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[Effect of Xinfeng Capsule on Beclin1/PI3K-AKT-mTOR of Adjuvant Arthritis Rats]
Abstract:
Objective To observe expression levels of autophagy related 5,7,12 mRNA (Atg5, 7,12), microtubule-associated protein 1 light chain 3 (LC3-II), Beclin1, phosphatidylinositol 3-kinase (PI3K) , protein kinase B (AKT) , mammalian target of rapamycin (mTOR) , IL-1 β, TNF-α, IL-4, and IL- 10 in adjuvant arthritis (AA) rats, and effects of Xinfeng Capsule (XFC) on them. Methods Totally 48 male SD rats were divided into 4 groups, i.e., the control group, the model group, the Western medicine (WM) group (leflunomide, 5. 0 mg/kg) , the Chinese medicine (CM) group (Xinfeng Capsule, 3.0 g/kg) , 12 in each group. Thirty days after medication body weight (BW) , toe swelling degree (E%) , arthritis in- dex (AI) , and pathological changes of ankle joint and ultrastructural changes were observed. mRNA ex- pressions of Atg5, 7, 12, protein expressions of LC3-L , Beclin1 , PI3K, AKT, mTOR, serum contents of IL-1 β, TNF-α, IL-4, and IL-10 were detected. Results Compared with the normal group, E%, Al, IL-1 β and TNF-α increased; BW, levels of IL-4 and IL-10, mRNA expressions of Atg5 and Atg12, protein ex- pressions of LC3-ll and Beclin1 decreased (P <0.01, P <0.05), protein expressions of PI3K, AKT, mTOR increased (P<0.01) in the model group. Compared with the model group, E%, Al, mRNA expres- sions of IL-1β , TNF-α-, and Atg12, protein expressions of PI3K, AKT, and mTOR decreased (P <0.01, P<0.05), IL-4, IL-10, protein expressions of LC3-II and Beclinl increased (P <0.01, P <0.05) in the two medicated groups. Atg5 mRNA expression decreased (P <0.01) , Atg7 mRNA expression increased (P < 0.05) in the WM group. Compared with the WM group,BW, IL-4, mRNA expressions of Atg5 and Atg12, protein expressions of PI3K and mTOR increased in the CM group (P <0.01 , P <0. 05). Conclusions The level of autophagy in AA rats was decreased, leading to excessive proliferation of synovial cells, swollen joints, elevated proinflammatory factors, decreased inflammatory factors, resulting in inflamma- tory reactions of joints. XFC could improve Al, toe swelling degree, and expressions of synovium autoph- agy related genes and proteins.
Insights
Xinfeng Capsule (XFC) treatment in adjuvant arthritis (AA) rats improved joint inflammation by modulating autophagy-related genes and proteins. XFC normalized levels of pro-inflammatory cytokines and enhanced autophagy markers, reducing swelling and arthritis index.
Area of Science:
- Immunology and Molecular Biology
- Pharmacology and Traditional Chinese Medicine
Background:
- Adjuvant arthritis (AA) is an inflammatory condition characterized by joint swelling and damage.
- Autophagy dysfunction is implicated in the pathogenesis of inflammatory arthritis.
- Understanding the molecular mechanisms of AA and potential therapeutic interventions is crucial.
Purpose of the Study:
- To investigate the expression levels of autophagy-related genes and proteins (Atg5, Atg7, Atg12, LC3-II, Beclin1) and inflammatory cytokines (IL-1β, TNF-α, IL-4, IL-10) in AA rats.
- To evaluate the therapeutic effects of Xinfeng Capsule (XFC) on AA in rats.
- To explore the impact of XFC on autophagy pathways and inflammatory responses in AA.
Main Methods:
- Forty-eight male SD rats were divided into control, AA model, Western medicine (leflunomide), and XFC treatment groups.
- AA was induced in rats, followed by 30 days of treatment.
- Body weight, toe swelling, arthritis index, and pathological changes were assessed.
- mRNA and protein expression levels of autophagy markers and serum cytokine levels were measured.
Main Results:
- AA rats exhibited increased toe swelling, arthritis index, IL-1β, and TNF-α, with decreased IL-4, IL-10, and autophagy markers (Atg5, Atg12, LC3-II, Beclin1).
- XFC treatment significantly reduced toe swelling, arthritis index, and pro-inflammatory cytokines (IL-1β, TNF-α).
- XFC treatment increased autophagy markers (LC3-II, Beclin1) and anti-inflammatory cytokines (IL-4, IL-10), while decreasing PI3K, AKT, and mTOR expression.
Conclusions:
- The study suggests that decreased autophagy contributes to synovial cell proliferation and joint inflammation in AA rats.
- Xinfeng Capsule demonstrates therapeutic potential in ameliorating AA by restoring autophagy and modulating inflammatory cytokine profiles.
- XFC effectively improves arthritis index, reduces toe swelling, and modulates the expression of autophagy-related genes and proteins in AA rats.
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