2. Academic Validation
  3. Mori fructus-derived extracellular vesicle-like nanoparticles regulate dyslipidemia and prevent atherosclerosis progression via miRNAs

Mori fructus-derived extracellular vesicle-like nanoparticles regulate dyslipidemia and prevent atherosclerosis progression via miRNAs

  • Phytomedicine. 2025 Oct:146:157128. doi: 10.1016/j.phymed.2025.157128.
Yunchan Sui 1,  Xiaoyu Sun 1,  Qisijing Liu 2,  Guangwei Qi 1,  Yanze Yang 1,  Xinyue Zhang 1,  Opoku Bonsu Francis 1,  Yucheng Wang 1,  Rui Liu 1,  Xiaoge Li 1,  Miaomiao Jiang 3,  Xintong Wang 1,  Yan Zhu 1,  Mengmeng Yang 4,  Ruiqiao Li 5,  Xiankuan Li 6,  Han Zhang 7,  Qilong Wang 8,  Ling Leng 9
Affiliations

Affiliations

  • 1 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 2 Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, 300071, China.
  • 3 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Chinese Medicine Modernization, Tianjin, 301617, China.
  • 4 Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.
  • 5 Laboratory Animal Center, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 6 Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 7 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Ministry of Education, Tianjin, 301617, China. Electronic address: zhanghan0023@126.com.
  • 8 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Chinese Medicine Modernization, Tianjin, 301617, China. Electronic address: wangqilong_00@tjutcm.edu.cn.
  • 9 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Chinese Medicine Modernization, Tianjin, 301617, China. Electronic address: lengling@tjutcm.edu.cn.
PMID: 40815949 DOI: 10.1016/j.phymed.2025.157128
Abstract

Background: Atherosclerosis, driven majorly by dyslipidemia, is a major risk factor for acute and chronic cardiovascular diseases. Hence, the development of bioactive products that can regulate lipid metabolism and prevent the onset and progression of atherosclerosis is urgently needed.

Purpose: This study aims to investigate the effect of Mori fructus-derived extracellular vesicle-like nanoparticles (MFEVLPs) on lipid abnormality and atherosclerosis progression.

Methods: MFEVLPs were isolated by ultracentrifugation and purified using a sucrose density gradient centrifuge. They were then characterized by TEM and NTA. The miRNA profile was detected using small RNA-seq. FFA-stimulated HepG2 cells and high-fat-diet-fed apoE-/- mice (including models, MFEVLPs-treated groups, and atorvastatin-treated group) were used to investigate the effect of MFEVLPs on lipid abnormality and atherosclerosis progression. miRNA mimics and luciferase assay were used to analyze the interactions between MFEVLPs-derived miRNAs and target genes.

Results: MFEVLPs reduced plaque area and augmented plaque stability in apoE-/- mice. MFEVLP suppressed liver lipid synthesis and decreased liver and serum lipid content in vitro and in vivo. The MFEVLPs contained a large number of miRNAs, of which 20 miRNAs could target genes related to lipogenesis (SREBP1, FAS, and ACC) and Cholesterol biosynthesis (HMGCR). MFEVLPs-derived miRNAs, such as miR398-y, miR160-z, miR165-y, miR166-y, and miR5168-y, were successfully delivered into the blood and accumulated in the liver of mice. Furthermore, MFEVLPs-derived miRNAs specifically bound to the 3'-UTR sequence of HMGCR and suppressed its expression.

Conclusions: Collectively, our results for the first time demonstrated that MFEVLPs could prevent dyslipidemia and atherosclerosis. We also found that MFEVLPs-derived miRNAs could target genes related to lipogenesis and Cholesterol biosynthesis, offering new treatment modalities for the prevention of dyslipidemia-induced disorders.

Keywords

Atherosclerosis; Dyslipidemia; HMGCR; Mori fructus-derived extracellular vesicle-like nanoparticle; miRNA.

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