Objective To explore the preventive effect and mechanism of tea polyphenols on morphine-induced constipation. Methods Female Kunming mice were randomly divided into 4 groups (10 mice per group), including blank control group, model control group, tea polyphenols group and tea polyphenols + morphine group. Tea polyphenols group and tea polyphenols + morphine group were pretreated with 100 mg·kg-1 of tea polyphenols for 4 days, meanwhile blank control group and model control group were preteated with 0.1 mL·kg-1 of 0.5% CMC-Na for 4 days. On the fourth day model control group and tea polyphenols + morphine group were intraperitoneal injected 20 mg kg-1 morphine, otherwise blank control group and tea polyphenols group were injected with 0.1 mL·kg-1 of 0.9% sodium chloride solution. Then mice were given 0.2 mL of 5% ink solution by intragastric administration 15 min later. The latency to paw licking was detected in hot plate test to evaluate the effect of tea polyphenols on morphine analgesia. The levele of motilin (MLT), substance P (SP) and somatostatin (SS) in intestinal tissue were determined by enzyme-linked immunosorbent assay (ELISA) among groups. Results Compared with the blank control group, the length of propelling ink and the propelling rate of ink were significantly lower in the model control group (P<0.01), meanwhile tea polyphenols group were much higher(P<0.05). Compared with model control group, the length of propelling ink and the propelling rate of ink were significantly higher in tea polyphenols + morphine group mice (P<0.05). The first paw licking time of control group and tea polyphenols group were (8.64 + 2.72)s and (9.11 + 2.13) s, and the time of model control group and tea polyphenols + morphine group were (18.79±3.58)s and (20.10±3.72) s. The contents of MLT and SP were reduced in model control group (P<0.05), but significantly increased in tea polyphenols group (P<0.05) compared with blank control group. Compared with the model control group, MLT and SP had an obviously increase in tea polyphenols + morphine group (P<0.05). Compared with blank control group, the content of SS was increased in model control group, but decreased markedly in tea polyphenols group and tea polyphenols + morphine group (P<0.05). Conclusion Tea polyphenols can prevent the morphine-induced constipation without decreasing the analgesic effect of morphine, which is related to the regulation of the content of MLT, SP and SS.
Fig.1
Content of motilin,substance P and somatostatin in four groups of mice(x¯±s,n=10) Compared with blank control group,*1P<0.05;Compared with model control group,*2P<0.05
目前研究表明,动物被给予吗啡后,肠神经被抑制,神经递质P物质等释放减少,类似消化期间移行性复合运动(migrating motor complex,MMC)Ⅲ相样运动减弱[2],最终导致便秘。MMCⅢ能使整个消化道在消化间期有断续的运动,从而清除胃肠内容物,同时也引起肠道菌群迁移、导致菌群生态失衡[2]。而MMC的启动和调节需要神经因素和胃肠激素的参与,与胃动素、P物质和生长抑素密切相关[16]。胃动素是一种兴奋胃肠活动的脑肠肽。激动肠道胃动素受体,能促进胞内三磷酸腺苷含量上升,收缩平滑肌,参与启动MMCⅢ[17]。而P物质是一种速激肽,由肠壁内的肠神经细胞体分泌,在特定神经冲动的刺激下可被释放,增加空肠、回肠和结肠平滑肌收缩,促进肠道蠕动[17]。胃动素和P物质的增加均有促进肠蠕动的作用。而本实验发现,茶多酚+吗啡组便秘改善时,肠内胃动素和P物质表达也较模型对照组增加,提示茶多酚促进胃肠蠕动的作用与增加肠内胃动素和P物质含量有关。生长抑素是一种神经激素,主要有14个氨基酸残基和28个氨基酸残基两种形式,能抑制胃肠蠕动,还能减少促进胃肠蠕动的激素如胃动素、胃泌素等释放[16]。本实验结果显示,与模型对照组比较,茶多酚+吗啡组肠内生长抑素有明显减少,提示茶多酚也通过减少肠内生长抑素含量,间接促进胃动素等的含量,增加肠蠕动,缓解吗啡所致便秘。茶多酚能有效预防吗啡导致的便秘,是通过增加小肠内胃动素和P物质,同时减少生长抑素来实现的。
AFZALM,SAFER AM,MENONM.Green tea polyphenols and their potential role in health and disease[J].Inflammo-pharmacology,2015,23(4):151-161.
There is a growing body of evidence that plant polyphenols such as resveratrol, anthocyanins, catechins, and terpenes like taxol are effectively used in the treatment of chronic conditions including cancer, Alzheimer, Parkinsonism, diabetes, aging, etc. The link between oxidative stress and inflammation is well accepted. Thus, the mechanism of action of these natural products is partly believed to be through their significant antioxidant properties. The main constituent of green tea, with clinical significance, is epigallocatechin gallate (EGCG). It has been associated with antitumor, anti-Alzheimer, and anti-aging properties, improve redox status at the tissue level possibly preventing system level structural damage. This review focuses on EGCG and its potential therapeutic role in health and disease.
KONR,IKARASHIN,HAYAKAWAA,et al.Morphine-induced constipation develops with increased aquaporin-3 expression in the colon via increased serotonin secretion[J].Toxicol Sci,2015,145(2):337-347.
Abstract Aquaporin-3 (AQP3) is a water channel that is predominantly expressed in the colon, where it plays a critical role in the regulation of fecal water content. This study investigated the role of AQP3 in the colon in morphine-induced constipation. AQP3 expression levels in the colon were analyzed after oral morphine administration to rats. The degree of constipation was analyzed after the combined administration of HgCl 2 (AQP3 inhibitor) or fluoxetine (5-HT reuptake transporter [SERT] inhibitor) and morphine. The mechanism by which morphine increased AQP3 expression was examined in HT-29 cells. AQP3 expression levels in rat colon were increased during morphine-induced constipation. The combination of HgCl2 and morphine improved morphine-induced constipation. Treatment with morphine in HT-29 cells did not change AQP3 expression. However, 5-HT treatment significantly increased the AQP3 expression level and the nuclear translocation of peroxisome proliferator-activated receptor gamma (PPAR纬) 1 h after treatment. Pretreatment with fluoxetine significantly suppressed these increases. Fluoxetine pretreatment suppressed the development of morphine-induced constipation and the associated increase in AQP3 expression in the colon. The results suggest that morphine increases the AQP3 expression level in the colon, which promotes water absorption from the luminal side to the vascular side and causes constipation. This study also showed that morphine-induced 5-HT secreted from the colon was taken into cells by SERT and activated PPAR纬, which subsequently increased AQP3 expression levels. 漏 The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Polyphenols derived from tea are thought to be important for human health. We show using a combination of particle tracking microrheology and small-angle neutron scattering that polyphenols acts as cross-linkers for purified gastrointestinal mucin, derived from the stomach and the duodenum. Both naturally derived purified polyphenols, and green and black tea extracts are shown to act as cross-linkers. The main active cross-linking component is found to be the galloylated forms of catechins. The viscosity, elasticity and relaxation time of the mucin solutions experience an order of magnitude change in value upon addition of the polyphenol cross-linkers. Similarly small-angle neutron scattering experiments demonstrate a sol-gel transition with the addition of polyphenols, with a large increase in the scattering at low angles, which is attributed to the formation of large scale (>10 nm) heterogeneities during gelation. Cross-linking of mucins by polyphenols is thus expected to have an impact on the physicochemical environment of both the stomach and duodenum; polyphenols are expected to modulate the barrier properties of mucus, nutrient absorption through mucus and the viscoelastic microenvironments of intestinal bacteria.
VODNAR DC.Green tea increases the survival yield of bifidobacteria in simulated gastrointestinal environment and during refrigerated conditions[J].Chem Central J,2012,6(1):61.
The well-known prebiotics are carbohydrates but their effects may not always be beneficial, as they can also encourage the growth of non-probiotic bacteria such as Eubacterium biforme and Clostridium perfringens. Therefore, new alternatives such as non-carbohydrate sources to stimulate the growth of probiotics are needed. The aim of this work was to evaluate (I) the green tea polyphenols by HPLC-LC/MS and (II) the protective effect of green tea extract on viability and stability of B. infantis ATCC 15697 and B. breve ATCC 15700 microencapsulated in chitosan coated alginate microcapsules during exposure to simulated gastrointestinal conditions and refrigerated storage.The major compound identified by HPLC-LC/MS in green tea was epigallocatechin gallate followed by caffeine and epigallocatechin. The survival yield of probiotic bacteria in microcapsules with 10% GT during storage at 4°C, demonstrated significantly (P65<650.05) higher number of survival bacteria. Microencapsulated B.infantis and B. breve with 5% and 10% GT showed a significantly (P65<650.05) improved survival under simulated gastric conditions (pH 2.0, 265h) and bile solution (3%, 265h) when they were compared with microencapsulation without GT addition.The results of this study suggest that green tea coencapsulated with B. infantis or B. breve exert a protective effect of bacteria during exposure to gastrointestinal conditions and refrigerated storage. For a health perspective, the results confirm the growing interest probiotic bacteria and the perceived benefit of increasing their numbers in the gastrointestinal tract by microencapsulation.
CHEN CY,TSAI CY.Ghrelin and motilin in the gastroin-testinal system[J].Curr Pharm Design,2012,18(31):4755-4765.
Human ghrelin and human motilin, belonging to the ghrelin/motilin-related peptide family, share 36% amino acid sequence identity, while the human ghrelin receptor exhibits a remarkable 50% overall identity with the human motilin receptor. In addition to their structural resemblance, ghrelin and motilin are the only two mammalian hormones known to decrease in the postprandial period. Ghrelin and motilin participate in initiating the migrating motor complex in the stomach, and stimulate gastrointestinal motility, accelerate gastric emptying, and induce "gastric hunger". In addition to modulating the release of growth hormone and gut motility, ghrelin plays a crucial role in the secretion and protection of the stomach and colon. Ghrelin mimetics and motilin agonists are currently being developed to reverse gastrointestinal hypomotility disorders. With additional appetite-enhancing, adiposity-promoting, and anti-inflammatory effects, ghrelin and rikkunshito (a traditional Japanese herb enhancing acyl ghrelin signaling) are superior to motilin in the treatment of cancer-related anorexia and cachexia, post-chemotherapy symptoms, rheumatological diseases, age-related frailty, as well as post-operative, septic, and post-burn gut ileus.
HOOGERWERF WA,SARNA SK.Tachykinin receptors as drug targets for motility disorders[J].Dig Dis,2006,24(1/2):83-90.
The tachykinins and their receptors are strategically distributed within the gut wall, spinal cord, and central nervous system to be potential targets of therapeutic agents for gastrointestinal motility disorders. However, the development of effective tachykinin receptor agonists or antagonists to treat these disorders has had very limited success so far. This is, in part, due to the complex and multilevel of regulation of gastrointestinal motility function and the challenges faced in targeting the specific type of gut contraction to normalize function in disease state.
CHAUDHURIL,BASUS,SETHP,et al.Prokinetic effect of black tea on gastrointestinal motility[J].Life Sci,2000,66(9):847-854.
The gastrokinetic effects of hot water extract of black tea [Camellia sinensis, (L) O. Kuntze (Theaceae)] on gastrointestinal motility were studied both in vivo and in vitro. The extract significantly accelerated the gastrointestinal transit (GIT) in vivo in mice. These facilitatory effect was reduced after pretreatment with atropine, hemicholinium-3, morphine, indomethacin, McN-A-343 and L-arginine. In guinea pig ileum, the extract facilitated the peristaltic reflex in response to pressures in normal preparation. The black tea extract and L-NMMA (nitric oxide synthase inhibitor) significantly reduced the electrical field stimulated nonadrenergic, noncholinergic (NANC) relaxation of isolated rat fundal strips. The extract markedly enhanced the tonic ('hump') responses to transmural stimulation in longitudinal muscle of guinea pig ileum which was unaltered in the presence of atropine. These findings suggest a cholinergic involvement and a partial role of prostaglandin and nitric oxide in the mechanism of action of black tea extract on gastrointestinal motility. To determine the effective constituents in black tea responsible for this activity, the effect of black tea polyphenols on GIT were also studied. Thearubigin fraction (but not theaflavin) accelerated GIT significantly which suggests its involvement in the prokinetic effect of black tea.
... 目前研究表明,动物被给予吗啡后,肠神经被抑制,神经递质P物质等释放减少,类似消化期间移行性复合运动(migrating motor complex,MMC)Ⅲ相样运动减弱[2],最终导致便秘.MMCⅢ能使整个消化道在消化间期有断续的运动,从而清除胃肠内容物,同时也引起肠道菌群迁移、导致菌群生态失衡[2].而MMC的启动和调节需要神经因素和胃肠激素的参与,与胃动素、P物质和生长抑素密切相关[16].胃动素是一种兴奋胃肠活动的脑肠肽.激动肠道胃动素受体,能促进胞内三磷酸腺苷含量上升,收缩平滑肌,参与启动MMCⅢ[17].而P物质是一种速激肽,由肠壁内的肠神经细胞体分泌,在特定神经冲动的刺激下可被释放,增加空肠、回肠和结肠平滑肌收缩,促进肠道蠕动[17].胃动素和P物质的增加均有促进肠蠕动的作用.而本实验发现,茶多酚+吗啡组便秘改善时,肠内胃动素和P物质表达也较模型对照组增加,提示茶多酚促进胃肠蠕动的作用与增加肠内胃动素和P物质含量有关.生长抑素是一种神经激素,主要有14个氨基酸残基和28个氨基酸残基两种形式,能抑制胃肠蠕动,还能减少促进胃肠蠕动的激素如胃动素、胃泌素等释放[16].本实验结果显示,与模型对照组比较,茶多酚+吗啡组肠内生长抑素有明显减少,提示茶多酚也通过减少肠内生长抑素含量,间接促进胃动素等的含量,增加肠蠕动,缓解吗啡所致便秘.茶多酚能有效预防吗啡导致的便秘,是通过增加小肠内胃动素和P物质,同时减少生长抑素来实现的. ...
Ghrelin and motilin in the gastroin-testinal system
2
2012
... 目前研究表明,动物被给予吗啡后,肠神经被抑制,神经递质P物质等释放减少,类似消化期间移行性复合运动(migrating motor complex,MMC)Ⅲ相样运动减弱[2],最终导致便秘.MMCⅢ能使整个消化道在消化间期有断续的运动,从而清除胃肠内容物,同时也引起肠道菌群迁移、导致菌群生态失衡[2].而MMC的启动和调节需要神经因素和胃肠激素的参与,与胃动素、P物质和生长抑素密切相关[16].胃动素是一种兴奋胃肠活动的脑肠肽.激动肠道胃动素受体,能促进胞内三磷酸腺苷含量上升,收缩平滑肌,参与启动MMCⅢ[17].而P物质是一种速激肽,由肠壁内的肠神经细胞体分泌,在特定神经冲动的刺激下可被释放,增加空肠、回肠和结肠平滑肌收缩,促进肠道蠕动[17].胃动素和P物质的增加均有促进肠蠕动的作用.而本实验发现,茶多酚+吗啡组便秘改善时,肠内胃动素和P物质表达也较模型对照组增加,提示茶多酚促进胃肠蠕动的作用与增加肠内胃动素和P物质含量有关.生长抑素是一种神经激素,主要有14个氨基酸残基和28个氨基酸残基两种形式,能抑制胃肠蠕动,还能减少促进胃肠蠕动的激素如胃动素、胃泌素等释放[16].本实验结果显示,与模型对照组比较,茶多酚+吗啡组肠内生长抑素有明显减少,提示茶多酚也通过减少肠内生长抑素含量,间接促进胃动素等的含量,增加肠蠕动,缓解吗啡所致便秘.茶多酚能有效预防吗啡导致的便秘,是通过增加小肠内胃动素和P物质,同时减少生长抑素来实现的. ...
Tachykinin receptors as drug targets for motility disorders
2
2006
... 目前研究表明,动物被给予吗啡后,肠神经被抑制,神经递质P物质等释放减少,类似消化期间移行性复合运动(migrating motor complex,MMC)Ⅲ相样运动减弱[2],最终导致便秘.MMCⅢ能使整个消化道在消化间期有断续的运动,从而清除胃肠内容物,同时也引起肠道菌群迁移、导致菌群生态失衡[2].而MMC的启动和调节需要神经因素和胃肠激素的参与,与胃动素、P物质和生长抑素密切相关[16].胃动素是一种兴奋胃肠活动的脑肠肽.激动肠道胃动素受体,能促进胞内三磷酸腺苷含量上升,收缩平滑肌,参与启动MMCⅢ[17].而P物质是一种速激肽,由肠壁内的肠神经细胞体分泌,在特定神经冲动的刺激下可被释放,增加空肠、回肠和结肠平滑肌收缩,促进肠道蠕动[17].胃动素和P物质的增加均有促进肠蠕动的作用.而本实验发现,茶多酚+吗啡组便秘改善时,肠内胃动素和P物质表达也较模型对照组增加,提示茶多酚促进胃肠蠕动的作用与增加肠内胃动素和P物质含量有关.生长抑素是一种神经激素,主要有14个氨基酸残基和28个氨基酸残基两种形式,能抑制胃肠蠕动,还能减少促进胃肠蠕动的激素如胃动素、胃泌素等释放[16].本实验结果显示,与模型对照组比较,茶多酚+吗啡组肠内生长抑素有明显减少,提示茶多酚也通过减少肠内生长抑素含量,间接促进胃动素等的含量,增加肠蠕动,缓解吗啡所致便秘.茶多酚能有效预防吗啡导致的便秘,是通过增加小肠内胃动素和P物质,同时减少生长抑素来实现的. ...
, 刘异
