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.

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

“…Chondrocytes were separated from the joints of SD rats or volunteers by enzymatic digestion and cultured as described previously [29]. Briefly, the cartilage specimen was cut into pieces followed dissociation with 0.25% trypsin (Solabio, China) for 30 min, and then incubation with 2 mg/mL collagenase type II (Gibco, USA) in alpha-modified Eagle’s medium (α-MEM; Gibco, USA) for 4 h. After centrifugation at 1000 rpm for 5 min, the chondrocytes were cultured in Dulbecco’s MEM (DMEM) High Glucose (Gibco, USA) containing 10% (v/v) fetal bovine serum (FBS; Zhejiang Tianhang Biotechnology Ltd., China) and 1% (v/v) penicillin/streptomycin (Solarbio, China), and then incubated at 37°C under 5% CO 2 .…”

Chondroprotective and anti‐inflammatory effects of amurensin H by regulating TLR4/Syk/NF‐κB signals

“…DNA content was measured by a spectrofluorometer using Hoechst 33258 dye at 460 nm (emission) and 360 nm (excitation). A series of diluted chondrocytes (1 × 10 6 cells) were used as a control . The total intracellular sGAG secretion was qualitied spectrophotometrically at 525 nm using 1,9‐dimethylmethylene blue dye (Sigma) with chondroitin sulphate (Sigma) as a standard, and normalized to the total DNA content.…”

“…Chondrocytes at P1 were seeded on coverslips onside 6-well plates (2 × 10 4 /well) and treated by IL-1β for 48 hours, then fixed by 4% were used as a control. 24 The total intracellular sGAG secretion was qualitied spectrophotometrically at 525 nm using 1,9-dimethylmethylene blue dye (Sigma) with chondroitin sulphate (Sigma) as a standard, and normalized to the total DNA content.…”

Nitric Oxide Nanosensors for Predicting the Development of Osteoarthritis in Rat Model

“…Primary articular chondrocytes were isolated from the knee joints of the neonatal Sprague−Dawley (SD) rats (3−7 days old, Animal Resources Centre of Guangxi Medical University, Nanning, Guangxi, China) through collagenase digestion as described previously. 16 Briefly, cartilage was separated from the joints, sectioned into pieces, dissociated with 2 mg/mL collagenase type II (Gibco), and cultured in α-modified Eagle's medium (Gibco) containing 10% (v/v) fetal bovine serum (Gibco) and 1% (v/v) penicillin/streptomycin (Solarbio). Chondrocytes at passage 2 were used for further studies.…”