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Grape polyphenols and propolis mixture inhibits inflammatory mediator release from human leukocytes and reduces clinical scores in experimental arthritis
Affiliation:1. Univ. de Bordeaux, Laboratoire d‘Immunologie, INSERM U1035, Faculté de Pharmacie, F-33076 Bordeaux, France;2. Univ. de Bordeaux, ISVV, Polyphénols Biotech, Groupe d‘Etude des Substances Végétales à Activité Biologique, EA 3675, F-33140 Villenave d‘Ornon, France;1. Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Mexico;2. Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., Mexico;1. Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan;2. Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan;1. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 001, UP, India;2. Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226 001, UP, India;1. Malaysian Institute of Pharmaceuticals and Nutraceuticals, Ministry of Science, Technology and Innovation, Malaysia;2. Universiti Teknologi MARA Negeri Sembilan, Kampus Kuala Pilah, Beting, 72000 Kuala Pilah, Negeri Sembilan, Malaysia;3. Universiti Sains Malaysia, Penang, Malaysia;4. Forest Research Institute Malaysia, 52109 Kepong, Selangor, Malaysia;1. Department of Geriatric Gastroenterology, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China;2. Department of Respiratory Medicine, the Affiliated Nanjing Children Hospital to Nanjing Medical University, Nanjing 210029, PR China;3. Department of Pharmacy, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China;4. Department of Oncology, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China;1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China;2. Department of Medicinal Chemistry and Pharmaceutical Analysis, Logistics College of Chinese People′s Armed Police Forces, Tianjin 300162, China
Abstract:Polyphenols from red fruits and bee-derived propolis (PR) are bioactive natural products in various in vitro and in vivo models. The present study shows that hematotoxicity-free doses of grape polyphenols (GPE) and PR differentially decreased the secretion of pro-inflammatory cytokines from activated human peripheral blood leucocytes. While GPE inhibited the monocytes/macrophage response, propolis decreased both monokines and interferon γ (IFNγ) production. When used together, their distinct effects lead to the attenuation of all inflammatory mediators, as supported by a significant modulation of the transcriptomic profile of pro-inflammatory genes in human leukocytes. To enforce in vitro data, GPE + PR were tested for their ability to improve clinical scores and cachexia in chronic rat adjuvant-induced arthritis (AA). Extracts significantly reduced arthritis scores and cachexia, and this effect was more significant in animals receiving continuous low doses compared to those receiving five different high doses. Animals treated daily had significantly better clinical scores than corticoid-treated rats. Together, these findings indicate that the GPE + PR combination induces potent anti-inflammatory activity due to their complementary immune cell modulation.
Keywords:Inflammation  Grape polyphenols  Anthocyanins  Propolis  Rheumatoid arthritis  Macrophage
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