PMID- 32290267
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20240328
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 25
IP  - 7
DP  - 2020 Apr 10
TI  - Chemical Constituents with GNMT-Promoter-Enhancing and NRF2-Reduction Activities 
      from Taiwan Agarwood Excoecaria formosana.
LID - 10.3390/molecules25071746 [doi]
LID - 1746
AB  - Hepatocellular carcinoma (HCC) is considered to be a silent killer, and was the 
      fourth leading global cause of cancer deaths in 2018. For now, sorafenib is the 
      only approved drug for advanced HCC treatment. The introduction of additional 
      chemopreventive agents and/or adjuvant therapies may be helpful for the treatment 
      of HCC. After screening 3000 methanolic extracts from the Formosan plant extract 
      bank, Excoecaria formosana showed glycine N-methyltransferase 
      (GNMT)-promoter-enhancing and nuclear factor erythroid 2-related factor 2 
      (NRF2)-suppressing activities. Further, the investigation of the whole plant of 
      E. formosana led to the isolation of a new steroid, 
      7alpha-hydroperoxysitosterol-3-O-beta-d-(6-O-palmitoyl)glucopyranoside (1); two new 
      coumarinolignans, excoecoumarin A (2) and excoecoumarin B (3); a new diterpene, 
      excoeterpenol A (4); and 40 known compounds (5-44). Among them, Compounds 38 and 
      40-44 at a 100 muM concentration showed a 2.97 +/- 0.27-, 3.17 +/- 1.03-, 2.73 +/- 
      0.23-, 2.63 +/- 0.14-, 6.57 +/- 0.13-, and 2.62 +/- 0.05-fold increase in GNMT promoter 
      activity, respectively. In addition, Compounds 40 and 43 could reduce NRF2 
      activity, a transcription factor associated with drug resistance, in Huh7 cells 
      with relative activity of 33.1 +/- 0.2% and 45.2 +/- 2.5%. These results provided the 
      basis for the utilization of Taiwan agarwood for the development of anti-HCC 
      agents.
FAU - Wu, Ho-Cheng
AU  - Wu HC
AD  - Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical 
      University, Kaohsiung 807, Taiwan.
FAU - Cheng, Ming-Jen
AU  - Cheng MJ
AD  - Bioresource Collection and Research Center (BCRC), Food Industry Research and 
      Development Institute (FIRDI), Hsinchu 300, Taiwan.
FAU - Yen, Chia-Hung
AU  - Yen CH
AUID- ORCID: 0000-0002-6939-5528
AD  - Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical 
      University, Kaohsiung 807, Taiwan.
AD  - Drug Development and Value Creation Research Center, Kaohsiung Medical 
      University, Kaohsiung 807, Taiwan.
FAU - Chen, Yi-Ming Arthur
AU  - Chen YA
AD  - Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of 
      Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
AD  - Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei 
      112, Taiwan.
FAU - Chen, Yi-Siao
AU  - Chen YS
AD  - Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, 
      Kaohsiung Medical University, Kaohsiung 807, Taiwan.
FAU - Chen, Ih-Sheng
AU  - Chen IS
AD  - School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 
      807, Taiwan.
FAU - Chang, Hsun-Shuo
AU  - Chang HS
AUID- ORCID: 0000-0003-2745-139X
AD  - Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical 
      University, Kaohsiung 807, Taiwan.
AD  - Drug Development and Value Creation Research Center, Kaohsiung Medical 
      University, Kaohsiung 807, Taiwan.
AD  - School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 
      807, Taiwan.
AD  - Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 
      807, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20200410
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Plant Extracts)
RN  - EC 2.1.1.20 (Glycine N-Methyltransferase)
SB  - IM
MH  - Euphorbiaceae/*chemistry
MH  - Gene Expression Regulation/*drug effects
MH  - Glycine N-Methyltransferase/*genetics
MH  - Humans
MH  - Molecular Structure
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Oxidation-Reduction/drug effects
MH  - Plant Extracts/*chemistry/*pharmacology
MH  - *Promoter Regions, Genetic
MH  - Structure-Activity Relationship
MH  - Taiwan
PMC - PMC7181199
OTO - NOTNLM
OT  - Euphorbiaceae
OT  - Excoecaria formosana
OT  - GNMT promoter activity
OT  - NRF2 activity
OT  - secondary metabolites
COIS- The authors declare no conflicts of interest.
EDAT- 2020/04/16 06:00
MHDA- 2021/01/05 06:00
PMCR- 2020/04/10
CRDT- 2020/04/16 06:00
PHST- 2020/03/06 00:00 [received]
PHST- 2020/04/05 00:00 [revised]
PHST- 2020/04/07 00:00 [accepted]
PHST- 2020/04/16 06:00 [entrez]
PHST- 2020/04/16 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2020/04/10 00:00 [pmc-release]
AID - molecules25071746 [pii]
AID - molecules-25-01746 [pii]
AID - 10.3390/molecules25071746 [doi]
PST - epublish
SO  - Molecules. 2020 Apr 10;25(7):1746. doi: 10.3390/molecules25071746.