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[Experimental Study on Paeoniflorin Inhibiting mTOR Signaling Pathway in Adjuvant Arthritis Rats]
Cheng-Gui Miao1, You-Yi Xiong1, Mei-Song Qin1
1Food and Drug College, Anhui Science and Technology University, Fengyang 233100, China.
Objective:
To study the effect of paeoniflorin (PF) on mTOR signal in synovial fibroblast-like synoviocytes (FLS) in rats with adjuvant arthritis.
Methods:
AA model rats were prepared by complete Freun's adjuvant injection in foot-plantar, the PF was injected to rats in AA + PF 100 μg / mL group, AA + PF 200 μg / mL group and AA + PF 400 μg / mL group by the tail vein injection at the dose of 0.1 mL/200 g body mass, and the effects of three doses of PF on arthritis scores in AA rats were studied. The modeling rats and control rats were sacrificed at 28 d after modeling, then the synovium was separeated from rat articular, the FLS were cultured. The effect of PF on the expression of mTOR and MMP3 in AA FLS was detected by the real time qPCR. The effect on the cytokine IL-1, IL-6 was detected by ELISA, and the Western blot was used to investigate the role of PF in the mTOR phosphorylation. Furthermore, FLS were transfected with mTOR vectors, and the effect of mTOR overexpression on the PF roles was detected by real time qPCR and ELISA.
Results:
The tail vein injection of PF can significantly reduce the AA rat arthritis score. Compared with AA group, the expression of mTOR in AA+PF 1 μg/mL, AA+PF 2 μg/mL, AA+PF 4 μg/mL was significantly decreased at 48 h after dosing. Compared with AA group, the relative expression of p-mTOR protein in PF 2 μg/mL group was also decreased. Compared with AA group at 48 h after dosing, the levels of IL-1, IL-6 and MMP3 in AA+PF 1 μg/mL, AA+PF 2 μg/mL, AA+PF 4 μg/ mL were significantly decreased, respectively. Compared with PF 2 μg/mL group, the relative expression of IL-1, IL-6 and MMP3 in PF 2 μg/mL+mTOR vectors was increased.
Conclusion:
PF can significantly inhibit the pathology of AA rats, and its mechanism may be related to the inhibition of mTOR signal in FLS of AA rats.
Insights
Paeoniflorin (PF) effectively reduces arthritis symptoms in rats by inhibiting the mTOR signaling pathway in synovial cells. This study highlights PF as a potential therapeutic agent for inflammatory joint diseases.
Area of Science:
- Pharmacology
- Immunology
- Molecular Biology
Background:
- Adjuvant arthritis (AA) is an inflammatory condition affecting synovial fibroblast-like synoviocytes (FLS).
- The mTOR signaling pathway plays a crucial role in the pathogenesis of inflammatory diseases.
Purpose of the Study:
- To investigate the therapeutic effects of paeoniflorin (PF) on adjuvant arthritis (AA) in rats.
- To elucidate the mechanism of PF action, specifically its impact on the mTOR signaling pathway in FLS.
Main Methods:
- An AA rat model was established using complete Freund's adjuvant.
- Paeoniflorin (PF) was administered at varying doses (100, 200, 400 μg/mL) via tail vein injection.
- Expression levels of mTOR, p-mTOR, MMP3, IL-1, and IL-6 were analyzed using qPCR, ELISA, and Western blot.
- FLS were transfected with mTOR vectors to assess the role of mTOR overexpression.
Main Results:
- PF treatment significantly reduced arthritis scores in AA rats.
- PF administration led to decreased expression of mTOR, p-mTOR, IL-1, IL-6, and MMP3 in FLS.
- Overexpression of mTOR partially reversed the inhibitory effects of PF on IL-1, IL-6, and MMP3 levels.
Conclusions:
- Paeoniflorin (PF) demonstrates significant anti-arthritic effects in a rat model.
- PF exerts its therapeutic action by inhibiting the mTOR signaling pathway in fibroblast-like synoviocytes (FLS).
- PF shows potential as a novel therapeutic agent for managing adjuvant arthritis.
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