PMID- 37896119
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231030
IS  - 2223-7747 (Print)
IS  - 2223-7747 (Electronic)
IS  - 2223-7747 (Linking)
VI  - 12
IP  - 20
DP  - 2023 Oct 23
TI  - Inhibitory Activity of Natural cis-Khellactone on Soluble Epoxide Hydrolase and 
      Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 
      Cells.
LID - 10.3390/plants12203656 [doi]
LID - 3656
AB  - The pursuit of anti-inflammatory agents has led to intensive research on the 
      inhibition of soluble epoxide hydrolase (sEH) and cytokine production using 
      medicinal plants. In this study, we evaluated the efficacy of cis-khellactone, a 
      compound isolated for the first time from the roots of Peucedanum japonicum. The 
      compound was found to be a competitive inhibitor of sEH, exhibiting an IC(50) 
      value of 3.1 +/- 2.5 microM and k(i) value of 3.5 microM. Molecular docking and dynamics 
      simulations illustrated the binding pose of (-)cis-khellactone within the active 
      site of sEH. The results suggest that binding of the inhibitor to the enzyme is 
      largely dependent on the Trp336-Gln384 loop within the active site. Further, 
      cis-khellactone was found to inhibit pro-inflammatory cytokines, including NO, 
      iNOS, IL-1beta, and IL-4. These findings affirm that cis-khellactone could serve as 
      a natural therapeutic candidate for the treatment of inflammation.
FAU - Kim, Jang Hoon
AU  - Kim JH
AD  - Department of Herbal Crop Research, National Institute of Horticultural and 
      Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of Korea.
FAU - Park, Ji Hyeon
AU  - Park JH
AD  - Institute of Health Science, Jeonju University, 303 Cheonjam-ro, Wansan-gu, 
      Jeonju-si 55069, Jeollabuk-do, Republic of Korea.
FAU - Koo, Sung Cheol
AU  - Koo SC
AD  - Department of Herbal Crop Research, National Institute of Horticultural and 
      Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of Korea.
FAU - Huh, Yun-Chan
AU  - Huh YC
AD  - Department of Herbal Crop Research, National Institute of Horticultural and 
      Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of Korea.
FAU - Hur, Mok
AU  - Hur M
AD  - Department of Herbal Crop Research, National Institute of Horticultural and 
      Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of Korea.
FAU - Park, Woo Tae
AU  - Park WT
AD  - Department of Herbal Crop Research, National Institute of Horticultural and 
      Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of Korea.
FAU - Moon, Youn-Ho
AU  - Moon YH
AD  - Department of Herbal Crop Research, National Institute of Horticultural and 
      Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of Korea.
FAU - Kim, Tae Il
AU  - Kim TI
AD  - Department of Herbal Crop Research, National Institute of Horticultural and 
      Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of Korea.
FAU - Cho, Byoung Ok
AU  - Cho BO
AUID- ORCID: 0000-0001-8272-2282
AD  - Institute of Health Science, Jeonju University, 303 Cheonjam-ro, Wansan-gu, 
      Jeonju-si 55069, Jeollabuk-do, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20231023
PL  - Switzerland
TA  - Plants (Basel)
JT  - Plants (Basel, Switzerland)
JID - 101596181
PMC - PMC10610198
OTO - NOTNLM
OT  - anti-inflammation
OT  - cis-khellactone
OT  - competitive inhibitor
OT  - molecular simulation
OT  - soluble epoxide hydrolase
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/28 11:46
MHDA- 2023/10/28 11:47
PMCR- 2023/10/23
CRDT- 2023/10/28 01:25
PHST- 2023/09/12 00:00 [received]
PHST- 2023/10/16 00:00 [revised]
PHST- 2023/10/18 00:00 [accepted]
PHST- 2023/10/28 11:47 [medline]
PHST- 2023/10/28 11:46 [pubmed]
PHST- 2023/10/28 01:25 [entrez]
PHST- 2023/10/23 00:00 [pmc-release]
AID - plants12203656 [pii]
AID - plants-12-03656 [pii]
AID - 10.3390/plants12203656 [doi]
PST - epublish
SO  - Plants (Basel). 2023 Oct 23;12(20):3656. doi: 10.3390/plants12203656.