Anti-inflammatory Actions of Herbal Formula Gyejibokryeong-Hwan Regulated by Inhibiting Chemokine Production and STAT1 Activation in HaCaT Cells

• Published in: Biological & pharmaceutical bulletin 2015/03/01, Vol.38(3), pp.425-434
• Main Authors: Jeong, Soo-Jin, Lim, Hye-Sun, Seo, Chang-Seob, Jin, Seong-Eun, Yoo, Sae-Rom, Lee, Nari, Shin, Hyeun-Kyoo
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Cell Line; chemokine; Chemokines - genetics; Chemokines - metabolism; Dermatitis - drug therapy; Dermatitis - metabolism; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - metabolism; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Gyejibokryeong-hwan; Humans; Inflammation - drug therapy; Inflammation - metabolism; Interferon-gamma - metabolism; keratinocyte; Keratinocytes - drug effects; Keratinocytes - metabolism; Phosphorylation; Phytotherapy; RNA, Messenger - metabolism; signal transducer and activator of transcription 1; Signal Transduction; Skin - drug effects; Skin - metabolism; skin inflammation; STAT1 Transcription Factor - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b14-00660

Gyejibokryeong-hwan (GJBRH; Keishi-bukuryo-gan in Japan and Guizhi Fuling Wan in China) is a traditional herbal formula comprising five medicinal herbs and is used to treat climacteric syndrome. GJBRH has been shown to exhibit biological activity against diabetes, diabetic nephropathy, atherosclerosis, ischemia, and cancer. However, there is no scientific evidence of its activities against skin inflammation, including atopic dermatitis. We used the HaCaT human keratinocyte cell line to investigate the effects of GJBRH on skin inflammation. No significant cytotoxicity was observed in cells treated with GJBRH up to a concentration of 1000 µg/mL. Exposure to the proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) significantly increased HaCaT cell production of the following chemokines: macrophage-derived chemokine (MDC)/CCL22; regulated on activation, normal T-cell expressed and secreted (RANTES)/CCL5; and interleukin-8 (IL-8). In contrast, GJBRH significantly reduced the production of MDC, RANTES, and IL-8 compared with control cells simulated with TNF-α and IFN-γ. Consistently, GJBRH suppressed the mRNA expression of MDC, RANTES, and IL-8 in TNF-α and IFN-γ-treated cells. Treatment with GJBRH markedly inhibited phosphorylation of signal transducer and activator of transcription 1 (STAT1) in HaCaT cells stimulated with TNF-α and IFN-γ. Our findings indicate that GJBRH impairs TNF-α and IFN-γ-mediated inflammatory chemokine production and STAT1 phosphorylation in keratinocytes. We suggest that GJBRH may be a potent therapeutic agent for inflammatory skin disorders.