Jodina rhombifolia leaves lyophilized aqueous extract decreases ethanol intake and preference in adolescent male Wistar rats.

The leaves of Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) are utilized as anti-alcoholic in Argentine folk medicine. This study was designed to investigate the anti-alcohol properties in adolescent male Wistar rats (postnatal day 29; 83-105 g of weight). We utilized the "self-administration model", which ethanol was offered in the standard home-cage through 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. The results obtained show that repeated administration of J. rhombifolia lyophilized extract, markedly reduced ethanol voluntary intake on dose dependent bases. The magnitude in reduction of daily ethanol intake was approximately 29%, 44% and 68%, for the rat groups treated with 62.5, 125 and 250 mg/kg of extract, respectively. Ethanol preference (proportion of ethanol intake versus total fluid intake) was significantly reduced: 21.37% ± 0.79 (0 mg/kg); 15.83% ± 0.93 (62.5 mg/kg); 15.22% ± 1.30 (125 mg/kg) and 9.38% ± 0.57 (250 mg/kg). Daily food intake was significantly higher (p<0.05) in the group treated with 250 mg/kg of JRLE in comparison with vehicle-dose group; the reduction in ethanol intake was associated with a compensatory increase in food intake, probably because in the control group animals a part of the total caloric intake was supplied by ethanol. Treatment was very well tolerated by all animals and without apparent side-effects. These results contribute to the scientific validation of the antialcoholic indication of this botanic species in Argentine folk medicine.

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.

Effect of dehydroleucodine on intestinal transit: structural basis of the interaction with the α(2)-adrenergic receptor.

The activity of dehydroleucodine, a sesquiterpene lactone obtained from Artemisia douglasiana, was studied in mice small intestinal transit. Its mechanism was evaluated in the presence of several adrenergic and cholinergic antagonist drugs and one opioid antagonist. Docking of dehydroleucodine into the homology model of the α2-adrenergic receptor allowed us to analyze the structural basis of their interactions. The experiments showed that dehydroleucodine delayed intestinal transit. The docking of dehydroleucodine showed a unique binding site, equivalent to the binding site of carozolol in the ß-adrenergic receptor. The results suggested that dehydroleucodine produced an inhibitory effect on intestinal transit. Its action could be mediated, at least in part, through the α2-adrenergic receptor.

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 A(2)-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-3ß-ol (lupeol), 12-ursen-3ß-ol (α-amyrin) and 12-oleanen-3ß-ol (ß-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-ulcerogenic and anti-inflammatory activity of the methanolic extract of Larrea divaricata Cav. in rat.

Larrea divaricata Cav. (Zygophyllaceae) is used in popular medicine as anti-inflammatory and anti-rheumatic drug, containing higher amounts of nordihydroguaiaretic acid, a well-known free radical scavenger. Here we describe the gastric anti-ulcerogenic effect of the methanolic extract of Larrea divaricata (LdME) leaves in rat, using absolute ethanol and HCl 0.6N as necrotizing agents, and the effect of blocking endogenous sulfhydryl (SH) groups with N-ethylmaleimide (NEM). We also studied the anti-inflammatory activity of LdME in two rat experimental models: cotton pellet induced granuloma and arthritis induced by adjuvant-carrageenan. Influence of treatment in body weight and some lymphoid organs was evaluated. Finally, the free radical scavenging capacity of LdME was determined by the method of 1,1-diphenyl-2-picrylhydrazyl (DPPH) inhibition. LdME demonstrated anti-ulcerogenic effect in rats, and it was shown that the endogenous SH compounds were not involved in the mechanism of action. LdME also showed inhibitory activity in the applied models of inflammation, being more effective in the acute phase. No effect was observed concerning the weight of spleen, thymus and body. The extract proved to possess elevated free radical scavenging capacity which may contribute to the observed gastric anti-ulcerogenic and anti-inflammatory activity.

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.

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.