PMID- 32724488
OWN - NLM
STAT- MEDLINE
DCOM- 20210528
LR  - 20210528
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2020
DP  - 2020
TI  - Astragalus membranaceus Injection Suppresses Production of Interleukin-6 by 
      Activating Autophagy through the AMPK-mTOR Pathway in 
      Lipopolysaccharide-Stimulated Macrophages.
PG  - 1364147
LID - 10.1155/2020/1364147 [doi]
LID - 1364147
AB  - Astragalus membranaceus (AM), used in traditional Chinese medicine, has been 
      shown to enhance immune functions, and recently, its anti-inflammatory effects 
      were identified. However, the mechanisms of action remain unclear. Most studies 
      have shown that autophagy might be involved in the immune response of the body, 
      including inflammation. Here, we developed an inflammatory model by stimulating 
      macrophages with lipopolysaccharides (LPS) to explore the anti-inflammatory 
      effect and mechanisms of AM injection from the perspective of the regulation of 
      autophagy. Immunoblot, immunofluorescence, and ELISA were used to determine the 
      effects of AM injection on the production of interleukin-6 (IL-6) and alterations 
      of autophagy markers. It was found that AM injection reduced the expression of 
      IL-6 in LPS-stimulated macrophages and reversed the LPS-induced inhibition of 
      cellular autophagy. After treatment with inhibitors of signaling pathways, it was 
      shown that LPS downregulated autophagy and upregulated the production of IL-6 in 
      macrophages via the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) 
      pathway. AM injection reversed the effects of LPS by activating the AMP-activated 
      protein kinase (AMPK) instead of inhibiting Akt. These results were further 
      confirmed by testing activators and siRNA silencing of AMPK. Hence, these 2 
      distinct signaling molecules appear to exert opposite effects on mTOR, which 
      integrates information from multiple upstream signaling pathways, negatively 
      regulating autophagy. In addition, we demonstrated that autophagy might play a 
      key role in regulating the production of IL-6 by testing activators and 
      inhibitors of autophagy and siRNA silencing of ATG5. These findings showed that 
      AM injection might enhance autophagy by activating AMPK and might further play a 
      repressive effect on the LPS-stimulated expression of IL-6. This study explored 
      the relationship between autophagy, signaling pathways, and the production of 
      inflammatory factors in a model of endotoxin infection and treatment with AM 
      injection.
CI  - Copyright (c) 2020 Xiaoyan Zhang et al.
FAU - Zhang, Xiaoyan
AU  - Zhang X
AUID- ORCID: 0000-0001-8837-2770
AD  - School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, 
      China.
AD  - Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases 
      Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, 
      Jinzhong 030619, China.
AD  - Department of Laboratory Medicine, Fenyang College of Shanxi Medical University, 
      Fenyang 032200, China.
FAU - Liang, Taigang
AU  - Liang T
AUID- ORCID: 0000-0002-0674-329X
AD  - School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, 
      China.
AD  - Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases 
      Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, 
      Jinzhong 030619, China.
FAU - Yang, Wanxia
AU  - Yang W
AUID- ORCID: 0000-0002-8649-4288
AD  - Department of Laboratory Medicine, Fenyang College of Shanxi Medical University, 
      Fenyang 032200, China.
FAU - Zhang, Lanfang
AU  - Zhang L
AUID- ORCID: 0000-0002-7882-112X
AD  - Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases 
      Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, 
      Jinzhong 030619, China.
FAU - Wu, Shuting
AU  - Wu S
AUID- ORCID: 0000-0001-6770-1782
AD  - Department of Laboratory Medicine, Fenyang College of Shanxi Medical University, 
      Fenyang 032200, China.
FAU - Yan, Chaoqun
AU  - Yan C
AUID- ORCID: 0000-0002-2025-5655
AD  - School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, 
      China.
FAU - Li, Qingshan
AU  - Li Q
AUID- ORCID: 0000-0003-3201-7934
AD  - School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, 
      China.
AD  - Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases 
      Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, 
      Jinzhong 030619, China.
LA  - eng
PT  - Journal Article
DEP - 20200704
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Astragalus Plant/*chemistry
MH  - Injections
MH  - Interleukin-6/*metabolism
MH  - Lipopolysaccharides/*metabolism
MH  - Macrophages/*metabolism
MH  - Medicine, Chinese Traditional/*methods
MH  - Mice
MH  - Transfection
PMC - PMC7364262
COIS- The authors declare no conflict of interest.
EDAT- 2020/07/30 06:00
MHDA- 2021/05/29 06:00
PMCR- 2020/07/04
CRDT- 2020/07/30 06:00
PHST- 2020/02/23 00:00 [received]
PHST- 2020/05/06 00:00 [revised]
PHST- 2020/05/07 00:00 [accepted]
PHST- 2020/07/30 06:00 [entrez]
PHST- 2020/07/30 06:00 [pubmed]
PHST- 2021/05/29 06:00 [medline]
PHST- 2020/07/04 00:00 [pmc-release]
AID - 10.1155/2020/1364147 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2020 Jul 4;2020:1364147. doi: 10.1155/2020/1364147. 
      eCollection 2020.