Dyslipidemia is a significant risk factor for chronic kidney disease (CKD). Coenzyme Q10 (CoQ10), commonly recognized as a dietary supplement, exhibits a wide range of biological activities. This study aimed to investigate the efficacy of CoQ10 in mitigating renal damage in apolipoprotein E-deficient (ApoE^-/-) mice subjected to a high-fat diet (HFD). The findings revealed that a 12-week supplementation of CoQ10 (1800 mg/kg diet) significantly decreased HFD-induced elevations in levels of renal function parameters, including serum uric acid (SUA; from (54.84 ± 6.35) to (37.96 ± 5.25) μmol/L; P < 0.001), creatinine (SCr; from (22.72 ± 2.69) to (14.02 ± 2.72) μmol/L; P < 0.001), and blood urea nitrogen (BUN; from (5.79 ± 0.65) to (3.70 ± 1.01) mmol/L; P < 0.001). Moreover, CoQ10 supplementation significantly ameliorated HFD-induced pathological alterations, lipid accumulation (P < 0.01), oxidative stress (P < 0.01), inflammation (P < 0.05), and fibrosis (P < 0.01) in the kidneys. Furthermore, untargeted lipidomics analysis of the kidneys demonstrated that CoQ10 effectively promoted the recovery of differential lipid species, primarily including glycerophospholipids (GP), glycerolipids (GL), and sphingolipids (SP) in HFD-fed mice (P < 0.05). Additionally, targeted lipidomic analysis of GP suggested that a HFD led to an increase in renal concentrations of various lipid metabolites, primarily within the osphatidylcholines (PC) and 1-(1Z-alkenyl),2-acylglycerophosphoethanolamines (PE_P) classes. These alterations were favorably restored by CoQ10 supplementation (P < 0.05). Furthermore, Western blot analysis demonstrated that CoQ10 significantly downregulated renal PI3K/Akt (P < 0.01) and TLR4/MyD88/NFκB (P < 0.05) signaling pathways in HFD-fed mice. Consequently, this study suggests that CoQ10 exerts a potent regulatory effect on lipid metabolism disorders induced by a HFD, thereby contributing to the mitigation of renal injury under hyperlipidemic conditions.

Monocyte-mediated inflammatory responses play a key role in the progression of atherosclerosis. Anthocyanins are polyphenolic flavonoids that are abundant in various dark-colored vegetables, fruits and cereals, which possess a wide range of biological activities. Cyanidin-3-O-β-glucoside (Cy-3-g) is an important anthocyanin monomer. The current study aimed to explore the effects of black rice-derived Cy-3-g on lipopolysaccharide (LPS)-induced inflammatory responses in Tohoku hospital pediatrics-1 (THP-1) as well as its possible mechanism of action. Crudeanthocyanins from black rice were obtained by extraction with ethanol-hydrochloric acid solution and macroporous resin adsorption and purified by medium-pressure liquid chromatography with UV detection. Cy-3-g with a purity greater than 96.5% was obtained. THP-1 monocytes were sequentially incubated with different concentrations (0, 0.1, 0.25 and 0.5 μg/mL) Cy-3-g for 4 h, and LPS (50 ng/mL) for additional 48 h. The levels of interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α in the culture were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of the genes encoding IL-1β, IL-6, IL-8, IL-10, TNF-α, Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 were measured by quantitative polymerase chain reaction (PCR). Moreover, the protein expression levels of TLR4, NF-κB p65 and inhibitor of NF-κB (IκBα) were detected by Western blot. The LPS-induced increase in the relative mRNA expression levels and release levels of IL-1β, IL-6 and TNF-α in THP-1 cells was significantly inhibited by all concentrations of Cy-3-g tested (P < 0.05, P < 0.01 and P < 0.001, respectively). Cy-3-g at 0.25 and 0.50 μg/mL significantly blunted the inhibitory effect of LPS on IL-10 mRNA expression (P < 0.01 and P < 0.001, respectively). Cy-3-g at 0.10, 0.25 and 0.50 μg/mL significantly mitigated the inhibitory effect of LPS on IL-10 release (P < 0.05, P < 0.01 and P < 0.001, respectively), but had no significant influence on LPS-induced promotion of IL-8 mRNA expression and release levels (P > 0.05). Cy-3-g at 0.25 and 0.50 μg/mL significantly inhibited the mRNA and protein expression of TLR4 and NF-κB p65 (P < 0.05, P < 0.01 and P < 0.001, respectively), suppressed the expression of phosphorylated IκBα and NF-κB, and inhibited LPS-induced IκBα degradation. Bay11-7082, a specific inhibitor of NF-κB, significantly decreased the release of IL-1β, IL-6 and TNF-α in LPS-stimulated THP-1 cells (P < 0.001), but had no synergistic effects with 0.50 μg/mL Cy-3-g (P > 0.05). Black rice-derived Cy-3-g exerts a protective effect on LPS-induced inflammatory injury of THP-1 monocytes possibly through down-regulating the TLR4/NF-κB signaling pathway.

Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases. Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein (ox-LDL) particles, a process that induces atherothrombosis. Sulforaphane (SFN) is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities. The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo. Using a series of platelet functional assays in human platelets in vitro, we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation (surface CD62P expression). Mechanistically, studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases, leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling, and resultant inhibition of NADPH oxidase 2 (NOX2) -dependent generation of reactive oxygen species (ROS). Moreover, 12-week supplementation of SFN-enriched broccoli sprout extract (BSE, 0.06% diet) in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity. Studies using pharmacological inhibitors of CD36, protein kinase A (PKA) and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling. Thus, through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity, SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.