Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is the active ingredient of turmeric, which has a long history of being consumed as a dietary spice.1) In addition, turmeric is widely used in traditional Indian medicine to treat biliary disorders, anorexia, cough, diabetic complications, hepatic disorders, rheumatism, and sinusitis.2) Extensive investigation over the past five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type 2 diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits human immunodeficiency virus (HIV) replication, enhances wound healing, protects against liver injury, increases bile secretion, protects from cataract formation, and protects against pulmonary toxicity and fibrosis.3-5) Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects.In spite of these attractive properties of curcumin, information on the therapeutic efficiency of curcumin has been limited, partly due to its poor oral bioavailability. 6) Curcumin was found to be poorly soluble in water, the maximum solubility of which in aqueous buffer (pH 5.0) was reported to be as low as 11 ng/ml.7) The limited solubility of curcumin, as well as extensive systemic metabolism, could be responsible for the low bioavailability of curcumin after oral delivery. [8][9][10] In addition, curcumin in solution may be sensitive to UV light, and so marked photochemical degradation could occur under UV exposure, 11) leading to difficulty in its handling for clinical use.A number of efforts have been made to design a soluble formulation of curcumin, but no suitable delivery options have been found so far. We have developed an effective preparation of curcumin, a nano-particle colloidal dispersion, with improved oral bioavailability, and named it THER-ACURMIN. It has the following unique properties: 1) it is an effective preparation for new health care products (beverages, food, and supplements) which may be taken at a much lower dosage; 2) it is soluble in water, which is a must for an effective beverage product; 3) the preparation is highly stable in light (UV), and, therefore, can be put into transparent PET bottles; 4) it is heat-stable, including high temperature sterilization conditions; 5) the preparation has no unpleasant odor or taste.The main purpose of this study was to provide evidence to support the improved bioavailability and alcohol-toxicity-reducing effect of THERACURMIN through oral delivery. We evaluated the plasma pharmacokinetics of this new curcumin preparation and compared the results with curcumin powder after oral administration in rats and healthy human subjects. We also investigated the effect of THERACURMIN on the toxicity of alcohol following drinking. MATERIALS AND METHODS Preparation of Curcumin Powder and THERACUR-MINCurcumin powder was extracted...

Central corticotropin-releasing factor (CRF) delays gastric emptying through the autonomic nervous system. CRF plays an important role in mediating delayed gastric emptying induced by stress. However, it is not clear whether a sympathetic or parasympathetic pathway is involved in the mechanism of central CRF-induced inhibition of solid gastric emptying. The purpose of this study was to investigate whether 1) CRF inhibits solid gastric emptying via a peripheral sympathetic pathway and 2) stress-induced inhibition of solid gastric emptying is mediated via a central CRF and peripheral sympathetic pathways. Using male Sprague-Dawley rats, CRF was injected intracisternally with or without various adrenergic-blocking agents. To investigate whether central CRF-induced inhibition of solid gastric emptying is mediated via a peripheral sympathetic pathway, rats underwent celiac ganglionectomy 1 wk before the gastric emptying study. After solid meal ingestion (90 min), gastric emptying was calculated. To investigate the role of endogenous CRF in stress-induced delayed gastric emptying, a CRF type2 receptor antagonist, astressin2-B, was intracisternally administered. Rats were subjected to a restraint stress immediately after the feeding. Intracisternal injection of CRF (0.1-1.0 microg) dose-dependently inhibited solid gastric emptying. The inhibitory effect of CRF on solid gastric emptying was significantly blocked by guanethidine, propranolol, and celiac ganglionectomy but not by phentolamine. Restraint stress significantly delayed solid gastric emptying, which was improved by astressin2-B, guanethidine, and celiac ganglionectomy. Our research suggests that restraint stress inhibits solid gastric emptying via a central CRF type2 receptor and peripheral sympathetic neural pathway in rats.

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Although restraint stress accelerates colonic transit via a central corticotropin-releasing factor (CRF), the precise mechanism still remains unclear. We tested the hypothesis that restraint stress and central CRF stimulate colonic motility and transit via a vagal pathway and 5-HT3 receptors of the proximal colon in rats. 51Cr was injected via the catheter positioned in the proximal colon to measure colonic transit. The rats were subjected to a restraint stress for 90 min or received intracisternal injection of CRF. Ninety minutes after the administration of 51Cr, the entire colon was removed, and the geometric center (GC) was calculated. Four force transducers were sutured on the proximal, mid, and distal colon to record colonic motility. Restraint stress accelerated colonic transit (GC of 6.7 ± 0.4, n = 6) compared with nonrestraint controls (GC of 5.1 ± 0.2, n = 6). Intracisternal injection of CRF (1.0 μg) also accelerated colonic transit (GC of 7.0 ± 0.2, n = 6) compared with saline-injected group (GC of 4.6 ± 0.5, n = 6). Restraint stress-induced acceleration of colonic transit was reduced by perivagal capsaicin treatment. Intracisternal injection of CRF antagonists (10 μg astressin) abolished restraint stress-induced acceleration of colonic transit. Stimulated colonic transit and motility induced by restraint stress and CRF were significantly reduced by the intraluminal administration of 5-HT3 antagonist ondansetron (5 × 10−6 M; 1 ml) into the proximal colon. Restraint stress and intracisternal injection of CRF significantly increased the luminal content of 5-HT of the proximal colon. It is suggested that restraint stress stimulates colonic motility via central CRF and peripheral 5-HT3 receptors in conscious rats.