. Consequently, RAME may potentially be used for treatment of atopic dermatitis.

3,5-Di-C-β-D-glucopyranosyl phloroacetophenone, a major component of Melicope ptelefolia, suppresses fibroblast activation and alleviates arthritis in a mouse model: Potential therapeutics for rheumatoid arthritis

Melicope ptelefolia has been traditionally used to treat rheumatism and fever. The present study aimed to investigate the therapeutic effect of 3,5-di-C-β-d-glucopyranosyl phloroacetophenone (βGP), a main component of M. ptelefolia, on rheumatoid arthritis (RA). A model of collagen-induced arthritis (CIA) was established in mice using the RAW 264.7 murine macrophage cell line and mouse embryonic fibroblasts (MEFs). The clinical scores of arthritis, swelling, histopathological findings, and micro-computed tomography in CIA mouse paws were assessed. The levels of anti-type II collagen antibody and cytokines were determined in the plasma and cell culture supernatant, respectively. Protein and gene expression levels were analyzed by western blot and reverse transcription-quantitative polymerase chain reaction analyses. βGP significantly decreased the gross arthritic scores of CIA mice and joint swelling, and decreased articular inflammation, cartilage degradation and bone erosion. However, βGP did not exert any effect on anti-type II collagen immunoglobulin G plasma levels or inflammatory cytokine expression in macrophages. βGP significantly suppressed the expression of interleukin-6 and leukemia inhibitory factor and decreased the phosphorylation of signal transducer and activator of transcription 3, and expression of receptor activator of nuclear factor-κB ligand in tumor necrosis factor-α-stimulated MEFs and in CIA mouse paws. Osteoclast-related gene expression was significantly reduced in CIA mouse paws. Taken together, βGP suppressed the development of RA by regulating the activation of synovial fibroblasts.

A new flavonoid from Stellera chamaejasme L., stechamone, alleviated 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in a murine model

ABSTRACT Stellera chamaejasme L. (family Thymelaeaceae), also known as ‘Langdu’, has been traditionally used to treat of skin‐related diseases, such as, psoriasis and skin ulcers. The aim of this study was to identify the biologically active component of S. chamaejasme and evaluate its preventive effects on IL‐4 and mast cell degranulation in RBL‐2H3 cells and on the development of atopic dermatitis (AD) in 2,4‐dinitrochlorobenzene (DNCB)‐treated SKH‐1 hairless mice. A novel flavonoid, genkwanin 5‐O‐xylosyl(1→2)glucoside (named stechamone), and three known compounds (umbelliferone, luteolin, and luteolin‐7‐O‐glucoside) were isolated from the aerial parts of S. chamaejasme using chromatographic methods. Of these four compounds, stechamone most potently inhibited IL‐4 production and mast cell degranulation in RBL‐2H3 cells. Topical application of 0.5% stechamone improved atopic skin symptoms, including, erythema (redness), pruritus (itching), exudation (weeping), excoriation (peeling), and lichenification (skin thickening) in DNCB‐treated AD mice by accelerating skin barrier recovery function and suppressing inflammatory cell infiltration. In addition, stechamone attenuated DNCB‐induced increases in IL‐4 (an inflammatory TH2 cytokine) expression and in serum IgE levels in our murine model of AD. DNCB induced AD‐like skin lesions, but treatment with stechamone exhibited strong anti‐atopic activity by regulating skin barrier function and reducing inflammatory responses. The results obtained suggest stechamone is a potential anti‐atopic agent and treatment for skin inflammatory diseases. HIGHLIGHTSA new flavonoid, stechamone, was isolated from Stellera chamaejasme.Stechamone exhibited potent IL‐4 inhibitory activity in RBL‐2H3 cells.2,4‐dinitrochlorobenzene was used to induce atopic dermatitis (AD) in hairless mice.Stechamone appeared to exert strong anti‐AD effects on DNCB‐stimulated mice.