Suppressive Effect of Huzhentongfeng on Experimental Gouty Arthritis: An In Vivo and In Vitro Study

Abstract

Background Huzhentongfeng (HZTF) is an extract from four Chinese medical herbs for treating gout. This study aims to evaluate its antigout activity and preliminary explore its mechanism in vivo and in vitro. Methods The rats were intragastrically administered with HZTF for 5 days and then injected 0.1 ml (10 mg) of MSU crystals to their joints for generating a gout model to analyze the paw volume and histopathology of joint synovial tissues of rats with different doses. We also investigated the antioxidant capacity of HZTF in vitro using indication including lipid peroxidation, DPPH·, and ABTS+ radical-scavenging capacity; besides, we used qRT-PCR to measure the effect of HZTF on interleukin (IL)-1β, caspase-1, NLRP3, and NQO1 expression in hydrogen peroxide-stimulated RAW264.7 macrophages and IL-1β, IL-6, and tumor necrosis factor (TNF)-α in MSU crystal-induced THP-1 monocytes. Confocal microscopy analysis was used to observe the dimerization of ASC adapter proteins. In addition, we also established quality standard of HZTF by using the high-performance liquid chromatography (HPLC) method. Results HZTF could significantly suppress the paw swelling and neutrophil infiltration induced by MSU intra-articular injection in rats compared with the control group. HZTF also showed inhibition effects of inflammatory cytokines (IL-1β, IL-6, and TNF-α) secretion at 25.00 and 50.00 μg/ml in MSU-induced THP-1 cells but showed no effects of IL-1β, IL-6, and TNF-α mRNA expression in MSU-induced THP-1 cells. Furthermore, confocal microscopy analysis showed that HZTF could prevent the oligomerization of ASC. Moreover, HZTF also showed effects in cell-free and cell-base tests of antioxidant capacity. Conclusion The results prove that HZTF possessed the potential preventive effect against gout arthritis, and the effect may be attributed to its preventing effect on neutrophil infiltration and proinflammatory cytokines secretion such as IL-1β, IL-6, and TNF-α which were caused by the activation of inflammasome.

Glucagon-Like Peptide-1 Receptor Regulates Macrophage Migration in Monosodium Urate-Induced Peritoneal Inflammation

“…As a common form of inflammatory arthritis caused by the deposition of uric acid in joints, gout can be very painful and debilitating (20,21). Accumulating evidence suggests that disease activity is strongly associated with the activation of macrophages.…”

Tongbixiao Pills Improve Gout by Reducing Uric Acid Levels and Inhibiting Inflammation

“… 24 Studies have confirmed that traditional Chinese medicine can further affect the deposition of MSU crystals by inhibiting the degradation of proteoglycans. 25 Crystal preparation was done according to the method described by Coderre, 26 , 27 with some adjustments. All reagents were prepared under pyrogen-free conditions.…”

Natural Products as a Novel Therapeutic Strategy for NLRP3 Inflammasome-Mediated Gout

“…HZTF also showed inhibited inflammatory cytokines (IL-1β, IL-6, and TNF-α) secretion in MSU-induced THP-1 cells and could prevent the oligomerization of ASC. Moreover, HZTF also demonstrated antioxidant capacity in cell-free and cell-base tests ( Wu et al, 2019 ).…”