Traditional Chinese Medicine Da-Cheng-Qi-Tang Ameliorates Impaired Gastrointestinal Motility and Intestinal Inflammatory Response in a Mouse Model of Postoperative Ileus.

This study was to explore the therapeutic effect and mechanism of the traditional Chinese medicine with the formula Da-Cheng-Qi-Tang (T-DCQT) and a modified Da-Cheng-Qi-Tang (M-DCQT) in a postoperative ileus (POI) mouse model. POI was induced via small bowel manipulation, and T-DCQT or M-DCQT was given by enema. The intestinal motility was measured with a charcoal mixture gavage. The intestinal tissues were collected for further studies by histopathological, qPCR, immunohistochemical staining, and Western blotting. Levels of inflammatory cytokines in blood were determined using a high-throughput liquid chip. We found that gastrointestinal dysfunction was alleviated after administration of either a T-DCQT or M-DCQT enema. Increased expression of NF-κB, p38 MAPK, and TLR4 in the intestinal tissues of POI mice were reversed following treatment. IL-1α, IL-6, MIP-1ß, and IL-17 levels were significantly reduced at 24 h and 48 h following treatment, while the MCP-1 level was only observed to be reduced at 24 h after the treatment. Furthermore, compared with the T-DCQT effect, M-DCQT treatment was more effective in alleviating the increased IL-6, MIP-1ß, and IL-1α levels. So, we draw a conclusion that T-DCQT or M-DCOT could ameliorate the POI-associated inflammatory response and improve GI motility in a POI mouse model.

Antibacterial Activity and Anti-Quorum Sensing Mediated Phenotype in Response to Essential Oil from Melaleuca bracteata Leaves.

The prominent antibacterial and quorum sensing (QS) inhibition activity of aromatic plants can be used as a novel intervention strategy for attenuating bacterial pathogenicity. In the present work, a total of 29 chemical components were identified in the essential oil (EO) of Melaleuca bracteata leaves by gas chromatography-mass spectrometry (GC-MS). The principal component was methyleugenol, followed by methyl trans-cinnamate, with relative contents of 90.46% and 4.25%, respectively. Meanwhile, the antibacterial activity and the QS inhibitory activity of M. bracteata EO were first evaluated here. Antibacterial activity assay and MIC detection against seven pathogens (Dickeya dadantii Onc5, Staphylococcus aureus ATCC25933, Pseudomonas spp., Escherichia coli ATCC25922, Serratia marcescens MG1, Pseudomonas aeruginosa PAO1 and Chromobacterium violaceum ATCC31532) demonstrated that S. aureus ATCC25933 and S. marcescens MG1 had the higher sensitivity to M. bracteata EO, while P. aeruginosa PAO1 displayed the strongest resistance to M. bracteata EO. An anti-QS (anti-quorum sensing) assay revealed that at sub-minimal inhibitory concentrations (sub-MICs), M. bracteata EO strongly interfered with the phenotype, including violacein production, biofilm biomass, and swarming motility, as well as N-hexanoyl-L-homoserine lactone (C6-HSL) production (i.e., a signaling molecule in C. violaceum ATCC31532) of C. violaceum. Detection of C6-HSL indicated that M. bracteata EO was capable of not only inhibiting C6-HSL production in C. violaceum, but also degrading the C6-HSL. Importantly, changes of exogenous C6-HSL production in C. violaceum CV026 revealed a possible interaction between M. bracteata EO and a regulatory protein (cviR). Additionally, quantitative real-time polymerase chain reaction (RT-qPCR) analysis demonstrated that the expression of QS-related genes (cviI, cviR, vioABCDE, hmsNR, lasA-B, pilE1, pilE3, and hcnB) was significantly suppressed. Conclusively, these results indicated that M. bracteata EO can act as a potential antibacterial agent and QS inhibitor (QSI) against pathogens, preventing and controlling bacterial contamination.

Effects of berberine in the gastrointestinal tract - a review of actions and therapeutic implications.

Berberine is an isoquinoline alkaloid present in several plant species, including Coptis sp. and Berberis sp. In traditional medicine, extracts of berberine are used in the treatment of diarrhea of different origins. Recent studies have shown that berberine and its derivatives have significant biological effects on gastrointestinal (GI) and other functions and may become therapeutics for the treatment of diarrhea, gastroenteritis, diabetes, hyperlipidemia, cardiovascular diseases and inflammatory conditions. This paper summarizes the current knowledge on the actions of berberine in the GI tract. Binding and target sites, activated intracellular pathways, as well as the absorption and metabolism of berberine are discussed. Effects that may be useful in future clinical treatment, like antidiarrheal, anti-inflammatory and antitumor effects are critically reviewed and potential clinical applications are presented in detail.

Inhibiting roles of berberine in gut movement of rodents are related to activation of the endogenous opioid system.

Although Berberine (BER) is popular in treating gastrointestinal (GI) disorders, its mechanisms are not clear yet. In order to investigate the effects and possible mechanism of BER on GI motility in rodents, we first explored GI motility by recording the myoelectrical activity of jejunum and colon in rats, and upper GI transit with a charcoal marker in mice. Then, the plasma levels of gastrin, motilin, somatostatin and glucagon-like-peptide-1 (Glp-1) were measured by ELISA or radioimmunoassay (RIA). Furthermore, endogenous opioid-peptides (ß-endorphin, dynorphin-A, met-enkephalin) were detected by RIA after treatment with BER. Our results showed that BER concentration-dependently inhibited myoelectrical activity and GI transit, which can be antagonized by opioid-receptor antagonists to different extents. The elevated somatostatin and Glp-1, and decreased gastrin and motilin in plasma, which were caused by BER application, also could be antagonized by the opioid-receptor antagonists. Additionally, plasma level of ß-endorphin, but not dynorphin-A and met-enkephalin, was increased by applying BER. Taken together, these studies show that BER plays inhibiting roles on GI motility and up-regulating roles on somatostatin, Glp-1 and down-regulating roles on gastrin, motilin. The pharmacological mechanisms of BER on GI motility and plasma levels of GI hormones were discovered to be closely related to endogenous opioid system.

The Chinese herbal preparation Qing Yi Tang (QYT) improves intestinal myoelectrical activity and increases intestinal transit during acute pancreatitis in rodents.

The aim was to investigate alterations of intestinal motility in models of acute pancreatitis and to investigate the effects of the Chinese herbal preparation Qing Yi Tang (QYT) on these alterations. Upper gastrointestinal transit was evaluated in mice following induction of mild acute pancreatitis (MAP) using caerulein. Myoelectrical activity was recorded in rats after induction of severe acute pancreatitis (SAP) using sodium deoxycholate (SDOC). The contractility of jejunum segments was evaluated in the presence of SDOC, lipopolysaccharide (LPS) and trypsin. QYT accelerated the transit in MAP mice in a concentration dependent manner. Slow wave activity of smooth muscle in rat stomach and jejunum remained unchanged following SAP, but the spiking activity was significantly decreased, with bursts of 7.2 +/- 2.6/10 min compared with 47.9 +/- 13.2/10 min without SAP (p < 0.01). QYT reversed this decrease. Additionally, the amplitudes of slow waves and spikes were enhanced by QYT in SAP rats. The tension and amplitude of spontaneous contractile activity was reduced by SDOC and LPS and increased by trypsin. Gastrointestinal (GI) transit is altered by SAP but not by MAP. The Chinese herbal preparation QYT improves disturbed motility in AP by stimulating myoelectrical activity and accelerating GI transit.

Effect of Qingyitang on activity of intracellular Ca2+-Mg2+-ATPase in rats with acute pancreatitis.

AIM: To study the change of intracellular calcium-magnesium ATPase (Ca(2+)-Mg(2+)-ATPase) activity in pancreas, liver and kidney tissues of rats with acute pancreatitis (AP), and to investigate the effects of Qingyitang (QYT) (Decoction for clearing the pancreas) and tetrandrine (Tet) and vitamin E (VitE) on the activity of Ca(2+)-Mg(2+)-ATPase. METHODS: One hundred and five Sprague-Dawley rats were randomly divided into: normal control group, AP group, treatment group with QYT (1 ml/100 g) or Tet (0.4 ml/100 g) or VitE (100 mg/kg). AP model was prepared by a retrograde injection of sodium taurocholate into the pancreatic duct. Tissues of pancreas, liver and kidney of the animals were taken at 1 h, 5 h, 10 h respectively after AP induction, and the activity of Ca(2+)-Mg(2+)-ATPase was studied using enzyme-histochemistry staining. Meanwhile, the expression of Ca(2+)-Mg(2+)-ATPase of the tissues was studied by RT-PCR. RESULTS: The results showed that the positive rate of Ca(2+)-Mg(2+)-ATPase in AP group (8.3%, 25%, 29.2%) was lower than that in normal control group (100%) in all tissues (P<0.01), the positive rate of Ca(2+)-Mg(2+)-ATPase in treatment group with QYT (58.3%, 83.3%, 83.3%), Tet (50.0%, 70.8%, 75.0%) and VitE (54.2%, 75.0%, 79.2%) was higher than that in AP group (8.3%, 25.0%, 29.2%) in all tissues (P<0.01). RT-PCR results demonstrated that in treatment groups Ca(2+)-Mg(2+)-ATPase gene expression in pancreas tissue was higher than that in AP group at the observing time points, and the expression at 5 h was higher than that at 1 h. The expression of Ca(2+)-Mg(2+)-ATPase in liver tissue was positive, but without significant difference between different groups. CONCLUSION: The activity and expression of intracellular Ca(2+)-Mg(2+)-ATPase decreased in rats with AP, suggesting that Ca(2+)-Mg(2+)-ATPase may contribute to the occurrence and development of cellular calcium overload in AP. QYT, Tet and VitE can increase the activity and expression of Ca(2+)-Mg(2+)-ATPase and may relieve intracellular calcium overload to protect the tissue and cells from injuries.

[Therapeutic effect of qingyi decoction and tetrandrine in treating severe acute pancreatitis in miniature pigs and serum drug level determination].

OBJECTIVE: To investigate the therapeutic effect of Qingyi Decoction (QYD) and tetrandrine (Tet), used singly or combind, in treating miniature pigs with severe acute pancreatitis (SAP) and its mechanism. METHODS: Thirty-two Guizhou miniature pigs were made into SAP model by pancreatic duct retrograde injection of 5% sodium taurocholate. They were randomly divided into 4 groups: the control group, the QYD group, the Tet group and the combined treated group. The serum amylase activity and interleukin-1 and 6 (IL-1, IL-6) contents in serum from vena cava and portal vein were tested by biochemistry and radioimmunoassay (RIA). Serum emodin and plasma Tet levels were measured by high performance liquid chromatography (HPLC) 24, 48 and 72 hrs after treatment. And the pathological changes of pancreas, lung and liver were observed under microscope. RESULTS: The mortality of SAP pigs was reduced significantly and the inflammatory injury of the organs was ameliorated obviously in all treated groups, and the increased amylase activity and IL-1, IL-6 levels was attenuated. The therapeutic effect was much more obvious, and the plasma Tet level at different time points were much higher in the combined treated group than those in the other two groups treated by single drug (P < 0.01). CONCLUSION: Both QYD and Tet could treat effectively SAP through multiple pathways, combination of them reveals an elevation of serum drug concentration and shows a synergistic effect.

Effects of Tetrandrine and QYT on ICAM-1 and SOD gene expression in pancreas and liver of rats with acute pancreatitis.

AIM: Available experimental evidence from both clinical and animal models shows that both Chinese medicines tetrandine (Tet) and Qing Yi Tong (QYT) have positive treatment effects on acute pancreatitis (AP). This investigation was conducted to explore the treatment mechanisms of Tet and QYT on AP at the molecular level and thereby explain their therapeutic affects. It included an investigation of the effects of these drugs on gene expression of both intercellular adhesion molecule 1 (ICAM-1) and superoxide dismutase (Mn-SOD and Cu, Zn-SOD) in a rat model with AP. METHODS: AP in the test rats was induced by subjecting them to laparotomy followed by a retrograde injection of 4 % sodium taurocholate into the bilio-pancreatic duct. The test rats with AP were divided into three groups. One was treated with Tet, one with QYT, and one with normal saline solution. The sham-operated control group (SO) rats were only subjected to laparotomy. They were given no further treatment. For the Tet group, Tet was injected intraperitoneally, and for the QYT group, QYT was given with a nose-gastric catheter. These procedures were done at both 10 min and 5 h after AP induction. The levels of ICAM-1 mRNA expression and of SOD (Mn-SOD and Cu, Zn-SOD) mRNA expression in the pancreas and liver tissues were measured by RT-PCR at 1, 5, and 10 h after AP induction. RESULTS: When compared with the SO group during the observation time, rats with AP showed a higher expression of ICAM and a lower expression of Mn-SOD in both pancreas and liver tissues, and a lower expression of Cu, Zn-SOD in the pancreas. Tet treatment attenuated changes in the expression of both ICAM-1, and SOD (Mn-SOD and Cu, Zn-SOD) to a significant degree. A similar effect on the expression of SOD (Mn-SOD and Cu, Zn-SOD) was also found in the QYT group, but no obvious suppressive effect on ICAM-1 expression was observed. CONCLUSION: The results of this study suggest that one of the main mechanisms of Tet and QYT in treating AP is to enhance anti-oxidation of the body. The results also suggest that the anti-inflammatory effect of Tet is involved in the reduction of ICAM-1 expression. This explains why Tet and QYT are beneficial in treating AP.