Isoforskolin and forskolin attenuate lipopolysaccharide-induced inflammation through TLR4/MyD88/NF-κB cascades in human mononuclear leukocytes.

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.

• Authors: Xiaohua Du, Rui Shi, Youlan Wang, Wenjuang Wu, Shibo Sun, Zelan Dai, Chen Chen, Zhiying Weng, Xian Li, Qian Liu, Liyan Zhang, Mayer Saidian, Weimin Yang
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 33 Issue 3 Pg. 602-609 (Mar 2019) ISSN: 1099-1573 [Electronic] England
• PMID: 30637903 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

Chemical References

• Cytokines
• Lipopolysaccharides
• MYD88 protein, human
• Myeloid Differentiation Factor 88
• NF-kappa B
• TLR4 protein, human
• Toll-Like Receptor 4
• Colforsin

Topics

• Colforsin (pharmacology)
• Cytokines (analysis)
• Humans
• Inflammation (drug therapy)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Lipopolysaccharides (toxicity)
• Myeloid Differentiation Factor 88 (physiology)
• NF-kappa B (physiology)
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (physiology)