ABSTRACT
Piper betle Linn. is a Pan-Asiatic plant having several beneficial properties. Protein glycation and advanced glycation end products (AGEs) formation are associated with different pathophysiological conditions, including diabetes mellitus. Our study aims to find the effect of methanolic extract of P. betle leaves on in vitro protein glycation in bovine serum albumin (BSA)-glucose model. The extract inhibits glucose-induced glycation, thiol group modification and carbonyl formation in BSA in dose-dependent manner. It inhibits different stages of protein glycation, as demonstrated by using glycation models: hemoglobin-d-gluconolactone (for early stage, Amadori product formation), BSA-methylglyoxal (for middle stage, formation of oxidative cleavage products) and BSA-glucose (for last stage, formation of AGEs) systems. Several phenolic compounds are isolated from the extract. Considering their relative amounts present in the extract, rutin appears to be the most active antiglycating agent. The extract of P. betle leaf may thus have beneficial effect in preventing protein glycation and associated complications in pathological conditions.
Subject(s)
Animals , Cattle , Glycosylation/drug effects , Phenols/analysis , Piper betle/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Serum Albumin, Bovine/metabolism , Time FactorsABSTRACT
This study investigates if glycyrrhizin, a constituent of licorice (Glycyrrhiza glabra) root, is able to treat the complications (insulin resistance, hyperglycemia, dyslipidemia and oxidative stress) of metabolic syndrome. Metabolic syndrome was induced in rats by feeding a fructose-enriched (60%) diet for six weeks, after which single dose of glycyrrhizin (50 mg/kg body weight) was administered intraperitoneally. Different biochemical parameters from blood were estimated during three weeks after treatment. Then the rats were sacrificed to collect skeletal muscle tissue. Glycyrrhizin reduced the enhanced levels of blood glucose, insulin and lipids in metabolic syndrome group. Increased advanced glycation end products of hemoglobin, glycohemoglobin, hemoglobin-mediated iron release and iron-mediated free radical reactions (arachidonic acid and deoxyribose degradation) in metabolic syndrome were inhibited by glycyrrhizin treatment. Reduced activities of enzymatic antioxidants (superoxide dismutase and catalase) and elevated oxidative stress markers (malonaldehyde, fructosamine, hemoglobin carbonyl content and DNA damage) in metabolic syndrome were reversed to almost normal levels by glycyrrhizin. The decreased levels of peroxisome proliferator activated receptor (PPAR) and glucose transporter 4 (GLUT4) proteins in skeletal muscle of metabolic syndrome group were elevated by glycyrrhizin, indicating improved fatty acid oxidation and glucose homeostasis.
Subject(s)
Animals , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Body Weight/drug effects , DNA Damage , Diet , Disease Models, Animal , Dyslipidemias/blood , Dyslipidemias/complications , Dyslipidemias/drug therapy , Free Radical Scavengers/metabolism , Fructose/adverse effects , Glucose Transporter Type 4/metabolism , Glycyrrhizic Acid/pharmacology , Glycyrrhizic Acid/therapeutic use , Hemoglobins/metabolism , Hyperglycemia/blood , Hyperglycemia/complications , Hyperglycemia/drug therapy , Insulin/blood , Insulin Resistance , Lipids/blood , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Metabolic Syndrome/blood , Metabolic Syndrome/chemically induced , Metabolic Syndrome/complications , Metabolic Syndrome/drug therapy , Muscles/drug effects , Muscles/metabolism , Oxidative Stress/drug effects , PPAR gamma/metabolism , Rats , Rats, Wistar , Tissue ExtractsABSTRACT
Protoporphyrin IX and its derivatives are used as photosensitizers in the photodynamic therapy of cancer. Protoporphyrin IX penetrates into human red blood cells and releases oxygen from them. This leads to a change in the morphology of the cells. Spectrophotometric studies reveal that protoporphyrin IX interacts with haemoglobin and myoglobin forming ground state complexes. For both proteins, the binding affinity constant decreases, while the possible number of binding sites increases, as the aggregation state of the porphyrin is increased. The interactions lead to conformational changes of both haemoglobin and myoglobin as observed in circular dichroism studies. Upon binding with the proteins, protoporphyrin IX releases the heme-bound oxygen from the oxyproteins, which is dependent on the stoichiometric ratios of the porphyrin : protein. The peroxidase activities of haemoglobin and myoglobin are potentiated by the protein-porphyrin complexation. Possible mechanisms underlying the relation between the porphyrin-induced structural modifications of the heme proteins and alterations in their functional properties have been discussed. The findings may have a role in establishing efficacy of therapeutic uses of porphyrins as well as in elucidating their mechanisms of action as therapeutic agents.