Toll-like receptor 4 inhibition reduces vascular inflammation in spontaneously hypertensive rats.

AIMS: Hypertension is associated with increased levels of circulating cytokines and recent studies have shown that innate immunity contributes to hypertension. The mechanisms which hypertension stimulates immune response remain unclear, but may involve formation of neo-antigens that activate the immune system. Toll like receptor 4 (TLR4) is an innate immune receptor that binds a wide spectrum of exogenous (lipopolysaccharide) and endogenous ligands. TLR4 signaling leads to activation of nuclear factor kappa B (NFκB) and transcription of genes involved in inflammatory response. We previously demonstrated that TLR4 blockade reduces blood pressure and the augmented vascular contractility in spontaneously hypertensive rats (SHR). Here we hypothesized that inhibition of TLR4 ameliorates the vascular inflammatory process by a NFκB signaling pathway. MAIN METHODS: SHR and Wistar rats were treated with anti-TLR4 antibody (1µg/day) or unspecific IgG for 15days (i.p.). KEY FINDINGS: Anti-TLR4 treatment decreased production of reactive oxygen species and expression of IL-6 cytokine in mesenteric resistance arteries from SHR, when compared with IgG-treated SHR. Anti-TLR4 treatment also abolished the increased vascular reactivity to noradrenaline observed in IgG-treated SHR, as described before, and inhibition of NFκB decreased noradrenaline responses only in IgG-treated SHR. Mesenteric arteries from SHR treated with anti-TLR4 displayed decreased expression of MyD88, but not TRIF, key molecules in TLR4 signaling. Phosphorylation of p38 and NF-κB p65 were decreased in arteries from anti-TLR4-treated SHR versus IgG-treated SHR. SIGNIFICANCE: Together, these results suggest that TLR4 is a key player in hypertension and vascular inflammatory process by a NFκB signaling pathway.

Anti-inflammatory and antinociceptive effects of Rosmarinus officinalis L. essential oil in experimental animal models.

Rosmarinus officinalis L. (Family Lamiaceae), popularly named rosemary, is a common household plant grown in many parts of the world, including Brazil. Rosemary leaves are used for food flavoring and have been used in folk medicine for many conditions; they have antispasmodic, analgesic, antirheumatic, carminative, cholagogue, diuretic, expectorant, and antiepileptic effects. The objective of this study was to evaluate the effects of rosemary essential oil (REO) on experimental models of nociception and inflammation in animals. The anti-inflammatory effect of REO was evaluated by inflammatory exudate volume and leukocyte migration in carrageenan-induced pleurisy and carrageenan-induced paw edema tests in rats. Antinociception was evaluated using the acetic acid-induced writhing and hot plate tests in mice. REO (500 mg/kg) significantly reduced the volume of pleural exudate and slightly decreased the number of cells that had migrated compared with the control animals. At doses of 250, 500, and 750 mg/kg, REO significantly inhibited carrageenan-induced edema 1-4 hours after injection of the phlogistic agent. In the hot plate test, REO administration (125, 250, and 500 mg/kg) showed unremarkable effects on response latency, whereas control injection of meperidine induced significant antinociceptive effects. REO at doses of 70, 125, and 250 mg/kg had a significant antinociceptive effect in the acetic acid-induced abdominal writhing test compared with control animals. These data suggest that REO possesses anti-inflammatory and peripheral antinociceptive activity.