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Isoforskolin and forskolin attenuate lipopolysaccharide-induced inflammation through TLR4/MyD88/NF-κB cascades in human mononuclear leukocytes
- Source :
- Phytotherapy Research. 33:602-609
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- 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-κB) signaling. Mononuclear leukocytes (MLs) from healthy donors' blood samples were separated by using density gradient centrifugation. Protein levels of TLR4, MyD88, and NF-κB were detected using western blot and inflammatory cytokines interleukin (IL) 1β, IL-2, IL-6, IL-21, IL-23, tumor necrosis factor (TNF) α, and TNF-β 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-κB in MLs and the production of IL-1β, IL-2, IL-6, IL-21, IL-23, TNF-α, and TNF-β in supernatants of MLs. Despite treatment with ISOF and FSK prior to LPS, the protein levels of TLR4, MyD88, NF-κB, IL-1β, IL-2, IL-6, IL-21, IL-23, TNF-α, and TNF-β 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-1β and TNF-α, in which TLR4/MyD88/NF-κB signal pathway could be involved.
- Subjects :
- Pharmacology
0303 health sciences
Forskolin
Lipopolysaccharide
030302 biochemistry & molecular biology
Interleukin
Inflammation
Molecular biology
Proinflammatory cytokine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
chemistry
030220 oncology & carcinogenesis
medicine
TLR4
Tumor necrosis factor alpha
medicine.symptom
Receptor
Subjects
Details
- ISSN :
- 0951418X
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Phytotherapy Research
- Accession number :
- edsair.doi...........83c513040c490fbc0773011effd95fd5