Cudratricusxanthone A from Cudrania tricuspidata suppresses pro-inflammatory mediators through expression of anti-inflammatory heme oxygenase-1 in RAW264.7 macrophages |
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| Affiliation: | 1. Institute for Radiological Imaging Science, Wonkwang University, Iksan 570-749, Republic of Korea;2. College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea;1. Lendület Evolutionary Ecology Research Group, Plant Protection Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary;2. Dipartimento di Biologia, Università di Padova, Padova, Italy;3. Konrad Lorenz Institute of Ethology, Department of Integrative Biology and Evolution, University of Veterinary Medicine of Vienna, Vienna, Austria;1. Department of Psychology, University of British Columbia, Vancouver, BC, Canada;2. Department of Zoology, University of British Columbia, Vancouver, BC, Canada;3. Graduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada;4. Brain Research Centre, University of British Columbia, Vancouver, BC, Canada;1. Laboratory of Physiology of Nutrition and Development, Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil;2. Laboratory of Cell Culture, Department of Histology and Embryology, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil;1. Key Laboratory of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Ministry of Education, Nanchang 330004, China;2. Department of Pharmaceutical and Biological Engineering, Sichuan University, Chengdu 610065, China;1. Dept. of Hematology/Oncology, University Medical Center Göttingen, 37099 Göttingen, Germany;2. Dept. of Medical Statistics, University Medical Center Göttingen, 37099 Göttingen, Germany;3. Dept. of Developmental Biochemistry, University Medical Center Göttingen, 37099 Göttingen, Germany |
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| Abstract: | Cudratricusxanthone A (CTXA), isolated from the roots of Cudrania tricuspidata Bureau (Moraceae) has an isoprenylated xanthone skeleton that is known to exert a variety of biological activities. In the present study, we demonstrated that CTXA inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide (NO) synthase (iNOS) expression, and thereby reduced COX-2-derived prostaglandin E2 (PGE2) and iNOS-derived NO production in lipopolysaccharide (LPS)-stimulated macrophages. Similarly, CTXA suppressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production. Moreover, CTXA inhibited the induced phosphorylation and degradation of IκB-α as well as the LPS-induced increase in p65 in the nuclear fraction of macrophages. CTXA also induced heme oxygenase-1 (HO-1) expression and increased heme oxygenase (HO) activity in RAW264.7 macrophages. We also demonstrated that the effects of CTXA on LPS-induced PGE2, NO, TNF-α, and IL-1β production were partially reversed by the HO-1 inhibitor tin protoporphyrin, suggesting that CTXA-induced HO-1 expression was partly responsible for the resulting anti-inflammatory effects of the drug. Thus CTXA was shown to be an effective HO-1 inducer, capable of inhibiting macrophage-derived pro-inflammatory mediators. |
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