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.

Involvement of endogenous opioid peptides in the peripheral antinociceptive effect induced by the coffee specific diterpene kahweol.

BACKGROUND: Kahweol is a diterpene present in the oil derived from coffee beans. Although several pharmacological activities of kahweol are already well described in the literature, no study was done in order to assess the analgesic activity of this substance. Thus, the aim of this study was to investigate the possible peripheral antinociceptive effect of kahweol. Considering that the opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, the present study also evaluated the endogenous opioids involvement in this effect. METHODS: The rat paw pressure test was used, and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2µg/paw). All drugs were administered subcutaneously in the hindpaws of male Wistar rats. The expression of ß-endorphin was examined by immunohistochemistry in the skin tissue samples of the plantar surface of rat right hindpaws. RESULTS: Intraplantar injection of kahweol (40 and 80µg) induced significant peripheral antinociception. The antinociceptive effect of kahweol was due to a local peripheral action because the higher dose (80µg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (50 and 100µg/paw) prevented action of kahweol (80µg/paw) and the aminopeptidases inhibitor bestatin (400µg/paw) potentiated the antinociceptive effect of kahweol (40µg/paw). Furthermore, kahweol treatment increased the intensity of ß-endorphin immunoreactivity in the epithelium of rat paws. CONCLUSIONS: The results discussed here provide evidence that kahweol treatment has peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.

Cafestol, a coffee-specific diterpene, induces peripheral antinociception mediated by endogenous opioid peptides.

The opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, including non-steroidal anti-inflammatory drugs and α(2) -adrenoceptor agonists. The aims of the present study were to investigate the possible peripheral antinociceptive effect of cafestol, a diterpene present in the oil derived from coffee beans, and to evaluate the involvement of opioid peptides in its effect. The rat paw pressure test was used to assess antinocipeptive effects. Hyperalgesia was induced by intraplantar injection of prostaglandin E(2) (2 µg/paw). All drugs were locally administered into the hind-paws of male Wistar rats. Intraplantar injection of cafestol (20, 40 and 80 µg) induced peripheral antinociception. The antinociceptive effect of cafestol was due to a local action because the higher dose (80 µg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (25, 50 and 100 µg/paw) prevented the action of cafestol (80 µg/paw), whereas the aminopeptidase inhibitor bestatin (400 µg/paw) potentiated the antinociceptive effect of cafestol (40 µg/paw). The results of the present study provide evidence that cafestol treatment has a peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.

Evaluation of exercise and potassium chloride supplementation on blood pressure and nociceptive threshold in hypertensive rats.

Hypertensive subjects present an increased nociceptive threshold, and the lack or delay of pain perception may impede detection of angina and myocardial infarction. Nutritional interventions, like potassium chloride (KCl) diet supplementation, and exercises are common nonpharmacological indications for treating hypertension. Spontaneous hypertensive rats (SHR) and normotensive male Wistar rats were submitted to a combination of exercise and KCl diet supplementation. Exercise reduced the nociceptive threshold in SHR; however, this effect was inhibited by KCl supplementation. Exercise and KCl supplementation did not alter systolic blood pressure. Reduction of the nociceptive threshold by exercise may be important for the detection of angina and myocardial infarction in hypertensive individuals.