Pharmacological potential of Maytenus species and isolated constituents, especially tingenone, for treatment of painful inflammatory diseases

ABSTRACT Uses of medicinal plants by people around the world significantly contribute and guide biologically active compounds research that can be useful in the combat against various diseases. Due to a great chemical and structural variety found in their vegetal structures it consolidates ethnopharmacology as an important science for the pharmaceutical section. Inserted in the diversity of medicinal plants, is the Maytenus genus, whose research has already revealed lots of isolated substances which are responsible for a great variety of biological activities, among which we cite analgesic and anti-inflammatory, for the treatment of inflammatory diseases such as rheumatoid arthritis, gastritis, ulcers and gastrointestinal disorders. The aim of this review article is to make a compendium of the Maytenus genus and its isolated chemical compounds, among them tingenone. The elucidation of its mechanism of action reveals promising sources for the development of new drugs specially targeted for the treatment of painful inflammatory diseases.

Design, synthesis and evaluation of novel feruloyl-donepezil hybrids as potential multitarget drugs for the treatment of Alzheimer's disease.

A novel series of feruloyl-donepezil hybrid compounds were designed, synthesized and evaluated as multitarget drug candidates for the treatment of Alzheimer's Disease (AD). In vitro results revealed potent acetylcholinesterase (AChE) inhibitory activity for some of these compounds and all of them showed moderate antioxidant properties. Compounds 12a, 12b and 12c were the most potent AChE inhibitors, highlighting 12a with IC50 = 0.46 µM. In addition, these three most promising compounds exhibited significant in vivo anti-inflammatory activity in the mice paw edema, pleurisy and formalin-induced hyperalgesy models, in vitro metal chelator activity for Cu2+ and Fe2+, and neuroprotection of human neuronal cells against oxidative damage. Molecular docking studies corroborated the in vitro inhibitory mode of interaction of these active compounds on AChE. Based on these data, compound 12a was identified as a novel promising drug prototype candidate for the treatment of AD with innovative structural feature and multitarget effects.

Prostaglandins mediate zymosan-induced sickness behavior in mice.

Previous studies have demonstrated that zymosan, a cell wall component of the yeast Saccharomyces cerevisiae, induces inflammation in experimental models. However, few studies have evaluated the potential of zymosan to induce sickness behavior, a central motivational state that allows an organism to cope with infection. To determine whether zymosan administration results in sickness behavior, mice were submitted to the forced swim (FST) and open field (OFT) tests 2, 6, and 24 h after treatment with zymosan (1, 10, or 100 mg/kg). Additionally, to evaluate the possible relationship between zymosan-induced sickness behavior and prostaglandin synthesis, mice were pretreated with the cyclooxygenase inhibitors indomethacin (10 mg/kg) and nimesulide (5 mg/kg) and the glucocorticoid drug dexamethasone (1 mg/kg). Zymosan induced time-dependent decreases in locomotor activity in the OFT, and an increase in immobility in the FST, and increased plasma levels of corticosterone at 2 h. Pretreatment with indomethacin, nimesulide, or dexamethasone blocked zymosan-induced behavioral changes in both the FST and OFT at 2 h post administration. These findings confirm previous observations that zymosan induces sickness behavior. Furthermore, our results provide new evidence that prostaglandin synthesis is necessary for this effect, as anti-inflammatory drugs that inhibit prostaglandin synthesis attenuated zymosan-induced behavioral changes.

Anti-inflammatory and antinociceptive effects of the hydroethanolic extract of the flowers of Pyrostegia venusta in mice

Pyrostegia venusta (Ker Gawl.) Miers, Bignoniaceae, is native to the Brazilian Cerrado and popularly known as "cipó-de-são-joão". In Brazilian folk medicine, the flowers of P. venusta are used as a general tonic and a treatment for diarrhea, vitiligo, cough, and common infections and inflammatory diseases of the respiratory system. Nevertheless, there are still no studies on its possible anti-inflammatory and antinociceptive effects. The P. venusta hydroethanolic extract (PvHE) was used to evaluate the anti-inflammatory and analgesic effects in carrageenan-induced paw edema, peritonitis induced by lipopolysaccharide, acetic acid-induced writhing, and formalin-induced paw-licking tests in Swiss male mice. PvHE at doses of 30-300 mg/kg p.o. demonstrated anti-inflammatory effect. PvHE reduced paw edema induced by carrageenan and inhibited leukocyte recruitment into the peritoneal cavity. The extracts showed antinociceptive activity in acetic acid-induced writhing and formalin tests. Our results showed that the PvHE demonstrated anti-inflammatory and antinociceptive action in mice. All the anti-inflammatory actions obtained are also suggested to due the presence of acacetin-7-O-β-glucopyranoside.

Pyrostegia venusta attenuate the sickness behavior induced by lipopolysaccharide in mice.

AIM OF THE STUDY: Pyrostegia venusta (Ker.) Miers (Bignoniaceae) is native to the Brazilian Cerrado and popularly known as "cipó-de-são-joão." In traditional Brazilian medicine, the Pyrostegia venusta are used as a general tonic as well as a treatment for diarrhea, vitiligo, cough, and common diseases of the respiratory system related to infections, such as bronchitis, flu and cold. This study was conducted to evaluate the effects of a hydroethanolic extract of flowers of Pyrostegia venusta on sickness behaviors induced by lipopolysaccharide in mice. MATERIALS AND METHODS: To evaluate the effects of orally administered Pyrostegia venusta hydroethanolic extract (PvHE) on lipopolysaccharide-induced sickness behaviors, mice were submitted to the forced swim test (FST) and the open field test. RESULTS: Lipopolysaccharide (LPS, 100 µg/kg, i.p.) administration increased the time spent floating in the FST and depressed locomotor activity in the open field. Pretreatment with PvHE at test doses of 100 and 300 mg/kg, p.o. attenuated the behavioral changes induced by LPS in the FST and open field test. This effect was similar to pretreatment with dexamethasone (1 mg/kg), which is a steroidal drug that inhibits immune and inflammatory responses, including cytokine production. CONCLUSION: The extract of Pyrostegia venusta attenuated the depressive-like and exploratory behaviors induced by lipopolysaccharide. Thus, our results supported previous claims of the usefulness of these plants in traditional therapies and suggest that these plants may be useful in the treatment of disorders that induced sickness behavior, such as flu and cold.