PMID- 38417185
OWN - NLM
STAT- MEDLINE
DCOM- 20240412
LR  - 20240412
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 391
DP  - 2024 Apr
TI  - Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 
      polarization via TLR4/MyD88/NF-kappaB signaling pathway.
PG  - 117478
LID - S0021-9150(24)00038-8 [pii]
LID - 10.1016/j.atherosclerosis.2024.117478 [doi]
AB  - BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease 
      characterized by lipid infiltration and plaque formation in blood vessel walls. 
      Ganoderic acids (GA), a class of major bioactive compounds isolated from the 
      Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological 
      activities. This study aimed to determine the anti-atherosclerotic effect of GA 
      and reveal the pharmacological mechanism. METHODS: ApoE(-/-) mice were fed a 
      high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify 
      the effect of GA. Network pharmacological analysis was performed to predict the 
      anti-atherosclerotic mechanisms. An invitro cell model was used to explore the 
      effect of GA on macrophage polarization and the possible mechanism involved in 
      bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with 
      lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found 
      that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and 
      increased plaque stability, as evidenced by decreased plaque in the aorta, 
      reduced necrotic core size and increased collagen/lipid ratio in lesions. GA 
      reduced the proportion of M1 macrophages in plaques, but had no effect on M2 
      macrophages. In vitro experiments showed that GA (1, 5, 25 mug/mL) significantly 
      decreased the proportion of CD86(+) macrophages and the mRNA levels of IL-6, 
      IL-1beta, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 
      macrophage polarization by regulating TLR4/MyD88/NF-kappaB signaling pathway. 
      CONCLUSIONS: This study demonstrated that GA play an important role in plaque 
      stability and macrophage polarization. GA exert the anti-atherosclerotic effect 
      partly by regulating TLR4/MyD88/NF-kappaB signaling pathways to inhibit M1 
      polarization of macrophages. Our study provides theoretical basis and 
      experimental data for the pharmacological activity and mechanisms of GA against 
      AS.
CI  - Copyright (c) 2024 Elsevier B.V. All rights reserved.
FAU - Quan, Ya-Zhu
AU  - Quan YZ
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Ma, Ang
AU  - Ma A
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China; Artemisinin Research Center, Institute of Chinese Materia Medica, 
      China Academy of Chinese Medical Sciences, Beijing, 100007, China.
FAU - Ren, Chao-Qun
AU  - Ren CQ
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - An, Yong-Pan
AU  - An YP
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Qiao, Pan-Shuang
AU  - Qiao PS
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Gao, Cai
AU  - Gao C
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Zhang, Yu-Kun
AU  - Zhang YK
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China; Chongqing Key Laboratory of Development and Utilization of Genuine 
      Medicinal Materials in Three Gorges Reservoir Area, Chongqing Three Gorges 
      Medical College, Chongqing, 404020, China.
FAU - Li, Xiao-Wei
AU  - Li XW
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China; China Resources Pharmaceutical Group Limited, Beijing, 100000, 
      China.
FAU - Lin, Si-Mei
AU  - Lin SM
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Li, Nan-Nan
AU  - Li NN
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Chen, Di-Long
AU  - Chen DL
AD  - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal 
      Materials in Three Gorges Reservoir Area, Chongqing Three Gorges Medical College, 
      Chongqing, 404020, China.
FAU - Pan, Yan
AU  - Pan Y
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Zhou, Hong
AU  - Zhou H
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Lin, Dong-Mei
AU  - Lin DM
AD  - China National Engineering Research Center on JUNCAO Technology, Fujian 
      Agriculture and Forestry University, Fuzhou, 350002, China.
FAU - Lin, Shu-Qian
AU  - Lin SQ
AD  - China National Engineering Research Center on JUNCAO Technology, Fujian 
      Agriculture and Forestry University, Fuzhou, 350002, China.
FAU - Li, Min
AU  - Li M
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China.
FAU - Yang, Bao-Xue
AU  - Yang BX
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Department of 
      Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 
      100191, China. Electronic address: baoxue@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240208
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (NF-kappa B)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Lipids)
SB  - IM
MH  - Mice
MH  - Animals
MH  - NF-kappa B/metabolism
MH  - Myeloid Differentiation Factor 88/metabolism/pharmacology
MH  - Toll-Like Receptor 4/metabolism
MH  - *Atherosclerosis/drug therapy/prevention & control/genetics
MH  - *Plaque, Atherosclerotic/metabolism
MH  - Signal Transduction
MH  - Macrophages/metabolism
MH  - Lipids
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Ganoderic acid
OT  - Ganoderma lucidum
OT  - Inflammation
OT  - Macrophage polarization
OT  - Nuclear factor-kappa B
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/02/28 18:42
MHDA- 2024/04/12 06:44
CRDT- 2024/02/28 18:00
PHST- 2023/01/31 00:00 [received]
PHST- 2024/02/01 00:00 [revised]
PHST- 2024/02/07 00:00 [accepted]
PHST- 2024/04/12 06:44 [medline]
PHST- 2024/02/28 18:42 [pubmed]
PHST- 2024/02/28 18:00 [entrez]
AID - S0021-9150(24)00038-8 [pii]
AID - 10.1016/j.atherosclerosis.2024.117478 [doi]
PST - ppublish
SO  - Atherosclerosis. 2024 Apr;391:117478. doi: 10.1016/j.atherosclerosis.2024.117478. 
      Epub 2024 Feb 8.