AMPK/α-Ketoglutarate Axis Regulates Intestinal Water and Ion Homeostasis in Young Pigs.

Water and ion absorption via sensitive aquaporins (AQPs) and ion channels is of critical importance in intestinal health. However, whether α-ketoglutarate (AKG) could improve intestinal water and ion homeostasis in lipopolysaccharide (LPS)-challenged piglets and whether the AMP-activated protein kinase (AMPK) pathway is involved remains largely unknown. This study was conducted to investigate the effect of dietary AKG supplementation on the small intestinal water and ion homeostasis through modulating the AMPK pathway in a piglet diarrhea model. A total of 32 weaned piglets were used in a 2 × 2 factorial design; the major factors were diet (basal diet or 1% AKG diet) and challenge (Escherichia coli LPS or saline). The results showed that LPS challenge increased the diarrhea index and affected the concentrations of serum Na+, K+, Cl-, glucose, and AKG and its metabolites in piglets fed the basal or AKG diet. However, the addition of AKG attenuated diarrhea incidence and reversed these serum parameter concentrations. Most AQPs (e.g., AQP1, AQP3, AQP4, AQP5, AQP8, AQP10, and AQP11) and ion transporters (NHE3, ENaC, and DRA/PAT1) were widely distributed in the duodenum and jejunum of piglets. We also found that AKG up-regulated the expression of intestinal epithelial AQPs while inhibiting the expression of ion transporters. LPS challenge decreased (P < 0.05) the gene and protein expression of the AMPK pathway (AMPKα1, AMPKα2, SIRT1, PGC-1α, ACC, and TORC2) in the jejunum and ileum. Notably, AKG supplementation enhanced the abundance of these proteins in the LPS-challenged piglets. Collectively, AKG plays an important role in increasing water and ion homeostasis through modulating the AMPK pathway. Our novel finding has important implications for the prevention and treatment of gut dysfunction in neonates.

Phytosterols on growth performance, antioxidant enzymes and intestinal morphology in weaned piglets.

BACKGROUND: Plant extracts have been used widely to improve growth, lower cholesterol, and exert antioxidative defense and antimicrobial activities in animal production. The present study aimed to investigate the effects of dietary phytosterols (PS) on growth performance, antioxidant enzymes and intestinal morphology in weaned piglets. RESULTS: A total of 120 crossbred piglets, weighing 9.58 ± 0.26 kg, were randomly allocated to three treatments: control, PS (0.2 g kg-1 ) and polymyxin E (0.04 g kg-1 , antibiotic control). Compared to the control, PS or polymyxin E supplementation decreased diarrhea rate, serum cholesterol and malondialdehyde (MDA) of the piglets (P < 0.05). Liver MDA was significantly decreased in PS-fed piglets compared to the control (P < 0.05), although there was no difference between the control and polymyxin E-fed piglets. PS increased the villous height/crypt depth ratio of the duodenum and jejunum compared to the control (P < 0.05). Polymyxin E supplementation in piglets did not alter the villous height/crypt depth ratio but raised the villous height and crypt depth of the duodenum compared to the control (P < 0.05). CONCLUSION: The results of the present study indicated that PS could decrease diarrhea rate, lower serum cholesterol, reduce lipid peroxidation and ameliorate intestinal morphology in weaned piglets. In addition, PS exerted better amelioration on intestinal morphology than polymyxin E in piglets. © 2017 Society of Chemical Industry.

Gut modulatory and butyrylcholinesterase inhibitory activities of Gaultheria trichophylla.

CONTEXT: Gaultheria trichophylla Royle (Ericaceae) and related species have been used in the traditional system of medicine for the treatment of diarrhoea, pain and inflammation. OBJECTIVE: The present investigation explores G. trichophylla for its potential activity in hyperactive gut disorders. MATERIALS AND METHODS: Antidiarrheal activity was evaluated on castor oil induced diarrhoea in mice with reference to standard drug verapamil. Gut modulatory activity was performed on isolated jejunum tissue preparations on spontaneous and high potassium induced contractions. Butyrylcholinesterase (BChE) inhibitory activity was performed with an in vitro study. Extract was tested for toxicity in mice. RESULTS: In the in vivo studies, the methanol extract of G. trichophylla and verapamil significantly (p < 0.05, 0.01, 0.001) inhibited the frequency of defecation as well as wetting of faeces when compared with the negative control. The methanol (Gt. MeOH) extract of G. trichophylla caused a dose-dependent inhibitory effect on spontaneous contractions in isolated rabbit jejunum preparations and exhibited a partial inhibitory effect against high K+ (80 mM) induced precontractions. Gt. MeOH shifted the Ca2+ concentration-response curves (CRCs) to the right, suggesting calcium channel blocking like constituents. In an in vitro assay Gt. MeOH inhibited BChE enzyme with an IC50 values of 35.52 ± 1.17 µg/mL. The extract showed no toxicity in mice at the dose of 3 g/kg. DISCUSSION AND CONCLUSION: This study provides evidence that G. trichophylla possesses combinations of inhibitory and stimulatory effects mediated through possible cholinergic and less potent calcium blocking constituents, respectively. The latter may be responsible for the antidiarrheal effect.

Effects of Wei Chang An pill on enzyme activity and levels of vasoactive peptide and substance P in the small intestine of rats with compound diarrhea.

OBJECTIVE: To investigate the regulatory effects of Wei Chang An Pill (WCAP) on enzyme activity and gastrointestinal hormones in the small intestine of rats with compound diarrhea. METHODS: Forty Wistar rats were randomly divided into a control, diarrhea model, and WCAP high, medium, and low dose groups. The control group was not treated, and the model group was administered intragastric distilled water. The WCAP groups were given WCAP suspension, 80, 60 or 40 mg x kg(-1) x d(-1), for 4 days. Stool properties were observed. After the experiment, thymus and spleen indices were measured, and the activities of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), and disaccharidase (lactase) in the small intestinal mucous membrane, and levels of substance P (SP) and vasoactive peptide (VIP) in the colon were determined. RESULTS: Compared with the control group, thymus and spleen indices were significantly decreased, LDH, MDH, and disaccharidase activity in the small intestine was decreased, and SP and VIP levels in the colon were significantly increased in the diarrhea model group. Compared with the model group, thymus and spleen indices were significantly increased, and LDH, MDH, and disaccharidase activity in the small intestine and SP and VIP levels in the colon were significantly decreased in the WCAP medium dose group. CONCLUSION: The diarrhea model rats exhibited pathological changes including atrophy of the thymus and spleen, decreased enzyme activity in the small intestine, and gastrointestinal hormone disturbance. WCAP can increase the activity of intestinal digestive enzymes and regulate gastrointestinal hormones, thereby relieving diarrhea.

Effect of aqueous leaf extract of Momordica charantia on intestinal enzyme activities in diarrhoeagenic mice.

BACKGROUND: Momordica charantia (MC), an annual tropical plant has been reported to possess numerous medicinal properties. The aqueous extract of the plant had been earlier evaluated for its anti-diarrhoeal potential in castor oil-induced diarrhoea model. OBJECTIVE: The objective of the present study is to evaluate the effect of aqueous leaf extract of M. charantia on the activities of the intestinal enzymes in castor oil-induced diarrhoeagenic mice for 48 h-duration. METHODS: Diarrhoea was induced by oral administration of castor oil in mice. Mice in Group 1 were given distilled water; Group 2 received 0.2 ml of castor oil. Groups 3-4 received 100, 200 and 400 mg/kg body weight of the aqueous leaf extract respectively. The animals were sacrificed by cervical dislocation at 0, 2, 5, 7, 24, and 48 hours. Enzymatic activities and protein concentration in the intestinal mucosa homogenate were then analyzed at 0, 2, 5, 7, 24, and 48 hours. RESULTS: Effect of graded doses (100-400 mg/kg) of M. charantia on intestinal alkaline phosphatase showed decrease in activity at 48 hours, while the reductive effect was significantly expressed in the castor oil than in the control and extract treated groups. Disaccharidases (lactase, maltase and sucrase) activities were significantly reduced in the castor oil group when compared with the extract treated groups and the control. The reduction in protein concentration was also observed in the castor oil group compared to the control and extract treated groups. CONCLUSION: The aqueous leaf extract of MC increased enzymes activities (maltase, sucrase and lactase) in the extract treated diarrhoeagenic mice enhancing the absorptive role of these enzymes in the small intestine. This could prevent malnutrition and loss of these enzymes in diarrhoeal conditions.

Anti-diarrhoeal and gastro-intestinal potentials of the aqueous extract of Phyllanthus amarus (Euphorbiaceae).

The anti-diarrhoeal and gastro-intestinal protective potentials of aqueous extract of leaves of Phyllanthus amarus were investigated in mice. Graded doses of the aqueous extract (100-800 mg/kg) administered orally produced a dose-related inhibition of gut meal travel distance in normal mice. The highest intestinal transit inhibition of 31.65% was obtained with 400 mg/kg. In castor oil induced diarrhoea in mice, P. amarus extract (400 mg/kg) delayed the onset of diarrhoea, reduced frequency of defecation and reduced gut meal travel distance significantly resulting in intestinal transit inhibition of 79.94% compared to 86.92% produced by morphine (100 mg/kg). In addition, the activities of some intestinal mucosa enzymes (maltase, sucrase, lactase and alkaline phosphatase) in mice pretreated with extract before castor oil were not as severely depressed as those in the control (castor oil treated mice). Phytochemical screening revealed the presence of many secondary metabolites. The results are discussed with a view to establishing the basis of the use of this plant in traditional medicine for treatment of diarrhoea and other gastrointestinal disorders.

[Effect of phosphaden and unithiol on the cyclase system of the small intestine mucosa in rabbits in experimental salmonellosis]. / Vliianie fosfadena i unitiola na tsiklaznuiu sistemu slizistoi tonkoi kishki krolika pri éksperimental'nom sal'monelleze.

The study was made on 59 chinchilla rabbits. S. typhimurium 1847 live culture was introduced into the lumen of an isolated loop of the thin intestine. The activity of adenylate cyclase (AC), guanylate cyclase (GC), the levels of cyclic adenosine 3,5-monophosphate (cAMP), cyclic guanosine 3,5-monophosphate (cGMP), the activity of cAMP- and cGMP-phosphodiesterases were determined in the mucous membrane of the ligated part of the intestine. Considerable fluid accumulation in the loop, activation of AC and cGMP-phosphodiesterase, a rise in the level of cAMP and a drop in the level of cGMP in the mucosa of the ligated part of the intestine were registered. In one group of the animals phosphadene and in the other group unitiol were introduced into the infected intestinal loop; as a result, a decrease in the accumulation of fluid in the loop, on the average, by 40% and a tendency to an increase in the level of cAMP and a drop in the level of cGMP in the mucous membrane of the ligated part of the intestine were observed. Changes in the level of cGMP play, seemingly, a more important role in the development of diarrhea in salmonellosis.

Temproary intestinal lactase deficiency in light-treated jaundiced infants.

The intestinal lactase activity in six newborn jaundiced light-treated infants with diarrhea and in eight normal controls were compared by lactose tolerance test (LTT). The ability to hydrolyze lactose was minimal in the jaundiced infants during light-treatment compared to the controls which could absorb lactose very well. Peroral intestinal biopsies were taken from the newborn jaundiced infants during light-treatment. By histochemical technique no intestinal lactase activity was found in these intestines. When the jaundiced infants with diarrhea were given lactose-free diet, the stools normalized. The effect was reversed when breast milk was given while the baby was still jaundiced and light-treated. These findings indicate that the increased amounts of unconjugated bilirubin in the intestine of jaundiced infants during light-treatment inhibit the intestinal brush-border lactase. When the icterus fades the lactase is again active. The practical consequence is to give light-treated infants lactose-free diet if they get diarrhea, and to reintroduce breast milk or other lactose containing diet when the baby is no longer icteric.