Rice Bran Extract Protected against LPS-Induced Neuroinflammation in Mice through Targeting PPAR-γ Nuclear Receptor.

PPAR-γ anti-inflammatory functions have received significant attention since its agonists have been shown to exert a wide range of protective effects in many experimental models of neurologic diseases. Rice bran is very rich in polyunsaturated fatty acids, which are reported to act as PPAR-γ partial agonists. Herein, the anti-inflammatory effect of rice bran extract (RBE) through PPAR-γ activation was evaluated in LPS-induced neuroinflammatory mouse model in comparison to pioglitazone (PG) using 80 Swiss albino mice. RBE (100 mg/kg) and PG (30 mg/kg) were given orally for 21 days and LPS (0.25 mg/kg) was injected intraperitoneally for the last 7 days. TNF-α and COX-2 brain contents were evaluated by real-time PCR and immunohistochemical analysis. In addition, NFκB binding to its response element was evaluated alongside with the effect of treatments on IκB gene expression. Furthermore, PPAR-γ sumoylation was also studied. Finally, histopathological examination was performed for different brain areas. RBE administration was found to protect against the LPS-induced inflammatory effects by decreasing the inflammatory mediator expression in mice brains. It also decreased PPAR-γ sumoylation without significant effect on IκB expression or NFκB binding to its response element. The majority of the effects were attenuated in presence of PPAR-γ antagonist (GW9662). Level of significance was set to P < 0.05. Such findings highlight the agonistic effect of RBE component(s) on PPAR-γ and support the hypothesis of involvement of PPAR-γ activation in its neuroprotective effect.

Formulation and evaluation of metoclopramide solid lipid nanoparticles for rectal suppository.

OBJECTIVES: The purpose of this study was to formulate and characterize metoclopramide solid lipid nanoparticles (MCP-SLNs) and incorporating it into suppository bases for treatment of nausea and vomiting, produced with chemotherapeutic agents, using one dose per day. METHODS: MCP-SLNs was prepared using high shear homogenization (hot homogenization) technique using different surfactants (tween 80, poloxamer 407, poloxamer 188 and cremophore) in two different concentrations (2.5% and 5%) then solid lipid nanoparticle (SLN), whose release percentage above 50%, was incorporated into suppository for treatment of nausea and vomiting. The prepared SLN and suppositories were then evaluated and characterized. KEY FINDINGS: Formulation of poloxamer 407 with compritol and drug (F9) produced highest in-vitro % release (80%). Transmission electron microscopy showed that SLN had round and spherical shape in form of solid dispersion or drug-enriched core. Particle size analysis of SLN showed a size range of 24.99-396.8 nm. Negative zeta potential proves complete drug entrapment. In-vivo study of MCP-SLN suppositories produced the same %GE as the market metoclopramide (MCP) suppository (Primperan) with sustained release effect. CONCLUSION: MCP-SLN suppositories (formula F) can reverse decrease in %GE because of emesis with sustained release effect. So it succeeded to be an alternative to MCP suppositories with no multiple dosing.

Antiapoptotic effect of DDB against hepatic ischemia-reperfusion injury.

BACKGROUND AND AIM: Dimethyl-Diphenyl-Bicarboxylate (DDB) is a hepatoprotectant used in treatment of chronic viral hepatitis. The mechanism of DDB against liver injury needs further elucidation. Our objective is to explore whether DDB exerts hepatoprotective effect against hepatic ischemia reperfusion injury (I/R) and to identify its potential effect on apoptotic cell death targeting the extrinsic apoptotic pathway. METHODS: Rats were divided into four groups: Group I (sham-operated), Group II (I/R group), Group III (DDB Pretreated group): where rats were treated with DDB at 3 dose levels (100 mg/kg, 300 mg/kg, 500 mg/kg) for 10 days, then subjected to I/R and Group IV (DDB treated group): rats were treated with DDB at the same dose levels but without being subjected to I/R. Serum alanine aminotransferase (ALT) & aspartate aminotransferase (AST), tissue levels of GSH, MDA & tumor necrosis factor alpha (TNF-α), activity of signaling Caspases 3, 8, 9 as well as expression of nuclear factor-κB (NF-κB) were measured. End point of apoptosis was detected by DNA fragmentation. RESULTS: DDB administration before I/R, significantly attenuated elevated levels of ALT, AST, MDA and TNF-α and increased GSH content. There were significant decrease in caspases activities, expression of NF-κB as well as DNA fragmentation. DDB administration to normal rats, inhibited lipid peroxidation, enhanced antioxidant activity, decreased TNF-α and downregulated expression of NF-κB. These effects are dose-dependent. CONCLUSION: DDB exerts potent antioxidant effect in normal and injured livers. It inhibited hepatic I/R induced apoptosis through inhibiting signaling Caspases 3, 8, 9, TNF-α production which regulates the extrinsic apoptotic pathway and down regulates NF-κB expression in liver tissue.

Effect of capsaicin on bile secretion in the rat.

Capsaicin is a popular food ingredient. This study aimed to determine if capsaicin can affect bile flow and bile protein secretion, and the extent to which capsaicin can reach bile in the rat. The effect of capsaicin was studied in anesthetized rats equipped with cannulas inserted into the common bile duct. Capsaicin was administered by intragastric, intraduodenal (4-400 microg/ml; 10-1,000 microg/kg), intravenous (10 microg/kg) routes or applied on the serosal surface of the duodenum at 4 microg/ml. The administration of capsaicin decreased bile flow in comparison to the corresponding basal values, the maximum effect being reached at a concentration of 400 microg/ml of intragastric capsaicin (30.2%; p < 0.01), and 40 microg/ml (30.8%; p < 0.01) of intraduodenal capsaicin, 75 min after drug administration. Meanwhile, a decrease of 24.7 and 40% was observed 60 min after serosal and intravenous capsaicin administration, respectively. Biliary protein secretion was also reduced following capsaicin administration. High-performance liquid chromatography (HPLC) analysis showed that capsaicin was readily excreted into bile, peak levels were reached 75 or 60 min following its intragastric or intraduodenal administration, respectively (range 100-248 and 144-698.6 ng/ml after intragastric or intraduodenal capsaicin at 4-400 microg/ml, respectively). Capsaicin concentrations of 86 and 75 ng/ml could be detected in bile 15 min after intravenous administration or serosal application of the agent, respectively. Results suggest that capsaicin is readily absorbed after its intragastric or intraduodenal administration and goes through hepatobiliary excretion. Results also indicate that administration of capsaicin reduces bile flow and biliary proteins in the rat.