Pharmacokinetics and metabolism of ligustilide, a major bioactive component in Rhizoma Chuanxiong, in the rat.
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Ligustilide is the most abundant bioactive ingredient in Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. The present study reported, for the first time, the pharmacokinetics of ligustilide, administered in its pure form and in an herbal extract, in rats. After i.v. administration of pure ligustilide, it was distributed extensively (V(d), 3.76 +/- 1.23 l/kg) and eliminated rapidly (t(1/2), 0.31 +/- 0.12 h). The i.v. clearance (CL) of ligustilide after Chuanxiong extract administration was significantly higher than that dosed in its pure form [CL, 20.35 +/- 3.05 versus 9.14 +/- 1.27 l/h/kg, p < 0.01; area under the curve (AUC), 0.79 +/- 0.10 versus 1.81 +/- 0.24 mg x h/l, p < 0.01], suggesting significant interaction between ligustilide and components present in the extract. Dose-dependent pharmacokinetics was observed after i.p. administration, and a significantly higher dose-normalized AUC (1.77 +/- 0.23 mg x h/l) at 52 mg/kg was obtained than that at 26 mg/kg (0.93 +/- 0.07 mg x h/l, p < 0.05). Oral bioavailability of ligustilide was low (2.6%), which was partly because of extensive first-pass metabolism in the liver. Seven metabolites of ligustilide were identified, and three of them were unequivocally characterized as butylidenephthalide, senkyunolide I, and senkyunolide H. These three compounds also occurred naturally in the herb and were reported to be bioactive. (+info)
In vitro behavior of human intestinal mucosa. The influence of acetyl choline on ion transport.
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The possibility that the autonomic nervous system may influence the function of intestinal mucosa was investigated by assessing the effect of acetyl choline on ion transport in human intestine. Isolated pieces of stripped ileal mucosa were mounted in Perspex flux-chambers and bathed in isotonic glucose Ringer's solution. Acetyl choline caused a rise in mean potential difference (8.8-12.3 mV, P less than 0.002) and short circuit current (287.7-417.2 muA-cm-2, P less than 0.01) (n = 12), observable at a concentration of 0.01 mM and maximal at 0.1 mM. This effect was enhanced by neostigmine and blocked by atropine. Isotopic flux determinations revealed a change from a small mean net Cl absorption (58) to a net Cl secretion (-4.3mueq-cm-2-h-1P less than 0.001) due predominantly to an increase in the serosal to mucosal unidirectional flux of Cl (10.63-14.35 mueq-cm-2-h-1P less than 0.05) and a smaller reduction in the mucosal to serosal flux (11.22 to 10.02 mueq-cm-2-h-1P less than 0.05). Unidirectional and net Na transport was unaffected. A similar electrical and ion transport response was observed in a single study of two pieces of jejunal mucosa. In the absence of glucose net chloride secretion was produced and again an insignificant effect on net sodium transport was noted. Acetyl choline did not provoke a sustained effect on mucosal cyclic adenine nucleotide levels although a short-lived cyclic adenine nucleotide response was seen in some tissues 20-30 s after drug addition. These studies demonstrate that acetyl choline does influence human intestinal ion transport by stimulating chloride secretion and suggest a possible mechanism by which the parasympathetic nervous system could be concerned in the control of ion transport. (+info)
Mechanism and site of small intestinal uptake of vitamin D3 in pharmacological concentrations.
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The site and mechanism of initial uptake of 1,2-3H vitamin D3 pharmacological concentrations was investigated using everted rat small bowel sacs incubated in a micellar medium. The mean +/- SE uptake rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 6.7 +/- 0.26, 7.8 +/- 0.54, and 3.3 +/- 0.20 nmole/min/100 mg tissue, respectively. Incubation with the addition of 10(-3) M 2,4-dinitrophenol, or 10(-3) M KCN, or under nitrogen atmosphere did not change (P greater than 0.05) the above rates of absorption. Incremental increases in the concentration of vitamin D in the incubation medium up to 1200 muM resulted in a linear increase in the uptake rate indicating lack of saturation kinetics. In all the above experiments, greater rate of uptake of the vitamin occurred in the proximal and medial small bowel than the distal small bowel (P less than 0.01). The above experiments indicate that vitamin D3 in this range of concentrations is taken up by enterocytes by a nonsaturable passive diffusion mechanism showing no evidence for carrier mediation. The rate of intestinal uptake is highest in the proximal and medial segments of the small bowel. (+info)
The Syrian hamster: a reproducible model for studying changes in intestinal fluid secretion in response to enterotoxin challenge.
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Syrian hamsters respond in a predictable and reproducible manner to intragastric administration of purified cholera enterotoxin by intraluminal accumulation of fluid in the small bowel, cecum, and proximal colon. In the majority of animals this process is self limiting, and recovery occurs with full reabsorption of intestinal fluid by 30 to 35 h. The secretory response to 75 mug of cholera toxin has been defined, and the model was utilized to study the inhibitory effects of indomethacin, polymyxin B sulfate, glucose electrolyte solutions, and colchicine. These studies demonstrate its potential usefulness as a convenient and inexpensive technique for evaluation of pharmacological agents that might inhibit intestinal fluid secretion. (+info)
Effects of salinity on intestinal bicarbonate secretion and compensatory regulation of acid-base balance in Opsanus beta.
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