Anti-inflammatory and antinociceptive activity of epiisopiloturine, an imidazole alkaloid isolated from Pilocarpus microphyllus.

The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of epiisopiloturine (1), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus. The anti-inflammatory activity of 1 was evaluated using several agents that induce paw edema and peritonitis in Swiss mice. Paw tissue and peritoneal fluid samples were obtained to determine myeloperoxidase (MPO) activity or tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels. The antinociceptive activity was evaluated by acetic acid-induced writhing, the hot plate test, and pain induction using formalin. Compared to vehicle treatment, pretreatment with 1 (0.1, 0.3, and 1 mg/kg, ip) of mice significantly reduced carrageenan-induced paw edema (p < 0.05). Furthermore, compound 1 at a dose of 1 mg/kg effectively inhibited edema induced by dextran sulfate, serotonin, and bradykinin, but had no effect on histamine-induced edema. The administration of 1 (1 mg/kg) following carrageenan-induced peritonitis reduced total and differential peritoneal leukocyte counts and also carrageenan-induced paw MPO activity and TNF-α and IL-1ß levels in the peritoneal cavity. Pretreatment with 1 also reduced acetic acid-induced writhing and inhibited the first and second phases of the formalin test, but did not alter response latency in the hot plate test. Pretreatment with naloxone reversed the antinociceptive effect of 1.

The skin secretion of the amphibian Phyllomedusa nordestina: a source of antimicrobial and antiprotozoal peptides.

Antimicrobial peptides (AMPs) from the dermaseptin and phylloseptin families were isolated from the skin secretion of Phyllomedusa nordestina, a recently described amphibian species from Northeastern Brazil. One dermaseptin and three phylloseptins were chosen for solid phase peptide synthesis. The antiprotozoal and antimicrobial activities of the synthetic peptides were determined, as well as their cytotoxicity in mouse peritoneal cells. AMPs are being considered as frameworks for the development of novel drugs inspired by their mechanism of action.

Terminalia fagifolia Mart. & Zucc. elicits vasorelaxation of rat thoracic aorta through nitric oxide and K+ channels dependent mechanism.

Terminalia fagifolia Mart. & Zucc. (Combretaceae) is a plant commonly found in the regions of the Brazilian cerrado, popularly used for the treatment of gastrointestinal disorders. There are no reports in the literature on the use of T. fagifolia for the treatment of the cardiovascular system conditions. Nevertheless, plants of the same genus, such as Terminalia arjuna (Roxb.) Wight & Arn and Terminalia superba Engler & Diels, present cardioprotective, hypotensive and vasodilatating effects. In light of this, the aim of the study was to investigate the effect of the ethanolic extract (Tf-EE) and of its aqueous (Tf-AQF), hexanic (Tf-HEXF) and hydroethanolic (Tf-HAF) partition fractions obtained from the stem bark of T. fagifolia Mart. & Zucc. The effects of the extract and partition fractions of T. fagifolia were evaluated on isometric tensions in the thoracic aorta rings of Wistar rats (250-300 g). Tf-EE, Tf-HEXF and Tf-HAF presented a concentration-dependent vasorelaxant effect, and Tf-AQF presented a vasorelaxant effect that was more potent in the presence of endothelium. The relaxation curves of the aorta promoted by the fraction investigated were attenuated in the presence of the following pharmacological tools: L-NAME, ODQ or PTIO. The vasorelaxant effect of the aorta promoted by Tf-AQF was attenuated in the presence of TEA and 4-AP. Tf-EE induced a concentration-dependent and endothelium-independent vasorelaxation. Tf-HAF and Tf-HEXF presented concentration-dependent and vascular-endothelium-independent vasorelaxation, but did not obtain 100% of relaxation. On the other hand, Tf-AQF presented concentration-dependent vasorelaxation that was more potent in aorta rings with vascular endothelium. The relaxant mechanism induced by the Tf-AQF involves the NO/sGC/cGMP pathway and channels Kv.

Riparin A, a compound from Aniba riparia, attenuate the inflammatory response by modulation of neutrophil migration.

Inflammation is a local tissue response to attacks characterized by vascular and cellular events, including intense oxidative stress. Riparin A, a compound obtained from Aniba riparia, has been shown to have antioxidant activity and cytotoxicity in vitro. This study was aimed at evaluating the anti-inflammatory effect of riparin A against acute inflammation. The results of our evaluations in various experimental models indicated that riparin A reduced paw edema induced by carrageenan, compound 48/80, histamine, and serotonin. Furthermore, it decreased leukocyte and neutrophil counts, myeloperoxidase activity, thiobarbituric acid reactive substance (TBARS) levels, and cytokine (tumor necrosis factor-α and interleukin-1ß) levels increased by carrageenan-induced peritonitis, and reversed glutathione levels. Riparin A also reduced carrageenan-induced adhesion and rolling of leukocytes on epithelial cells and did not produce gastric-damage as compared with indomethacin. In conclusion, the data show that riparin A reduces inflammatory response by inhibiting vascular and cellular events, modulating neutrophil migration, inhibiting proinflammatory cytokine production, and reducing oxidative stress.

Phytol, a diterpene alcohol, inhibits the inflammatory response by reducing cytokine production and oxidative stress.

Studies have shown that diterpenes have anti-inflammatory and redox-protective pharmacological activities. The present study aimed to investigate the anti-inflammatory properties of phytol, a diterpene alcohol, in a mouse model of acute inflammation, and phytol effect on leukocyte recruitment, cytokines levels, and oxidative stress. The anti-inflammatory activities of phytol were assessed by measuring paw edema induced by different inflammatory agents (e.g., λ-carrageenan, compound 48/80, histamine, serotonin, bradykinin, and prostaglandin E2 [PGE2 ]), myeloperoxidase (MPO) activity, peritonitis model and cytokine levels. Further, oxidative stress was evaluated by determining glutathione (GSH) levels and malondialdehyde (MDA) concentration. The results showed that phytol (7.5, 25, 50, and 75 mg/kg) significantly reduced carrageenan-induced paw edema, in a dose-dependent manner. In addition, phytol (75 mg/kg) inhibited compound 48/80-, histamine-, serotonin-, bradykinin- and PGE2 -induced paw edema. It also inhibited the recruitment of total leukocytes and neutrophils; decreased MPO activity, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels, and MDA concentration; and increased GSH levels during carrageenan-induced acute inflammation. These results suggest that phytol attenuates the inflammatory response by inhibiting neutrophil migration that is partly caused by reduction in IL-1ß and TNF-α levels and oxidative stress.