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1.
Future Microbiol ; 19: 213-226, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37934065

ABSTRACT

Aim: To evaluate the effects of whey protein (WP) supplementation (1.24 mg/g, 24 days) in rats with autism spectrum disorder (ASD) induced by valproic acid (400 mg/kg, single dose). Materials & methods: Wistar rats (14 days old) were divided into four groups: control, ASD, ASD plus WP and WP. Results: WP increased bacterial diversity and the number of colonies. Bacteria from the Firmicutes phylum were predominantly found in the supplemented groups (p < 0.05). WP also improved the animals' memory in the Y-maze test and decreased the time that male animals spent in the 'solitary chamber' (p < 0.05). Conclusion: WP supplementation positively influenced gut microbiota, along with memory.


Thousands of bacteria live in the human intestine. These bacteria help with many functions in the body and are so important that they can communicate with the brain. When the types and abundance of these bacteria change, brain activity can also change. This may be the case in some children with autism spectrum disorder (ASD), who may have an increase in harmful types of bacteria and a decrease in beneficial types of bacteria in the gut. Whey protein is a commonly used protein supplement for muscle growth. However, many studies have shown its benefits for gut bacteria. The authors investigated the effects of whey protein in animals with symptoms of ASD and showed that supplementation with whey protein increased the number of beneficial bacteria. In addition, the rats given whey protein had better memory. ASD-induced rats were less sociable, spending more time by themselves. However, male animals treated with whey protein spent less time alone. Supplementation with whey protein was beneficial for gut bacteria and memory in rats.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Gastrointestinal Microbiome , Male , Rats , Animals , Autistic Disorder/chemically induced , Autistic Disorder/drug therapy , Whey Proteins , Valproic Acid/pharmacology , Rats, Wistar , Autism Spectrum Disorder/chemically induced , Autism Spectrum Disorder/drug therapy , Autism Spectrum Disorder/microbiology , Bacteria , Dietary Supplements
2.
Bioorg Chem ; 114: 105157, 2021 09.
Article in English | MEDLINE | ID: mdl-34328855

ABSTRACT

A new library of hybrid compounds that combine the functional parts of glibenclamide and pioglitazone was designed and developed. Compounds were screened for their antihyperglycemic effects on the glucose tolerance curve. This approach provided a single molecule that optimizes the pharmacological activities of two drugs used for the treatment of diabetes mellitus type 2 (DM2) and that have distinct biological activities, potentially minimizing the adverse effects of the original drugs. From a total of 15 compounds, 7 were evaluated in vivo; the compound 2; 4- [2- (2-phenyl-4-oxo-1,3-thiazolidin-3-yl) ethyl] benzene-1-sulfonamide (PTEBS) was selected to study its mechanism of action on glucose and lipid homeostasis in acute and chronic animal models related to DM2. PTEBS reduced glycemia and increased serum insulin in hyperglycemic rats, and elevated in vitro insulin production from isolated pancreatic islets. This compound increased the glycogen content in hepatic and muscular tissue. Moreover, PTEBS stimulated the uptake of glucose in soleus muscle through a signaling pathway similar to that of insulin, stimulating translocation and protein synthesis of glucose transporter 4 (GLUT4). PTEBS was effective in increasing insulin sensitivity in resistance rats by stimulating increased muscle glucose uptake, among other mechanisms. In addition, this compound reduced total triglycerides in a tolerance test to lipids and reduced advanced glycation end products (AGES), without altering lactate dehydrogenase (LDH) activity. Thus, we suggest that PTEBS may have similar effects to the respective prototypes, which may improve the therapeutic efficacy of these molecules and decrease adverse effects in the long-term.


Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Type 2/drug therapy , Glyburide/pharmacology , Hyperglycemia/drug therapy , Hypoglycemic Agents/pharmacology , Pioglitazone/pharmacology , Animals , Dose-Response Relationship, Drug , Glyburide/chemistry , Homeostasis/drug effects , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/chemistry , Insulin Resistance , Molecular Structure , Pioglitazone/chemistry , Rats , Structure-Activity Relationship
3.
Eur J Pharmacol ; 907: 174250, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34118223

ABSTRACT

We studied the effect and the mechanisms of action of 2α,3ß,23-trihydroxyolean-12-ene (THO), from Croton heterodoxus Baill. (Euphorbiaceae), in glucose uptake in hyperglycemic rats. The effect of in vivo pretreatment with THO in hyperglycemic rats was analyzed. The in vitro effects of THO were observed in adipocytes and in adipose tissue. THO reduced glycemia, in part by increasing serum insulin and augmenting the disposal of glucose as glycogen in hepatocytes but did not change the serum concentration of glucagon-like peptide-1. THO increased glucose uptake in adipocytes and in adipose tissue by a mechanism dependent on phosphatidylinositol 3-kinase vesicular traffic and on the process of vesicle fusion at the plasma membrane in regions containing cholesterol, indicating the involvement of glucose transporter-4 (GLUT4). This triterpene may act solely via the activation and translocation of GLUT4 (rather than via nuclear actions, such as upregulation of GLUT4 synthesis), since THO did not alter the amount of GLUT4 mRNA or the content of GLUT4. Consistent with these data, the stimulatory effect of this triterpene on the quantity of GLUT4 in the membrane fraction was dependent upon p38 phosphorylation. In this experimental model, orally administered 10 mg/kg THO did not modulate extracellular serum lactate dehydrogenase. In conclusion, THO decreases hyperglycemia by increasing serum insulin and hepatic glycogen content. The THO mechanism of action on adipose tissue for glucose uptake is suggested to be via GLUT4 translocation stimulation mediated by a p38-dependent mechanism. THO is a potential antihyperglycemic agent that acts in a target tissue for glucose homeostasis.


Subject(s)
Insulin , Blood Glucose/metabolism , Glucose , Homeostasis/drug effects , Hypoglycemic Agents/pharmacology , Insulin/metabolism
4.
Chem Biol Interact ; 330: 109198, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32692981

ABSTRACT

Quercetin 3-O-beta-d-glucopyranoside (isoquercetin) is one of the most frequent metabolites of the Passiflora ligularis Juss. The purpose of this study was to investigate the effect of the aqueous extract and ethanol fraction from P. ligularis Juss leaves on glycaemia and the mechanism of action of isoquercetin on glucose uptake. In the glucose tolerance test, the aqueous extract and ethanol fraction from P. ligularis Juss (125 mg/kg to 500 mg/kg o. g.) reduced glycaemia and increased the hepatic and muscular glycogen content. Phytochemical analysis evidenced the dominant presence of isoquercetin in the extract and fraction from leaves of P. ligularis Juss. Isoquercetin mediates the stimulatory effect on glucose uptake independent of insulin receptor activation but, involve PI3K, MAPK, MEK/ERK pathways and de novo protein synthesis to GLUT-4 translocation. Overall findings revealed that isoquercetin and aqueous extract and ethanol fraction of P. ligularis Juss leaves might be a promising functional food or medicine for the treatment or prevention of diabetes.


Subject(s)
Glucose/pharmacokinetics , Muscle, Skeletal/metabolism , Passiflora/chemistry , Quercetin/analogs & derivatives , Animals , Biological Transport , Diabetes Mellitus/prevention & control , Glucose Transporter Type 4/metabolism , Phytochemicals/analysis , Plant Extracts/chemistry , Plant Leaves/chemistry , Quercetin/isolation & purification , Quercetin/pharmacology , Rats
5.
Cell Calcium ; 80: 56-62, 2019 06.
Article in English | MEDLINE | ID: mdl-30965223

ABSTRACT

Astragalin is a flavonol glycoside with several biological activities, including antidiabetic properties. The objective of this study was to investigate the effects of astragalin on glycaemia and insulin secretion, in vivo, and on calcium influx and insulin secretion in isolated rat pancreatic islets, ex vivo. Astragalin (1 and 10 mg / kg) was administered by oral gavage to fasted Wistar rats and serum glucose and plasma insulin were measured. Isolated pancreatic islets were used to measure basal insulin secretion and calcium influx. Astragalin (10 mg/ kg) decreased glycaemia and increased insulin secretion significantly at 15-180 min, respectively, in the glucose tolerance test. In isolated pancreatic cells, astragalin (100 µM) stimulated calcium influx through a mechanism involving ATP-dependent potassium channels, L-type voltage-dependent calcium channels, the sarcoendoplasmic reticulum calcium transport ATPase (SERCA), PKC and PKA. These findings highlight the dietary coadjuvant, astragalin, as a potential insulin secretagogue that may contribute to glucose homeostasis.


Subject(s)
Calcium Signaling/drug effects , Glucose/metabolism , Hypoglycemic Agents/therapeutic use , Insulin Secretion/drug effects , Islets of Langerhans/metabolism , Kaempferols/therapeutic use , Animals , Calcium Channels, L-Type/metabolism , Cells, Cultured , Cyclic AMP-Dependent Protein Kinases/metabolism , Dietary Supplements , Homeostasis , Islets of Langerhans/pathology , KATP Channels/metabolism , Male , Protein Kinase C/metabolism , Rats , Rats, Wistar , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
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