Antihyperglycemic Effect of Lavandula pedunculata: In Vivo, In Vitro and Ex Vivo Approaches.

Lavandula pedunculata (Mill.) Cav. (LP) is one of lavender species traditionally used in Morocco to prevent or cure diabetes, alone or in the form of polyherbal preparations (PHP). Therefore, the primary objective of this study was to test the antihyperglycemic effect of the aqueous extract of LP, alone and in combination with Punica granatum L. (PG) and Trigonella foenum-graecum L. (FGK). The secondary objective was to explore some mechanisms of action on the digestive functions. The antihyperglycemic effect of the aqueous extract of LP, alone and in combination with PG and FGK, was studied in vivo using an oral glucose tolerance test (OGTT). In addition, LP extract was tested on the activities of some digestive enzymes (pancreatic α-amylase and intestinal α-glucosidase) in vitro and on the intestinal absorption of glucose ex vivo using a short-circuit current (Isc) technique. Acute and chronic oral administration of LP aqueous extract reduced the peak of the glucose concentration (30 min, p < 0.01) and the area under the curve (AUC, p < 0.01). The effect of LP + PG was at the same amplitude to that of the positive control Metformin (MET). LP aqueous extract inhibited the pancreatic α-amylase with an IC50 almost identical to acarbose (0.44 ± 0.05 mg/mL and 0.36 ± 0.02 mg/mL, respectively), as well as the intestinal α-glucosidase, (IC50 = 131 ± 20 µg/mL) and the intestinal glucose absorption (IC50 = 81.28 ± 4.01 µg/mL) in concentration-dependent manners. LP aqueous extract exhibited potent actions on hyperglycemia, with an inhibition on digestive enzymes and glucose absorption. In addition, the combination with PG and FGK enhanced oral glucose tolerance in rats. These findings back up the traditional use of LP in type 2 diabetes treatment and the effectiveness of the alternative and combinative poly-phytotherapy (ACPP).

Arbutus unedo L., (Ericaceae) inhibits intestinal glucose absorption and improves glucose tolerance in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Arbutus unedo L., (Ericaceae) is one of the most traditional plants commonly used to treat diabetes in people living in Eastern Morocco region particularly in Taza and Beni Mellal. AIM OF THE STUDY: The aim of the study was to find if there is a scientific support to the ethnopharmacological relevance use of Arbutus unedo L., roots bark (AU) to treat diabetes. MATERIALS AND METHODS: We studied the effects of crude aqueous extract of AU on intestinal glucose absorption using short-circuit current technique in vitro and oral glucose tolerance test in vivo. RESULTS: The aqueous extract of AU (10 µg/mL to 1 mg/mL) induced concentration-dependent inhibition of sodium-dependent glucose transport across isolated mouse jejunum. The maximal inhibition was obtained with 1 mg/mL, which exhibited more than 80% of the Phloridzin inhibition with an IC50 close to 216 µg/mL. A 6-week AU ingestion (2 g/(kg day)), improved oral glucose tolerance as efficiently as metformin (300 mg/(kg day)). Arbutus unedo L. and metformin also reduced body weight. CONCLUSIONS: Arbutus unedo L. roots bark aqueous extract directly inhibited the electrogenic intestinal absorption of glucose in vitro. In addition it improved oral glucose tolerance and lowered body weight in rats after chronic oral administration in vivo. These results add a scientific support to the ethnopharmacological relevance use of Arbutus unedo L. roots bark to treat diabetes.

Origanum majorana L. extract exhibit positive cooperative effects on the main mechanisms involved in acute infectious diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L. (Lamiaceae) is commonly used in Moroccan folk medicine to treat infantile colic, abdominal discomfort and diarrhea. Liquid stools and abdominal discomfort observed in acute infectious diarrhea are the consequences of imbalance between intestinal water secretion and absorption in the lumen, and relaxation of smooth muscle surrounding the intestinal mucosa. AIM OF THE STUDY: The objective of our study was to see if aqueous extract of Origanum majorana L. (AEOM) may exhibit an effect on those deleterious mechanisms. MATERIALS AND METHODS: The effect of AEOM on electrogenic Cl- secretion and Na+ absorption, the two main mechanisms underlying water movement in the intestine, was assessed on intestinal pieces of mice intestine mounted, in vitro, in Ussing chambers. AEOM effect on muscle relaxation was measured on rat intestinal smooth muscle mounted in an isotonic transducer. RESULTS: 1) AEOM placed on the serosal (i.e. blood) side of the piece of jejunum entirely inhibited in a concentration-dependent manner the Forskolin-induced electrogenic chloride secretion, with an IC50 = 654 ±â€¯8 µg/mL. 2) AEOM placed on the mucosal (i.e. luminal) side stimulated in a concentration-dependent manner an electrogenic Na+ absorption, with an IC50 = 476.9 ±â€¯1 µg/mL. 3) AEOM (1 mg/mL) inhibition of Forskolin-induced electrogenic secretion was almost entirely prevented by prior exposure to Ca++ channels or neurotransmitters inhibitors. 4) AEOM (1 mg/mL) proabsorptive effect was greater in the ileum and progressively declined in the jejunum, distal colon and proximal colon (minimal). 5) AEOM inhibited in a concentration-dependent manner smooth muscle Carbachol or KCl induced contraction, with an IC50 = 1.64 ±â€¯0.2 mg/mL or 1.92 ±â€¯0.8 mg/mL, respectively. CONCLUSION: the present results indicate that aqueous extract of Origanum majorana L. exhibit positive cooperative effects on the main mechanisms that are involved in acute infectious diarrhea.

Vitamin A status in healthy women eating traditionally prepared spirulina (Dihé) in the Chad Lake area.

BACKGROUND: Chad Lake is a central place in a region with a high prevalence of vitamin A deficiency. Spirulina, a natural source of ß-carotene, is traditionally produced and eaten as "Dihé" around Chad Lake. ß-carotene spirulina has been found to have a high conversion factor to retinol. The aim of the study was to assess if the retinol status between healthy women eating spirulina Dihé daily (SPI+) and not (SPI-) in the Chad Lake area was different. METHODS: This study was observational: 88 healthy women were recruited and selected according to clinical criteria and their willingness to participate. They were divided in two groups according to their Dihé daily consumption: those who eat Dihé (SPI+; n = 35) and those who do not (SPI-; n = 35). After anthropometric and dietary assessments, blood retinol, ß-carotene, retinol binding, and inflammatory/nutritional proteins were measured. RESULTS: The diet between groups was identical, except for ß-carotene consumption, which was higher in SPI+ than in SPI- (10.8 vs. 1.8 mg/day). The serum retinol and ß-carotene concentrations were significantly higher in SPI+ than in SPI- at 1.26 ± 0.36 µmol/l versus 1.03 ± 0.31 µmol/l (p = 0.008) and 0.59 ±0.37 µmol/l versus 0.46± 0.31 µmol/l (p = 0.04), respectively. Seventy-seven percent of SPI+ versus 29% of SPI- had an adequate blood retinol value (p = 0.01). CONCLUSION: The results confirm that ß-carotene in spirulina is an effective positive modulator of blood retinol status. Dihé is a potential natural source of ß-carotene to achieve a proper vitamin A status in healthy women living near Chad Lake.

Nutrient Recommendations for Growing-up Milk: A Report of an Expert Panel.

Utilization of expert recommendations in the development of food and beverage nutritional profiles represents an opportunity to merge science and food manufacturing to deliver nutritionally optimized products into the marketplace. This report details expert panel guidelines for the design of a nutritional product for children one to six years of age. This interaction demonstrates the essential synergy between academia and food manufacturers in translating nutrient recommendations to food for their delivery to a population. Important factors for such translation are the identification of applicable nutrient recommendations and selection of an appropriate delivery matrix. This report demonstrates the translation of expert nutritional recommendations to a milk-based product for children--one to six years of age.

Metronidazole or Cotrimoxazole therapy is associated with a decrease in intestinal bioavailability of common antiretroviral drugs.

Metronidazole (MTZ) and Cotrimoxazole (CTX) are used in HIV/AIDS patients eligible for antiretroviral treatment. The objective of this animal study was to determine whether pre-treatment with antibiotics affects the intestinal bioavailability of Atazanavir (ATV) and Ritonavir (RTV). After oral administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV net transepithelial fluxes (Jnet). 1. In control rats, the mucus thickness was 43.3±7.6 µm and 40.7±6.9 µm, in proximal and distal colon, respectively. In proximal colon, the thickness was 57.2±8.8 and 58.2±6.9 µm after MTZ and CTX, respectively whereas in distal colon, the thickness was 121.1±38.4 and 170.5±35.0 µm (P<0.05) respectively. 2. Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was observed both in proximal (-0.36±0.02 µg.hr(-1) cm(-2)) and distal colon (-0.30±0.08 µg.hr(-1) cm(-2)). After MTZ and CTX, it was increased in the proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by 3 fold and 5 fold, respectively. 4. In control, there was no net active RTV transport either in proximal (+0.01±0.01 µg.hr(-1) cm(-2)) or distal colon (+0.04±0.01 µg.hr(-1) cm(-2)). After MTZ and CTX, secretion was increased 5 fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold, respectively in the distal colon (p<0.001). In conclusion, after MTZ and CTX therapy, the mucus layer was enlarged, passive permeability was decreased and ATV and RTV were actively secreted by the colonic epithelium suggesting that, in rat, the intestinal bioavailability of ATV and RTV is impaired after antibiotic therapy.

Time course of bacterial diversity in stool samples of malnourished children with cholera receiving treatment.

BACKGROUND: Recent nutritional interventions have targeted colonic functions in patients with infectious diarrhea during rehydration and during recovery from malnutrition, with the assumption that the effects will be influenced by metabolism of complex carbohydrates by colonic bacteria. However, the diversity of colonic bacteria in patients with cholera is not known. AIM: To study the diversity of colonic bacteria in malnourished children with cholera before and during treatment with oral rehydration salt solutions containing 1 of these 3 substrates: glucose, rice, or amylase-resistant starch. PATIENTS AND METHODS: Serial fecal samples were collected from 30 malnourished children with cholera until completion of rehydration and partial nutritional recovery; 11 malnourished children without diarrhea; and 6 better nourished children. Polymerase chain reaction, using universal primers for 16S rDNA, was performed on chromosomal DNA extracted from the stool samples, and the products were separated by temporal temperature gradient gel electrophoresis. RESULTS: The Vibrio cholerae band was detected in all children at enrollment and disappeared within 2 days. On day 2, a rapid and significant increase in the band numbers was observed, which was followed by a steady increase until day 28. After full recovery from cholera and partial recovery from malnutrition, the number of bands (11.5+/-2.8) was lower than in healthy children (22.2+/-1.3). On day 3, the number of bands was greater with rice or amylase-resistant starch than with glucose (P<.05). CONCLUSIONS: Bacterial diversity was markedly but transiently altered in severely malnourished children with cholera receiving therapy.

Safety of rapid intravenous rehydration and comparative efficacy of 3 oral rehydration solutions in the treatment of severely malnourished children with dehydrating cholera.

OBJECTIVES: Assess the safety of rapid intravenous rehydration of severely malnourished children and compare the efficacy of 3 formulations of oral rehydration salts solutions. PATIENTS AND METHODS: A group of 175 severely malnourished children of either sex (weight/length <70% of National Center for Health Statistics median), ages 6 to 36 months with cholera, were randomly assigned to receive 1 of 3 oral rehydration solutions (ORSs): glucose-ORS (n=58), glucose-ORS plus 50 g/L of amylase-resistant starch (n=59), or rice-ORS (n=58). Severely dehydrated children at enrollment were administered 100 mL/kg of an intravenous solution for 4 to 6 hours before randomisation, and those with some dehydration were randomised on enrollment. The electrolytes of the 3 ORSs were identical. In acute and convalescence phases, treatment was similar other than the nature of the ORSs. RESULTS: Intravenous fluid (mean) administered to 149 study children was 103 mL/kg (95% confidence interval [CI] 96-109), and all were rehydrated within 6 hours. None of them developed overhydration or heart failure. During the first 24 hours, stool output (31%; 95% CI 14%-42%; P=0.004) and the ORS intake (26%; 95% CI 12%-37%; P=0.002) of children receiving rice-ORS were significantly less compared with children receiving glucose-ORS. The mean duration of diarrhoea in all children (66 hours; 95% CI 62-71), and time to attain 80% of median weight/length (7.15+/-2.81 days) were not different. CONCLUSIONS: Dehydration in severely malnourished children can safely be corrected within 6 hours. All study ORSs were equally efficient in correcting dehydration. Rice-ORS significantly reduced the stool output and ORS intake, confirming previous reports.

Effects on faecal microbiota of dietary and acidic oligosaccharides in children during partial formula feeding.

OBJECTIVE: To test the safety and effect on faecal microbiota of a formula with prebiotic oligosaccharides alone or in combination with acidic oligosaccharides in infants at the age of partial formula feeding. PATIENTS AND METHODS: The study was a double-blind, placebo-controlled, randomised intervention trial in which 82 healthy, full-term, partially breast-fed children, from 1 week to 3 months old, were given 1 of the following formulae: whey-based formula (control group), whey-based formula with galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS group), or whey-based formula with galacto- and long-chain fructo-oligosaccharides added with pectin-derived acidic oligosaccharides (scGOS/lcFOS/pAOS group). Children were studied for the duration of the partial formula feeding period and every 2 weeks for 2 months after breast-feeding cessation. The total bacteria count and the proportion of 7 bacterial families were determined using in situ hybridisation coupled to flow cytometry. RESULTS: The total bacterial count did not alter with time or type of feeding (9.9 +/- 0.1 log10 cells per gram wet weight). Compared with the control group, there was an increase of the Bifidobacterium genus (P = 0.0001), and a decrease of proportions for the Bacteroides group (P = 0.02) and the Clostridium coccoides group (P = 0.01) in both oligosaccharide groups. The proportion of bifidobacteria was significantly higher in the scGOS/lcFOS/pAOS compared with the scGOS/lcFOS group (P < 0.01). CONCLUSIONS: Infant formulae appear to be clinically safe and effective on infant microbiota. They minimize the alteration of faecal microbiota after cessation of breast-feeding and promote bifidobacteria proportions, with a stronger effect when acidic oligosaccharides are present.

Recent issues in energy-protein malnutrition in children.

Thirty years ago, protein deficiency was perceived to be the major nutritional problem of children in developing countries. Later on increasing the energy intake of young children during the complementary feeding period became a priority. Early studies on the pathophysiology of malnutrition are now turned into strategic and practical consequences for the prevention and treatment of severe malnutrition, four of which are presented. (1) Almost half of the deaths worldwide are due to being underweight. Nowadays, well-defined preventive and curative interventions have been identified. (2) An efficient and rigorous technique based on linear programming is now available to design a diet suitable for the complementary feeding period using locally available foods with a minimum budget to cover the nutritional requirements of at least 97% of the children. (3) Managing acute malnutrition in emergencies has greatly improved by the use of a spread that a child can eat directly without the addition of water (often called Ready-to-Use Therapeutic Food) and Community Therapeutic Care that treats the majority of severely malnourished children at home. (4) Recent data strongly suggest that it is possible to avoid death due to careful and rapid rehydration despite the high purging rate even if many of the risk factors for mortality are present in these severely malnourished children. Recovery from malnutrition was achieved in 7 days.

Water and electrolyte salvage in an animal model of dehydration and malnutrition.

BACKGROUND AND AIM: Recently, a new oral rehydration solution (ORS) called Resomal has been designed specifically for children with severe malnutrition. The aim of this study was to assess the effect of malnutrition on renal and intestinal responses to dehydration, and to compare intestinal water and electrolyte absorption from Resomal and from the standard World Health Organization-Oral Rehydration Solution (WHO-ORS). METHOD: Malnutrition was achieved in a rabbit model by feeding the animals daily for 30 days with half the amount of food that a well-nourished group of control animals had consumed on the previous day. Dehydration was achieved by water deprivation for 46 hours in both control and malnourished rabbits. At 46 hours, dehydration was assessed by changes in body weight, urinary volume and osmolarity, and blood urea nitrogen concentration. At that time active colonic and jejunal mucosal electrolyte transport in Ussing chambers was also measured. Small intestinal absorption of water, sodium, and potassium was measured in vivo during intestinal perfusion of the two ORSs and in vitro by measurement of mucosal electrogenic glucose-stimulated sodium absorption across intestinal patches. RESULTS: Compared to controls (C), well-nourished but dehydrated (C+D) animals lost 12% of their body weight, with an 87% reduction in urine volume, a 110% increase in urine osmolality, and a 94% increase in blood urea nitrogen. In the colon of C+D animals, short-circuit current (Isc) and net sodium transepithelial flux (JNa+ net) were increased. Almost identical results were obtained in malnourished and dehydrated (M+D) animals. In the jejunum, net in vivo absorption of water (JWater), sodium (JNa+), and potassium (JK+) were increased during standard ORS infusion in both dehydrated groups. During Resomal infusion, water absorption was the same as seen with WHO-ORS, but sodium absorption was reduced, and potassium absorption was increased in both well-nourished and malnourished dehydrated animals. In vitro, compared to controls, the glucose-stimulated short-circuit current (DeltaIsc), JNa+ net and G were increased in both dehydrated groups. CONCLUSION: During experimental dehydration, the kidney and large intestine salvage water and electrolytes, thus reducing the consequences of dehydration. These findings indicate that jejunal water absorption from Resomal and WHO-ORS is increased during dehydration, but Resomal allows for less sodium and more potassium to be absorbed, both in well-nourished and malnourished dehydrated rabbits.

Homocysteine prevents total parenteral nutrition (TPN)-induced cholestasis without changes in hepatic oxidative stress in the rat.

BACKGROUND: The role of oxidative stress in total parenteral nutrition (TPN)-associated cholestasis with liver glutathione depletion was recently shown. The aims of this study were to test the appearance of cholestasis and oxidative stress during TPN, and the hypothesis that reducing oxidative stress with a precursor of glutathione (GSH), homocysteine, would restore bile flow. METHODS: Three groups of rats (weight, 179-278 g) were studied: 1) D/aa group received dextrose and amino acids (3.4 g/d); 2) D/aa/L group received the same amount of amino acids, and lipids were added on an equicaloric basis (50 kcal/d) with a lowered amount of dextrose; and 3) a control group, which received dextrose perfusion and had free access to chow. A subgroup of D/aa/L rats (n = 6) received a TPN solution containing homocysteine. After 5 days of TPN, bile was collected during 2 hours. In liver homogenates, GSH, thiobarbituric acid reactive substances (TBARS), and carbonyl content of proteins (Prot-CO) were measured to test the level of oxidative stress and hepatic lipid and protein oxidation. RESULTS: After TPN, bile flow was significantly lower in the D/aa group than in the control group. Addition of lipids further decreased bile flow. Addition of homocysteine to TPN with lipids significantly increased bile flow. Aspartate aminotransferase increased significantly in both TPN groups compared with the control group. gamma-Glutamyl transpeptidase was not different among TPN groups. An increased hepatic lipid oxidation was demonstrated by TBARS level in both TPN groups when compared with the control group. However, the liver GSH contents were not different. Protein oxidation was also significantly increased by TPN. The addition of homocysteine to TPN solution increased bile flow without liver injury or changes of lipid and protein oxidation. DISCUSSION: This study shows that TPN administered to rats induces a decrease of bile flow and an oxidative stress but that the two changes are not directly correlated. Addition of lipids further impairs bile flow but does not increase the occurrence of liver injury. Consequently, it seems more likely that TPN primarily induces a cholestatic effect that in turn induces an oxidative stress rather than inducing an oxidative stress that leads to cholestasis. However, an association of both mechanisms is not totally excluded.

Palm versus soybean oil on intestinal recovery from malnutrition in Guinea pigs.

Recent recommendations on feeding malnourished children do not provide indication on the nature of dietary lipids. Our aim was to compare the effect of palm oil (mainly saturated and monounsaturated fatty acids) and soybean oil (mainly polyunsaturated fatty acids) on the recovery from malnutrition in guinea pigs. In a first experiment, guinea pigs received a balanced (control group) or a maize (malnourished group) diet for 7, 12, and 21 d. In a second experiment, after 12 d of malnutrition, guinea pigs received a rehabilitation diet containing palm or soybean oil. Both rehabilitation diets allowed a partial recovery from the severe weight loss induced by malnutrition. Thiobarbituric acid reactive substances content, measured in intestinal homogenates, increased in malnourished guinea pigs compared with control animals (40%, p < 0.05) and returned to near control values after rehabilitation with palm (10%) but not soybean (43%) oil diet. Intestinal short-circuit current, assessed in jejunal segments mounted in Ussing chambers, increased progressively during malnutrition (p < 0.001) and returned to near control values with both rehabilitation diets. Compared with control animals, the cell turnover (Ki-67 index assessed by immunohistochemistry detection of the Ki-67 antigen) decreased after soybean (-60%, p < 0.01) but not after palm oil. These results confirm that experimental polydeficient malnutrition induces oxidative stress and dysfunction in the intestine. They show a differential effect of palm and soybean oil on these intestinal measurements, suggesting that the composition of dietary lipids may be important in the treatment of malnutrition.