PMID- 30637903
OWN - NLM
STAT- MEDLINE
DCOM- 20190611
LR  - 20210109
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Print)
IS  - 0951-418X (Linking)
VI  - 33
IP  - 3
DP  - 2019 Mar
TI  - Isoforskolin and forskolin attenuate lipopolysaccharide-induced inflammation 
      through TLR4/MyD88/NF-kappaB cascades in human mononuclear leukocytes.
PG  - 602-609
LID - 10.1002/ptr.6248 [doi]
AB  - The principal active component of isoforskolin (ISOF) is from the plant Coleus 
      forskohlii, native to China, which has attracted much attention for its 
      biological effects. We hypothesize that ISOF and forskolin (FSK) pretreatment 
      attenuates inflammation induced by lipopolysaccharide (LPS) related to toll-like 
      receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor 
      kappa B (NF-kappaB) signaling. Mononuclear leukocytes (MLs) from healthy donors' 
      blood samples were separated by using density gradient centrifugation. Protein 
      levels of TLR4, MyD88, and NF-kappaB were detected using western blot and 
      inflammatory cytokines interleukin (IL) 1beta, IL-2, IL-6, IL-21, IL-23, tumor 
      necrosis factor (TNF) alpha, and TNF-beta were tested by enzyme-linked immunosorbent 
      assay and Quantibody array in MLs. Our results showed that LPS augmented the 
      protein levels of TLR4, MyD88, and NF-kappaB in MLs and the production of IL-1beta, 
      IL-2, IL-6, IL-21, IL-23, TNF-alpha, and TNF-beta in supernatants of MLs. Despite 
      treatment with ISOF and FSK prior to LPS, the protein levels of TLR4, MyD88, 
      NF-kappaB, IL-1beta, IL-2, IL-6, IL-21, IL-23, TNF-alpha, and TNF-beta in MLs were apparently 
      decreased. roflumilast (RF) and dexamethasone (DM) had a similar effect on MLs 
      with ISOF and FSK. Our results, for the first time, have shown that ISOF and FSK 
      attenuate inflammation in MLs induced by LPS through down-regulating protein 
      levels of IL-1beta and TNF-alpha, in which TLR4/MyD88/NF-kappaB signal pathway could be 
      involved.
CI  - (c) 2019 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
FAU - Du, Xiaohua
AU  - Du X
AUID- ORCID: 0000-0003-1777-024X
AD  - School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for 
      Natural Products, Kunming Medical University, Kunming, China.
AD  - First Affiliated Hospital of Kunming Medical University, Kunming, China.
FAU - Shi, Rui
AU  - Shi R
AD  - School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for 
      Natural Products, Kunming Medical University, Kunming, China.
FAU - Wang, Youlan
AU  - Wang Y
AD  - Kunming Medical Science Research Institute, Kunming, China.
FAU - Wu, Wenjuang
AU  - Wu W
AD  - Second Affiliated Hospital of Kunming Medical University, Kunming, China.
FAU - Sun, Shibo
AU  - Sun S
AD  - First Affiliated Hospital of Kunming Medical University, Kunming, China.
FAU - Dai, Zelan
AU  - Dai Z
AD  - School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for 
      Natural Products, Kunming Medical University, Kunming, China.
FAU - Chen, Chen
AU  - Chen C
AD  - School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for 
      Natural Products, Kunming Medical University, Kunming, China.
FAU - Weng, Zhiying
AU  - Weng Z
AD  - School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for 
      Natural Products, Kunming Medical University, Kunming, China.
FAU - Li, Xian
AU  - Li X
AD  - School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for 
      Natural Products, Kunming Medical University, Kunming, China.
FAU - Liu, Qian
AU  - Liu Q
AD  - First Affiliated Hospital of Kunming Medical University, Kunming, China.
FAU - Zhang, Liyan
AU  - Zhang L
AD  - First Affiliated Hospital of Kunming Medical University, Kunming, China.
FAU - Saidian, Mayer
AU  - Saidian M
AD  - Beckman Laser Institute, University of California, Irvine, California.
AD  - The Institute for Drug Research, School of Pharmacy, Hebrew University of 
      Jerusalem, Jerusalem, Israel.
FAU - Yang, Weimin
AU  - Yang W
AUID- ORCID: 0000-0001-7505-7122
AD  - School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for 
      Natural Products, Kunming Medical University, Kunming, China.
LA  - eng
GR  - No.ZD2015009 and 2015C009Y/Yunnan Provincial Department of Education/
GR  - 2017FA043/Yunnan Provincial Science and Technology Department/
GR  - 2014BC012/Yunnan Provincial Science and Technology Department/
GR  - 2014IA033/Yunnan Provincial Science and Technology Department/
GR  - 2017FE467-028/Yunnan Provincial Science and Technology Department/
GR  - 2017FE467-019/Yunnan Provincial Science and Technology Department/
GR  - 2018FE001-026/Yunnan Provincial Science and Technology Department/
GR  - 2017IC041/Yunnan Provincial Science and Technology Department/
GR  - 81860012/National Natural Science Foundation of China/
GR  - 81402991/National Natural Science Foundation of China/
GR  - 81560589/National Natural Science Foundation of China/
GR  - 81173110/National Natural Science Foundation of China/
GR  - 81870037/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20190114
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 1F7A44V6OU (Colforsin)
SB  - IM
MH  - Colforsin/*pharmacology
MH  - Cytokines/analysis
MH  - Humans
MH  - Inflammation/*drug therapy
MH  - Leukocytes, Mononuclear/*drug effects/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Myeloid Differentiation Factor 88/*physiology
MH  - NF-kappa B/*physiology
MH  - Signal Transduction/*drug effects
MH  - Toll-Like Receptor 4/*physiology
PMC - PMC6590664
OTO - NOTNLM
OT  - FSK
OT  - ISOF
OT  - MyD88
OT  - NF-kappaB
OT  - TLR4
OT  - inflammation
COIS- The funders had no role in the study design, data collection and analysis, 
      decision to publish, or preparation of the manuscript. The authors state no 
      conflict of interest.
EDAT- 2019/01/15 06:00
MHDA- 2019/06/14 06:00
PMCR- 2019/06/24
CRDT- 2019/01/15 06:00
PHST- 2018/02/03 00:00 [received]
PHST- 2018/11/02 00:00 [revised]
PHST- 2018/11/12 00:00 [accepted]
PHST- 2019/01/15 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2019/01/15 06:00 [entrez]
PHST- 2019/06/24 00:00 [pmc-release]
AID - PTR6248 [pii]
AID - 10.1002/ptr.6248 [doi]
PST - ppublish
SO  - Phytother Res. 2019 Mar;33(3):602-609. doi: 10.1002/ptr.6248. Epub 2019 Jan 14.