PMID- 37782374
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20231102
IS  - 1976-3786 (Electronic)
IS  - 0253-6269 (Linking)
VI  - 46
IP  - 9-10
DP  - 2023 Oct
TI  - 2-Geranyl-1-methoxyerythrabyssin II alleviates lipid accumulation and 
      inflammation in hepatocytes through AMPK activation and AKT inhibition.
PG  - 808-824
LID - 10.1007/s12272-023-01464-z [doi]
AB  - A growing proportion of the global adult and pediatric populations are currently 
      affected by nonalcoholic steatohepatitis (NASH), leading to rising rates of liver 
      fibrosis and hepatocellular carcinoma without effective pharmacotherapy. Here, we 
      investigated whether 2-geranyl-1-methoxyerythrabyssin II (GMET), isolated from 
      Lespedeza bicolor, could alleviate lipid accumulation and inflammatory responses 
      in a NASH model. GMET exhibited potent in vitro and in vivo effects against lipid 
      accumulation and attenuated inflammatory responses without cytotoxicity. 
      Mechanistically, GMET inhibits acetyl-CoA carboxylase (ACC), sterol regulatory 
      element-binding proteins-1c (SREBP1), and mammalian target of rapamycin (mTOR), 
      and activates PPARalpha by activating AMP-activated kinase (AMPK), leading to the 
      alleviation of lipid accumulation. In addition, GMET suppresses the NF-kappaB pathway 
      by activating AMPK and inhibiting the activated protein kinase B (AKT)/IkappaB-kinase 
      (IKK) pathway, leading to the inhibition of the inflammatory response in 
      hepatocytes. All these protective effects of GMET on lipid accumulation and 
      inflammation in vivo and in vitro were largely abolished by co-treatment with 
      dorsomorphin, an AMPK inhibitor. In conclusion, GMET alleviated lipid 
      accumulation and inflammation to preserve normal hepatocyte function in 
      steatohepatitis. Thus, GMET is a novel potential multi-targeting compound to 
      improve steatohepatitis.
CI  - (c) 2023. The Pharmaceutical Society of Korea.
FAU - Xi, Yiyuan
AU  - Xi Y
AD  - The Clinical Research Center, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, 325000, Zhejiang, China.
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam 
      National University, Gwangju, 61186, Korea.
AD  - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of 
      Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, 
      Wenzhou, 325000, China.
FAU - Kim, Soeun
AU  - Kim S
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam 
      National University, Gwangju, 61186, Korea.
FAU - Nguyen, Thi Thanh Thuy
AU  - Nguyen TTT
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam 
      National University, Gwangju, 61186, Korea.
FAU - Lee, Phil Jun
AU  - Lee PJ
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam 
      National University, Gwangju, 61186, Korea.
FAU - Zheng, Jujia
AU  - Zheng J
AD  - The Clinical Research Center, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, 325000, Zhejiang, China.
AD  - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of 
      Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, 
      Wenzhou, 325000, China.
FAU - Lin, Zhuofeng
AU  - Lin Z
AD  - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of 
      Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, 
      Wenzhou, 325000, China. zhuofenglin@wzmc.edu.cn.
FAU - Cho, Namki
AU  - Cho N
AUID- ORCID: 0000-0002-9936-3463
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam 
      National University, Gwangju, 61186, Korea. cnamki@jnu.ac.kr.
LA  - eng
GR  - NRF-2022R1C1C1009626/Ministry of Science and ICT, South Korea/
PT  - Journal Article
DEP - 20231002
PL  - Korea (South)
TA  - Arch Pharm Res
JT  - Archives of pharmacal research
JID - 8000036
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (1-methoxyerythrabyssin II)
RN  - 0 (Lipids)
SB  - IM
MH  - Child
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Non-alcoholic Fatty Liver Disease/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Lipid Metabolism
MH  - Hepatocytes
MH  - Inflammation/metabolism
MH  - Lipids
MH  - Liver
MH  - Mice, Inbred C57BL
MH  - Mammals/metabolism
OTO - NOTNLM
OT  - AMPK
OT  - Inflammation
OT  - Lespedeza bicolor
OT  - Lipid accumulation
OT  - Nonalcoholic steatohepatitis
OT  - Pterocarpan
EDAT- 2023/10/02 12:43
MHDA- 2023/11/02 12:47
CRDT- 2023/10/02 11:06
PHST- 2022/10/12 00:00 [received]
PHST- 2023/09/12 00:00 [accepted]
PHST- 2023/11/02 12:47 [medline]
PHST- 2023/10/02 12:43 [pubmed]
PHST- 2023/10/02 11:06 [entrez]
AID - 10.1007/s12272-023-01464-z [pii]
AID - 10.1007/s12272-023-01464-z [doi]
PST - ppublish
SO  - Arch Pharm Res. 2023 Oct;46(9-10):808-824. doi: 10.1007/s12272-023-01464-z. Epub 
      2023 Oct 2.