Xuan Ma1, Meng Hao2, Ming Hui Zhang2, Ya Zeng2, Qing Qing Yang2, Lu Zhao2, Chen Yang Fan2, Zhi Hong Ji3, Ke Ao Li2, Zhi Jian Li4, Mirzat Maimaiti2, Ji Hong Nie5,6. 1. College of Pharmacy, Xinjiang Medical University, Xinjiang, Urumqi, 830011, China. 2. Xinjiang Qimu Medical Research Institute, Xinjiang, Urumqi, 830002, China. 3. Xinjiang Key Laboratory of Generic Technology of Traditional Chinese Medicine (Ethnic Medicine) Pharmacy, Xinjiang, Urumqi, 830002, China. 4. Xinjiang Uygur Medical Research Institute, Xinjiang, Urumqi, 830011, China. 5. Department of Pharmacy, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University, Xinjiang, Urumqi, 830011, China. xjnjh411@163.com. 6. Xinjiang Key Laboratory of Processing and Research of Traditional Chinese Medicine, Xinjiang, Urumqi, 830011, China. xjnjh411@163.com.
Abstract
BACKGROUND: Compound Turkish gall ointment (CTGO) has a long history of being widely used as a folk medicine in Xinjiang for the treatment of eczema. CTGO is currently in the pre-investigational new drug application stage, but its pharmacological mechanisms of action have not yet been clarified. METHODS: First, a sensitive and reliable ultra-high performance liquid chromatography-Q exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) technique was established. Second, an integrative strategy of network analysis and molecular docking based on identified and retrieved ingredients was implemented to investigate the potential targets and pathways involved in the treatment of eczema with CTGO. Finally, Sprague-Dawley (SD) rats with eczema were prepared to verify the predicted results. The skin conditions of the rats were observed, evaluated, and scored. Skin tissues were observed by hematoxylin-eosin (HE) staining, and the levels of serum interferon-γ (IFN-γ) and interleukin-4 (IL-4) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: A total of 29 compounds were identified. We found 38 active components and 58 targets for the treatment of eczema, which included 118 signaling pathways related to inflammation, immunity, and apoptosis. CTGO significantly improved the skin surface and histopathological characteristics of eczema-affected rats, downregulated the expression of IL-4, TLR4, NF-κB (p65), IL-1β, and TNF-α, and upregulated the expression level of IFN-γ. CONCLUSION: We predicted and validated our prediction that CTGO may be used to treat eczema by affecting the TLR4/NF-κB signaling pathway, which provides guidance for future experimental studies.
BACKGROUND: Compound Turkish gall ointment (CTGO) has a long history of being widely used as a folk medicine in Xinjiang for the treatment of eczema. CTGO is currently in the pre-investigational new drug application stage, but its pharmacological mechanisms of action have not yet been clarified. METHODS: First, a sensitive and reliable ultra-high performance liquid chromatography-Q exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) technique was established. Second, an integrative strategy of network analysis and molecular docking based on identified and retrieved ingredients was implemented to investigate the potential targets and pathways involved in the treatment of eczema with CTGO. Finally, Sprague-Dawley (SD) rats with eczema were prepared to verify the predicted results. The skin conditions of the rats were observed, evaluated, and scored. Skin tissues were observed by hematoxylin-eosin (HE) staining, and the levels of serum interferon-γ (IFN-γ) and interleukin-4 (IL-4) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: A total of 29 compounds were identified. We found 38 active components and 58 targets for the treatment of eczema, which included 118 signaling pathways related to inflammation, immunity, and apoptosis. CTGO significantly improved the skin surface and histopathological characteristics of eczema-affected rats, downregulated the expression of IL-4, TLR4, NF-κB (p65), IL-1β, and TNF-α, and upregulated the expression level of IFN-γ. CONCLUSION: We predicted and validated our prediction that CTGO may be used to treat eczema by affecting the TLR4/NF-κB signaling pathway, which provides guidance for future experimental studies.
Authors: Stephan Weidinger; Natalija Novak; Norman Klopp; Hansjörg Baurecht; Stefan Wagenpfeil; Lars Rummler; Johannes Ring; Heidrun Behrendt; Thomas Illig Journal: J Allergy Clin Immunol Date: 2006-06-06 Impact factor: 10.793
Authors: Julia K Gittler; Avner Shemer; Mayte Suárez-Fariñas; Judilyn Fuentes-Duculan; Kara J Gulewicz; Claire Q F Wang; Hiroshi Mitsui; Irma Cardinale; Cristina de Guzman Strong; James G Krueger; Emma Guttman-Yassky Journal: J Allergy Clin Immunol Date: 2012-08-27 Impact factor: 10.793