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.
and lipid oxidation. In the present study, we aimed to investigate the effects of probucol on high fat-high cholesterol (HFHC) diet-induced hyperlipidemia and atherosclerotic lesions, and the effects of oxidative stress in mice. Thirty male C57BL/6 J mice and thirty male apo E knockout (apoE -/-) mice were randomly divided into three groups (control group, HFHC group and HFHC-probucol group; n ¼ 10, each group). The animals in control group were fed normal diet. HFHC mice were fed a high fat/high cholesterol diet (15% lard and 0.25% cholesterol). HFHC-probucol group was supplemented with 0.5% probucol in HFHC diet. We examined the correlative index at the end of 12 weeks. The levels of serum lipid were increased in HFHC groups compared with the control group (P < 0.05), and were significantly lowered in probucol treatment group compared with respective HFHC group (P < 0.05). Serious lesions of the aorta in C57BL/6 J mice were not observed. HFHC and probucol treatment resulted in a significant reduction of aorta lesion area in apoE -/mice compared with HFHC group. Probucol contributed to a significant decrease of lipid content of the liver tissue in both C57BL/6 J and apoE -/mice as showed by hematoxylin-eosin staining. Furthermore, compared with respective control groups, the serum (MDA) contents, oxidized low density lipioprotein (ox-LDL) contents, C-reactive protein (CRP) activity, and glutathione S-transferase (GST) activity were increased, and the levels of total antioxidative capacity (T-AOC), total superoxide dismutase (T-SOD) activity, and paraoxonase 1 (PON1) activity were decreased in HFHC-treatment mice (P < 0.05), and these changes were attenuated or reversed by probucol treatment (P < 0.05). Probucol improved PON1 activities and upregulated PON1, CRP mRNA expression in liver (P < 0.05). These results show that probucol contributed significantly to prevent the oxidative stress, upregulate the PON1 expressions in the livers and increase the serum PON1 activity in the high fat-high cholesterol diet-induced hyperlipidemic mice, suggesting the potential therapeutic effects of probucol in atherosclerosis.
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