PMID- 35966555
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220816
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 9
DP  - 2022
TI  - Three polymethoxyflavones from the peel of Citrus reticulata "Chachi" inhibits 
      oxidized low-density lipoprotein-induced macrophage-derived foam cell formation.
PG  - 924551
LID - 10.3389/fcvm.2022.924551 [doi]
LID - 924551
AB  - Foam cell formation is the hallmark of the development and progression of 
      atherosclerosis. The aim of this study was to investigate the regulatory effects 
      of three polymethoxyflavones (PMFs), namely, tangeretin (TAN), 
      5,6,7,3',4',5'-hexamethoxyflavone (HxMF), and 3,5,6,7,8,3',4'-heptamethoxyflavone 
      (HpMF) on macrophage-derived foam cell formation and to further explore the 
      molecular mechanisms. The RAW264.7 macrophage-derived foam cell model was 
      successfully induced by oxidized low-density lipoprotein (ox-LDL) (80 mug/ml). It 
      showed that TAN, HxMF, and HpMF alleviated ox-LDL-induced NO release while also 
      inhibiting the expression of IL-1beta, IL-6, and TNF-alpha in RAW264.7 cells. Uptake of 
      excess ox-LDL was inhibited by TAN, HxMF, and HpMF, resulting in the reduction of 
      its foam cell formation. Moreover, TAN, HxMF, and HpMF promoted HDL-mediated 
      cholesterol efflux. Western blot experiment showed that TAN, HxMF, and HpMF 
      inhibited the expression of scavenger receptor class A type I (SRA1) and cluster 
      of differentiation 36 (CD36), while upregulating peroxisome 
      proliferator-activated receptor gamma (PPARgamma), liver X receptor alpha (LXRalpha), 
      phospholipid ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor 
      class B type I (SRB1) expression. Together, our findings suggested that PMFs 
      inhibited foam cell formation might inhibit lipid uptake via downregulating 
      SRA1/CD36 expression and promote cholesterol efflux from foam cells via 
      upregulating PPARgamma/LXRalpha/ABCG1/SRB1 expression. This antiatherosclerotic activity 
      is expected to provide new insights into the development of healthcare uses for 
      PMFs.
CI  - Copyright (c) 2022 Liang, Liang, He, Chen, Xu, Tu, Zhang, Qiu, Zhang, Huang and Xu.
FAU - Liang, Pu-Lin
AU  - Liang PL
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Liang, Qian-Wen
AU  - Liang QW
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - He, Pei-Wen
AU  - He PW
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Chen, Xue-Lian
AU  - Chen XL
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Xu, Ya
AU  - Xu Y
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Tu, Hai-Sheng
AU  - Tu HS
AD  - School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 
      Guangzhou, China.
FAU - Zhang, Liang
AU  - Zhang L
AD  - State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural 
      University, Hefei, China.
FAU - Qiu, Xiao-Hui
AU  - Qiu XH
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
AD  - Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese 
      Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 
      China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Huang, Zhi-Hai
AU  - Huang ZH
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Xu, Wen
AU  - Xu W
AD  - Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong 
      Provincial Medical Products Administration, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
AD  - Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20220728
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC9366847
OTO - NOTNLM
OT  - atherosclerosis
OT  - foam cells
OT  - inflammation
OT  - lipid metabolism
OT  - polymethoxyflavones
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/16 06:00
MHDA- 2022/08/16 06:01
PMCR- 2022/01/01
CRDT- 2022/08/15 03:43
PHST- 2022/04/26 00:00 [received]
PHST- 2022/07/04 00:00 [accepted]
PHST- 2022/08/15 03:43 [entrez]
PHST- 2022/08/16 06:00 [pubmed]
PHST- 2022/08/16 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2022.924551 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2022 Jul 28;9:924551. doi: 10.3389/fcvm.2022.924551. 
      eCollection 2022.