title: Chondro-Protective and Antiarthritic Effects of Sulfonamido-Based Gallate-ZXHA-TC in Vitro and in Vivo.
abstract: The effects of gallic acid (GA) on arthritis are limited by weak antioxidant effects and inferior biological properties of GA. We recently described a new series of synthesized GA derivatives by coupling with sulfonamides. Among these analogs, a novel compound synthesized from GA and sulfadimoxine (SDM) named ZXHA-TC exhibited the most robust anti-inflammatory potential. In this current study, the chondro-protective and antiarthritic effects of ZXHA-TC were investigated both in vitro and in vivo. In the in vitro study, ZXHA-TC exerted chondro-protective effects as evidenced by promoting cell proliferation and the maintaining of the phenotype of articular chondrocytes treated with interleukin-1-beta (IL-1β). The potential of ZXHA-TC to slow the progress of osteoarthritis (OA) was suggested by a reduction in matrix metalloproteinases (MMPs) and the up-regulation of the tissue inhibitor of metalloproteinase-1 (TIMP-1). In a rabbit anterior cruciate ligament transaction (ACLT) model of OA, ZXHA-TC exerted a protective effect on arthritis as assessed by macroscopic scores, histological, qRT-PCR, and immunohistochemical analyses. The effects of ZXHA-TC on inhibiting the production of inflammatory mediators in OA may be mediated partly by the suppression of the PI3K/AKT pathway or MAPK cascades, leading to NF-κB inactivation. Thus, this study indicates that ZXHA-TC may be developed as a potential therapeutic agent for OA.
authors.affiliation: Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Guangxi Medical University , Nanning, 530021, China.|Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University , Nanning, 530021, China.|Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University , Nanning, 530021, China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Cell Biology & Genetics, School of Premedical Sciences, Guangxi Medical University , Nanning, Guangxi 530021, China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Guangxi Institute of Traditional Medical and Pharmaceutical Sciences , Nanning, 530022, China.|School of Chemistry and Chemical Engineering, Guangxi University , Nanning, 530004, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.affiliation: Guangxi Institute of Traditional Medical and Pharmaceutical Sciences , Nanning, 530022, China.
authors.forename: Buming
authors.initials: B
authors.lastname: Liu
authors.affiliation: School of Chemistry and Chemical Engineering, Guangxi University , Nanning, 530004, China.
authors.forename: Cuiwu
authors.initials: C
authors.lastname: Lin
authors.affiliation: Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Guangxi Medical University , Nanning, 530021, China.|Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University , Nanning, 530021, China.|Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University , Nanning, 530021, China.|The Medical and Scientific Research Center, Guangxi Medical University , Nanning, 530021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Guangxi Medical University , Nanning, 530021, China.|Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University , Nanning, 530021, China.|Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University , Nanning, 530021, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D015536:Down-Regulation; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000627:therapeutic use*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use*; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C000622577:ZXHA-TC compound; D005707:Gallic Acid