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已发表论文
新痹通灵通过抑制 Mapt 表达改善胶原诱导性关节炎小鼠的关节组织损伤：一项全基因组测序研究
Authors Guo Y, Tian M, Liu Y, Ma J, Li Y, Hou Y, Wang Y
Received 31 July 2025
Accepted for publication 29 October 2025
Published 8 November 2025 Volume 2025:18 Pages 15597—15614
DOI https://doi.org/10.2147/JIR.S557354
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Ujjwol Risal
Yunke Guo,1,* Mengjiang Tian,2,* Yang Liu,2 Jue Ma,2 Yang Li,2 Yu Hou,3 Yue Wang1
1Department of Rheumatism, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Rheumatism, Traditional Chinese Medicine Hospital of Ili Kazakh Autonomous Prefecture, Ili, Xinjiang, 835000, People’s Republic of China; 3First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yue Wang, Department of Rheumatism, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu, 210029, People’s Republic of China, Email wangyue2020l@163.com
Objective: Rheumatoid arthritis (RA) affects 1% of the global population, with joint destruction leading to disability. While current biologics (eg, TNF-α inhibitors) and small-molecule therapies (eg, JAK inhibitors) have significantly improved symptom control and slowed radiographic progression in many patients, unresolved challenges remain in simultaneously addressing mitochondrial dysfunction and synovial inflammation—the core drivers of joint destruction. This study aimed to investigate the molecular mechanism by which New Bitongling (NBTL) mitigates joint damage in collagen-induced arthritis (CIA) mice through regulation of the microtubule-associated protein tau (Mapt).
Methods: Male C57BL/6 mice (6 weeks old, specific pathogen-free) were used to establish the collagen-induced arthritis (CIA) model and randomly assigned to three groups: control, model, and NBTL intervention. Clinical symptoms were evaluated using the arthritis index (AI), paw swelling volume (measured by water displacement), and behavioral tests (sucrose preference test and open-field test). Histopathological changes were assessed via hematoxylin-eosin (HE) and Safranin O-Fast Green staining. Molecular mechanisms were analyzed using Western blotting, flow cytometry, and mitochondrial membrane potential (JC-1 staining) assays. Western blotting analyzed apoptosis-related proteins and the Sirtuin 1 (Sirt1)/Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway, flow cytometry measured reactive oxygen species (ROS) levels, and JC-1 fluorescence staining evaluated mitochondrial membrane potential. Genome-wide sequencing identified Mapt as the key target, with functional validation conducted through siRNA knockdown and adeno-associated virus (AAV) Mapt overexpression. Statistical analyses included repeated-measures Analysis of Variance (ANOVA) with Tukey’s post-hoc test and P< 0.05 was considered significant.
Results: NBTL treatment significantly reduced AI scores, paw swelling, and joint deformities while improving behavioral indicators. Histological analysis revealed attenuated synovial inflammation, pannus formation, and bone erosion in the NBTL group. Moreover, pro-inflammatory mediators were downregulated in NBTL-treated mice, accompanied by reduced Bax/cleaved-caspase3 and elevated Bcl-2 expression (P< 0.05). NBTL restored mitochondrial membrane potential, activated the Sirt1/PGC-1α pathway, reduced ROS levels, and decreased oxidative stress damage (P< 0.05). Mapt overexpression exacerbated joint damage, whereas Mapt silencing or NBTL intervention reversed these effects. Genome-wide sequencing confirmed that NBTL modulates mitochondrial homeostasis and inflammatory responses via Mapt inhibition.
Conclusion: This study demonstrates that New bitongling ameliorates joint damage in collagen-induced arthritis mice by suppressing microtubule-associated protein tau expression, restoring mitochondrial function, and modulating synovial inflammation. These findings provide preclinical evidence supporting further investigation of New bitongling as a novel therapeutic agent for rheumatoid arthritis.
Keywords: new bitongling, rheumatoid arthritis, Mapt protein, gastrointestinal microbiome, Sirtuin 1
1Department of Rheumatism, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Rheumatism, Traditional Chinese Medicine Hospital of Ili Kazakh Autonomous Prefecture, Ili, Xinjiang, 835000, People’s Republic of China; 3First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yue Wang, Department of Rheumatism, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu, 210029, People’s Republic of China, Email wangyue2020l@163.com
Objective: Rheumatoid arthritis (RA) affects 1% of the global population, with joint destruction leading to disability. While current biologics (eg, TNF-α inhibitors) and small-molecule therapies (eg, JAK inhibitors) have significantly improved symptom control and slowed radiographic progression in many patients, unresolved challenges remain in simultaneously addressing mitochondrial dysfunction and synovial inflammation—the core drivers of joint destruction. This study aimed to investigate the molecular mechanism by which New Bitongling (NBTL) mitigates joint damage in collagen-induced arthritis (CIA) mice through regulation of the microtubule-associated protein tau (Mapt).
Methods: Male C57BL/6 mice (6 weeks old, specific pathogen-free) were used to establish the collagen-induced arthritis (CIA) model and randomly assigned to three groups: control, model, and NBTL intervention. Clinical symptoms were evaluated using the arthritis index (AI), paw swelling volume (measured by water displacement), and behavioral tests (sucrose preference test and open-field test). Histopathological changes were assessed via hematoxylin-eosin (HE) and Safranin O-Fast Green staining. Molecular mechanisms were analyzed using Western blotting, flow cytometry, and mitochondrial membrane potential (JC-1 staining) assays. Western blotting analyzed apoptosis-related proteins and the Sirtuin 1 (Sirt1)/Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway, flow cytometry measured reactive oxygen species (ROS) levels, and JC-1 fluorescence staining evaluated mitochondrial membrane potential. Genome-wide sequencing identified Mapt as the key target, with functional validation conducted through siRNA knockdown and adeno-associated virus (AAV) Mapt overexpression. Statistical analyses included repeated-measures Analysis of Variance (ANOVA) with Tukey’s post-hoc test and P< 0.05 was considered significant.
Results: NBTL treatment significantly reduced AI scores, paw swelling, and joint deformities while improving behavioral indicators. Histological analysis revealed attenuated synovial inflammation, pannus formation, and bone erosion in the NBTL group. Moreover, pro-inflammatory mediators were downregulated in NBTL-treated mice, accompanied by reduced Bax/cleaved-caspase3 and elevated Bcl-2 expression (P< 0.05). NBTL restored mitochondrial membrane potential, activated the Sirt1/PGC-1α pathway, reduced ROS levels, and decreased oxidative stress damage (P< 0.05). Mapt overexpression exacerbated joint damage, whereas Mapt silencing or NBTL intervention reversed these effects. Genome-wide sequencing confirmed that NBTL modulates mitochondrial homeostasis and inflammatory responses via Mapt inhibition.
Conclusion: This study demonstrates that New bitongling ameliorates joint damage in collagen-induced arthritis mice by suppressing microtubule-associated protein tau expression, restoring mitochondrial function, and modulating synovial inflammation. These findings provide preclinical evidence supporting further investigation of New bitongling as a novel therapeutic agent for rheumatoid arthritis.
Keywords: new bitongling, rheumatoid arthritis, Mapt protein, gastrointestinal microbiome, Sirtuin 1