机构：[1]School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, China[2]First Affiliated Hospital of Kunming Medical University, Kunming, China昆明医科大学附属第一医院[3]Kunming Medical Science Research Institute, Kunming, China昆明医科大学附属第一医院[4]Second Affiliated Hospital of Kunming Medical University, Kunming, China[5]Beckman Laser Institute, University of California, Irvine, California[6]The Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel
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-kappa B) signaling. Mononuclear leukocytes (MLs) from healthy donors' blood samples were separated by using density gradient centrifugation. Protein levels of TLR4, MyD88, and NF-kappa B were detected using western blot and inflammatory cytokines interleukin (IL) 1 beta, 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-kappa B in MLs and the production of IL-1 beta, 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-kappa B, IL-1 beta, 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-1 beta and TNF-alpha, in which TLR4/MyD88/NF-kappa B signal pathway could be involved.
基金：
Yunnan Provincial Department of Education [ZD2015009, 2015C009Y]; Yunnan Provincial Science and Technology Department [2017FA043, 2014BC012, 2014IA033, 2017FE467-028, 2017FE467-019, 2018FE001-026, 2017IC041]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81860012, 81402991, 81560589, 81173110, 81870037]
第一作者机构：[1]School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, China[2]First Affiliated Hospital of Kunming Medical University, Kunming, China
通讯作者：
通讯机构：[*1]Beckman Laser Institute, University of California, Irvine, CA 92612.[*2]School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
推荐引用方式(GB/T 7714)：
Du Xiaohua,Shi Rui,Wang Youlan,et al.Isoforskolin and forskolin attenuate lipopolysaccharide-induced inflammation through TLR4/MyD88/NF-kappa B cascades in human mononuclear leukocytes[J].PHYTOTHERAPY RESEARCH.2019,33(3):602-609.doi:10.1002/ptr.6248.
APA：
Du, Xiaohua,Shi, Rui,Wang, Youlan,Wu, Wenjuang,Sun, Shibo...&Yang, Weimin.(2019).Isoforskolin and forskolin attenuate lipopolysaccharide-induced inflammation through TLR4/MyD88/NF-kappa B cascades in human mononuclear leukocytes.PHYTOTHERAPY RESEARCH,33,(3)
MLA：
Du, Xiaohua,et al."Isoforskolin and forskolin attenuate lipopolysaccharide-induced inflammation through TLR4/MyD88/NF-kappa B cascades in human mononuclear leukocytes".PHYTOTHERAPY RESEARCH 33..3(2019):602-609
