Rutin attenuates the progression of intervertebral disc degeneration in rats

doi:10.12307/2023.117

Abstract

Abstract: BACKGROUND: Rutin has various pharmacological activities including anti-oxidant, anti-inflammatory, anti-apoptotic, vasoprotective, neuroprotective, and cardioprotective properties, which can be used to treat diseases such as cancer, diabetes, hypertension, and hypercholesterolemia. However, it has been less studied in the treatment of intervertebral disc degenerative diseases.
OBJECTIVE: To investigate the regulatory effect of rutin on intervertebral disc degeneration in rats and its mechanism.
METHODS: Nucleus pulposus cells were isolated from the postnatal rat nucleus pulposus tissue and then treated with rutin (10, 50, 100, 200, or 400 μmol/L) and interleukin-1β (10 μg/L). Cell viability and expression of inflammatory factor and oxidative stress factors were detected. Production of cellular metabolic enzymes, matrix degradation, and cell apoptosis were also observed. Furthermore, treatment of nucleus pulposus cells with R-spondin1, a WNT/β-catenin pathway activator, and the expression of β-catenin, c-Myc, and Cyclin D1 were detected. The 26 out of 36 Sprague-Dawley rats were randomly selected, to construct animal models of intervertebral disc degeneration using a needle fiber loop. One week later, the model was evaluated by magnetic resonance imaging. The rest 10 rats were used as controls. Rats with successful modeling were randomly divided into a model group and a rutin group. Rats in the rutin group were intragastrically treated with 40 mg/kg rutin for 8 weeks, while those in the model group were treated with an equal volume of normal saline. The Pfirrmann grading system was used to grade the degree of intervertebral disc degeneration. The serum levels of interleukin-6, type II collagen and caspase-3 were detected using ELISA. The protein levels of Aggrecan and inducible nitric oxide synthase in rat nucleus pulposus tissue were measured using western blot assay.
RESULTS AND CONCLUSION: (1) Cell experiment: 100 μmol/L rutin completely alleviated the toxicity of interleukin-1β to nucleus pulposus cells, decreased the expression of interleukin-6, tumor necrosis factor-α, cyclooxyganese-2, inducible nitric oxide synthase, matrix metalloproteinases-3, 9, 13, and ADAMTS-5, inhibited the degradation of type II collagen and Aggrecan, and reduced apoptosis in nucleus pulposus cells. Whereas, treatment with R-spondin1 could reverse the effects of rutin. (2) In vivo experiments showed that compared with the model group, treatment with rutin decreased interleukin-6 level, increased type II collagen level, decreased caspase-3 activity, downregulated inducible nitric oxide synthase level in nucleus pulposus tissue, and upregulated Aggrecan level, indicating an obvious improvement in intervertebral disc degeneration. To conclude, rutin could improve intervertebral disc degeneration in rats through anti-inflammation, anti-oxidation, and inhibition of matrix degradation.

Key words: intervertebral disc degeneration, rutin, anti-oxidation, anti-inflammation, the WNT/β-catenin pathway

CLC Number:

Xu Dayong, Li Yunpeng, Wei Jingmei, Liu Ruyin. Rutin attenuates the progression of intervertebral disc degeneration in rats[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(14): 2139-2145.

Figures/Tables 7

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