Weeksmaher6363

7 macrophages. Mechanistically, FEE suppressed protein overexpression of TLR-4 and its downstream signals, MyD88 protein, phosphorylated inhibitory κB-α, NF-κB-P65 and MAPK p38, as well as phosphorylation of phosphoinositide 3-kinase (PI3K) p85α at Tyr607 and Akt at Ser473 in LPS-stimulated macrophages. The mode of the anti-inflammatory action of FEE was similar to that of TAK-242 (a selective TLR-4 inhibitor). CONCLUSIONS The present results demonstrate that FEE inhibit inflammatory responses via the TLR-4-mediated signaling pathway. Our findings go a new insight into the mechanisms underlying anti-inflammatory action of the herb, and provide a better understanding of its use for inflammatory diseases. ETHNOPHARMACOLOGICAL RELEVANCE The Si-miao-yong-an decoction (SMYAD) is a famous traditional Chinese medicinal formula that has been used for centuries in ancient China for treating thromboangiitis obliterans. Because of its long history of use, it has been used to treat patients in China for thousands of years. In recent years, SMYAD has been widely used for treating cardiovascular and endocrine diseases. It was shown to significantly increase high-density lipoprotein-cholesterol levels and reduce total cholesterol and low-density lipoprotein-cholesterol levels in the serum. AIM OF THE STUDY Herein, a serum metabonomics approach based on the HPLC-MS/MS method was adopted to evaluate the therapeutic effect of SMYAD on high-fat diet-induced hyperlipidemia, and investigate the mechanisms for treating hyperlipidemia. MATERIALS AND METHODS Firstly, the change in body weight, liver histopathology, and serum biochemistry, including that in the levels of hepatotoxicity-related enzymes, oxidative stress indexes, and etabolism, TCA cycle, bile acid metabolism, and glucose metabolism were identified and confirmed, to clarify the mechanism of action of SMYAD. Ac-PHSCN-NH2 Integrin antagonist CONCLUSION Using metabonomics technology, it was predicted that the therapeutic effects of SMYAD were associated with its anti-oxidation as well as anti-inflammatory activities and the adjustment of the pyruvate, taurine as well as hypotaurine metabolism pathways in the hyperlipidemic state. This study provided evidence regarding the clinical application of SMYAD and thoroughly explored the mechanism underlying the action of this traditional Chinese medicine. V.ETHNOPHARMACOLOGICAL RELEVANCE In Iranian traditional medicine, Cuminum cyminum is a unique medicinal herb for pain relief. Cuminaldehyde has been distinguished as the major constituent of C. cyminum seeds; even though, the analgesic effect of cuminaldehyde has not yet been examined. AIM OF THE STUDY The nobility of this study was to assess cuminaldehyde effect on nociceptive and neuropathic pains; furthermore, evaluation of its possible mechanisms of action. MATERIALS AND METHODS Hot plate, formalin, and acetic acid-induced writhing tests were used to evaluate nociception in mice. Naloxone (opioid receptors antagonist), L-arginine (nitric oxide (NO) precursor), L-NAME (NO synthase inhibitor), sodium nitroprusside (NO donor), methylene blue (guanylyl cyclase inhibitor), sildenafil (phosphodiesterase inhibitor), and glibenclamide (KATP channel blocker) were used to determine the implication of opioid receptors and L-arginine/NO/cGMP/KATP channel pathway. Allodynia and hyperalgesia were investigated in the CCI 1β. CONCLUSION It was attained magnificently that cuminaldehyde exerts antinociceptive and antineuropathic effects through the involvement of opioid receptors, L-arginine/NO/cGMP pathway, and anti-inflammatory function. ETHNOPHARMACOLOGICAL RELEVANCE Ilicis Rotundae Cortex (IRC), a Chinese crude drug, has been widely utilized in Guangdong and Guangxi provinces of China to treat or prevent cardiovascular diseases. AIM OF STUDY This investigation aims to study the lipid-lowering effect of IRC, as well as the regulating effect on the endogenous metabolites in hyperlipidemia rats. MATERIALS AND METHODS High-fat diet induced hyperlipidemia rats were administrated with different doses of IRC extract (0.5, 1.0 and 2.0 g/kg/day) for 5 weeks. Simvastatin was used as the positive control. Body weight, serum lipid levels and histopathology of liver were evaluated. The metabolic profiles of plasma, urine and cecum content were analyzed using UPLC/Q-TOF-MS/MS-based metabolomics approach coupled with multivariate data analysis. RESULTS The levels of serum TC, TG, LDL-C, AST and ALT were significantly decreased and HDL-C level was increased in IRC treatment groups. The hepatic histomorphology was partially restored. 23, 26 and 15 metabolites in plasma, urine and cecum content were determined as the biological biomarkers, respectively. IRC extract could partially recover the disturbed metabolic pathways of bile acid metabolism, linoleic acid metabolism, arachidonic acid metabolism, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycerophospholipid metabolism, synthesis and degradation of ketone bodies, sphingolipid metabolism and riboflavin metabolism. CONCLUSION This study demonstrated that IRC could effectively improve the serum lipids and partially restore the hepatic histomorphology. The underlying metabolic mechanism mainly included improving the metabolism of bile acids, glycerophospholipid, sphingolipid, fatty acid and amino acid. This is the first study on the lipid-lowering effect of IRC from the perspective of metabolomics. Attention-deficit/hyperactivity disorder (ADHD) poses debilitating impairments in the neurobehavioral systems governing reward-related processes-key to the control of motivated behaviors. Individuals with ADHD may rely on a motivational control system that favors cue-driven habits-rooted in the posterior putamen-over caudate and prefrontal cortex-driven goal-directed behaviors. We examined the neurobehavioral correlates of motivational control in ADHD. Twenty-five adults with ADHD and 25 neurotypicals underwent fMRI while training on two stimulus-response-outcome associations. A devaluation procedure followed, whereby they were selectively satiated on one of the snack outcomes, decreasing its value. A subsequent extinction test determined outcome-sensitivity (i.e., whether responses towards devalued snack diminished). Despite behavioral similarities, the ADHD group displayed a distinct neural signature marked by enhanced posterior putamen activation as a function of training. This region also displayed diminished functional connectivity with the dorsal anterior cingulate cortex, which is associated with top-down control.