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Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis.
- Source :
- Chinese Medicine; 1/28/2023, Vol. 18 Issue 1, p1-14, 14p
- Publication Year :
- 2023
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- BIOLOGICAL models
CYTOKINES
C-reactive protein
BIOMARKERS
HERBAL medicine
COMBINATION drug therapy
OSTEOCLASTS
STAINS & staining (Microscopy)
ANIMAL experimentation
INFLAMMATION
SERUM
METABOLISM
BLOOD collection
PROTEOMICS
METHOTREXATE
SEVERITY of illness index
CELLULAR signal transduction
BIOINFORMATICS
RHEUMATOID arthritis
ENZYME-linked immunosorbent assay
DRUG synergism
GENOTYPES
FACTOR analysis
DESCRIPTIVE statistics
MASS spectrometry
RESEARCH funding
FOLIC acid
CLUSTER analysis (Statistics)
DATA analysis software
CHINESE medicine
MICE
PHENOTYPES
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 17498546
- Volume :
- 18
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Chinese Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 161551233
- Full Text :
- https://doi.org/10.1186/s13020-023-00709-9