Strong Hypoglycemic Effect Research Articles

Optimization of the production of Momordica charantia L. Var. abbreviata Ser. protein hydrolysates with hypoglycemic effect using Alcalase

Momordica charantia L. Var. abbreviata Ser. protein was hydrolyzed using six different proteases. The results showed Alcalase 2.4L to have the best hydrolyzing capacity, followed by Pancreatin. In addition, Alcalase hydrolysate had stronger hypoglycemic effect than that of Pancreatin hydrolysate at the same dose. Alcalase was chosen to produce M. charantia L. Var. abbreviata Ser. protein hydrolysates (MCPHs) with hypoglycemic effect. Response surface methodology (RSM) was applied to optimize the hydrolysis conditions using Alcalase. Model equation was proposed with regard to the effect of enzyme/substrate ratio, pH and temperature. The optimum values for enzyme/substrate ratio, pH and temperature were found to be 2.37%, 9.2 and 57°C respectively.

HYPOGLYCEMIC EFFECT OF SEMIPURIFIED PEPTIDES FROM MOMORDICA CHARANTIA L. VAR. ABBREVIATA SER. IN ALLOXAN-INDUCED DIABETIC MICE

ABSTRACT Hypoglycemic effect of semipurified peptides from an aqueous extract of Momordica charantia L. var. abbreviata Ser. (MCV) in alloxan-induced diabetic mice was investigated. MC2-1, a semipurified peptide fraction from MCV produced a significant hypoglycemic effect in diabetic mice when compared to the diabetic control group. In a long-term study, mice were treated with MC2-1 and glibenclamide, respectively, once a day, for 28 days. Repeated oral administration of MC2-1 reduced significantly the fasting blood glucose level during the 28 days of treatment. Furthermore, MC2-1 significantly reduced hepatic malondialdehyde level, glycogen content, serum cholesterol, triglyceride and low-density lipoprotein cholesterol levels. At the same time, MC2-1 markedly increased high-density lipoprotein cholesterol and serum insulin levels after 28 days of treatment in diabetic mice. Loss in body weight was also prevented in diabetic mice. Hence, MC2-1 can be incorporated as a supplement in health-care food, drugs and/or combined with other hypoglycemic drugs. PRACTICAL APPLICATIONS The present study showed that peptide fraction MC2-1 obtained from an aqueous Momordica charantia L. var. abbreviata Ser. (MCV) extract has a strong hypoglycemic effect in alloxan-induced mice. MC2-1 administered at a dose of 20 mg/kg has a similar or even stronger hypoglycemic effect as that produced by the MCV aqueous extract administered at a dose of 500 mg/kg. The study revealed that MC2-1 is the main fraction with hypoglycemic effect in MCV aqueous extract. Through the removal of compounds with little or no hypoglycemic effect, the dosage needed for diabetes prevention and control is significantly reduced. At the same time, the compounds present in the aqueous extract, which could affect blood glucose level lowering effect, are minimized. MC2-1 can be added as supplement in health-care food, drugs or combined with other hypoglycemic drugs. In addition, the present study revealed the mechanism of action of the hypoglycemic fraction.

Metallokinetic characteristics of antidiabetic bis(allixinato)oxovanadium(IV)-related complexes in the blood of rat

The antidiabetic effect of vanadium is a widely accepted phenomenon; some oxovanadium(IV) complexes have been found to normalize high blood glucose levels in both type 1 and type 2 diabetic animals. In light of the future clinical use of these complexes, the relationship among their chemical structures, physicochemical properties, metallokinetics, and antidiabetic activities must be closely investigated. Recently, we found that among bis(3-hydroxypyronato)oxovanadium(IV) [VO(3hp)(2)] related complexes, bis(allixinato)oxovanadium(IV) [VO(alx)(2)] exhibits a relatively strong hypoglycemic effect in diabetic animals. Next, we examined its metallokinetics in the blood of rats that received five VO(3hp)(2)-related complexes by the blood circulation monitoring-electron paramagnetic resonance method. The metallokinetic parameters were obtained from the blood clearance curves based on a two-compartment model; most parameters, such as area under the concentration curve and mean residence time, correlated significantly with the in vitro insulinomimetic activity in terms of 1/IC(50) (IC(50) is the 50% inhibitory concentration of the complex required for the release of free fatty acids in adipocytes) and the lipophilicity of the complex (log P (com)). The oxovanadium(IV) concentration was significantly higher and the species resided longer in the blood of rats that received VO(alx)(2) than in the blood of rats that received VO(3hp)(2) or bis(kojato)oxovanadium(IV); VO(alx)(2) also exhibited higher log P (com) and 1/IC(50) values. On the basis of these results, we propose that the introduction of lipophilic groups at the C2 and C6 positions of the 3hp ligand is an effective method to enhance the hypoglycemic effect of the complexes, as supported by the observed in vivo exposure and residence in the blood.

Codelivery of a tea extract prevents morbidity and mortality associated with oral vanadate therapy in streptozotocin-induced diabetic rats

Oral administration of vanadate has a strong hypoglycemic effect but results in toxic side effects like life-threatening diarrhea. Tea is known to have potent antidiarrhea effects. We investigated the potential of suspending the vanadate in a tea decoction to reduce the diarrhetic action of vanadate. A concentrated extract of Lichee black tea was, therefore, added to sodium orthovanadate. Streptozotocin (STZ)-induced diabetic rats were orally gavaged with vanadate suspended in water or in the tea decoction, or with the tea extract alone. Blood glucose levels were assessed daily over 11 weeks with levels greater than 10 mmol/L warranting therapeutic intervention. Both the vanadate/water and vanadate/tea solutions acutely reduced blood glucose. The tea extract alone had no effect. The majority of vanadate/water-treated rats developed diarrhea and mortality rates approached 40%. Vanadate/tea-treated diabetic rats experienced no diarrhea or mortality and liver and kidney analyses (plasma ALT and creatinine, blood urea nitrogen [BUN], and urine-specific gravity) were normal. Animals treated with vanadate/tea retained blood glucose levels less than 10 mmol/L for an average of 24 consecutive days without subsequent treatments. Cataract formation was completely prevented. The mechanism of action of vanadate may have involved β-cell stimulation because vanadate/tea-treated diabetic rats exhibited normal plasma insulin levels. In summary, because of its long-lasting effects, oral administration, and lack of side effects, vanadate/tea represents a potentially important alternative therapy for an insuluin-defecient diabetic state.

Encapsulation of Hydrophilic and Lipophilic Drugs in PLGA Nanoparticles by the Nanoprecipitation Method

The purpose of this study was to assess the relative advantages and drawbacks of the nanoprecipitation–solvent displacement method for a range of drugs with respect to the particle size and drug encapsulation in polylactic-co-glycolic acid (PLGA) nanoparticles. The particle size analysis indicated a unimodal particle size distribution in all systems, with a mean diameter of 160–170 nm, except for insulin nanoparticles, which showed a smaller particle size. The results of the encapsulation efficiency analysis demonstrated that more lipophilic drugs, such as cyclosporin and indomethacin, do not suffer from the problems of drug leakage to the external medium, resulting in improved drug content in the nanoparticles. In spite of the fact that valproic acid is a liquid that is very sparingly soluble in water, very low encapsulation efficiency was obtained. Ketoprofen, a drug sparingly soluble in water, demonstrated intermediate values of encapsulation that were well correlated with its intermediate lipophilicity. More hydrophilic drugs, such as vancomycin and phenobarbital, were poorly encapsulated in PLGA nanoparticles. Insulin was preferentially surface bound on the PLGA nanoparticles. However, a strong hypoglycemic effect of the insulin was observed after administration of the suspension of PLGA nanoparticles with surface-bound insulin to the ileum loop of male Wistar rats.

Effects of phospholipid chain length, concentration, charge, and vesicle size on pulmonary insulin absorption.

Non drug loaded lipid vesicles have been investigated as promoters of pulmonary insulin absorption. Physical mixtures of liposomes with insulin were delivered intratracheally to rats by direct instillation method at an insulin dose level of 1 U/kg. The overall hypoglycemic response, represented by area above the curve (AAC), correlated linearly with the lipid concentration for both the neutral and charged liposome-insulin preparations. The strongest response was observed with the positively charged liposomes followed by negatively charged and neutral liposome-insulin mixtures. Further toxicological studies indicated that charge-inducing agents, i.e., stearylamine and dicetylphosphate, can cause apparent disruption of pulmonary epithelial cells. From the difference of overall hypoglycemic response (AAC) among various formulations, it appears that the stronger hypoglycemic effect following positively charged liposome-insulin mixture is due to the membrane destabilizing effect on stearylamine. Optimum hypoglycemic effect was observed with a medium acyl-chain lipid (C10). The cumulative hypoglycemic response appeared to correlate inversely with the acyl carbon number of the phospholipid component from C10 to C18. The overall hypoglycemic effect does not appear to change within the liposomal size range of 0.1 micron - 1.98 microns, indicating that insulin absorption following intratracheal instillation is independent of the vesicle size within the range studied. Phospholipid promoted insulin pulmonary absorption is significantly dependent on the concentration, charge and acyl chain length of the phospholipids.

Antiketogenic and hypoglycemic effects of aminocarnitine and acylaminocarnitines.

DL-Aminocarnitine (DL-3-amino-4-trimethylaminobutyrate) is a potent, noncovalent inhibitor of carnitine palmitoyltransferase (palmitoyl-CoA:L-carnitine O-palmitoyltransferase, EC 2.3.1.21). Here we show that decanoyl-DL-aminocarnitine and palmitoyl-DL-aminocarnitine inhibit carnitine palmitoyltransferase in vitro about 7-fold and 100-fold more effectively than does aminocarnitine. Aminocarnitine and its decanoyl and palmitoyl derivatives are active in vivo following oral or parenteral administration and, at doses of 0.3 mmol/kg or less, inhibit the oxidation of [14C]palmitate to 14CO2 by 45-70% in mice. Larger doses do not significantly increase the extent of inhibition, a finding suggesting that substantial carnitine palmitoyltransferase-independent long-chain fatty acid oxidation may occur in vivo. Small doses of aminocarnitine and palmitoylaminocarnitine prevent the development of ketoacidemia in fasted, normal mice and reverse the ketoacidemia observed in diabetic mice. Aminocarnitine has a strong hypoglycemic effect in fasted diabetic mice; a single dose (0.3 mmol/kg) normalizes plasma glucose levels within 4-8 hr and remains effective for at least 12 hr.

Hydrazonopropionic acids, a class of hypoglycemic substances. 1. Hypoglycemic effect of 2-(phenylethylhydrazono)- and 2-(2-cyclohexyl-ethylhydrazono)-propionic acid.

The two hydrazone-compounds 2-(phenylethylhydrazono)-propionic acid (PEHP) and 2-(2-cyclohexyl-ethylhydrazono)-propionic acid (CHEHP) significantly lowered the blood glucose level in several laboratory animals fasted 48 hours (guinea pigs, mice, hamsters and rats). In the guinea pig, PEHP produced a three times stronger hypoglycemic effect than phenelzine, its corresponding hydrazine. Conversely both hydrazono compounds decreased the monoamine oxidase activity much less, than phenelzine. CHEHP (145 mumol/kg) inhibited this enzyme by less than 14%. After oral administration both hydrazones (200 mumol/kg) also produced a distinct hypoglycemic effect. The blood glucose lowering properties of the two hydrazones were most manifest in fasted guinea pigs, diabetic mice and rats with streptozotozin diabetes.