Activation of brown adipose tissue thermogenesis by electrical stimulation to the dorsal surface of the tissue in rats.

Brown adipose tissue (BAT) is a heat-producing organ that plays an important role in maintenance of energy homeostasis. The purpose of this study was to test a novel method for stimulating BAT thermogenesis in rats. Application of electrical field stimulation to the dorsal surface of interscapular BAT caused a substantial rise in tissue temperature without affecting rectal temperature. The electrical stimulation failed to raise BAT temperature on the 2nd day after surgical sympathetic denervation. This is unlikely to be due to loss of thermogenic capacity, since neither UCP1 contents nor norepinephrine-induced thermogenesis were diminished 2 days after the denervation. A pharmacological experiment revealed that the BAT thermogenesis induced after electrical stimulation is mediated through ß-adrenoceptors. The present study demonstrates that electrical stimulation applied to the dorsal surface of BAT is able to activate thermogenesis of BAT through mediation of norepinephrine released from sympathetic nerves. Our findings may provide a basis for developing a novel therapeutic procedure for obesity and related disorders.

Intraluminal administration of zingerol, a non-pungent analogue of zingerone, inhibits colonic motility in rats.

Zingerone, a pungent component of ginger, may exert beneficial therapeutic effects on hypermotility-induced diarrhea because it has the ability to inhibit contractions of colonic smooth muscles. However, the pungency is undesirable for possible therapeutic use. The purpose of this study was to examine effects of zingerol, a non-pungent analogue of zingerone, in rats. Colonic motility in vivo was evaluated by measuring intraluminal pressure changes and expelled fluid volume from the colon in anesthetized rats. Mechanical contractile activities of isolated colonic segments were also recorded. Intracolonic administration of zingerol attenuated colonic motility in vivo without affecting blood pressure and heart rate in a manner similar to that of zingerone. Zingerol also inhibited spontaneous contractile movements in isolated colonic segments, suggesting that zingerol directly acts on the colon. Zingerol had no effect on jejunal motility, although zingerone showed an inhibitory effect to the jejunum. These findings suggest that zingerol can inhibit colonic motility without adverse effects on small intestinal motility and the cardiovascular system. The non-pungent property of zingerol will be useful as an oral or suppository medicine for treating diarrhea and other gastrointestinal disorders.

Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats.

Ginger (rhizome of Zingiber officinale Roscoe) is an herbal medicine for the treatment of gastrointestinal disorders including constipation and diarrhea. Zingerone is a likely active constituent responsible for the antidiarrheal activity of ginger. The current study was designed to characterize pharmacological actions of zingerone on colonic motility. To evaluate pharmacological effects of zingerone on colonic motility, we used isolated colonic segments from rats, in which mechanical responses were recorded in the longitudinal direction. In addition, we evaluated the effects on colonic motility in vivo by measuring intraluminal pressure changes and expelled fluid volume from the colon in anesthetized rats. Zingerone was applied to the lumen of the colon to allow the drug to access from the mucosal side. Zingerone inhibited spontaneous contractile movements in the isolated colonic segments in a dose-dependent manner. The inhibitory effects of zingerone on colonic movements were not affected by pretreatment with capsazepine, a typical antagonist of transient receptor potential vanilloid 1. In addition, tetrodotoxin, a blocker of voltage-dependent sodium channels on neurons, did not affect the suppression of colonic movements by zingerone, suggesting that zingerone acts on the smooth muscles directly. Zingerone also attenuated colonic motility in vivo without affecting blood pressure and heart rate. The effects were reversible and reproducible. Our findings suggest that zingerone can inhibit colonic motility via direct action on smooth muscles. Zingerone might exert beneficial therapeutic effects on hypermotility-induced diarrhea by abrogating excessive gastrointestinal motility.

Extract of grains of paradise and its active principle 6-paradol trigger thermogenesis of brown adipose tissue in rats.

Grains of paradise (GP) is a species of the ginger family, Zingiberaceae, extracts of which have a pungent, peppery taste due to an aromatic ketone, 6-paradol. The aim of this study was to explore the thermogenic effects of GP extracts and of 6-paradol. Efferent discharges from sympathetic nerves entering the interscapular brown adipose tissue were recorded. Intragastric injection of a GP extract or 6-paradol enhanced the efferent discharges of the sympathetic nerves in a dose-dependent manner. The enhanced nerve discharges were sustained for as long as 3h. The rats did not become desensitized to the stimulatory effects these compounds on sympathetic nerve activity. The tissue temperature of brown adipose tissue showed significant increase in rats injected with 6-paradol. These results demonstrate that GP extracts and 6-paradol activate thermogenesis in brown adipose tissue, and may open up new avenues for the regulation of weight loss and weight maintenance.

Contractile properties of esophageal striated muscle: comparison with cardiac and skeletal muscles in rats.

The external muscle layer of the mammalian esophagus consists of striated muscles. We investigated the contractile properties of esophageal striated muscle by comparison with those of skeletal and cardiac muscles. Electrical field stimulation with single pulses evoked twitch-like contractile responses in esophageal muscle, similar to those in skeletal muscle in duration and similar to those in cardiac muscle in amplitude. The contractions of esophageal muscle were not affected by an inhibitor of gap junctions. Contractile responses induced by high potassium or caffeine in esophageal muscle were analogous to those in skeletal muscle. High-frequency stimulation induced a transient summation of contractions followed by sustained contractions with amplitudes similar to those of twitch-like contractions, although a large summation was observed in skeletal muscle. The results demonstrate that esophageal muscle has properties similar but not identical to those of skeletal muscle and that some specific properties may be beneficial for esophageal peristalsis.

Extract from Calotropis procera latex activates murine macrophages.

Calotropis procera latex has long been used in traditional medicines. Extracts from C. procera latex have been reported to have various pharmacological actions, including protection from myocardial infarction, hepatoprotective action, antitumor activity, antinociceptive, and pro- and anti-inflammatory actions. To evaluate the immunomodulatory functions of the water-soluble C. procera extract (CPE), we investigated its ability to activate macrophages-effector cells in inflammatory and immune responses. Intraperitoneal injection of CPE in mice (2 mg/mouse) induced migration of macrophages to the intraperitoneal cavity, confirming the proinflammatory effects of water-soluble CPE. The direct effects of CPE on macrophages were then assessed by measuring the production of nitric oxide (NO) as an indicator for macrophage activation. Addition of CPE (1-10 microg/ml) to the culture medium of the murine monocyte/macrophage cell line RAW264.7 caused an increase in NO production in a time- and dose-dependent manner. CPE-elicited NO production was blocked by application of an inhibitor of inducible nitric oxide synthase (iNOS). Expression of iNOS mRNA was induced by treatment of cultured macrophages with CPE. Injection of CPE in mice also resulted in an increase in plasma NO level. The results suggest that CPE activates macrophages and facilitates NO production via up-regulation of iNOS gene expression.

Capsaicin pretreatment attenuates LPS-induced hypothermia through TRPV1-independent mechanisms in chicken.

It has been demonstrated that chicken TRPV1 (transient receptor potential vanilloid of subtype-1) is insensitive to capsaicin (CAP), and therefore, a chicken model is suitable to analyze the CAP-sensitive TRPV1-independent pathway. We elucidated here the possible involvement of the pathway in hypothermia induced by bacterial endotoxin (lipopolysaccharide, LPS) in chickens. Chicks were pretreated with CAP (10 mg/kg, iv) at 1, 2 and 3 days of age to desensitize them towards the CAP-sensitive pathway. An intravenous injection of LPS in 4-day-old chicks caused progressive hypothermia, ending with collapse and 78% mortality within 12 h after injection. The CAP pretreatment rescued the LPS-induced endotoxin shock and hypothermia in chicks. LPS-induced iNOS expression as well as NO production in liver and lung was suppressed by CAP pretreatment. CAP pretreatment also attenuated hypothermia due to exposure of chicks to cold ambient temperature. These findings suggest that a CAP-sensitive TRPV1-independent pathway may be involved in pathophysiological hypothermic reactions through the mediation of NO in chickens.