PMID- 32028186
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20200729
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 68
DP  - 2020 Mar
TI  - Patriscabrin F from the roots of Patrinia scabra attenuates LPS-induced 
      inflammation by downregulating NF-kappaB, AP-1, IRF3, and STAT1/3 activation in RAW 
      264.7 macrophages.
PG  - 153167
LID - S0944-7113(19)30483-0 [pii]
LID - 10.1016/j.phymed.2019.153167 [doi]
AB  - BACKGROUND: The roots of Partrinia scabra have been used as a medicinal herb in 
      Asia. We previously reported that the inhibitory effect of patriscabrin F on 
      lipopolysaccharide (LPS)-induced nitric oxide (NO) production was the most potent 
      than that of other isolated iridoids from the roots of P. scabra. PURPOSE: We 
      investigated the anti-inflammatory activity of patriscabrin F as an active 
      compound of P. scabra and related signaling cascade in LPS-activated macrophages. 
      METHOD: The anti-inflammatory activities of patriscabrin F were determined 
      according to its inhibitory effects on NO, prostaglandin E(2) (PGE(2)), and 
      pro-inflammatory cytokines. The molecular mechanisms were revealed by analyzing 
      nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), interferon regulatory 
      factor 3 (IRF3), and Janus kinase (JAK)/signal transducer and activator of 
      transcription (STAT) pathway. RESULTS: Patriscabrin F inhibited the LPS-induced 
      production of NO, PGE(2,) tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, 
      and IL-6 in both bone-marrow derived macrophages (BMDMs) and RAW 264.7 
      macrophages. Patriscabrin F downregulated LPS-induced inducible nitric oxide 
      synthase (iNOS) and cyclooxygenase-2 (COX-2), TNF-alpha, IL-1beta, and IL-6 at the 
      transcriptional level. Patriscabrin F suppressed LPS-induced NF-kappaB activation by 
      decreasing p65 nuclear translocation, inhibitory kappaBalpha (IkappaBalpha) phosphorylation, and 
      IkappaB kinase (IKK)alpha/beta phosphorylation. Patriscabrin F attenuated LPS-induced AP-1 
      activity by inhibiting c-Fos phosphorylation. Patriscabrin F suppressed the 
      LPS-induced phosphorylation of IRF3, JAK1/JAK2, and STAT1/STAT3. CONCLUSION: 
      Taken together, our findings suggest patriscabrin F may exhibit anti-inflammatory 
      properties via the inhibition of NF-kappaB, AP-1, IRF3, and JAK-STAT activation in 
      LPS-induced macrophages.
CI  - Copyright (c) 2020 Elsevier GmbH. All rights reserved.
FAU - Shin, Ji-Sun
AU  - Shin JS
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, South Korea.
FAU - Kang, Shin-Young
AU  - Kang SY
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, South Korea; Department of Life and Nanopharmaceutical 
      Sciences, College of Pharmacy, Kyung Hee University, Seoul, South Korea.
FAU - Lee, Hwi-Ho
AU  - Lee HH
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, South Korea.
FAU - Kim, Seo-Yeon
AU  - Kim SY
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, South Korea; Department of Life and Nanopharmaceutical 
      Sciences, College of Pharmacy, Kyung Hee University, Seoul, South Korea.
FAU - Lee, Da Hye
AU  - Lee DH
AD  - Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee 
      University, Seoul, South Korea.
FAU - Jang, Dae-Sik
AU  - Jang DS
AD  - Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee 
      University, Seoul, South Korea.
FAU - Lee, Kyung-Tae
AU  - Lee KT
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, South Korea; Department of Life and Nanopharmaceutical 
      Sciences, College of Pharmacy, Kyung Hee University, Seoul, South Korea. 
      Electronic address: ktlee@khu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20200123
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Irf3 protein, mouse)
RN  - 0 (Iridoids)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (patriscabrin f)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Cyclooxygenase 2/metabolism
MH  - Down-Regulation/drug effects
MH  - Inflammation/*drug therapy/*metabolism/pathology
MH  - Interferon Regulatory Factor-3/metabolism
MH  - Iridoids/*pharmacology/therapeutic use
MH  - Lipopolysaccharides/toxicity
MH  - Macrophages/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Patrinia/*chemistry
MH  - Plant Roots/chemistry
MH  - RAW 264.7 Cells
MH  - STAT1 Transcription Factor/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Transcription Factor AP-1/metabolism
OTO - NOTNLM
OT  - AP-1
OT  - Macrophages
OT  - NF-Kappab
OT  - Non-glycosidic iridoid
OT  - Patrinia scabra
OT  - Patriscabrin F
COIS- Declaration of Competing Interest The authors declare that there are no conflicts 
      of interest.
EDAT- 2020/02/07 06:00
MHDA- 2020/05/12 06:00
CRDT- 2020/02/07 06:00
PHST- 2019/07/31 00:00 [received]
PHST- 2019/12/26 00:00 [revised]
PHST- 2019/12/29 00:00 [accepted]
PHST- 2020/02/07 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2020/02/07 06:00 [entrez]
AID - S0944-7113(19)30483-0 [pii]
AID - 10.1016/j.phymed.2019.153167 [doi]
PST - ppublish
SO  - Phytomedicine. 2020 Mar;68:153167. doi: 10.1016/j.phymed.2019.153167. Epub 2020 
      Jan 23.