Alejandra Ester Rotelli

Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat.

The anti-inflammatory activities of three flavonoids were investigated in rats using the Mizushima et al. model of acute and chronic inflammation. Intraperitoneal administration of rutin, quercetin (flavonols) and hesperidin (flavanone), given at daily doses equivalent to 80 mg/kg, inhibited both acute and chronic phases of this experimental model of inflammation. Rutin was the most active in the chronic phase.

Comparative study of flavonoids in experimental models of inflammation

The anti-inflammatory activities of flavonols (quercetin, rutin and morin) and flavanones (hesperetin and hesperidin) were investigated in animal models of acute and chronic inflammation. Rutin was only effective in the chronic process, principally in adjuvant arthritis. On neurogenic inflammation induced by xylene, only the flavanones were effective; besides, these compounds were the most effective on subchronic process. The most important compound in reducing paw oedema induced by carrageenan was quercetin.

Structural basis of the anti-inflammatory activity of melatonin.

The anti-inflammatory activity of melatonin (CAS 73-31-4) was examined, using the rat paw edema model, and compared with the non-steroidal anti-inflammatory drug (NSAID) indometacin (CAS 53-86-1) which exerts its effects by inhibition of prostaglandin production on acute inflammation. The experiments showed that melatonin has an important effect on acute inflammatory processes acting as an inhibitor in a similar manner to indometacin. The structural interactions of melatonin with cyclooxygenase (COX), the pharmacological target of NSAIDs, were investigated using computer graphics applications. The results indicated that melatonin has an excellent steric and electronic complementarity with COX. It was found, similarly to previously studied crystal structures of protein-inhibitor complexes, that almost all interactions were of the hydrophobic type but for the typical carboxylate or electronegative group interaction, at the mouth of the active site channel, with Arg 120 and Tyr 355. Therefore, it seems possible that melatonin might bind to the active site of COX-1 and COX-2 suggesting that it may act as a natural inhibitor of the functions of cyclooxygenase modulating in a natural manner the activity of this enzyme.

Anti-inflammatory effect of Acacia visco extracts in animal models

The aqueous and organic extracts of Acacia visco Lor. Ap Griseb (Fabaceae) were tested for anti-inflammatory activity in experimental models in rat. Besides, the free-radical scavenging capacity of extracts from A. visco was determined. The extracts revealed anti-inflammatory effect against carrageenan-induced oedema, phospholipase A2-induced oedema, cotton pellet-induced granuloma and they did not show acute toxic effect. Among the class of compounds characterized from A. visco leaves, the triterpenoid 20(29)-lupen-3β-ol (lupeol), 12-ursen-3β-ol (α-amyrin) and 12-oleanen-3β-ol (β-amyrin) may be mainly responsible for the pharmacological activities.

Structural basis of the anti-inflammatory activity of quercetin: inhibition of the 5-hydroxytryptamine type 2 receptor.

The anti-inflammatory activity of quercetin was evaluated through serotonin-induced rat-paw edema. The experiments showed that quercetin had an important effect on acute inflammatory processes. Docking of serotonin and quercetin into the homology model of the 5-Hydroxytryptamine Type 2 Receptor allowed to analyze the structural basis of the anti-inflammatory activity. Results showed that serotonin and quercetin bind in the same region of the active site with a similar binding energy but quercetin has a much bigger inhibition constant. Therefore, it seems possible that quercetin may act as a natural inhibitor of the receptor blocking the acute inflammation generated by serotonin.

Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain.

Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action.

Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain.

Extracts rich in cysteine proteases obtained from fruits of Pseudananas macrodontes (Pm), Bromelia balansae (Bb), and B. hieronymi (Bh) have previously shown an anti-inflammatory effect on animal models. Given the close relationship between hemostasis and inflammation, it is attractive to investigate therapeutic agents capable of modulating both systems. The aim of this work was to study the effect of Pm, Bb, and Bh on fibrin(ogen) and blood coagulation compared with stem bromelain (Bro). Action on fibrinogen was electrophoretically and spectrophotometrically evaluated, fibrinolytic activity was measured both electrophoretically and by the fibrin plate assay, and the effect on blood coagulation was studied by conventional coagulation tests (PT and APPT). All extracts showed the same proteolytic preference for fibrinogen subunits, that is A&agr; > B&bgr;, whereas &ggr; was partially hydrolyzed by 100-fold concentration increase. Unlike Bro, cysteine proteases of Pm, Bb, and Bh increased absorbance at 540 nm of fibrinogen solution, suggesting thrombin-like activity, which was time-dependent and reached maximum values at lower concentration. All extracts showed the same proteolytic preference for fibrin subunits; however Pm, Bb, and Bh showed lower fibrinolytic activity than Bro at the assayed concentrations. Although Bb acted only as anticoagulant, Pm, Bh, and unexpectedly Bro showed dual action on blood coagulation: at low concentration showed procoagulant effect and at high concentration anticoagulant effect. Results reveal new plant species as potential sources of pharmacological agents for the treatment of a wide range of hemostatic disorders as well as to wound healing.

Records of Medicinal Plants Utilized as Gastroprotective and for Treatment of Gastrointestinal Ulcers, Gastritis, and Heartburn in Argentina: A Survey of the Literature

Traditional knowledge available on 148 plant species used in Argentina for gastroprotection and treating gastrointestinal ulcers, gastritis, and heartburn, was compiled to analyze their taxonomic grouping, floristic richness, the life form, and organs used, and to determine their susceptibility to over-collection.

Evaluation of Anti-Inflammatory Activity of Pseudananas macrodontes (Morr.) Harms (Bromeliaceae) Fruit Extract in Rats

Several species of the family Bromeliaceae are characterized by the production of proteases in unusual amounts, especially in fruits. Bromelain, an extract rich in cysteine endopeptidases obtained from Ananas comosus L., and a few other proteases have been used as anti-inflammatory agents for some years, but bromelain is still mainly being used as alternative and/or complementary therapy to the treatment with glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. In this study, the anti-inflammatory action of a partially purified extract from Pseudananas macrodontes (Morr.) Harms fruits (PPEPm) is presented, whose main components are cysteine endopeptidases. The effect of PPEPm was assessed in carrageenan-induced and serotonin-induced rat paw edema, as well as in the cotton pellet granuloma model. Doses with equal proteolytic activity of PPEPm and bromelain produced significantly similar anti-inflammatory responses in the acute inflammatory models assayed, supporting the hypothesis that proteolytic activity could be responsible for the anti-inflammatory action. On the contrary, comparable anti-inflammatory effects of PPEPm and bromelain in the chronic inflammatory assay required a much lower proteolytic activity content of PPEPm, which could be due to a differential affinity for the protein target involved in this process.

Different effects of melatonin on experimental granulomatous inflammation.

Several experiments have detected that melatonin exerts a marked influence on the inflammatory process. In the present study we evaluated the effect of exogenous melatonin on the experimental granulomatous tissues in rat. Our data show that subcutaneous administration of different doses of melatonin given daily during 6 days at 9:00 h do not have significant action on the granuloma weight. On the other hand melatonin (4 mg/kg) administered at 17:00 h showed a remarkable action pro-inflammatory. However, this effect was abolished when the animals received previously higher doses of melatonin (40 mg/kg) at 9:00 h.