Qin Yu-Yao, Qin Zi-Yi, Liang Tao, Qin Dong-Er, Hua Sheng-Yi, Tan Ming-Hui, Guo Shun, Yang Fan, Shi Le, Yu Yun, Zhang Guang-Ji
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Emergency Room, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Immunobiology. 2025 Jul;230(4):152918. doi: 10.1016/j.imbio.2025.152918. Epub 2025 May 29.
Phellodendrine, a primary bioactive constituent of Phellodendron chinense Schneid (PCS), is crucial in its pharmacological profile. Phellodendrine exhibits potent anti-nephritic properties and demonstrates a marked inhibitory effect on the cellular immune response. However, the effects of phellodendrine on proteoglycan depletion and cartilage degeneration in gouty arthritis remain insufficiently understood. Therefore, the objective of this study is to elucidate the therapeutic potential and underlying mechanisms of phellodendrine chloride (PC) in the treatment of gouty arthritis.
A monosodium urate (MSU)-induced arthritis model in rats, along with a peritonitis model in mice, was developed, in combination with a chondrocyte model. Neutrophil proportions were quantified using flow cytometry. The expression levels of MMP-3, STAT3, and phosphorylated STAT3 (p-STAT3) in chondrocytes were determined by Western blot analysis. Proteoglycan levels in chondrocytes were assessed using toluidine blue staining and quantitative reverse transcription PCR (qRT-PCR). Joint swelling rates were monitored at 0-24 h in rats, and histopathological changes in joint tissues were subsequently analyzed.
Phellodendrine chloride mitigated the rise in neutrophil proportions within MSU-induced peritoneal lavage fluid in mice and decreased inflammatory cell infiltration in rat ankle tissues. Treatment with phellodendrine chloride led to a downregulation of MMP-3 protein levels and inhibited IL-1β-induced proteoglycan degradation in chondrocytes. Additionally, results from experiments combining IL-1β with AG490 or IL-6 demonstrated that phellodendrine chloride attenuated IL-1β-induced MMP-3 expression and proteoglycan degradation.
Our findings suggest that phellodendrine chloride mitigates gouty arthritis (GA) by modulating the IL-6/STAT3 signaling pathway.
黄柏碱是黄柏（PCS）的主要生物活性成分，在其药理特性中起关键作用。黄柏碱具有强大的抗肾炎特性，并对细胞免疫反应表现出显著的抑制作用。然而，黄柏碱对痛风性关节炎中蛋白聚糖消耗和软骨退变的影响仍了解不足。因此，本研究的目的是阐明氯化黄柏碱（PC）治疗痛风性关节炎的治疗潜力及潜在机制。
建立大鼠尿酸钠（MSU）诱导的关节炎模型以及小鼠腹膜炎模型，并结合软骨细胞模型。使用流式细胞术对中性粒细胞比例进行定量。通过蛋白质印迹分析确定软骨细胞中MMP-3、STAT3和磷酸化STAT3（p-STAT3）的表达水平。使用甲苯胺蓝染色和定量逆转录PCR（qRT-PCR）评估软骨细胞中的蛋白聚糖水平。在0-24小时监测大鼠的关节肿胀率，随后分析关节组织的组织病理学变化。
氯化黄柏碱减轻了小鼠MSU诱导的腹腔灌洗液中中性粒细胞比例的升高，并减少了大鼠踝关节组织中的炎性细胞浸润。氯化黄柏碱治疗导致MMP-3蛋白水平下调，并抑制了软骨细胞中IL-1β诱导的蛋白聚糖降解。此外，将IL-1β与AG490或IL-6联合的实验结果表明，氯化黄柏碱减弱了IL-1β诱导的MMP-3表达和蛋白聚糖降解。
我们的研究结果表明，氯化黄柏碱通过调节IL-6/STAT3信号通路减轻痛风性关节炎（GA）。
