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The effective constituent puerarin, from Pueraria lobata, inhibits the proliferation and inflammation of vascular smooth muscle in atherosclerosis through the miR-29b-3p/IGF1 pathway

Jianpeng Li  ^{1   2} , Yanan Li  ² , Xiangke Yuan  ² , Dengfeng Yao  ² , Zongyue Gao  ² , Zhaoyang Niu  ² , Zheng Wang  ³ , Yue Zhang  ⁴

Affiliations

Affiliations

• ¹ The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, China.
• ² Department of Peripheral Vascular, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou City, Henan Province, China.
• ³ Department of Nephrology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China.
• ⁴ Department of Peripheral Vascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine (Shandong Provincial Hospital of Traditional Chinese Medicine), Jinan City, Shandong Province, China.

• PMID: 36537316
• PMCID: PMC9788726
• DOI: 10.1080/13880209.2022.2099430

Free PMC article

Abstract

Context: Atherosclerosis (AS) is the main cause of cardiovascular and cerebrovascular diseases. Pueraria lobata (Willd.) Ohwi (Fabaceae) has a positive effect on improving these diseases.

Objective: The P. lobata effect on the proliferation and inflammation of vascular smooth muscle in AS and the potential mechanism were investigated.

Materials and methods: By feeding a high-fat diet to 8-week-old apolipoprotein E knockout mice, an atherosclerosis model was created. H&E and IHC staining were used to analyse the histopathology of mice. CCK-8, TUNEL, and scratch tests were used to detect cell proliferation, apoptosis, and migration after 24 h treatment, respectively. ELISA was performed to evaluate the level of IL-6 and IL-8. The target miRNA and its downstream target gene were screened by the bioinformatics method; RT-qPCR has conducted to analyse the expression of these genes.

Results: In the aortic tissue and serum of AS mice, puerarin can lower the expression of α-SMA and the inflammatory proteins IL-6 and IL-8. Puerarin (200 M) decreased hVSMC proliferation, migration, and IL-6 and IL-8 secretion by more than half. The inhibitory impact of puerarin on hVSMC was decreased by overexpression of miR-29b-3p. IGF1 was miR-29b-3p’s downstream target gene. IGF1 expression increased almost 3-fold in AS mice and hVSMC, but miR-29b-3p mimic inhibited it. The effect of miR-29b-3p on hVSMC was reversed when IGF1 was overexpressed.

Discussion and conclusions: Puerarin inhibits the proliferation and inflammation of vascular smooth muscle in AS through the miR-29b-3p/IGF1 pathway. Puerarin may have a beneficial effect in the treatment of atherosclerosis and offer a novel therapy option.

Keywords: Inflammatory factors; hVSMC.