Plumbagin Ameliorates Collagen-Induced Arthritis by Regulating Treg/Th17 Cell Imbalances and Suppressing Osteoclastogenesis
Authors: Zanjing Zhai
Hong Zhou
Jun Zhang
Han Qiao
Tingting Tang
Tingyu Wang
Xinyi Zheng
Jinwen Tu
Eryi Lu
Niandong Qian
Journal: Frontiers in Immunology (2019)
Discipline: IMMUNOLOGY
Keywords: Th17 cells; arthritis; inflammation; osteoclast; plumbagin.
Affiliations: Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia., Department of Stomatology, Shanghai Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Department of Orthopaedic Surgery, Shanghai Institute of Traumatology and Orthopaedics, Shanghai, China.

Abstract:  Objective: Plumbago zeylanica L. (with plumbagin as its active ingredients) has been used for centuries to treat conditions such as joint swelling, fractures, and bacterial infections, suggesting that it possesses anti-inflammatory and immunosuppressive properties. In the present study, we evaluated the potential anti-arthritic activity and related mechanisms of plumbagin. Methods: Collagen-induced arthritis (CIA) was initiated in Wistar rats with collagen type II. Plumbagin (2 and 6 mg/kg) was orally administered to rats with CIA from day 12 to day 32 post immunization. The effects of plumbagin on arthritis progression were assessed by paw swelling, clinical scoring, and histologic analysis. The percentage of Treg and Th17 were defined by flow cytometry or immunofluorescence (IF) staining. Bone erosion and resorption were assessed by micro-CT and histomorphometric analysis. Osteoclast differentiation was further determined by in vitro osteoclastogenesis assay. The molecular docking assay was used to determine the potential binding site of plumbagin. Results: Treatment with plumbagin significantly inhibited arthritis development, as well as suppressed the local and systemic inflammation. Plumbagin reciprocally regulated pro-inflammatory Th17 cell and immunosuppressive Treg cell populations. In addition, plumbagin protected inflammation-induced bone loss by inhibiting osteoclast formation and activity. Plumbagin markedly suppressed RANKL-stimulated osteoclast-specific gene expression by repressing NF-κB signaling activation and MAP kinase phosphorylation. Further study via molecular docking assay demonstrated that plumbagin bound to MET169 of JNK kinase and LYS138 and SER183 of p38 kinase. Conclusion: Plumbagin not only attenuates the immune-induced arthritis by inhibiting inflammation, but also protects bone erosion by directly inhibiting osteoclast formation and activity. These data suggest plumbagin is a promising new candidate drug for treating inflammatory joint diseases. 

Retracted: Yes

PubPeer comments:
 Same group: Figure 6: ![file] , 
 #1 I assume that the authors have probed for ERK, then stripped and reprobed for p-ERK, so the two panels **should** be similar - either ERK or p-ERK has for some reason been inverted. , 
 #2 I believe there is huge difference between SIMILAR and SAME. , 
 2020 retraction. https: www.frontiersin.org articles 10.3389 fimmu.2020.00112 full RETRACTION ARTICLE Front. Immunol., 23 January 2020 | https: doi.org 10.3389 fimmu.2020.00112 Retraction: Plumbagin Ameliorates Collagen-Induced Arthritis by Regulating Treg Th17 Cell Imbalances and Suppressing Osteoclastogenesis Frontiers Editorial Office* A Retraction of the Original Research Article Plumbagin Ameliorates Collagen-Induced Arthritis by Regulating Treg Th17 Cell Imbalances and Suppressing Osteoclastogenesis by Wang, T., Qiao, H., Zhai, Z., Zhang, J., Tu, J., Zheng, X., et al. (2019). Front. Immunol. 9:3102. doi: 10.3389 fimmu.2018.03102 The journal retracts the January 8, 2019 article cited above. Following publication, concerns regarding the integrity of the western blot images were brought to the attention of the Publisher. After an investigation by the Editorial Office and Chief Editors of the journal, image duplication and manipulation was revealed in Figure 6. The authors have failed to provide a satisfactory explanation following several requests. The authors do not agree to the retraction or the notice. The retraction of the article was approved by the Chief Editors of Frontiers in Immunology and the Editor-in-Chief of Frontiers. ,