title: Traditional herbal formula Jakyakgamcho-tang (Paeonia lactiflora and Glycyrrhiza uralensis) impairs inflammatory chemokine production by inhibiting activation of STAT1 and NF-κB in HaCaT cells.
abstract: A traditional herbal formula Jakyakgamcho-tang (JYGCT; Paeonia lactiflora and Glycyrrhiza uralensis) has been used for treatment of backache, muscle pain, acute abdominal pain, neuralgia, bronchial asthma, and painful peripheral neuropathy in Oriental medicine. We report on our experiments using the HaCaT human keratinocyte cell line showing that a traditional herbal formula JYGCT has inhibitory effects on inflammatory responses in skin. Stimulation with tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) caused a significant increase in the production of the following chemokines: thymus- and activation-regulated chemokine (TARC)/CCL17; macrophage-derived chemokine (MDC)/CCL22; regulated on activation, normal T-cell expressed and secreted (RANTES)/CCL5; and interleukin-8 (IL-8) in HaCaT cells. By contrast, treatment with JYGCT extract significantly reduced the production of TARC, MDC, RANTES, and IL-8, but caused no cytotoxicity, compared with TNF-α and IFN-γ-treated control cells. Consistently, JYGCT extract downregulated the mRNA expression of TARC, MDC, RANTES, and IL-8 induced by TNF-α and IFN-γ in a dose-dependent manner. In addition, TNF-α and IFN-γ markedly increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and the nuclear translocation of nuclear factor kappa B (NF-κB) in HaCaT cells. By contrast, TNF-α and IFN-γ-induced activation of STAT1 and NF-κB activation was inhibited by JYGCT treatment in a dose-dependent manner. Our data indicate that JYGCT attenuates TNF-α and IFN-γ-mediated chemokine production by targeting the STAT1 and NF-κB signalling in keratinocytes. Our findings suggest that JYGCT has potential as a therapeutic drug candidate for the treatment of inflammatory skin diseases.
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea; Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Chungcheongbuk-do 361-951, Republic of Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Lim
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Chang-Seob
authors.initials: CS
authors.lastname: Seo
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea; Division of Pharmacology, Pusan National University School of Korean Medicine, Yangsan City, Gyeongnam 626-870, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Seong-Eun
authors.initials: SE
authors.lastname: Jin
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Sae-Rom
authors.initials: SR
authors.lastname: Yoo
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea. Electronic address: hkshin@kiom.re.kr.
authors.forename: Hyeun-Kyoo
authors.initials: HK
authors.lastname: Shin
mesh_terms: D002460:Cell Line; D054414:Chemokine CCL17 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D029882:Glycyrrhiza uralensis / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D029596:Paeonia / Q000737:chemistry; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C106230:CCL17 protein, human; C515482:CCL22 protein, human; C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018946:Chemokine CCL5; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016209:Interleukin-8; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; C499903:jackyakamcho-tang; D007371:Interferon-gamma
keywords: Chemokine; Glycyrrhiza uralensis; Inflammation; Jakyakgamcho-tang; Paeonia lactiflora; STAT1/NF-κB