Effects of Pogonatherum paniceum (Lamk) Hack extract on antimitochondrial DNA mediated inflammation by attenuating Tlr9 expression in LPS-induced macrophages

BACKGROUND/OBJECTIVES@#Mitochondrial DNA leakage leads to inflammatory responses via endosome activation. This study aims to evaluate whether the perennial grass water extract (Pogonatherum paniceum) ameliorate mitochondrial DNA (mtDNA) leakage.MATERIALS/METHODS: The major bioactive constituents of P. paniceum (PPW) were investigated by high-performance liquid chromatography, after which their antioxidant activities were assessed. In addition, RAW 264.7 macrophages were stimulated with lipopolysaccharide, resulting in mitochondrial damage. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to examine the gene expression and cytokines. @*RESULTS@#Our results showed that PPW extract-treated activated cells significantly decrease reactive oxygen species and nitric oxide levels by reducing the p22 phox and iNOS expression and lowering cytokine-encoding genes, including IL-6, TNF-α, IL-1β, PG-E2 and IFN-γ relative to the lipopolysaccharide (LPS)-activated macrophages. Furthermore, we observed that LPS enhanced the mtDNA leaked into the cytoplasm, increasing the transcription of Tlr9 and signaling both MyD88/Irf7-dependent interferon and MyD88/NF-κb p65-dependent inflammatory cytokine mRNA expression but which was alleviated in the presence of PPW extract. @*CONCLUSIONS@#Our data show that PPW extract has antioxidant and anti-inflammatory activities by facilitating mtDNA leakage and lowering the Tlr9 expression and signaling activation.

Anti-insulin resistant effect of ferulic acid on high fat diet-induced obese mice

Objective: To evaluate the insulin sensitivity action of ferulic acid (FA) in skeletal muscle and hypothalamus of high-fat diet (HFD)-induced obese mice. Methods: Obese mouse model was induced by HFD (45 kcal% lard fat) for 16 weeks. After 8 weeks of HFD feeding, these obese mice were orally treated with FA at doses of 25 and 50 mg/kg/day for 8 weeks. At the end of all treatments, the epididymal fat, pancreas, skeletal muscle and hypothalamus were removed for biochemical parameter and protein expression examinations. Results: FA treatment significantly decreased leptin level in fat tissue and insulin level in pancreas (P < 0.05). Interestingly, obese mice treated with FA increased the protein expressions of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and phosphorylated-protein kinase B in both muscle and brain (P < 0.05). The phosphorylations of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase in muscle, and leptin receptor protein in hypothalamus were also increased (P < 0.05). The pancreatic islets histology showed smaller size in obese mice treated with FA compared to untreated obese mice. Conclusions: These findings indicate the beneficial effect of FA in improving insulin resistance in HFD-induced obese mice. These effects are probably mediated via modulating the insulin receptor substrate/phosphatidylinositol 3-kinase/protein kinase B or adenosine monophosphate-activated protein kinase pathways.

Vasoprotective effects of rice bran water extract on rats fed with high-fat diet

Objective To elucidate the protective effects of rice bran water extract on the expression of endothelial nitric oxide synthase (eNOS), nuclear factor-kappa B (NF-κB), and a cluster of differentiation 36 (CD36) in the vasculature of high-fat diet-fed rats. Methods Male Sprague-Dawley rats were divided into three groups. Group I served as control, Group II was treated with high-fat diet, and Group III was treated with high-fat diet and rice bran water extract at 2 205 mg/kg/day. After four weeks, the metabolic parameters, malondialdehyde as a marker of oxidative stress, and histological features of the aorta were evaluated. The levels of transcripts and proteins in aorta were determined by real-time PCR and Western blot analysis, respectively. Results In comparison with the Group II, rice bran water extract administration resulted in a significant reduction in body weight, visceral fat tissue weights, blood glucose levels, and serum total-cholesterol and free fatty acid levels in Group III. Serum triglyceride levels tended to decrease in the Group III. Also, rice bran water extract administration obviously decreased malondialdehyde levels in both serum and aorta. Interestingly, rice bran water extract treatment demonstrated a significant up-regulation of eNOS expression and down-regulation of NF-κB p65 and CD36 expressions. Nonetheless, all groups showed normal histology of aorta. Conclusions Rice bran water extract exhibited vasoprotective effects in the high-fat diet-induced obesity condition by modulating the expression of eNOS, NF-κB, and CD36 and metabolic parameters.