Hypothalamic TRPV4 channels participate in the medial preoptic activation of warmth-defence responses in Wistar male rats.

Recently, we have described, in non-genetically modified rats, that peripheral transient receptor potential vanilloid-4 (TRPV4) channels are activated and trigger warmth-defence responses at ambient temperatures of 26-30 °C. Evidence points to the presence of TRPV4 in the medial preoptic area, a region described to be involved in the activation of thermoeffector pathways, including those involved in heat loss. Thus, we tested the hypothesis that TRPV4 in the medial preoptic area modulates thermoregulation under warm conditions. To this end, under two ambient temperatures (21 and 28 °C), body temperature was measured in rats following blockade of preoptic TRPV4 with two antagonists, HC-067047 and GSK 2193874. Oxygen consumption, heat loss index and preferred ambient temperature were also determined in order to assess thermoeffector activity. Antagonism of central TRPV4 caused an increase in body temperature in rats exposed to 28 °C, but not in those exposed to 21 °C. The body temperature increase at 28 °C was accompanied by an increase in oxygen consumption and an earlier reduction of the heat loss index. In behavioural experiments, control animals previously exposed to warm ambient temperatures (28-30 °C) for 2 h selected colder temperatures in a thermogradient compared to those injected with HC-067047. Our results support the idea that preoptic TRPV4 modulates thermoregulation in a warm environment by activating both autonomic and behavioural heat loss responses. Thus, according to the present study and to that published recently by our group, the activation of warmth-defence responses by TRPV4 seems to be dependent on the activity of both peripheral and central channels.

Short-term menthol treatment promotes persistent thermogenesis without induction of compensatory food consumption in Wistar rats: implications for obesity control.

In this study, we aimed to evaluate the influence of daily repeated menthol treatments on body mass and thermoregulatory effectors in Wistar rats, considering that menthol is a transient receptor potential melastatin 8 channel agonist that mimics cold sensation and activates thermoregulatory cold-defense mechanisms in mammals, promoting hyperthermia and increasing energy expenditure, and has been suggested as an anti-obesity drug. Male Wistar rats were topically treated with 5% menthol for 3 or 9 consecutive days while body mass, food intake, abdominal temperature, metabolism, cutaneous vasoconstriction, and thermal preference were measured. Menthol promoted hyperthermia on all days of treatment, due to an increase in metabolism and cutaneous vasoconstriction, without affecting food intake, resulting in less mass gain in menthol-hyperthermic animals. As the treatment progressed, the menthol-induced increases in metabolism and hyperthermia were attenuated but not abolished. Moreover, cutaneous vasoconstriction was potentiated, and an increase in the warmth-seeking behavior was induced. Taken together, the results suggest that, although changes occur in thermoeffector recruitment during the course of short-term treatment, menthol is a promising drug to prevent body mass gain. NEW & NOTEWORTHY Menthol produces a persistent increase in energy expenditure, with limited compensatory thermoregulatory adaptations and, most unexpectedly, without affecting food intake. Thus short-term treatment with menthol results in less mass gain in treated animals compared with controls. Our results suggest that menthol is a promising drug for the prevention of obesity.

Effects of caffeoylquinic acid derivatives and C-flavonoid from Lychnophora ericoides on in vitro inflammatory mediator production.

In this study we aimed at evaluating the effect of the major polar constituents of the medicinal plant Lychnophora ericoides on the production of inflammatory mediators produced by LPS-stimulated U-937 cells. The 6,8-di-C-beta-glucosylapigenin (vicenin-2) presented no effect on tumor necrosis factor (TNF)-alpha production, but inhibited, in a dose-dependent manner, the production of prostaglandin (PG) E2 without altering the expression of cyclooxygenase (COX)-2 protein. 3,5-Dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid, at lower concentrations, had small but significant effects on reducing PGE2 levels; at higher doses these compounds stimulated PGE2 and also TNF-alpha production by the cells. All the caffeoylquinic acid derivatives, in a dose-dependent fashion, were able to inhibit monocyte chemoattractant protein-3 synthesis/release, with 4,5-DCQ being the most potent at the highest tested concentration. These results add important information on the effects of plant natural polyphenols, namely vicenin-2 and caffeoylquinic acid derivatives, on the production of inflammatory mediators by cultured cells.

Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid.

Phenolic compounds are numerous and ubiquitous in the plant kingdom, being particularly present in health-promoting foods. Epidemiological evidences suggest that the consumption of polyphenol-rich foods reduces the incidence of cancer, coronary heart disease and inflammation. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in human diet. Data obtained from in vivo and in vitro experiments show that CGA mostly presents antioxidant and anti-carcinogenic activities. However, the effects of CGA on the inflammatory reaction and on the related pain and fever processes have been explored less so far. Therefore, this study was designed to evaluate the anti-inflammatory, antinociceptive and antipyretic activities of CGA in rats. In comparison to control, CGA at doses 50 and 100 mg/kg inhibited carrageenin-induced paw edema beginning at the 2nd hour of the experimental procedure. Furthermore, at doses 50 and 100 mg/kg CGA also inhibited the number of flinches in the late phase of formalin-induced pain test. Such activities may be derived from the inhibitory action of CGA in the peripheral synthesis/release of inflammatory mediators involved in these responses. On the other hand, even at the highest tested dose (200 mg/kg), CGA did not inhibit the febrile response induced by lipopolysaccharide (LPS) in rats. Additional experiments are necessary in order to clarify the true target for the anti-inflammatory and analgesic effects of CGA.