ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Mikania glomerata Spreng. (MG) and Mikania laevigata Sch. Bip. ex Baker (ML), popularly known as guaco, are medicinal plants similar in morphology, chemical composition and medicinal uses. Both species are often used and sold without distinction; however, it is believed that their chemical composition is different. AIM: Thus, the aim of this study is to investigate if the aqueous extract of MG and ML present similar anti-inflammatory activity to the point of being used interchangeably. MATERIAL AND METHODS: Different doses of both extracts and coumarin were given to rats in different experimental models to assess the anti-inflammatory activity between these two species. For this, the animals were submitted to paw edema, pleurisy and degranulation of peritoneal mast cell and the extracts were also characterized by Ultra High Efficiency Liquid Chromatography coupled to Mass Spectrometry (UHPLC-MS). RESULTS: The chromatographic method showed that ML presents ten times more coumarin than MG. Oral administration of MG, ML and coumarin inhibited paw edema induced by carrageenan (400â¯mg/kg, 55% inhibition; 400â¯mg/kg, 57% inhibition; 75â¯mg/kg, 38% inhibition; pâ¯<â¯0.05, respectively). MG, ML and coumarin treatment also inhibited the edema induced by compound 48/80 (400â¯mg/kg, 56% inhibition; 400â¯mg/kg, 69% inhibition; 75â¯mg/kg, 40% inhibition; pâ¯<â¯0.05, respectively). MG, ML and coumarin did not prevent mast cell degranulation and the consequent histamine release in Wistar rat peritoneal mast cells induced by compound 48/80. MG did not inhibit cell infiltration in pleurisy nor the highest dose tested, while ML decreased the leukocyte migration (200 and 400â¯mg/kg, 23% and 30% inhibition; pâ¯<â¯0.001, respectively) and, to a lesser extent, coumarin also reduced cell infiltration (10, 50 and 75â¯mg/kg; 15%, 16% and 17% inhibition; pâ¯<â¯0.001, respectively). CONCLUSION: The variation of the results of the anti-inflammatory activity found in M. glomerata and M. laevigata demonstrates that these two species should not be used interchangeably. Coumarin, as already proven, has anti-inflammatory action however, we have suggested that it probably is not the only component responsible for this therapeutic effect in the extracts.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Edema/drug therapy , Mikania , Plant Extracts/therapeutic use , Pleurisy/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Carrageenan , Cell Degranulation/drug effects , Edema/chemically induced , Edema/immunology , Male , Mast Cells/drug effects , Mast Cells/physiology , Mikania/chemistry , Phytochemicals/analysis , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Pleurisy/chemically induced , Pleurisy/immunology , Rats, Wistar , p-Methoxy-N-methylphenethylamineABSTRACT
BACKGROUND: Nitric oxide is a key signalling molecule in the pathogenesis of inflammation, but its role in acute pancreatitis and related abdominal pain induced by secretory phospholipase A2 (sPLA2 ) from Crotalus durissus terrificus (Cdt) venom has not been investigated. METHODS: Male Wistar rats were i.v. injected with L-NAME (20 mg/kg), aminoguanidine (AG, 50 mg/kg), 7-nitroindazole (7-NI, 10 mg/kg) or vehicle 10 min before or 60 min after the injection of sPLA2 (300 µg/kg) into the common bile duct. After 4 h of sPLA2 injection, abdominal hyperalgesia and inflammation were assessed in addition to serum amylase, nitrite/nitrate (NOx), pancreas lipoperoxidation and 3-nitrotyrosine (3-NT) contents. RESULTS: sPLA2 -induced acute pancreatitis, related abdominal hyperalgesia, hyperamylasemia and increased concentration of NOx were not correlated with lipoperoxidation or increased 3-NT in the pancreas. Pretreatment with all the nitric oxide synthase (NOS) inhibitors significantly reduced abdominal mechanical hyperalgesia, but only iNOS blockade by AG suppressed pancreas oedema and serum NOx increase. The therapeutic approach with all the NOS inhibitors produced a similar reduction pattern of the abdominal hyperalgesia, but AG treatment also inhibited serum hyperamylasemia and NOx concentrations and pancreatic myeloperoxidase. The nNOS blockade by 7-NI treatment also inhibited myeloperoxidase activity in both pancreas and lung. CONCLUSIONS: Therapeutic blockade of iNOS or nNOS provides benefits in terms of inhibition of the acute pancreatitis-related abdominal hyperalgesia, while iNOS inhibition also ameliorates the inflammatory cell influx to the pancreas and reduces the resultant hyperamylasemia and NOx levels, thus representing alternative pharmacological strategies for treatment of clinical pancreatitis associated with increased PLA2 .
Subject(s)
Enzyme Inhibitors/therapeutic use , NG-Nitroarginine Methyl Ester/therapeutic use , Nitric Oxide Synthase Type II/antagonists & inhibitors , Pain/drug therapy , Pain/etiology , Pancreatitis/complications , Pancreatitis/drug therapy , Phospholipases A2, Secretory , Animals , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Male , Pancreas/enzymology , Pancreas/pathology , Pancreatitis/enzymology , Peroxidase/metabolism , Rats , Rats, Wistar , Thiobarbituric Acid Reactive Substances/metabolism , Tyrosine/analogs & derivatives , Tyrosine/metabolismABSTRACT
Physical exercise reduces the deleterious effects of cardiovascular and inflammatory disorders. The purpose of the present study was to evaluate the beneficial effects of physical training on the inflammatory responses following lung ischaemia-reperfusion (IR) in rats. Male Wistar rats were divided into sham-operated animals and sedentary and trained animals submitted to lung IR. The run training programme consisted of 5 sessions.week(-1), each lasting 60 min.day(-1), at 66% of maximal oxygen consumption for 8 weeks. The left pulmonary artery, bronchus and pulmonary vein were occluded for 90 min and reperfused for 2 h. Lung protein extravasation was measured as (125)I-human albumin accumulation, whereas lung neutrophil infiltration was measured as myeloperoxidase activity. Lung IR in sedentary rats resulted in marked increases in protein extravasation and neutrophil influx, and in significant elevations of serum tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels. Physical preconditioning attenuated the increased IR-induced protein leakage without affecting neutrophil influx. It also reduced serum TNF-alpha (and IL-1beta) levels, but had no effect on IL-10 levels. Plasma superoxide dismutase activity was significantly increased in trained IR rats. The present data show that physical preconditioning protects the rat lung from ischaemia-reperfusion injury by attenuating the pulmonary vascular permeability that may be a consequence of reduced levels of tumour necrosis factor-alpha and interleukin-1beta and elevated superoxide dismutase activity.
Subject(s)
Inflammation/prevention & control , Physical Conditioning, Animal , Reperfusion Injury/prevention & control , Respiratory Distress Syndrome/prevention & control , Animals , Cytokines/metabolism , Disease Models, Animal , Male , Rats , Rats, Wistar , Reperfusion Injury/pathology , RunningABSTRACT
Snake venom phospholipases A2 (PLA2) show a remarkable functional diversity. Among their toxic activities, some display the ability to cause rapid necrosis of skeletal muscle fibers, thus being myotoxic PLA2s. Besides myotoxicity, these enzymes evoke conspicuous inflammatory and nociceptive events in experimental models. Local inflammation and pain are important characteristics of snakebite envenomations inflicted by viperid and crotalid species, whose venoms are rich sources of myotoxic PLA2s. Since the discovery that mammalian PLA2 is a key enzyme in the release of arachidonic acid, the substrate for the synthesis of several lipid inflammatory mediators, much interest has been focused on this enzyme in the context of inflammation. The mechanisms involved in the proinflammatory action of secretory PLA2s are being actively investigated, and part of the knowledge on secretory PLA2 effects has been gained by using snake venom PLA2s as tools, due to their high structural homology with human secretory PLA2s. The inflammatory events evoked by PLA2s are primarily associated with enzymatic activity and to the release of arachidonic acid metabolites. However, catalytically inactive Lys49 PLA2s trigger inflammatory and nociceptive responses comparable to those of their catalytically active counterparts, thereby evidencing that these proteins promote inflammation and pain by mechanisms not related to phospholipid hydrolysis nor to mobilization of arachidonic acid. These studies have provided a boost to the research in this field and various approaches have been used to identify the amino acid residues and the specific sites of interaction of myotoxic PLA2s with cell membranes potentially involved in the PLA2-induced inflammatory and nociceptive effects. This work reviews the proinflammatory and nociceptive effects evoked by myotoxic PLA2s and their mechanisms of action.
Subject(s)
Inflammation/chemically induced , Nociceptors/drug effects , Phospholipases A/toxicity , Snake Venoms/toxicity , Snakes , Animals , Arachidonic Acid/metabolism , Hyperalgesia/metabolism , Phospholipases A2ABSTRACT
Snake venom phospholipases A2 (PLA2) show a remarkable functional diversity. Among their toxic activities, some display the ability to cause rapid necrosis of skeletal muscle fibers, thus being myotoxic PLA2s. Besides myotoxicity, these enzymes evoke conspicuous inflammatory and nociceptive events in experimental models. Local inflammation and pain are important characteristics of snakebite envenomations inflicted by viperid and crotalid species, whose venoms are rich sources of myotoxic PLA 2s. Since the discovery that mammalian PLA2is a key enzyme in the release of arachidonic acid, the substrate for the synthesis of several lipid inflammatory mediators, much interest has been focused on this enzyme in the context of inflammation. The mechanisms involved in the proinflammatory action of secretory PLA2s are being actively investigated, and part of the knowledge on secretory PLA2 effects has been gained by using snake venom PLA2s as tools, due to their high structural homology with human secretory PLA2s. The inflammatory events evoked by PLA2s are primarily associated with enzymatic activity and to the release of arachidonic acid metabolites. However, catalytically inactive Lys49 PLA2s trigger inflammatory and nociceptive responses comparable to those of their catalytically active counterparts, thereby evidencing that these proteins promote inflammation and pain by mechanisms not related to phospholipid hydrolysis nor to mobilization of arachidonic acid. These studies have provided a boost to the research in this field and various approaches have been used to identify the amino acid residues and the specific sites of interaction of myotoxic PLA2s with cell membranes potentially involved in the PLA2-induced inflammatory and nociceptive effects. This work reviews the proinflammatory and nociceptive effects evoked by myotoxic PLA2s and their mechanisms of action. © 2004 Published by Elsevier Ltd.