ABSTRACT
Angiotensin I-converting enzyme (ACE) inhibitory and hypotensive effects of 7 peptide fractions (Frs) of royal jelly protein hydrolysate (RJPH) were studied in comparison with those of RJPH alone. Fr 4 and Fr 5 were the highest in ACE inhibitory activity and yield, respectively. Molecular weights (MWs) of RJPH and Fr 1-Fr 7 were distributed from 100 to 5,000 and those of Fr 1-Fr 7 increased in order from Fr 1 to Fr 7. RJPH, Fr 3 and Fr 4 at doses of 10, 30 and 100mg/kg i.v. and Fr 5 and Fr 6 at doses of 30 and 100mg/kg i.v. caused transiently significant hypotensive effects in spontaneously hypertensive rats (SHR). Fr 3, Fr 4, Fr 5 and Fr 6 at a dose of 1,000mg/kg also caused significant hypotensive effects 3h, 4-5h, 7-8h and 8h after oral administration in SHR, respectively. RJPH caused a long-lasting hypotensive effect in proportion to the magnitude of the MWs of RJPH fractions. The hypotensive pattern of RJPH was similar to the combined pattern of Fr 3-Fr 6. From these results, it can be concluded that the long-lasting hypotensive effect of oral administration of RJPH is dependent on the MWs of its ACE inhibitory peptides and the time required to digest them.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antihypertensive Agents/pharmacology , Fatty Acids/pharmacology , Insect Proteins/pharmacology , Animals , Hydrolysis , Hypertension/drug therapy , Male , Rats , Rats, Inbred SHRABSTRACT
Royal jelly (RJ) is known to contain excellent nutrition and a variety of biological activities. The present study was designed to investigate the effects of RJ on insulin resistance (hyperinsulinemia) in fructose-drinking rats (FDR; insulin resistance animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. FDR showed significant increases in plasma levels of insulin and triglyceride, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin resistance), and systolic blood pressure, but not blood glucose levels, when compared with control rats. RJ (100, 300 mg/kg, p.o.) treatment for 8 weeks significantly decreased the plasma levels of insulin and triglyceride, HOMA-R, without affecting blood glucose or total cholesterol levels and tended to lower systolic blood pressure. In isolated and perfused mesenteric vascular beds of FDR, RJ treatment resulted in a significant reduction in sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and tended to increase the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with those in untreated FDR. However, RJ treatment did not significantly affect norepinephrine-induced vasoconstriction or CGRP-induced vasodilation. These results suggest that RJ could be an effective functional food to prevent insulin resistance associated with the development of hypertension.
Subject(s)
Fatty Acids/pharmacology , Fructose/adverse effects , Insulin Resistance , Administration, Oral , Animals , Blood Glucose/analysis , Blood Pressure/drug effects , Body Weight/drug effects , Cholesterol/blood , Drinking , Electric Stimulation , Fructose/administration & dosage , Hypertension/metabolism , Hypertension/physiopathology , Hypertension/prevention & control , Insulin/blood , Male , Mesenteric Arteries/drug effects , Mesenteric Arteries/innervation , Mesenteric Arteries/physiology , Perfusion , Peripheral Nervous System/physiology , Rats , Rats, Wistar , Triglycerides/blood , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effectsABSTRACT
We investigated whether artepillin C, a major component of Brazilian propolis, acts as a neurotrophic-like factor in rat PC12m3 cells, in which nerve growth factor (NGF)-induced neurite outgrowth is impaired. When cultures of PC12m3 cells were treated with artepillin C at a concentration of 20 microM, the frequency of neurite outgrowth induced by artepillin C was approximately 7-fold greater than that induced by NGF alone. Artepillin C induced-neurite outgrowth of PC12m3 cells was inhibited by the ERK inhibitor U0126 and by the p38 MAPK inhibitor SB203580. Although artepillin C-induced p38 MAPK activity was detected in PC12m3 cells, phosphorylation of ERK induced by artepillin C was not observed. On the other hand, artepillin C caused rapid activation of ERK and the time course of the activation was similar to that induced by NGF treatment in PC12 parental cells. However, NGF-induced neurite outgrowth was inhibited by artepillin C treatment. Interestingly, inhibition of ERK by U0126 completely prevented artepillin C-induced p38 MAPK phosphorylation of PC12m3 cells. These findings suggest that artepillin C-induced activation of p38 MAPK through the ERK signaling pathway is responsible for the neurite outgrowth of PC12m3 cells.
Subject(s)
MAP Kinase Signaling System/physiology , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Neurites/drug effects , Neurites/metabolism , Phenylpropionates/pharmacology , Propolis/chemistry , p38 Mitogen-Activated Protein Kinases/metabolism , Alkaloids/chemistry , Alkaloids/metabolism , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Apoptosis/drug effects , Enzyme Activation , Enzyme Inhibitors/metabolism , Humans , Mice , Molecular Structure , Neurites/ultrastructure , Nucleic Acid Synthesis Inhibitors/chemistry , Nucleic Acid Synthesis Inhibitors/pharmacology , PC12 Cells/cytology , PC12 Cells/drug effects , PC12 Cells/metabolism , Phenylpropionates/chemistry , Propolis/pharmacology , Pyridones/chemistry , Pyridones/metabolism , RatsABSTRACT
Propolis, a honeybee product, contains a variety of biologically active substances. The present study was designed to investigate the effects of propolis on insulin resistance induced by fructose-drinking rats (FDR; type 2 diabetic animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. FDR showed significant increases in plasma levels of insulin, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin resistance), body weight, and systolic blood pressure but not blood glucose levels, when compared with control rats. Brazilian propolis extract (100 and 300 mg/kg, p.o.) treatment for 8 weeks significantly decreased the plasma level of insulin, HOMA-R, and body weight, increased plasma triglyceride levels without affecting blood glucose and total cholesterol levels, and tended to decrease systolic blood pressure. In isolated and perfused mesenteric vascular beds of FDR, propolis treatment resulted in a significant reduction of sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS; 8 Hz) and tended to increase the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with those in untreated FDR. However, propolis treatment did not significantly affect norepinephrine-induced vasoconstriction and CGRP-induced vasodilation. These results suggest that propolis could be an effective functional food to prevent the development of insulin resistance.
Subject(s)
Fructose/administration & dosage , Hyperglycemia/prevention & control , Insulin Resistance , Propolis/therapeutic use , Animals , Blood Pressure/drug effects , Calcitonin Gene-Related Peptide/physiology , Disease Models, Animal , In Vitro Techniques , Insulin/blood , Male , Mesenteric Arteries/innervation , Propolis/administration & dosage , Propolis/pharmacology , Rats , Rats, Wistar , Sympathetic Nervous System/drug effects , Vasoconstriction/drug effectsABSTRACT
Royal jelly (RJ) is known to have abundant nutritional properties and a variety of biological activities. To investigate the effects of RJ on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic model, were treated for 4 weeks with RJ (10, 30, and 300 mg/kg, p.o.). RJ treatment tended to decrease systolic blood pressure and significantly decreased serum levels of insulin and the Homeostasis Model Assessment ratio, an index of insulin resistance. In isolated and perfused mesenteric vascular beds of OLETF rats, RJ treatment resulted in significant reduction of the sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and potentiation of the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with that in untreated OLETF rats. However, RJ treatment did not significantly affect norepinephrine-induced vasoconstriction and CGRP-induced vasodilation. These results suggest that RJ could be an effective and functional food to prevent the development of insulin resistance.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/therapy , Fatty Acids/administration & dosage , Fatty Acids/pharmacology , Insulin Resistance , Animals , Calcitonin Gene-Related Peptide/physiology , Disease Models, Animal , In Vitro Techniques , Insulin/blood , Mesenteric Arteries/drug effects , Mesenteric Arteries/innervation , Rats , Rats, Long-Evans , Sympathetic Nervous System/physiology , Systole/drug effects , Vasoconstriction/drug effectsABSTRACT
To clarify the suppression of postprandial blood glucose rise via alpha-glucosidase (AGH) inhibitory action by natural compounds, propolis was examined in this study. A single oral administration of propolis extract (50% methanol fraction on XAD-2 column chromatography) in Sprague-Dawley rats demonstrated a potent antihyperglycemic effect with the significant AUC(0-120 min) reduction of 38% at a dose of 20 mg/kg compared to that of controls. Among the active compounds isolated from the fraction, 3,4,5-tri-caffeoylquinic acid was found to be a prominent candidate that exerts the effect and shows a strong maltase-specific inhibition with an IC(50) value of 24 microM. In addition, the noncompetitive inhibition power apparently increased with the number of caffeoyl groups bound to quinic acid.
Subject(s)
Hypoglycemic Agents/pharmacology , Propolis , Quinic Acid/analogs & derivatives , Administration, Oral , Animals , Area Under Curve , Blood Glucose/drug effects , Brazil , Hypoglycemic Agents/chemistry , Male , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Propolis/chemistry , Quinic Acid/chemistry , Quinic Acid/pharmacology , Rats , Rats, Sprague-Dawley , Solubility , Time Factors , WaterABSTRACT
By using beta-cyclodextrin-inclusion as a unique technique, an efficient separation of pharmacologically active phenolic compounds from Brazilian propolis was achieved to provide one new compound, 3-(3-hydroxy-3-methyl-butyl)-5-prenyl-4-hydroxycinnamic acid, together with two common cinnamic acid derivatives, artepillin C and capillartemisin A, and two known flavanols, aromadendrin and 3,5,7-trihydroxy-4'-methoxyflavanol.
Subject(s)
Cyclodextrins/chemistry , Cyclodextrins/isolation & purification , Propolis/chemistry , Propolis/isolation & purificationABSTRACT
Two new long-chain alkanoic acid esters of lupeol were isolated together with known triterpenoids, alpha-amyrin, beta-amyrin, cycloartenol, lanosta-7,24-diene-3beta-ol and lupeol from Alecrim-propolis collected in Brazil. The structures were characterized by spectroscopic means.
Subject(s)
Esters/chemistry , Propolis/chemistry , Triterpenes/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Pentacyclic Triterpenes , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
In order to clarify the potential physiological function of royal jelly (RJ), we report here the gastrointestinal enzyme production of antihypertensive peptides from RJ. Intact RJ and its protein fraction did not retard the action of angiotensin I-converting enzyme (ACE) activity at all. However, development of ACE inhibition power of RJ was newly observed by pepsin hydrolysis (IC(50)=0.358 mg protein/mL), and the subsequent trypsin and chymotrypsin hydrolyses (IC(50)=0.099 mg protein/mL). Single oral administration of this gastrointestinal RJ hydrolysate (1 g/kg dose) in 10-week spontaneously hypertensive rat resulted in a significant reduction of systolic blood pressure of 22.7 plus minus 3.6 mmHg at 2 hr (P<0.05 vs. 0 hr by one-way ANOVA, n=7). Then, the RJ hydrolysate was fractionated with gel permeation chromatography to obtain the di- and tri-peptides (DTP) fraction. As a result of isolation from the DTP fraction by reversed phase-high performance liquid chromatography, eleven ACE inhibitory peptides were isolated from the DTP-RJ hydrolysate. Some of the ACE inhibitors were derived from the RJ-glycoprotein; eight peptides with the IC(50) value of <10 &mgr;M were identified from natural resources for the first time. Consequently, RJ protein was thought to be a good resource of ACE inhibitory peptides produced by the gastrointestinal enzyme hydrolyses.
