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Antiatherosclerotic effects of corilagin via suppression of the LOX-1/MyD88/NF-κB signaling pathway in vivo and in vitro

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Abstract

Corilagin, a natural polyphenol compound isolated from Phyllanthus urinaria L., exerts various pharmacological effects, such as antihyperglycemic, antitumor, and antioxidative stress properties, but the mechanisms underlying the antiatherosclerotic effects of corilagin have not been entirely elucidated. In the present study, we investigated the antiatherosclerotic effects of corilagin using a high-fat diet (HFD)-induced atherosclerotic rabbit model and ox-LDL-induced vascular smooth muscle cells (VSMCs) and explored the underlying molecular mechanisms. The serum lipid levels were measured through an enzymatic colorimetric assay. A histological analysis of rabbit aortas was performed after hematoxylin–eosin and oil red O staining. The proliferation of ox-LDL-induced VSMCs was detected using MTT assays, and the migration of cells was determined by wound scratch assays. In addition, the mRNA and protein expression levels of lectin-like ox-LDL receptor-1 (LOX-1), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNF-α) were detected by reverse transcription-polymerase chain reaction (RT–PCR) and Western blotting assays. Our results indicate that corilagin significantly reduced the serum levels of TC, TG and LDL-C, increased the HDL-C levels, decreased the intimal thickening in the thoracic aorta, and reduced the formation of foam cells in an HFD-induced rabbit atherosclerosis model. Moreover, corilagin suppressed the proliferation and migration of ox-LDL-induced VSMCs and reduced LOX-1, MyD88, NF-κB, MCP-1, and TNF-α mRNA and protein expression in vivo and in vitro. These data demonstrate that corilagin exerts antiatherosclerotic effects in vivo and in vitro and that the mechanisms may be closely associated with downregulation of the LOX-1/MyD88/NF-κB pathway.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81660613 and 81860665), by the Natural Science Foundation of Yunnan Province, China (Grant Nos. 2019FE001-191 and 202001AY070001-157), and by the Digitalization, Development and Application of Biotic Resources of Kunming Medical University (Grant No. 202002AA100007).

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  1. School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650500, People’s Republic of China

    Bo He, Deyun Chen, Xiaochao Zhang, Renhua Yang, Yuan Yang, Peng Chen & Zhiqiang Shen

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  1. Bo He
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  3. Xiaochao Zhang
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  4. Renhua Yang
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Contributions

PC and ZQS: conceptualization; BH and ZQS: methodology; BH, DYC, XCZ, RHY, and YY: validation; BH and DYC: writing—original draft preparation; PC and ZQS: writing—review and editing. All the authors have read and agreed to the submission of this manuscript.

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He, B., Chen, D., Zhang, X. et al. Antiatherosclerotic effects of corilagin via suppression of the LOX-1/MyD88/NF-κB signaling pathway in vivo and in vitro. J Nat Med 76, 389–401 (2022). https://doi.org/10.1007/s11418-021-01594-y

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