Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis

Chen，Yong1,2; Zhu，Xing wang3; Lai，Wing Fu4,5; Liu，Yong pu3; Xu，Xuan feng3; Liu，Li ming1; Chen，Yan juan1; Zhang，Chuan fu6; Wang，Guang yi7; Cheng，Zhi qiang1; Liu，Dong zhou1

2023-12-01

10.1186/s13020-023-00709-9

Chinese Medicine (United Kingdom)   Impact Factor & Quartile

1749-8546

Background: Elderly rheumatoid arthritis (ERA) population faces multiple treatment dilemma. Here we aim to investigate if Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) exhibit better effects in an ERA mice model. Methods: ERA mice model was established by adding D-galactose (Dgal) to collagen-induced arthritis (CIA) mice. The model was then assigned into control group (CIA + Dgal), MTX treatment group (MTX), GCNY treatment group (GCNY), and integrative treatment group (MTX + GCNY). Pathological scoring was performed to evaluate the severity between the groups. Proteomic analysis was applied to investigate the secretory phenotype of the ERA mouse model and the underlying mechanism of GCNY, MTX and their combination. Representative cytokines related to proteomic results were further validated by ELISAs. Results: CIA + Dgal mice showed more aggressive joints damage than the CIA mice. Besides changes in the inflammatory pathway such as Pi3k-Akt signaling pathway in both model, differential expressed proteins (DEPs) indicated metabolism-related pathways were more obvious in CIA + Dgal mice. Low-dose MTX failed to show pathological improvement in CIA + Dgal mice, while GCNY improved joints damage significantly. Besides down-regulated inflammation-related targets, GCNY-regulated DEPs (such as Apoc1 ~ 3, Grk2 and Creb3l3) were broadly enriched in metabolism-related pathways. MTX + GCNY showed the best therapeutic effect, and the DEPs enriched in a variety of inflammatory,metabolism and osteoclast differentiation signaling pathway. Notably, MTX + GCNY treatment up-regulated Dhfr, Cbr1, Shmt1 involved in folic acid biosynthesis and anti-folate resistance pathways indicated a coincidence synergic action. ELISAs confirmed CPR and Akt that elevated in CIA + Dgal mice were significantly ameliorated by treatments, and adding on GCNY elevated folic acid levels and its regulator Dhfr. Conclusion: Aging aggravated joints damage in CIA, which probably due to metabolic changes rather than more severe inflammation. GCNY showed significant effects in the ERA mice model especially when integrated with MTX to obtain a synergic action.

Aging Integrative treatment Rheumatoid arthritis Synergic action Traditional chinese medicine

English

First

Postdoctoral Research Foundation of China[2021M701438];

2-s2.0-85146935671

Scopus

1.Shenzhen People‘s Hospital (The Second Clinical Medical College of Jinan University and the First Affiliated Hospital to Southern University of Science and Technology),Shenzhen,China
2.Shenzhen Clinical Research Centre for Geriatrics,Shenzhen People‘s Hospital,Shenzhen,China
3.Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine,Guangzhou,China
4.Department of Applied Biology and Chemical Technology,Hong Kong Polytechnic University,Hong Kong
5.Department of Urology,Zhejiang Provincial People’s Hospital,Hangzhou Medical College,Hangzhou,Zhejiang,China
6.The Seventh People’s Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai,China
7.Guizhou Medical University affiliated Hospital,Guiyang,China

Chen，Yong,Zhu，Xing wang,Lai，Wing Fu,et al. Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis[J]. Chinese Medicine (United Kingdom),2023,18(1).

Chen，Yong.,Zhu，Xing wang.,Lai，Wing Fu.,Liu，Yong pu.,Xu，Xuan feng.,...&Liu，Dong zhou.(2023).Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis.Chinese Medicine (United Kingdom),18(1).

Chen，Yong,et al."Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis".Chinese Medicine (United Kingdom) 18.1(2023).