PMID- 37958556
OWN - NLM
STAT- MEDLINE
DCOM- 20231129
LR  - 20231129
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 21
DP  - 2023 Oct 25
TI  - Alismol Purified from the Tuber of Alisma orientale Relieves Acute Lung Injury in 
      Mice via Nrf2 Activation.
LID - 10.3390/ijms242115573 [doi]
LID - 15573
AB  - Since the ethanol extract of Alisma orientale Juzepzuk (EEAO) suppresses lung 
      inflammation by suppressing Nuclear Factor-kappa B (NF-kappaB) and activating Nuclear 
      Factor Erythroid 2-related Factor 2 (Nrf2), we set out to identify chemicals 
      constituting EEAO that suppress lung inflammation. Here, we provide evidence that 
      among the five most abundant chemical constituents identified by Ultra 
      Performance Liquid Chromatography (UPLC) and Nuclear Magnetic Resonance (NMR), 
      alismol is one of the candidate constituents that suppresses lung inflammation in 
      a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model and 
      protects mice from ALI-like symptoms. Alismol did not induce cytotoxicity or 
      reactive oxygen species (ROS). When administered to the lung of LPS-induced ALI 
      mice (n = 5/group), alismol decreased the level of neutrophils and of the 
      pro-inflammatory molecules, including Tumor Necrosis Factor-alpha (TNF-alpha), 
      Interleukin-1 beta (IL-1beta), Interleukin-6 (IL-6), Monocyte Chemoattractant 
      Protein-1 (MCP-1), Interferon-gamma (IFN-gamma), and Cyclooxygenase-2 (COX-2), 
      suggesting an anti-inflammatory activity of alismol. Consistent with these 
      findings, alismol ameliorated the key features of the inflamed lung of ALI, such 
      as high cellularity due to infiltrated inflammatory cells, the development of 
      hyaline membrane structure, and capillary destruction. Unlike EEAO, alismol did 
      not suppress NF-kappaB activity but rather activated Nrf2. Consequently, alismol 
      induced the expression of prototypic genes regulated by Nrf2, including Heme 
      Oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase-1 (NQO-1), and glutamyl 
      cysteine ligase catalytic units (GCLC). Alismol activating Nrf2 appears to be 
      associated with a decrease in the ubiquitination of Nrf2, a key suppressive 
      mechanism for Nrf2 activity. Together, our results suggest that alismol is a 
      chemical constituent of EEAO that contributes at least in part to suppressing 
      some of the key features of ALI by activating Nrf2.
FAU - Kim, Kyun Ha
AU  - Kim KH
AD  - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of 
      Korea.
FAU - Kim, Soyeon
AU  - Kim S
AUID- ORCID: 0000-0001-9879-1477
AD  - Department of Internal Medicine, Korean Medicine Hospital, Pusan National 
      University, Yangsan 50612, Republic of Korea.
FAU - Kwun, Min Jung
AU  - Kwun MJ
AD  - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of 
      Korea.
FAU - Lee, Ji Yeon
AU  - Lee JY
AD  - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of 
      Korea.
FAU - Oh, Sei-Ryang
AU  - Oh SR
AUID- ORCID: 0000-0002-9769-4779
AD  - Natural Medicine Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Cheongju 363-883, Republic of Korea.
FAU - Choi, Jun-Yong
AU  - Choi JY
AD  - Department of Internal Medicine, Korean Medicine Hospital, Pusan National 
      University, Yangsan 50612, Republic of Korea.
FAU - Joo, Myungsoo
AU  - Joo M
AUID- ORCID: 0000-0002-5417-1732
AD  - School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of 
      Korea.
LA  - eng
GR  - 2018R1A2A307565013 and 2020R1A2C1004267/NSF of Korea/
PT  - Journal Article
DEP - 20231025
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 87827-55-2 (alismol)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Acute Lung Injury/metabolism
MH  - *Alisma
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - Interleukin-6/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - NF-kappa B/metabolism
MH  - *Pneumonia/metabolism
PMC - PMC10647250
OTO - NOTNLM
OT  - Alisma orientale Juzepzuk
OT  - NF-kappaB
OT  - Nrf2
OT  - acute lung injury
OT  - alismol
OT  - mouse model
OT  - neutrophilic lung inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/14 06:43
MHDA- 2023/11/15 06:42
PMCR- 2023/10/25
CRDT- 2023/11/14 02:08
PHST- 2023/09/04 00:00 [received]
PHST- 2023/10/19 00:00 [revised]
PHST- 2023/10/20 00:00 [accepted]
PHST- 2023/11/15 06:42 [medline]
PHST- 2023/11/14 06:43 [pubmed]
PHST- 2023/11/14 02:08 [entrez]
PHST- 2023/10/25 00:00 [pmc-release]
AID - ijms242115573 [pii]
AID - ijms-24-15573 [pii]
AID - 10.3390/ijms242115573 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Oct 25;24(21):15573. doi: 10.3390/ijms242115573.