PMID- 36725236 OWN - NLM STAT- MEDLINE DCOM- 20230206 LR - 20230206 IS - 1001-5302 (Print) IS - 1001-5302 (Linking) VI - 48 IP - 2 DP - 2023 Jan TI - [Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway]. PG - 465-471 LID - 10.19540/j.cnki.cjcmm.20220726.403 [doi] AB - The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway. FAU - Ma, Xiao-Yu AU - Ma XY AD - School of Pharmacy, Shihezi University Shihezi 832000, China the First Affiliated Hospital of School of Medicine of Shihezi University Shihezi 832000, China. FAU - Zhao, Hao-Ran AU - Zhao HR AD - School of Pharmacy, Shihezi University Shihezi 832000, China the First Affiliated Hospital of School of Medicine of Shihezi University Shihezi 832000, China. FAU - Qiao, Hui-Lin AU - Qiao HL AD - School of Pharmacy, Shihezi University Shihezi 832000, China the First Affiliated Hospital of School of Medicine of Shihezi University Shihezi 832000, China. FAU - Zeng, You-Cheng AU - Zeng YC AD - School of Medicine, Shihezi University Shihezi 832000, China. FAU - Zhang, Xuan-Ming AU - Zhang XM AD - the First Affiliated Hospital of School of Medicine of Shihezi University Shihezi 832000, China School of Pharmacy, Shihezi University Shihezi 832000, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhongguo Zhong Yao Za Zhi JT - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JID - 8913656 RN - 0 (Apolipoproteins E) RN - 0 (Beclin-1) RN - 0 (Cholesterol, LDL) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 0 (Vascular Cell Adhesion Molecule-1) SB - IM MH - Animals MH - Mice MH - Apolipoproteins E MH - *Atherosclerosis/drug therapy/genetics MH - Beclin-1 MH - Cholesterol, LDL MH - Intercellular Adhesion Molecule-1 MH - Matrix Metalloproteinase 2/genetics MH - Matrix Metalloproteinase 9/genetics MH - Mice, Inbred C57BL MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - *Plaque, Atherosclerotic MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - TOR Serine-Threonine Kinases/genetics MH - Vascular Cell Adhesion Molecule-1/genetics OTO - NOTNLM OT - atherosclerosis OT - autophagy OT - total flavonoids of Ziziphora clinopodioides EDAT- 2023/02/02 06:00 MHDA- 2023/02/04 06:00 CRDT- 2023/02/01 21:03 PHST- 2023/02/01 21:03 [entrez] PHST- 2023/02/02 06:00 [pubmed] PHST- 2023/02/04 06:00 [medline] AID - 10.19540/j.cnki.cjcmm.20220726.403 [doi] PST - ppublish SO - Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(2):465-471. doi: 10.19540/j.cnki.cjcmm.20220726.403.