Lilian Eugenia Pelzer

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.

Acute and chronic antiinflammatory effects of plant flavonoids

The antiinflammatory activities of 30 flavonoids isolated from several plants of the Compositae family were investigated using carrageenan-induced mouse paw edema and cotton pellet-induced rat granuloma. Compounds were administered with a unique dose of 75 mg/kg i.p. in the acute test with carrageenan and 25 mg/kg/day in the chronic granuloma test. Flavonoids inhibit the development of the induced granuloma, mostly when a catechol or guaiacol-like B ring is contained in the compound structure, jaceosidin being the most active flavonoid screened. Flavonoids significantly inhibited the maximum edema response in the acute test. We conclude that several of the isolated flavonoids tested here showed antiinflammatory effects, depending on the experimental model used.

Antimicrobial activity of Artemisia douglasiana and dehydroleucodine against Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE The increasing resistance of Helicobacter pylori to antibiotics demands the search for novel compounds from plant based sources. Artemisia douglasiana Besser is widely used in Cuyo region (Argentina) as folk medicine for the treatment of gastric ailments. AIM OF STUDY Based on our previous studies that Artemisia douglasiana exert cytoprotective actions against ethanol-induced gastric mucosal injury we assayed the anti-Helicobacter pylori effect of the Artemisia douglasiana extract and its active compound, dehydroleucodine. MATERIALS AND METHODS The in vitro anti-bacterial activity of Artemisia douglasiana extract and its active compound, dehydroleucodine were determined against one standard strain and six clinical isolates of Helicobacter pylori by using the agar dilution methods. RESULTS The results showed that both dehydroleucodine and Artemisia douglasiana extract had activity against the microorganism with MICs between 1-8 and 60-120 mg/L, respectively. CONCLUSIONS Artemisia douglasiana may be a useful alternative treatment strategy principally in eradication of metronidazole and clarithromycin-resistant strain.

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.

Reduction in voluntary ethanol intake following repeated oral administration of Jodina rhombifolia lyophilized aqueous extract in male Wistar rats

ETHNOPHARMACOLOGICAL RELEVANCE The leaves of Jodina rhombifolia (Hook. & Arn.) Reissek (SANTALACEAE) is utilized in Argentine folk medicine for the treatment of alcoholism. AIM OF THE STUDY To evaluate the antialcoholic activity of Jodina rhombifolia lyophilized aqueous extract (JRLE) in male Wistar rats. MATERIALS AND METHODS Rats were housed individually in standard plastic cages with wood chip bedding. Throughout the duration of experiment, ethanol was offered in the standard home-cage; two-bottle free-choice regimen between an ethanolic solution (20% in tap water, v/v) and tap water with unlimited access for 24h per day for 10 consecutive days. Rats were administrated intragastrically twice daily (1 ml/200 g) for 10 consecutive days, with the control vehicle (distilled water) or one of the doses of JRLE (125, 250 and 500 mg/Kg weight). Body weight, ethanol, water and food intake were measured every day at the same hour during the 10 days of experimentation. RESULTS The reducing effect of JRLE on daily ethanol intake was evidenced from the first day of treatment and persisted throughout the entire treatment period. The treatment did not significantly affect daily water intake neither the body weight gain. Daily food intake was higher in rat groups treated with JRLE. CONCLUSION The results obtained in the present preliminary study show that repeated administration of JRLE, markedly reduces ethanol voluntary intake in male Wistar rats. The reduction of consumption was of remarkable magnitude and stable during the treatment 10-days.

Lethal effect of dehydroleucodine (DhL) on amphibian Bufo arenarum embryos

The dehydroleucodine is a sesquiterpene lactone isolated from Artemisia douglasiana Besser which is used in popular medicine. Toxicity tests using embryos of amphibian have been widely used in order to predict toxic effects of different compounds. However, to our knowledge, there are not studies focussed on the toxic effects of dehydroleucodine on Bufo arenarum, which is an anuran widely distributed in South America. The effect of dehydroleucodine on the survival of embryos was evaluated in an acute test during the early life stage of B. arenarum embryos. Lethality and the degree of adverse effects were dehydroleucodine dose-dependent. Overall, amphibian early life stages appeared to be more susceptible to the embryotoxicity associated with exposure to dehydroleucodine, especially at concentration greater that 3mM. This increased susceptibility may result from the relatively high rate of cellular differentiation and morphogenesis that occurs at this early stage of development.

Gastroprotective effects and antimicrobial activity of Lithraea molleoides and isolated compounds against Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE Lithraea molleoides (Vell.) Engl. (Anacardiaceae) is a medicinal plant traditionally used in South America to treat various ailments, including diseases of the digestive system. AIM OF THE STUDY To evaluate the in vivo antiulcer and antimicrobial activities against Helicobacter pylori of L. molleoides and its isolated compounds. MATERIALS AND METHODS Methanolic extract 250 and 500 mg/kg, (LmE 250 and LmE 500, respectively) and infusions, 10 g and 20 g en 100mL (LmI 10 and LmI 20, respectively) of L. molleoides was evaluated for antiulcer activity against 0.6N HCl, 0.2N NaOH, 200mg/kg acetilsalicilic acid and absolute ethanol-induced gastric ulcers in rats. The degree of erosion in the glandular part of the stomach was assessed from a scoring system. Acute toxicity in mice was also evaluated. The antiulcer effect of the isolated compounds (catechol, mannitol, rutin, gallic acid, ferulic acid and caffeic acid, 100mg/kg) was evaluated against absolute ethanol-induced gastric ulcers in rats. The anti-Helicobacter pylori activity of L. molleoides and isolated compounds was performed using broth dilution methods. RESULTS The LmE 250, LmE 500, LmI 10 and LmI 20 produced significant inhibition on the ulcer index in 0.6N HCl, 0.2N NaOH, 200mg/kg acetilsalicilic acid and absolute ethanol- induced gastric ulcers in rats. The isolated compounds, catechol, mannitol, rutin, ferulic acid and caffeic acid were active in absolute ethanol- induced gastric ulcers in rats. L. molleoides and different compounds showed antimicrobial activity in all strains tested. The lowest MIC value (0. 5 μg/mL) was obtained with catechol in six of eleven strains assayed. No signs of toxicity were observed with doses up to 2g/kg in an acute toxicity assay. CONCLUSION These findings indicate that L. molleoides displays potential antiulcerogenic and antimicrobial activities and the identification of active principles could support the use of this plant for the treatment of digestive affections.