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.
Highlights
The plant Coleus forskohlii is distributed primarily in India, Thailand, China, Egypt, and Brazil and has a history of use in the treatment of multiple diseases
Our results showed that LPS augmented the protein levels of toll‐like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF‐κB in Mononuclear leukocytes (MLs) and the production of IL‐ 1β, IL‐2, IL‐6, IL‐21, IL‐23, tumor necrosis factor (TNF)‐α, and TNF‐β in supernatants of MLs
Our previous study demonstrated that ISOF activated adenylyl cyclases (ACs) and increased cyclic adenosine monophosphate levels in rat liver homogenate, and it relaxed the contraction of isolated guinea pig lung and trachea smooth muscle induced by histamine (Wang & Cao, 2013)
Summary
The plant Coleus forskohlii is distributed primarily in India, Thailand, China, Egypt, and Brazil and has a history of use in the treatment of multiple diseases. Our previous study showed ISOF activated ACs, increased cAMP, and attenuated inflammation in ALI induced by lipopolysaccharide (LPS; Yang et al, 2011). Another study showed AC activation attenuated transmembrane toll‐like receptor 4 (TLR4) signaling in a murine macrophage cell line (RAW264.7) and bone marrow‐derived macrophages when stimulated with LPS (Cai, Du, Feng, et al, 2013). On the basis of the above factors and to better understand biological effects of ISOF, we hypothesized that ISOF and FSK pretreatment attenuated inflammatory reaction through down‐regulation inflammatory factors such as the protein levels of TNF‐α, IL‐1β, and other inflammatory factors in supernatant of mononuclear leukocytes (MLs) induced by LPS, and the mechanism of anti‐inflammation of ISOF partly related to TLR4/MyD88/NF‐κB signal pathway
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