PMID- 34790740
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220428
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 20
DP  - 2021 Oct
TI  - Lupeol reduces M1 macrophage polarization to attenuate immunologic dissonance and 
      fatty acid deposition in rats with diet-induced metabolic syndrome.
PG  - 1534
LID - 10.21037/atm-21-4561 [doi]
LID - 1534
AB  - BACKGROUND: This study aimed to investigate whether lupeol could inhibit the 
      inflammatory mediators associated with the regulation of macrophage phenotypes 
      and functions in rats with diet-induced metabolic syndrome (MS). METHODS: Forty 
      specific-pathogen-free Sprague Dawley rats were fed a high-fat diet (HFD) for 10 
      weeks to establish an MS model. Lupeol was prepared and administered to the rats 
      intraperitoneally at 20, 50, or 100 mg/kg (the lupeol 20 mg/kg, lupeol 50 mg/kg, 
      and lupeol 100 mg/kg groups respectively). After 28 days of continuous 
      intraperitoneal administration, rats were anesthesia and euthanasia. The obesity 
      index, blood glucose and lipid metabolism indexes of rats in each group were 
      measured. The levels of insulin and inflammatory factors in each group were 
      detected by enzyme-linked immunosorbent assay (ELISA) kits. The pathological 
      changes of liver tissue in rats were observed by hematoxylin and eosin (HE) and 
      oil red O staining. The polarization levels of M1 and M2 macrophages in 
      peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry. The 
      transcription levels of M1 and M2 macrophages markers were detected by qRT-PCR. 
      The expressions of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) 
      proteins in heart tissues of rats in each group were analyzed by Western 
      blotting. RESULTS: Lupeol significantly recovered fasting blood glucose and serum 
      insulin levels, and reduced the production of proinflammatory cytokines, 
      including interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), and monocyte 
      chemoattractant protein-1 (MCP-1), in the liver. It also elevated the expression 
      of anti-inflammatory cytokines, including IL-4 and IL-10, in the MS model. 
      Further, after treatment with lupeol, the levels of total cholesterol, 
      triacylglycerol and low-density lipoprotein (LDL) were decreased, and 
      high-density lipoprotein (HDL) were increased. Importantly, in the MS model 
      group, lupeol remarkably inhibited M1 macrophages polarization (F4/80(+)iNOS(+)) 
      while elevating M2 macrophages polarization (F4/80(+)CD206(+)) remarkably. At the 
      same time, the levels of M1 markers, including inducible nitric oxide synthase, 
      IL-1beta, IL-6, and TNF-alpha, were markedly inhibited, while those of M2 markers, such 
      as arginase-1, IL-10, CD206, and TGF-beta, were markedly elevated in the MS model 
      rats. CONCLUSIONS: Lupeol might promote M2 polarization of macrophages to relieve 
      damage caused by MS.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Li, Jin
AU  - Li J
AD  - Department of Traditional Chinese Medicine, The First Affiliated Hospital of 
      Harbin Medical University, Harbin, China.
FAU - Huang, Yuechen
AU  - Huang Y
AD  - Boli County Hospital of Traditional Chinese Medicine, Qitaihe, China.
FAU - Han, Yue
AU  - Han Y
AD  - Department of Ultrasound Medicine, The First Affiliated Hospital of Harbin 
      Medical University, Harbin, China.
FAU - Wang, Jiafu
AU  - Wang J
AD  - Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Zhang, Chun
AU  - Zhang C
AD  - Department of Traditional Chinese Medicine, The First Affiliated Hospital of 
      Harbin Medical University, Harbin, China.
FAU - Jiang, Jiuyang
AU  - Jiang J
AD  - Department of Traditional Chinese Medicine, The First Affiliated Hospital of 
      Harbin Medical University, Harbin, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8576680
OTO - NOTNLM
OT  - Lupeol
OT  - M1 macrophage
OT  - M2 macrophage
OT  - metabolic syndrome (MS)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/atm-21-4561). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/11/19 06:00
MHDA- 2021/11/19 06:01
PMCR- 2021/10/01
CRDT- 2021/11/18 07:02
PHST- 2021/08/06 00:00 [received]
PHST- 2021/10/13 00:00 [accepted]
PHST- 2021/11/18 07:02 [entrez]
PHST- 2021/11/19 06:00 [pubmed]
PHST- 2021/11/19 06:01 [medline]
PHST- 2021/10/01 00:00 [pmc-release]
AID - atm-09-20-1534 [pii]
AID - 10.21037/atm-21-4561 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Oct;9(20):1534. doi: 10.21037/atm-21-4561.