Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathway
Background: 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 o...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Immunobiology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S017129852500052X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849471500736790528 |
|---|---|
| author | Yu-yao Qin Zi-yi Qin Tao Liang Dong-er Qin Sheng-yi Hua Ming-hui Tan Shun Guo Fan Yang Le Shi Yun Yu Guang-ji Zhang |
| author_facet | Yu-yao Qin Zi-yi Qin Tao Liang Dong-er Qin Sheng-yi Hua Ming-hui Tan Shun Guo Fan Yang Le Shi Yun Yu Guang-ji Zhang |
| author_sort | Yu-yao Qin |
| collection | DOAJ |
| description | Background: 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. Methods: 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. Results: 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. Conclusion: Our findings suggest that phellodendrine chloride mitigates gouty arthritis (GA) by modulating the IL-6/STAT3 signaling pathway. |
| format | Article |
| id | doaj-art-b419c6c0c9c04f7fbef0e2ea883475dd |
| institution | Kabale University |
| issn | 0171-2985 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Immunobiology |
| spelling | doaj-art-b419c6c0c9c04f7fbef0e2ea883475dd2025-08-20T03:24:48ZengElsevierImmunobiology0171-29852025-07-01230415291810.1016/j.imbio.2025.152918Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathwayYu-yao Qin0Zi-yi Qin1Tao Liang2Dong-er Qin3Sheng-yi Hua4Ming-hui Tan5Shun Guo6Fan Yang7Le Shi8Yun Yu9Guang-ji Zhang10College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaCollege of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaCollege of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaCollege of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaEmergency Room, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaCollege of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Dermatology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Histology and Embryology, Medical College, Yangzhou University, Yangzhou, Jiangsu, ChinaCollege of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Correspondance to: Le Shi and Yun Yu, College of Pharmacy, Nanjing University of Chinese Medicine, 138 XianLin Road, Qixia District, Nanjing 210023, Jiangsu, PR China.College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Correspondance to: Le Shi and Yun Yu, College of Pharmacy, Nanjing University of Chinese Medicine, 138 XianLin Road, Qixia District, Nanjing 210023, Jiangsu, PR China.Medical school, Taizhou Polytechnic College, Taizhou, Jiangsu, China; Correspondance to: Guang-ji Zhang, Medical School, Taizhou Polytechnic College, 8 Tianxing Road, Pharmaceutical Hi-Tech Zone, Taizhou 225300, Jiangsu, PR China.Background: 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. Methods: 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. Results: 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. Conclusion: Our findings suggest that phellodendrine chloride mitigates gouty arthritis (GA) by modulating the IL-6/STAT3 signaling pathway.http://www.sciencedirect.com/science/article/pii/S017129852500052XPhellodendrine chlorideGouty arthritisChondrocytesSTAT3Proteoglycan |
| spellingShingle | Yu-yao Qin Zi-yi Qin Tao Liang Dong-er Qin Sheng-yi Hua Ming-hui Tan Shun Guo Fan Yang Le Shi Yun Yu Guang-ji Zhang Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathway Immunobiology Phellodendrine chloride Gouty arthritis Chondrocytes STAT3 Proteoglycan |
| title | Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathway |
| title_full | Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathway |
| title_fullStr | Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathway |
| title_full_unstemmed | Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathway |
| title_short | Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathway |
| title_sort | phellodendrine chloride alleviates gouty arthritis through il 6 stat3 signaling pathway |
| topic | Phellodendrine chloride Gouty arthritis Chondrocytes STAT3 Proteoglycan |
| url | http://www.sciencedirect.com/science/article/pii/S017129852500052X |
| work_keys_str_mv | AT yuyaoqin phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT ziyiqin phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT taoliang phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT dongerqin phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT shengyihua phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT minghuitan phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT shunguo phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT fanyang phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT leshi phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT yunyu phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway AT guangjizhang phellodendrinechloridealleviatesgoutyarthritisthroughil6stat3signalingpathway |