Oral drug bioavailability depends on gastrointestinal absorption, intestinal transporters and metabolism enzymes are the important factors in drug gastrointestinal absorption and they can also be induced or inhibited by the active ingredients of Chinese materia medica. This article presents important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of the active ingredients of Chinese materia medica, and points out the importance of research on transport and metabolism of the active ingredients of Chinese materia medica in Chinese extract and Chinese medicinal formulae.
Animals ; Carrier Proteins ; metabolism ; Gastrointestinal Tract ; enzymology ; metabolism ; Humans ; Intestines ; metabolism ; Materia Medica ; metabolism

The present study is aimed to investigate the in vitro metabolic interconversion between baicalin (BG) and baicalein (B) in rat liver, kidney, intestine and bladder. BG and B were separately incubated with rat hepatic, renal, and intestinal microsomes, as well as bladder homogenates, for 30 min. The metabolites were identified and quantified by HPLC and metabolic kinetic parameters were obtained by fitting the data to the Michaelis-Menten equation. In hepatic microsomes, renal microsomes and bladder homogenates, but not in intestinal microsomes, BG was transformed into B, the hydrolysis metabolite of BG, with K(m) values being (44.65 +/- 6.01), (92.73 +/- 11.41), (74.60 +/- 3.68) micromol x L(-1), respectively, and V(max) values being (12.32 +/- 0.56), (3.30 +/- 0.18), (5.93 +/- 0.12) micromol x min(-1) x g(-1) (protein), respectively. In incubations with hepatic, renal, and intestinal microsomes and bladder homogenates, B was also transformed into BG, the glucuronidation metabolite of B, with K(m) values being (67.46 +/- 10.49), (226.7 +/- 71.59), (177.3 +/- 35.85), and (18.33 +/- 2.53) micromol x L(-1), respectively, and V(max) values being (14.74 +/- 0.97), (5.91 +/- 1.03), (38.14 +/- 3.60), and (1.22 +/- 0.05) micromol x min(-1) x g(-1) (protein), respectively. The results showed that the activity of UDP-glucuronosyltranferase (UGT) in intestinal microsomes was the highest among the four organs, and the activities of UGT were higher than that of glucuronidase (GUS) in hepatic, renal and intestinal microsomes, but the activity of GUS was higher than that of UGT in bladder homogenates.
Animals ; Anti-Infective Agents ; pharmacokinetics ; Antioxidants ; pharmacokinetics ; Biotransformation ; Flavanones ; pharmacokinetics ; Flavonoids ; pharmacokinetics ; Glucuronidase ; metabolism ; Glucuronosyltransferase ; metabolism ; Hydrolysis ; Intestines ; enzymology ; metabolism ; Kidney ; enzymology ; metabolism ; Liver ; enzymology ; metabolism ; Male ; Microsomes ; enzymology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder ; enzymology ; metabolism

OBJECTIVETo investigate the effect of intraluminal administration of ulinastatin (a protease inhibitor) in the intestine on intestinal inflammation in rats with hemorrhagic shock.

METHODSTwenty-eight Wistar rats were randomized into control group (A), intestinal saline perfusion group (B), ulinastatin intestinal perfusion group (C), and intravenous ulinastatin injection group (D) (n=7). The mean arterial blood pressure (MAP) and survival time of the rats were recorded. The changes in human polymorphonuclear cell (PMN) CD11b expression were detected by flow cytometry. The leukocyte count was recorded at different time points after the treatment, and the pathology of the intestinal mucosa was observed comparatively.

RESULTSGroups C and D showed significantly slower reduction of the MAP than groups A and B after hemorrhagic shock (P<0.05). The survival time of the rats was the longest in group C (P<0.05). CD11b expression increased gradually during hemorrhagic shock in all the groups, but the expression level was the lowest in group C (P<0.05). Hemorrhagic shock caused a reduction in leukocyte counts, which remained the highest in group C (P<0.05). Group C also showed the least intestinal pathology among the 4 groups.

CONCLUSIONIntestinal perfusion of ulinastatin can lower the reduction rate of MAP, attenuate plasma activation and intestinal inflammation, and prolong the survival of rats with hemorrhagic shock. These results indicate an important role of protease in intestinal inflammation during hemorrhagic shock.

Animals ; Arterial Pressure ; Disease Models, Animal ; Glycoproteins ; administration & dosage ; pharmacology ; Inflammation ; enzymology ; metabolism ; Intestines ; enzymology ; metabolism ; Plasma ; metabolism ; Rats ; Rats, Wistar ; Shock, Hemorrhagic ; blood ; enzymology ; metabolism ; Trypsin Inhibitors ; administration & dosage ; pharmacology

In Korea, common whelk (Buccinum undatum) is a popular edible shellfish. The aim of this study was to observe the sensitization rate to common whelk and to characterize its allergens. We carried out skin prick test (SPT) in 1,700 patients with various allergic diseases. Specific IgE were detected by ELISA in the patient sera and ELISA inhibition tests were conducted. IgE-binding components were identified by means of SDS-PAGE and IgE-immunoblotting. The effects of diges-tive enzymes were evaluated in both raw and thermally treated extracts. SPT to common whelk was positive (> or =2+) in 83 (4.9%) patients studied. Twenty-four (38.7%) out of 62 SPT positive patients had high serum specific IgE to common whelk. ELISA inhibition test showed significant inhibitions by abalone as well as by common whelk. IgE-immunoblotting demonstrated three IgE-binding components (40, 71, 82 kDa), which were digested by simulated intestinal fluid and moderately digested by simulated gastric fluid, and the digestibility of allergens remained unchanged after thermal treatment. In conclusion, IgE-sensitization rate to com-mon whelk was 4.9% in allergy patients. IgE-immunoblotting demonstrated three IgE-binding components, which were degraded by digestive enzymes. Further studies are needed to evaluate the clinical significance of the sensitized patients to common whelk.
Allergens/immunology ; Animals ; Comparative Study ; Cookery ; Digestion/*physiology ; Food Handling/methods ; Food Hypersensitivity/diagnosis/*epidemiology/*immunology/metabolism ; Heat ; Humans ; Immunoglobulin E/*immunology/metabolism ; Intestines/enzymology ; Korea/epidemiology ; *Mollusca ; Research Support, Non-U.S. Gov't ; Shellfish/*adverse effects ; Skin Tests ; Stomach/enzymology

Glycyrrhizin is a major bioactive component of liquorice, which exerts multiple biochemical and pharmacological activities and is frequently used in combination with other drugs in the clinic. Mycophenolate mofetil (MMF), an immunosuppressant widely used in transplant patients, is metabolized by UDP-glucuronyltransferases (UGTs). Although significant evidence supports that glycyrrhizin could interact with the cytochrome P450s (CYPs), few studies have addressed its effects on UGTs. The present study aimed at investigating the regulatory effects of diammonium glycyrrhizinate (GLN) on UGTs in vitro and in vivo. We found that long-term administration of GLN in rats induced overall metabolism of MMF, which might be due to the induction of UGT1A protein expression. Hepatic UGT1A activity and UGT1A mRNA and protein expression were significantly increased in GLN-treated rats. UGT1A expression levels were also increased in the intestine, contradicting with the observed decrease in intestinal UGT1A activities. This phenomenon may be attributed to different concentrations of glycyrrhetinic acid (GA) in liver and intestine and the inhibitory effects of GA on UGT1A activity. In conclusion, our study revealed that GLN had multiple effects on the expression and activities of UGT1A isoforms, providing a basis for a better understanding of interactions between GLN and other drugs.
Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Glucuronosyltransferase ; chemistry ; metabolism ; Glycyrrhizic Acid ; chemistry ; pharmacology ; Herb-Drug Interactions ; Intestines ; chemistry ; drug effects ; enzymology ; Kinetics ; Liver ; chemistry ; drug effects ; enzymology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the dynamic time-phase expressions of key genes of brain-gut CaM signal pathway of spleen Qi deficiency rats and the intervention effect of Sijunzi decoction.

METHODMale Wistar rats were randomly divided into the normal control group, model 14 d, 21 d, 28 d groups, and Sijunzi decoction 14 d, 21 d, 28 d groups. Except for the normal control group, the remaining groups were included into the spleen Qi deficiency model with the bitter cold breaking Qi method (ig 7.5 g · kg⁻¹ · d⁻¹ of Rheum officinale, Fructus aurantii immaturus, Magnolia officinalis preparation) and the exhaustive swimming method. On the 7th day after the modeling, the Sijunzi decoction groups were orally administered with Sijunzi decoction 20 g · kg⁻¹ · d⁻¹. The expressions of key genes CaM/CaMK II of CaM signaling pathway in hippocampus and intestine at different time points by immunohistochemical method and Western blot. At the same time, the intervention effect of Sijunzi decoction on spleen Qi deficiency rats and its mechanism were analyzed.

RESULTSpleen Qi deficiency rats showed higher intestinal CaM/CaMK II expression and lower hippocampus CaM/CaMK II expression than normal rats (P < 0.05, P < 0.01). After the treatment of Sijunzi decoction, spleen Qi deficiency rats showed reduction in intestinal CaM/CaMK II expression and increase in hippocampus CaM/CaMK II expression (P < 0.05, P < 0.01).

CONCLUSIONThe formation of spleen Qi deficiency syndrome may be related to the high expression of CaM/CaMK II in small intestine tissues and its low expression in hippocampus tissues. Sijunzi decoction may achieve the therapeutic effect in spleen Qi deficiency syndrome by reducing the CaM/CaMK II expression in intestinal tissues and increasing it in hippocampus tissues.

Animals ; Brain ; drug effects ; enzymology ; metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; genetics ; metabolism ; Calmodulin ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Intestines ; drug effects ; enzymology ; metabolism ; Male ; Qi ; Rats ; Rats, Wistar ; Spleen ; drug effects ; Splenic Diseases ; drug therapy ; enzymology ; genetics ; metabolism

OBJECTIVEIn order to use facultative gut bacteria as an alternate to animals for the initial gastrointestinal toxicity screening of heavy metals, a comparative study on rat intestinal epithelial cells and resident gut bacteria was undertaken.

METHODSin vitro growth rate of four gut bacteria, dehydrogenase (DHA) and esterase (EA) activity test, intestinal epithelial and bacterial cell membrane enzymes and in situ effect of arsenite were analysed.

RESULTSGrowth profile of mixed resident population of gut bacteria and pure isolates of Escherichia coli, Pseudomonas sp., Lactobacillus sp., and Staphylococcus sp. revealed an arsenite (2-20 ppm) concentration-dependent inhibition. The viability pattern of epithelial cells also showed similar changes. DHA and EA tests revealed significant inhibition (40%-72%) with arsenite exposure of 5 and 10 ppm in isolated gut bacteria and epithelial cells. Decrease in membrane alkaline phosphatase and Ca2+ -Mg2+ -ATPase activities was in the range of 33%-55% in four bacteria at the arsenite exposure of 10 ppm, whereas it was 60%-65% in intestinal epithelial villus cells. in situ incubation of arsenite using intestinal loops also showed more or less similar changes in membrane enzymes of resident gut bacterial population and epithelial cells.

CONCLUSIONThe results indicate that facultative gut bacteria can be used as suitable in vitro model for the preliminary screening of arsenical gastrointestinal cytotoxic effects.

Animals ; Arsenites ; pharmacology ; Cell Membrane ; drug effects ; Culture Media ; Epithelial Cells ; drug effects ; enzymology ; microbiology ; Esterases ; metabolism ; Gram-Negative Bacteria ; drug effects ; enzymology ; growth & development ; Gram-Positive Bacteria ; drug effects ; enzymology ; growth & development ; Humans ; Intestines ; cytology ; drug effects ; microbiology ; Oxidoreductases ; metabolism ; Rats ; Teratogens ; pharmacology

OBJECTIVETo investigate the effects of Radix Salviae Miltiorrhiae, Radix Aconiti Lateralis Preparata and Rhizoma Anemarrhena on nitric oxide (NO) system of heart, liver, intestine, lung, kidney and serum in mice with endotoxemia, and to explore the potential molecular mechanism of the three kinds of traditional Chinese drugs.

METHODSModel mice of endotoxemia were established by intraperitoneally injected with E. coli. endotoxin at the dose of 6 mg/kg. The levels of NO, nitric oxide synthase ( NOS) and superoxide dismutase ( SOD) in heart, liver, intestine, lung, kidney and serum of mice were measured at the points after injection for 4 hours, 8 hours and 24 hours, respectively.

RESULTS(1) Radix Salviae Miltiorrhiae could significantly increase the contents of constitutive nitric oxide synthase (cNOS) and SOD in the above tissues and serum, while decrease the content of inducible nitric oxide synthase (iNOS). (2) As compared with the model group, Radix Aconiti Lateralis could significantly decrease the contents of iNOS and NO, increase content of SOD in heart, lung and kidney tissues. (3) N.-Nitro-L-arginine (L-NNA) significantly decreased the content of iNOS, NO and SOD in all above tissues and serum, and also decreased the content of cNOS in lung and kidney tissues and serum. (4) Rhizoma Anemarrhenae could significantly increase the concentrations of iNOS and NO and decrease content of SOD in liver, lung and kidney tissues than those in the model group.

CONCLUSIONRadix Salviae Miltiorrhiae and Radix Aconiti Lateralis have a protective effect on the endotoxemia mice by suppressing the content of iNOS to reduce the production of NO induced by iNOS. At the same time, Radix Salviae Miltiorrhiae can improve the mice symptoms by increasing the beneficial NO through the increasing production of cNOS. Rhizoma Anemarrhenae can aggravate the injury of endotoxemia mice by increasing the production of NO due to producing large numbers of iNOS. L-NNA, non-selective inhibitor of NOS, aggravates damage of tissues and increases mortality, though it can reduce the increase of iNOS and NO induced by lipopolysaccharide.

Aconitum ; Anemarrhena ; Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endotoxemia ; drug therapy ; enzymology ; metabolism ; Intestines ; metabolism ; Kidney ; metabolism ; Liver ; metabolism ; Mice ; Myocardium ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; antagonists & inhibitors ; metabolism ; Phytotherapy ; Salvia miltiorrhiza

OBJECTIVETo investigate the influence of Weichang'an pill on the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in model rats.

METHODAnimal model of compound diarrhea was induced by a lactose enriched diet in the Wistar rat, combining with restraint stress. Twenty four female Wistar rats were randomly divided into normal group, model group and 60 mg x kg(-1) x d(-1) Weichang'an pill group. The rate of weight increase, the incubation period of diarrhea and the diarrhea index were observed. Then 45 female Wistar rats randomly divided into five groups: control group, model group and Weichang'an pill groups of high, medium and low doses (80, 60, 40 mg x kg(-1) x d(-1)). The indexes of thymus and spleen were calculated. The activities of LDH, MDH and disaccharidase in intestinal organization were inspected. Serum D-xylose content and the AQP4 concentration in proximal colon were detected.

RESULTAfter taking Weichang'an pill for 4 days, the rate of weight increase in Weichang'an pill group was higher than the model group's. While the rate of diarrhea was lower significantly. So the best cycle of taking medicine was 4 days. The indexes of thymus and spleen of model group were decreased than that of control group. And the activities of LDH, MDH and disaccharidase in intestinal organization were also decreased. But the AQP4 concentration in proximal colon was increased. Compared with the model group, the indexes of thymus and spleen increased remarkably in the group of medium doses. Meanwhile, the activities of LDH, MDH and disaccharidase increased. But the AQP4 concentration didn't change.

CONCLUSIONWeichang'an pill has the effect of antidiarrhea. It can adjust the sugar's catabolism through increasing the activity of intestinal digestive ferment.

Animals ; Aquaporin 4 ; genetics ; metabolism ; Colon ; drug effects ; metabolism ; Disaccharidases ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Intestines ; drug effects ; enzymology ; Irritable Bowel Syndrome ; drug therapy ; enzymology ; genetics ; metabolism ; L-Lactate Dehydrogenase ; genetics ; metabolism ; Malate Dehydrogenase ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Spleen ; drug effects ; metabolism

OBJECTIVETo discuss the effect of matrine on nitric oxide (NO) and asymmetric methylarginine (ADMA) metabolism pathways in serum and tissues of mice with lipopolysaccharide (LPS) -induced intestine tissue inflammation.

METHODKunming mice were randomly divided into five groups: the normal control group, the LPS group and matrine (80, 40, 20 mg x kg(-1) x d(-1)) groups. The mice were intragastrically administered with drugs for 3 d (distilled water of the same volume for the normal control group and the LPS group). One hour after the last intragastrical administration, normal saline or LPS (1 mg x kg(-1)) were intraperitoneally injected. Twelve hours later, serum and tissues were collected to determine NO and ADMA levels and observe the pathological changes of intestinal tissues. The Western blot method was adopted to detect the protein expressions of arginine methyltransferases 1 (PRMT1) and dimethylarginine dimethylaminohydrolase 2 (DDAH2) in intestinal tissues.

RESULTCompared with the model group, matrine (80, 40, 20 mg x kg(-1) x d(-1)) groups showed lower NO content in serum and tissues, higher ADMA level in serum and increased PRMT1 expression in intestinal tissues, but without effect on DDAH2 expression.

CONCLUSIONMatrine could inhibit LPS-induced intestine tissue inflammation in mice. Its action mechanism is related to the decreased NO content in serum and tissues and increased ADMA level in serum and PRMT1 expression in intestinal tissues.

Alkaloids ; administration & dosage ; Animals ; Arginine ; analogs & derivatives ; blood ; metabolism ; Humans ; Inflammation ; Intestinal Diseases ; drug therapy ; enzymology ; immunology ; metabolism ; Intestines ; drug effects ; enzymology ; immunology ; metabolism ; Lipopolysaccharides ; adverse effects ; Male ; Mice ; Nitric Oxide ; blood ; metabolism ; Protein-Arginine N-Methyltransferases ; genetics ; metabolism ; Quinolizines ; administration & dosage