Strong Hypoglycemic Effect Research Articles

Impact of Bitter Gourd (Momordica charantia) Hypoglycemic Formulation on Biochemical Parameters in Alloxan-induced Diabetic Albino Rats

Introduction: Diabetes mellitus is a widespread endocrine disorder that leads to chronic hyperglycemia, posing significant health challenges globally. Effective management of blood glucose levels remains a critical goal in diabetes treatment. Recent studies have highlighted the potential of natural products in diabetes management. Momordica charantia, commonly known as bitter gourd, has been traditionally used for its purported hypoglycemic effects. This study aims to evaluate the efficacy of a methanolic extract of Momordica charantia in reducing blood glucose levels in an animal model of diabetes and compare its effectiveness to a standard antidiabetic medication, Glizid-M. Materials and Methods: The study utilized alloxan-induced diabetic albino rats to assess the hypoglycemic effects of the methanolic extract of Momordica charantia. Diabetic rats were divided into groups and administered varying doses of the extract: 150 mg/kg, 300 mg/kg, and 600 mg/kg. A control group received Glizid-M, and a baseline group received no treatment. Blood glucose levels were monitored at regular intervals to evaluate the efficacy of the extract in managing hyperglycemia. Results and Discussion: The administration of the methanolic extract of Momordica charantia resulted in a dose-dependent reduction in blood glucose levels. Among the tested dosages, the 600 mg/kg dose demonstrated a statistically significant decrease in blood glucose compared to the lower doses of 150 mg/kg and 300 mg/kg. The 600 mg/kg dosage showed comparable efficacy to the standard antidiabetic drug, Glizid-M, indicating a strong hypoglycemic effect. The results of this study suggest that Momordica charantia has a potent hypoglycemic effect, with its efficacy increasing with dosage. The significant reduction in blood glucose levels at the highest dosage implies that the extract may influence glucose metabolism effectively. The dose-dependent response highlights the importance of optimizing dosage for maximum therapeutic benefit. Comparison with Glizid-M further supports the potential of Momordica charantia as a viable alternative or complementary therapy in diabetes management. Conclusion: This study provides scientific validation for the use of Momordica charantia methanolic extract as a therapeutic agent for diabetes management. The observed dose-dependent reduction in blood glucose levels suggests its potential as an effective natural remedy for controlling hyperglycemia. Further research is warranted to explore the underlying mechanisms and long-term efficacy of this extract in diabetes treatment.

Identification of chemical components of large-leaf yellow tea by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry

Large-leaf yellow tea, a slightly fermented yellow tea that is unique to China, has a stronger hypoglycemic effect than other tea varieties, such as green and black tea. Research on large-leaf yellow tea has focused on its hypoglycemic effect owing to the lack of comprehensive techniques to characterize its chemical components; thus, its development and further promotion are limited. Therefore, the development of a reliable analytical method to fully characterize the chemical components of large-leaf yellow tea is urgently required. In this study, a reliable strategy based on the data-acquisition technology of ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q TOF/MS) was established to rapidly screen and analyze the main chemical components of large-leaf yellow tea by combining the information of neutral loss groups and characteristic fragment ions. The chromatographic separation experiments were performed on a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) with gradient elution using 0.1% formic acid aqueous solution and acetonitrile as the mobile phases. The flow rate was 0.2 mL/min, the sample volume was 2 μL, and the column temperature was 35 ℃. The mass spectral information of the components in a large-leaf yellow tea solution was collected using the full-information tandem MS (MSE) technique in positive and negative ion modes. The specific chemical components of large-leaf yellow tea was identified as follows. First, a self-established database of tea chemical components was constructed based on the literature. The mass spectral cleavage pathways of different types of compounds in large-leaf yellow tea were then sorted using reference substances, and the characteristics of the fragment ions and neutral loss groups were summarized. The precise mass-to-charge ratio of the target chemical components were then obtained based on the mass spectral information. Finally, the structures of the compounds in large-leaf yellow tea were confirmed based on their chromatographic retention times, mass spectral cleavage pathways, characteristic fragment ions, and neutral loss groups. A total of 87 chemical components, including 10 catechins, 32 flavonoids, 16 phenolic acids, 12 tannins, 6 theaflavins, and 11 compounds in other classes, were identified in large-leaf yellow tea. Representative compounds of various classes, including gallocatechin gallate, quercetin, vitexin, gallic acid, chlorogenic acid, 1,3,6-tri-O-galloyl-β-D-glucose, and theaflavin, were selected, and their characteristic fragment ions and neutral loss groups were investigated in detail to reveal the cleavage pathways of different types of compounds in large-leaf yellow tea. The UPLC-Q TOF/MS method established in this study can comprehensively identify the main chemical components of large-leaf yellow tea in a simple, highly sensitive, stable, and reliable manner. This study provides a scientific basis and data support for the discovery of functional ingredients and quality evaluation of large-leaf yellow tea.

Isorhamnetin as a potential therapeutic agent for diabetes mellitus through PGK1/AKT activation

Context Type 2 Diabetes Mellitus (T2D) is a significant health concern worldwide, necessitating novel therapeutic approaches beyond conventional treatments. Objective To assess isorhamnetin’s potential in improving insulin sensitivity and mitigating T2D characteristics through oxidative and glycative stress modulation. Materials and Methods T2D was induced in mice with a high-fat diet and streptozotocin injections. Isorhamnetin was administered at 10 mg/kg for 12 weeks. HepG2 cells were used to examine in vitro effects on stress markers and insulin sensitivity. Molecular effects on the PGK1 and AKT signalling pathway were also analyzed. Results The administration of isorhamnetin significantly impacted both in vivo and in vitro models. In HepG2 cells, oxidative and glycative stresses were markedly reduced, indicating a direct effect of isorhamnetin on cellular stress pathways, which are implicated in the deterioration of insulin sensitivity. Specifically, treated cells showed a notable decrease in markers of oxidative stress, such as malondialdehyde, and advanced glycation end products, highlighting isorhamnetin’s antioxidant and antiglycative properties. In vivo, isorhamnetin-treated mice exhibited substantially lower fasting glucose levels compared to untreated T2D mice, suggesting a strong hypoglycemic effect. Moreover, these mice showed improved insulin responsiveness, evidenced by enhanced glucose tolerance and insulin tolerance tests. The molecular investigation revealed that isorhamnetin activated PGK1, leading to the activation of the AKT signalling pathway, crucial for promoting glucose uptake and reducing insulin resistance. This molecular action underscores the potential mechanism through which isorhamnetin exerts its beneficial effects in T2D management. Discussion The study underscores isorhamnetin’s multifaceted role in T2D management, emphasizing its impact on oxidative and glycative stress reduction and molecular pathways critical for insulin sensitivity. Conclusion Isorhamnetin presents a promising avenue for T2D treatment, offering a novel approach to enhancing insulin sensitivity and managing glucose levels through the modulation of key molecular pathways. Further research is needed to translate these findings into clinical practice.

Effect of supplementation of purslane/Portulaca oleracea in hyperglycemic subjects

Background: Portulaca oleracea (Purslane) is an annual succulent medicinal plant grown all over the world containing diverse phytoconstituents. Several studies have reported its pharmacological effects like antihypertensive, anti-inflammatory, antioxidant, hypoglycemic, hypocholesterolemic, hypotriglyceridemic, neuro, hepato and nephro protective effects. Methods: Dried Portulaca oleracea leaves were incorporated into common food adjunct popularly known as karampodi/spice powder in south India. This spice powder was used for supplementation studies for 90 days (3months) among hyper glycemic subjects after obtaining a written informed consent. Biochemical parameters such as fasting, post lunch blood glucose levels, glycosylated hemoglobin, lipid profile, i.e., total cholesterol, low density lipoprotein cholesterol, triglycerides, high density lipoprotein cholesterol, very low-density lipoprotein cholesterol, kidney function test, liver function test were assessed. Baseline information, their medical history and 24-hour dietary recall was elicited from the subjects through a pretested schedule. Results: The results revealed that fasting, post lunch blood glucose levels, glycosylated hemoglobin, the total cholesterol levels and its fractions along with triglycerides were significantly decreased and HDL-C increased significantly in the test groups from pre-supplementation to during-supplementation and was stable at post-supplementation period. Conclusions: The results indicated that the spice powder which was rich in several polysaccharides, polyunsaturated fatty acids and phytochemicals/phytonutrients when supplemented to hyperglycemic subjects had a strong hypoglycemic, hypocholesterolemic and hypotriglyceridemic effect.

Hematological and Hypoglycemic Effects of Ethanolic Extract of Annona muricata Ripe Fruits Pulp on Streptozotocin-induced Diabetes in Rats: In vivo and In silico Studies

Diabetes mellitus has been a metabolic disorder characterized by interferences in the breakdown of carbohydrate, lipid, and protein as a result of insulin deficiency. Great efforts are ongoing in understanding and management of diabetes, and disease related complication. In this work, an attempt was made to study the hematological and hypoglycemic effects of Annona muricata ripe fruits pulp in Streptozotocin (STZ)-induced diabetic rats and validates its traditional claim. The forty-eight (48) Albino rat were divided into six groups which include normal, tests and controls. The diabetes–induced rats were fed orally with A. muricata ripe fruits pulp extract in concentrations of 750 mg, 1000 mg, and 2000 mg respectively. The results showed that the extract caused fasting blood sugar glucose levels to remarkably reduced to near normal. Hematological studies revealed that there were improvements in the hematological indices tested groups when compare with diabetes normal group. The molecular docking results indicate that the phytochemicals in A. muricata ripe fruit pulp have more affinity for aldose reductase followed by alpha-amylase and then alpha-glucosidase, and that montecristin, epoxymurin-A, dicaffeoylquinic acid, and kaempferol 3-O-rutinoside show higher affinity to the three targets than acarbose. These results indicate that ripe fruits pulp of A. muricata possesses a strong hypoglycemic effect in STZ–induced diabetic rats, thus supporting its traditional use in the management of diabetes mellitus.

Glycemic indices and effect of bitter leaf (Vernonia amygdalina) flavored non-alcoholic wheat beer (NAWB) on key carbohydrate metabolizing enzymes in high fat diet fed (HFD)/STZ-induced diabetic Wistar rats.

In a bid to make the use of functional food easier in the management and prevention of diseases, product development and fortification from/with functional foods have become the recent focus of research. This study, therefore, sought to exploit the recent trend in the brewing industry on the production of non-alcoholic beers by investigating the possibility of having a non-alcoholic beer flavored with bitter leaf, a known plant widely reported to have a strong hypoglycemic effect, as against the traditional use of hops, and the effect of the produced beer on the glycemic indices and various diabetic biochemical parameters that serve as biomarkers for type-2 diabetes (T2D). The glycemic indices, as well as the inhibitory potentials of bitter leaf-flavored Non-alcoholic wheat beer (NAWB) in ratios of 100%HP, 100%BL, 75:25BL, 50:50BL, and 25:75BL, on enzymes linked to a high-fat diet/streptozocin (HFD/STZ)-induced T2D albino Wistar rats were investigated. There were no significant difference (p > .05) between the starch (1.72-1.77 mg/100 mL), amylose (0.22-0.24 mg/100 mL), and amylopectin (1.49-1.53 mg/100 mL) contents of the various samples. The Glycemic Index (GI) of the samples ranged from 36 to 73 with 75:25Bl and 50:50BL have the lowest (36) values. The samples reduced blood glucose levels and inhibited pancreatic α-amylase, lipase, and intestinal α-glucosidase activity. The inhibitory potentials of these beer samples on α-amylase and α-glucosidase as well as their ability to reduce blood glucose levels in diabetic rats thus making the bitter leaf flavored NAWB a suitable healthy beverage for better glycemic control in diabetics. PRACTICAL APPLICATIONS: This study revealed the potential of producing non-alcoholic wheat beer flavored with bitter leaves as a possible substitute for hops. The potential inherent in bitter leaf in the management of type 2 diabetes can thus be made available through a far-reaching beverage medium such as non-alcoholic beer to help in the treatment/management of T2D. The results of this research could be an eye-opener to the possible utilization of bitter leaf and by extension other plants that have been reported in the management of T2D. The use of the bitter leaf as a substitute for hops in the production of non-alcoholic beer in the brewing industry could help in a health-oriented campaign for safe drinks that could be helpful in the control of blood glucose levels of diabetic patients.

Chitosan coating of zein-carboxymethylated short-chain amylose nanocomposites improves oral bioavailability of insulin in vitro and in vivo

Non-invasive means of insulin administration circumvent some of the inconveniences of injections. Oral administration in particular is convenient, pain-free, and allows favorable glucose homeostasis, but is subject to chemical instability, enzymatic degradation, and poor gastrointestinal absorption. Natural polymeric nanoparticles have emerged as a promising oral delivery system for peptide therapeutics due their safety, biocompatibility, and stability. In this study, self-assembled nanocomposites from chitosan (CS) and insulin-loaded, zein-carboxymethylated short-chain amylose (IN-Z-CSA) nanocomposites were synthesized to improve oral bioavailability of insulin. The optimized IN-Z-CSA/CS0.2% nanocomposites exhibited an average size of 311.32±6.98 nm, a low polydispersity index (0.227±0.01), a negative zeta potential (43.77±1.36 mV), an encapsulation efficiency of 89.6±0.9%, and a loading capacity of 6.8±0.4%. The IN-Z-CSA/CS0.2% nanocomposites were stable in storage conditions. The transepithelial permeability of the N-Z-CSA/CS0.2% nanocomposites was 12-fold higher than that of insulin. Cellular uptake studies revealed that the IN-Z-CSA/CS0.2% nanocomposites were internalized into Caco-2 cells by both endocytosis and a paracellular route. Additionally, in pharmacological studies, orally administered IN-Z-CSA/CS0.2% nanocomposites had a stronger hypoglycemic effect with a relative bioavailability of 15.19% compared with that of IN-Z-CSA1.0% nanocomposites. Furthermore, cell toxicity and in vivo tests revealed that the IN-Z-CSA/CS0.2% nanocomposites were biocompatible. Overall, these results indicate that the IN-Z-CSA/CS0.2% nanocomposites can improve oral bioavailability of insulin and are a promising delivery system for insulin or other peptide/protein drugs.

Cholesterol Prevents Hypoxia-Induced Hypoglycemia by Regulation of a Metabolic Ketogenic Shift.

Blood cholesterol levels have been connected to high-altitude adaptation. In the present study, we treated mice with high-cholesterol diets following exposure to acute hypoxic stress and evaluated the effects of the diets on whole-body, liver glucose, and liver fat metabolism. For rapid cholesterol liver uptake, 6-week-old male C57BL/J6 mice were fed with high-cholesterol/cholic acid (CH) diet for 6 weeks and then were exposed to gradual oxygen level reduction for 1 h and hypoxia at 7% oxygen for additional 1 hour using a hypoxic chamber. Animals were than sacrificed, and metabolic markers were evaluated. Hypoxic treatment had a strong hypoglycemic effect that was completely blunted by CH treatment. Decreases in gluconeogenesis and glycogenolysis as well as an increase in ketone body formation were observed. Such changes indicate a metabolic shift from glucose to fat utilization due to activation of the inducible nitric oxide synthase/AMPK axis in the CH-treated animals. Increased ketogenesis was also observed in vitro in hepatocytes after cholesterol treatment. In conclusion, our results show for the first time that cholesterol contributes to metabolic shift and adaptation to hypoxia in vivo and in vitro through induction of HIF-1α and iNOS expression.

A mini review on a Caralluma tuberculata N. E. Br. uncommon and wild succulents but having exciting pharmacological attributes

Caralluma tuberculata belongs to milky weed family Apocynaceae which upholds 424 genera. This natural medicinal plant is widely distributed in South Asia, Africa, Middle East, and Spain etc. Overall phytochemistry of Caralluma tuberculata is endowed with flurry of pharmacologically active constituents like pregnane glycosides and aglycones, flavanoid, saponins and titerpenes etc. Caralluma tuberculata and its various other species of this genus have been explored for their anti-inflammatory action, strong hypoglycemic and weight reduction effect, quite effective for rheumatoid arthritis, paralysis stomach disorders, abdominal pain, migraine, fever wound healing and cardiac problems. Present review focuses on the comprehensive profile of Caralluma tuberculata with respect to its highly valuable phytoconstituent along with their available pharmacological characteristics and therapeutic prospective. Keywords: Caralluma tuberculata; Desert Succulents; Antidiabetic; Cancer; Obesity; Pharmacological http://dx.doi.org/10.19045/bspab.2017.60080

Potential of single cationic amino acid molecule “Arginine” for stimulating oral absorption of insulin

We have reported that cell-penetrating peptides, such as oligoarginine, act as powerful absorption enhancers for the development of oral insulin delivery systems. However, the minimal essential sequence of oligoarginine that stimulates intestinal insulin absorption remains unclear. Therefore, the present study was conducted to clarify this minimum sequence of oligoarginine and to examine the effect of single cationic amino acid arginine on the intestinal and oral absorption of insulin. The results demonstrated that a remarkable enhancement of intestinal insulin absorption was observed after coadministration of insulin with l-arginine. The efficacy of d-forms of oligoarginine/arginine tended to decrease with a decreasing number of amino acid residues, whereas the effect of l-arginine was the strongest of any of the l-forms of oligoarginine/arginine. Interestingly, the effect of l-arginine was stronger than that of d-arginine at various concentrations, and the effect of other cationic amino acids such as lysine and histidine was relatively lower than that of arginine. In addition, no leakage of lactate dehydrogenase from the intestinal epithelium and no change in the transepithelial electrical resistance of a Caco-2 cell monolayer were detected after administration of l-arginine as the single amino acid, which suggests that there were no undesirable effects of arginine on the integrity of cell membranes and paracellular tight junctions. Oral administration study in mice demonstrated that the stronger hypoglycemic effects were observed after coadministration of insulin with l-arginine. In this study, we found that arginine is a key cationic amino acid for delivering insulin across intestinal epithelial barriers and hopefully accelerating the clinical development of oral insulin delivery systems.

Effects of the Tangningtongluo formula as an alternative strategy for diabetics via upregulation of insulin receptor substrate-1.

Tangningtongluo (TNTL), a traditional Chinese medicine, has been widely used in clinics for decades in southwest China. Its pharmacological properties and underlying molecular mechanisms remain unclear. The main goal of ethnopharmacology is to identify novel bioactive compounds derived from plants for use in indigenous medical practice. This knowledge can be used to develop novel pharmaceuticals. In the present study, hyperglycemic C57BL/KsJ-db/db (db/db) mice were used to test the effect of TNTL on microvasculature of the retina and hypoglycemia. Metformin (Met) was selected as a positive control. 26-week-old mice were randomly assigned to receive either the anti-diabetic agent Met [140 mg/kg body weight (BW)], 1.8, 0.9 or 0.45 g/kg BW TNTL, or a placebo. The fasting blood glucose, serum insulin and glycated hemoglobin levels were measured. Histopathologic examination of the pancreas was performed to confirm the hypoglycemic effect. Fluorescein angiography was applied to detect diabetes-induced retinal angioma in the db/db mice. TNTL intake significantly decreased the fasting blood glucose level in a dose-dependent manner. Additionally, TNTL intervention resulted in a significant decrease in the insulin resistance index. Notably, TNTL treatment markedly reduced the speed of retinal degeneration and mildly reversed microvascular caliber degeneration. Western blot analysis indicated that upregulation of phosphorylated insulin receptor substrate-1 (p-IRS-1) by the administration of TNTL may be strongly involved in the improvement of insulin resistance. In conclusion, TNTL exerted a strong hypoglycemic effect and reversed retinal degeneration via upregulation of ISR-1. The present findings provide important scientific evidence supporting TNTL as an effective alternative approach for the management of Type 2 diabetes mellitus.

Enhanced oral bioavailability of insulin using PLGA nanoparticles co-modified with cell-penetrating peptides and Engrailed secretion peptide (Sec)

Biodegradable polymer nanoparticle drug carriers are an attractive strategy for oral delivery of peptide and protein drugs. However, their ability to cross the intestinal epithelium membrane is largely limited. Therefore, in the present study, cell-penetrating peptides (R8, Tat, penetratin) and a secretion peptide (Sec) with N-terminal stearylation were introduced to modify nanoparticles (NPs) on the surface to improve oral bioavailability of peptide and protein drugs. In vitro studies conducted in Caco-2 cells showed the value of the apparent permeability coefficient (Papp) of the nanoparticles co-modified with Sec and penetratin (Sec-Pen-NPs) was about two-times greater than that of the nanoparticles modified with only penetratin (Pen-NPs), while the increase of transcellular transport of nanoparticles modified together with Sec and R8 (Sec-R8-NPs), or Sec and Tat (Sec-Tat-NPs), was not significant compared with nanoparticles modified with only R8 (R8-NPs) or Tat (Tat-NPs). Using insulin as the model drug, in vivo studies performed on rats indicated that compared to Pen-NPs, the relative bioavailability of insulin for Sec-Pen-NPs was 1.71-times increased after ileal segments administration, and stronger hypoglycemic effects was also observed. Therefore, the nanoparticles co-modified with penetratin and Sec could act as attractive carriers for oral delivery of insulin.

In vitro anti-diabetic activity of compounds from pithecellobium dulce fruit peel

Medicinal plants have been reported to play an important role in modulating glycemic responses and have preventive and therapeutic implications . The intestinal digestive enzymes plays a vital role in the carbohydrate digestion. The present investigation evaluated the possible action of isolated compounds through which pithecellobium dulce fruit peel exerts its hypoglycemic effect using suitable in vitro techniques. The isolated compounds were subjected to inhibitory effect of non-enzymatic glycosylation of hemoglobin assay and enzymatic alpha-amylase inhibition assay using specific standard invitro procedure. Non-enzymatic glycosylation of hemoglobin assay showed inhibitory activity of 73.7% and 53.9% at 1mg/ml. The IC 50 values of amylase inhibitory activity of compounds from pithecellobium dulce fruit peel was found to be 80.9% and 56.5% at 1mg/ml. Results in two different compounds revealed that the compound 1was found to be more potent than compound 2 at the concentrations 0.2mg/dl to 1.0mg/dl. The findings indicate Pithecellobium dulce fruit peel possess strong hypoglycemic effect and hence can be utilized as an adjunct in the management of diabetes mellitus.

Acute toxicity and the hypoglycemic action of n,n΄-(ethane-1,2-dyyil)bis(quinoline-2-carboxamide)

The results of the study of N,N΄-(ethane-1,2-dyyil)bis(quinoline-2-carboxamide) as a potential hypoglycemic agent on the model of alloxan diabetes, as well as in normoglycemic rats are presented, the “dose – effect” relationship and acute toxicity in various routes of administration have been determined. Proceeding from the theory of pharmacophores the test compound can be considered as a dimer of 2-(4,5-dihydroimidazol-2-yl)quinoline hydrochloride (BU 224), a blocker of I2-imidazoline receptors, but it is not a dimer in terms of organic chemistry. It has a strong hypoglycemic effect in intragastric administration in the dose range of 7.92-31.67 mg/kg. The maximum hypoglycemic effect is provided by the dose of 15.84 mg/kg. ED50 equals 11.64 mg/kg, the therapeutic index is 54.42 indicating a sufficient breadth of the therapeutic effect and safety of the test compound. In normoglycemia N,N΄-(ethane-1,2-dyyil)bis(quinoline-2-carboxamide) decreases the blood glucose level at the dose of 15.84 mg/kg, while the doses of 3.96 mg/kg and 7.92 mg/kg do not affect the blood glucose level, and it indicates that the features of pharmacodynamics and the hypoglycemic effect depend on the state of the carbohydrate metabolism. It has been shown that in hyperglycemia the hypoglycemic effect is observed starting at the dose of 7.92 mg/kg, and higher doses. However, in healthy animals, the aforesaid dose does not affect the blood glucose level. In the intraperitoneal administration the hypoglycemic effect is evident at the lower dose of 1.5 mg/kg exceeding metformin at the dose of 100 mg/kg by its hypoglycemic activity. In the intraperitoneal administration N,N΄-(ethane-1,2-dyyil)bis(quinoline-2-carboxamid) belongs to moderately toxic substances (toxicity of class III, LD50 = 10.005 mg/kg), in the intragastric administration – to low-toxic substances (toxicity of class IV, LD50 = 633.45 mg/kg).

Evaluation of hypoglycemic efficacy of tangningtongluo formula, a traditional Chinese Miao medicine, in two rodent animal models.

Traditional Chinese medicines largely lack adequate and scientifically rigorous evidence regarding efficacy and functional mechanisms. The present study was aimed to confirm the hypoglycemic effect of Tangningtongluo (TNTL) formula, a traditional Chinese Miao medicine, in two animal models: high-fat diet and streptozotocin- (STZ-) induced diabetic rats and C57BL/KsJ-db/db diabetic mice. After 4 weeks, TNTL intervention in STZ-induced diabetic rats yielded in significant improvement on the glucose tolerance test. Moreover, the islet histopathology showed that oral TNTL reduced the severity of islet necrosis in pancreases tissue. Compared with diabetic controls, a 12-week TNTL treatment regimen (dosages = 0.9, 1.8, and 3.6 g/kg) in db/db mice significantly decreased fasting glucose and HbA1c. Additionally, oral glucose tolerance in TNTL-treated mice improved significantly, compared with diabetic mice receiving metformin. Finally, tissue histopathology and biochemical index evaluations revealed significant improvement in TNTL-treated mice. Taken together, our results show that TNTL exerted a strong hypoglycemic effect in two diabetic rodent animal models, preserving β-cells in the pancreas islet and reducing the risk of diabetic retinopathy and nephropathy.

Extracts of Cordyceps militaris Lower Blood Glucose via the Stimulation of Cholinergic Activation and Insulin Secretion in Normal Rats

Previous studies have shown that Cordyceps militaris (CM) has a hypoglycemic effect, but the actual mechanism remains unclear. This study explored the hypoglycemic mechanism of aqueous extracts of CM in normal Wistar rats. First, the optimal dose of CM for lowering plasma glucose and insulin secretion was tested. Further, atropine and hemicholinium-3 (HC-3) were injected and a western blot was used to investigate insulin signaling. It was found that 10 mg/kg CM extracts had a stronger hypoglycemic effect than a higher dose (100 mg/kg); therefore, a dose of 10 mg/kg was used in subsequent experiments. In normal rats, CM extracts decreased plasma glucose by 21.0% and induced additional insulin secretion by 54.5% after 30 min. When atropine or HC-3 was injected, CM induced a hypoglycemic effect, but the enhancement of insulin secretion was blocked. By western blotting, significant increases in the insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) were observed after CM feeding. However, the elevation of these signaling proteins was abolished by atropine or HC-3. Taken together, these findings indicate that CM can lower plasma glucose via the stimulation of insulin secretion and cholinergic activation involved in the hypoglycemic mechanism of normal Wistar rats.

Purification, characterization and hypoglycemic activity of extracellular polysaccharides from Lachnum calyculiforme

Polysaccharides produced by Lachnum have been found as biologically active substances in recent years. Herein, extracellular polysaccharides from Lachnum calyculiforme (LEP) fermenting liquor was obtained by the process of Sevag deproteination, H2O2 decolorization and salting out. LEP-1 was separated and sequentially purified from LEP through DEAE-Cellulose 52 and Sephadex G-100 column chromatography. The results showed that LEP-1 was detected as the homogeneous component with molecular weight of about 445.363kDa by the high performance liquid gel permeation chromatography (HPGPC). Furthermore, we demonstrated that LEP-1 was glucose polymer by GC–MS analysis. IR and NMR spectroscopy (1H, 13C) analysis indicated that the glucose conformation was pyranose-type. Diabetic mice experiments showed that the LEP-1 had a strong hypoglycemic effect in alloxan diabetic mice with dose-dependent relationship.

Synthesis and Bioactivity Evaluation of Dipeptidyl Peptidase IV Resistant Glucagon-like Peptide-1 Analogues

Glucagon-like peptide -1 (GLP-1) is an incretin hormone displaying glucose-dependent stimulation of insulin secretion and trophic effects on the pancreatic β-cells. However, GLP-1 is rapidly degraded to GLP-1(9-36) by dipeptidyl peptidase-IV (DPP-IV), which removes the N-terminal dipeptide His(7)-Ala(8). The rapid inactivation of GLP-1 in the blood circulation limits its clinical application. Hence, we replaced the enzymatic hydrolyzation position Ala(8) with other natural amino acids. The GLP-1 analogues were synthesized rapidly and efficiently under microwave irradiation, using Fmoc/tBu orthogonal protection strategy. Studies on blood-glucose-lowering effect of GLP-1 analogues in vivo were undertaken using 10-week-old male Kunming mice. The metabolic stability was tested by incubation with dipeptidyl peptidase-IV (DPP-IV). Generally, Xaa(8)-GLP-1 analogues exhibit resistance to DPP-IV degradation in vitro and stronger hypoglycemic effect than GLP-1. This may help to understand the structure-activity relationship of GLP-1 analogues.

In vitro studies on the hypoglycemic potential of Ficus racemosa stem bark

Medicinal plants have been reported to play an important role in modulating glycemic responses and have preventive and therapeutic implications. Several mechanisms have been proposed for the antidiabetic effect of medicinal plants such as inhibition of carbohydrate-metabolizing enzymes, manipulation of glucose transporters, beta-cell regeneration and enhancing insulin-releasing activity. The present investigation evaluated the possible mechanism of action through which Ficus racemosa stem bark (Moraceae) exerts its hypoglycemic effect using suitable in vitro techniques. Ficus racemosa bark (FRB) exhibited significantly higher (P < or = 0.01) glucose-binding capacity than wheat bran (WB) and acarbose (ACB) consequently showed significantly higher (P < or = 0.01) retardation of glucose diffusion compared to WB and ACB. In case of amylolysis kinetics the liberation of glucose was greatly inhibited by FRB, as reflected by a significantly lower (P < or = 0.01) glucose diffusion rate in the system containing FRB compared to the control and acarbose. Furthermore, FRB significantly increased (P < or = 0.01) the rate of glucose transport across the yeast cell membrane and also in isolated rat hemi-diaphragm. The findings indicate F. racemosa bark to possess strong hypoglycemic effect and hence can be utilized as an adjunct in the management of diabetes mellitus.

Hypoglycemic effect of Basella rubra in streptozotocin induced diabetic albino rats

Great efforts are ongoing in understanding and management of diabetes, the disease and disease-related complications are increasingly unabated. In spite of the presence of known antidiabetic medicine in the pharmaceutical market, remedies from medicinal plants are used with success to treat this disease. In the present investigation an attempt is made to study the beneficial effects of Basella rubra in streptozotocin-induced diabetic rats and validate its traditional claim. The diabetes-induced rats were fed with Basella rubra (400 mg/100 gm body weight orally through a gavage), when tested after ingestion the fasting blood glucose levels were remarkably reduced to normal and liver glycogen content was remarkably increased. In pancreatic sections of diabetic rats fed with B. rubra, the islets were normal comparable to diabetic controlled rats (insulitis was observed). In liver, the changes caused after induction of diabetes was global microvesicular steatosis. The portal tracts appeared normal and central veins appeared congested, which was brought back to normal after feeding with B. rubra. While, in the kidney sections, of diabetic control rats and diabetic rats fed with B. rubra no histopathological changes were noticed. The results demonstrate that the leaf pulp of B. rubra possesses a strong hypoglycemic effect in streptozotocin-induced diabetic rats, thus supporting its traditional use in diabetes mellitus control. Key words: Basella rubra (B. rubra), hypoglycemic effect, pancreas, streptozotocin-induced diabetic rats, blood glucose.