title: A Novel Synthesized Sulfonamido-Based Gallate-JEZ-C as Potential Therapeutic Agents for Osteoarthritis.
abstract: Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on osteoarthritis (OA). However, GA has much weaker anti-oxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel compound named JEZ-C and analyzed its anti-arthritis and chondro-protective effects. Comparison of JEZ-C with its sources i.e. GA and Sulfamethoxazole (SMZ) was also performed. Results showed that JEZ-C could effectively inhibit the IL-1-mediated induction of MMP-1 and MMP-13 and could induce the expression of TIMP-1, which demonstrated its ability to reduce the progression of OA. JEZ-C 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. Meanwhile, expression of the collagen I gene was effectively downregulated, revealing the inhibition of chondrocytes dedifferentiation by JEZ-C. Hypertrophy that may lead to chondrocyte ossification was also undetectable in JEZ-C groups. The recommended dose of JEZ-C ranges from 6.25×10-7 μg/ml to 6.25×10-5 μg/ml, among which the most profound response was observed with 6.25×10-6 μg/ml. In contrast, its source products of GA and SMZ have a weak effect not only in the inhibition of OA but also in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed JEZ-C 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.
authors.forename: Shixiu
authors.initials: S
authors.lastname: Wei
authors.affiliation: The Medical and Scientific Research Center, Guangxi Medical University, Nanning, 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China; Guangxi Colleges and Universities Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zou
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: Cuiwu
authors.initials: C
authors.lastname: Lin
authors.affiliation: Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning, 530022, China.
authors.forename: Buming
authors.initials: B
authors.lastname: Liu
authors.affiliation: The Medical and Scientific Research Center, Guangxi Medical University, Nanning, 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China; Guangxi Colleges and Universities Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: The Medical and Scientific Research Center, Guangxi Medical University, Nanning, 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China; Guangxi Colleges and Universities Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects; D005707:Gallic Acid / Q000008:administration & dosage* / Q000138:chemical synthesis; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D013420:Sulfamethoxazole / Q000008:administration & dosage* / Q000138:chemical synthesis; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; C000606108:JEZ-C compound; D013449:Sulfonamides; D005707:Gallic Acid; D013420:Sulfamethoxazole