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Chicoric acid attenuates tumor necrosis factor-α-induced inflammation and apoptosis via the Nrf2/HO-1, PI3K/AKT and NF-κB signaling pathways in C28/I2 cells and ameliorates the progression of osteoarthritis in a rat model

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机构: [1]Key Laboratory of Drug-Targeting and Drug Delivery System of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China [2]School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China [3]Department of Pharmacy, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu 610041, China
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关键词: Chicoric acid Osteoarthritis Inflammation Apoptosis Nrf2

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Osteoarthritis (OA) is the most common arthritis, and is characterized by inflammation and cartilage degradation. Chicoric acid (CA), a bioactive caffeic acid derivative isolated from the root of Taraxacum mongolicumHand. - Mazz., has been reported to have anti-inflammatory effects. However, the therapeutic effects of CA on chondrocyte inflammation remain unknown. Our study aimed to explore the effect of CA on OA both in vivo and in vitro. In vitro, CA treatment significantly suppressed the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and IL-12 in tumor necrosis factor alpha (TNF-α)-induced human C28/I2 chondrocytes. Moreover, CA attenuated TNF-α induced degradation of the extracellular matrix (ECM) by upregulating the expression of collagen Ⅱ and aggrecan, and downregulating ADAMTS-5 and matrix metalloproteinases (MMPs). Additionally, CA treatment inhibited apoptosis in C28/I2 cells by upregulating of Bcl-2 levels, downregulating Bax and ROS levels, and activating the Nrf2/HO-1 pathway. Mechanistically, CA exerted an anti-inflammatory effect by inhibiting the PI3K/AKT and NF-κB signaling pathways, enhancing Nrf-2/HO-1 to limit the activation of NF-κB. In vivo experiments also proved the therapeutic effects of CA on OA in rats. These findings indicate that CA may become a new drug for the treatment of OA.Copyright © 2022 Elsevier B.V. All rights reserved.

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大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 药学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 药学
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第一作者机构: [1]Key Laboratory of Drug-Targeting and Drug Delivery System of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China [2]School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China
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