title: Effect of a novel synthesized sulfonamido-based gallate-SZNTC on chondrocytes metabolism in vitro.
abstract: The ideal therapeutic agent for treatment of osteoarthritis (OA) should have not only potent anti-inflammatory effect but also favorable biological properties to restore cartilage function. Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on OA (Singh et al., 2003) [1]. However, GA has much weaker antioxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel sulfonamido-based gallate named sodium salt of 3,4,5-trihydroxy-N-[4-(thiazol-2-ylsulfamoyl)-phenyl]-benzamide (SZNTC) and analyzed its chondro-protective and pharmacological effects. Comparison of SZNTC with GA and sulfathiazole sodium (ST-Na) was also performed. Results showed that SZNTC could effectively inhibit the Interleukin-1 (IL-1)-mediated induction of metalloproteinase-1 (MMP-1) and MMP-3 and could induce the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), which demonstrated ability to reduce the progression of OA. SZNTC can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Expression of the collagen I gene was effectively down-regulated, revealing the inhibition of chondrocytes dedifferentiation by SZNTC. Hypertrophy that may lead to chondrocyte ossification was also undetectable in SZNTC groups. The recommended dose of SZNTC ranges from 3.91μg/ml to 15.64μg/ml, among which the most profound response was observed with 7.82μg/ml. In contrast, its source products of GA and ST-Na have a weak effect in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed SZNTC as a promising novel agent in the treatment of chondral and osteochondral lesions.
authors.affiliation: The Medical and Scientific Research Center, Guangxi Medical University, Nanning 530021, China; Research Center for Regenerative Medicine, Guangxi Medical University, Nanning 530021, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The Medical and Scientific Research Center, Guangxi Medical University, Nanning 530021, China.
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, China; Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.affiliation: School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, China.
authors.forename: Cui-Wu
authors.initials: CW
authors.lastname: Lin
authors.affiliation: School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, China; Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China.
authors.forename: Bu-Ming
authors.initials: BM
authors.lastname: Liu
authors.affiliation: The Medical and Scientific Research Center, Guangxi Medical University, Nanning 530021, China; Research Center for Regenerative Medicine, Guangxi Medical University, Nanning 530021, China. Electronic address: zhengli224@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Research Center for Regenerative Medicine, Guangxi Medical University, Nanning 530021, China.
authors.forename: Jin-Min
authors.initials: JM
authors.lastname: Zhao
mesh_terms: D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects*; D005707:Gallic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013432:Sulfathiazoles / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: C000594958:3,4,5-trihydroxy-N-(4-(thiazol-2-ylsulfamoyl)-phenyl)-benzamide; D001549:Benzamides; D013432:Sulfathiazoles; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D005707:Gallic Acid; D020781:Matrix Metalloproteinase 1
keywords: Chondro-protective effect; Gallate acid; Modification; Osteoarthritis; Pharmacological effect; Sulfathiazole sodium