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Lentinula edodes (L. edodes), which imparts various health benefits to humans, is considered a novel source of soluble dietary fiber (SDF). In this study, ultrasonic-assisted hot-water method was used to extract SDF (U-SDF) from L. edodes, and physicochemical, antioxidant and hypoglycemic properties of the U-SDF were investigated. Physicochemical properties of U-SDF showed that water solubility, water holding capacity, swelling capacity, and oil holding capacity were higher than that the SDF extracted using hot water method without ultrasonication. The DPPH, •OH, and •O2- radical clearance rates indicated that U-SDF exhibited better antioxidant activities. U-SDF also exhibited notable α-amylase and α-glucosidase inhibition activities. Treatment with U-SDF alleviated glucose and peroxidation metabolism disorders in vivo. Histological analysis indicated that U-SDF improved the oxidative tissue damage in diabetic mice. These results provided a theoretical basis for the development and utilization of SDF derived from L. edodes.

Purpose: To screen the hypoglycemic active ingredients of Coptidis rhizoma, and study their targets as well as signal pathways via network pharmacology. Methods: Fifty-nine ingredients of Coptidis rhizoma were screened. Their targets were confirmed by comparing with the hypoglycemic targets in DrugBank databases. The relationship between ingredients and targets was revealed through String database. The ingredient-target-passageway network was constructed. Coptidis rhizoma was soaked in boiling water and concentrated. Rat models were rendered diabetic by the administration of streptozotocin (STZ) intraperitoneal injection. The hyperglycemic rats received Coptidis rhizoma extract (0.40 g/kg, once a day by gavage). Results: After four weeks of treatment, the blood glucose levels (BG) of all treated hyperglycemic rats decreased (p < 0.05). Twenty-four hypoglycemic active compounds were obtained after screening the extract of Coptidis rhizome via network pharmacology. These active compounds activated 13 targets, including D (2) dopamine receptor (DRD2), Insulin-like growth factor 1 receptor (IGF1R), 5- hydroxytryptamine receptor 2C (HTR2C), 5-hydroxytryptamine receptor 3A (HTR3A) and sodiumdependent noradrenaline transporter (SLC6A2). These targets were involved in 141 pathways, e.g., cAMP signaling pathway, chemokine signaling pathway, Rap1 signaling pathway, estrogen signaling pathway, and apelin signaling pathway. Conclusion: Coptidis rhizoma contains several active compounds that exhibit good hypoglycemic effects. Thus, there is a need for human studies on the hypoglycemic effects of Coptidis rhizome extracts. Keywords: Coptidis rhizome; Hypoglycemic effects; Network pharmacology; D (2) dopamine receptor (DRD2); Insulin-like growth factor 1 receptor

Background The history and the discovery of the benefits of traditional medicines are fascinating over wide variety of disease. Various molecules have been erupted from traditional medicine for various diseases through reverse pharmacology. In current scenario plant-based medicines backed by modern scientific evidences are one of the most promising therapies in diabetes management. Scope and approach Garlic (allicin), European barberry (berberine), Bitter gourd (charantin, polypeptide-p), Sweet potato (adiponectin, tiliroside), Orka (quercetin, hyperin) are some plants that have been used in folk medicine as well as traditional healing systems and are being assessed for their hypoglycemic effects in modern medicine. Key findings and conclusions “Old wine in new bottle” proverb applies traditional medicine in new modern medicine. Various novel delivery aspects have modified the pharmacokinetics of phytochemicals and indirectly enhance the bioavailability, which in turn gives fruitful effect of their therapeutic action.

The use of plants and their products for medical treatment is a quite common procedure in Brazil, especially for treatment of diabetes. In fact, several plants can demonstrate hypoglycemic effects in vitro assays. However, the use for human treatment requires the knowledge of their toxicological properties. The aim of this study was to evaluate the effect of protein extracts of Chrysobalanus icaco collected from natural habitats and of Eugenia astringens acquired from the market in Rio de Janeiro on the viability and migration of fibroblasts. E. astringens has a similar morphology as C. icaco and it is sold as Chrysobalanus in a popular market. Being a different plant, E. astringens expresses different proteins, and its protein extract has proved to possess higher toxic properties than C. icaco does. Cytotoxicity assays indicated that, as the protein extract concentration increases, fibroblast viability decreases. Only the E. astringens extract displayed cytotoxicity at all concentrations, in addition to reduced fibroblast migration. The results obtained in this study demonstrates that it is necessary integrative policies for rational use of medicinal plants and their commercialization, since the current use of medicinal plants may be inadequate, and it is of great importance for Public Health.

Allosteric activators of human glucokinase (GK) had revealed significant hypoglycemic effects for therapy of type-2 diabetes (T2D) in animal as well as human models. Some newer N-benzimidazol-2yl substituted benzamide analogues were prepared and assessed for activation of GK accompanied by molecular docking investigations for predicting the bonding interactions of these derivatives with the residues in allosteric site of GK protein. Amongst the derivatives synthesized, compounds 2 and 7 strongly increased catalytic action of GK (GK activation fold >2.0 in comparison to control) in vitro. The results of in-vitro testing were supported by the molecular docking investigations of these analogues with GK protein’s allosteric site residues (showed appreciable H-bond interactions with Arg63 residue of GK). Derivatives investigated in present study afforded few lead compounds for the discovery of harmless and strong allosteric GK activating compounds for treating T2D.

Gymnema sylvestre, a plant typical of India, has long been known for its hypoglycemic effects. The objective of this study was to evaluate the effect of G. sylvestre administration on glycemic cont...

Glechomae Herba is a Chinese herb, which has been used in China for thousands of years, mainly for the treatment of nephrolithiasis. This paper summarizes the modern research progress on Glechomae Herba from the aspects of botany, traditional medicinal use, phytochemistry, pharmacology, pharmacokinetics, analytical methods and quality control. In addition, it also points out the deficiencies of current research on this herb and provides possible directions for its development. So far, more than 190 chemical components have been isolated and identified from Glechomae Herba, including organic acids and their esters, volatile oils, flavonoids and their glycosides, terpenes and other chemical components. Its extracts and compounds have a wide range of pharmacological effects, including anti-stone, anti-inflammatory, bacteriostatic, cholagogic and diuretic, effect on ileum smooth muscle, anti-tumor effect on tumor and hypoglycemic effects. However, future studies should focus on drug metabolism, clarify its pharmacodynamic mechanism, and establish a reasonable quality control standards for Glechomae Herba.

Hypoglycemic effects was observed with Spirulina (Spirulinaplatensis) when given as leaf extract in normal and alloxan diabetic rat. In this study 150 rats were included and divided into three groups of ten rats in each group. First group was normal control (A), Second group was diabetic control (B), third group was diabetic with Spirulina treated (C). The rats were treated with aqueous extract of Spirulina at a dose rate of 20 mg/kg body weight respectively for 3 weeks. During experimental period, day 0, day 7, day 14 and day 21 blood samples were collected from all groups and determined their blood sugar level using diabetic kit. The blood glucose levels were reduced from 165.5±10.65 mg/dL to 158.17±5.49 mg/dL in group C after 3 weeks treatment. On the other hand the average body weight were increased from 255.67±7.35 g to 286.17±8.56 g in group C after 3 weeks treatment. From the findings it is concluded that the Spirulina can be used as anti-diabetogenic agent in food. Res. Agric., Livest. Fish.7(3): 475-479, December 2020

Background: Diabetes mellitus (DM) is among the diseases with high morbidity and mortality The pathogenesis of DM involves pancreatic s-cell damage or insulin sensitivity disorder that result in hyperglycemia. Tapak liman (Elephantopus scaber L) is known to have high flavonoid content. Flavonoids are antioxidants that play a role in reducing pancreatic s-cell damage or damage to other tissues, which potentially reduce blood glucose levels. Objective: To determine the hypoglycemic effects of tapak liman using the DM rat models. Methods: Twenty-eight Wistar albino rats (Rattus novergicus) were divided into four groups: the normal control group (KKn), not induced by streptozotocin-nicotinamide (STZ-NA) intraperitoneal; negative control group (KK-), induced by STZ-NA; treatment group 1 (KP1), induced by STZ-NA and 150 mg/kg body weight of tapak liman plant extract; and the treatment group 2 (KP2), induced by STZ-NA and 300 mg/kg body weight of tapak liman. Blood glucose levels were measured on the 7th day after STZ-NA induction and the 28th day after the administration of tapak liman plant extract. The results were analyzed for statistical significance. Results: There was a significant decrease in blood glucose levels in KP1 and KP2 (p= 0.05). The decrease in blood glucose in KP1 had not reached normal levels compared to KP2. Conclusion: Administration of tapak liman plant extract at a dose of 300 mg/kg body weight in DM rat models reduced blood glucose levels to normal.

Background: Ammodaucus leucotrichus (Apiaceae) is a medicinal plant widely used by the Moroccan population to treat various diseases including diabetes. Aims: The aim of this study was to evaluate the antidiabetic effect of the aqueous extract prepared from the fruits of this medicinal plant. Normal and streptozotocin-induced diabetic rats were treated orally by the extract of Ammodaucus leucotrichus (A. leucotrichus) at a dose of 10 mg/kg. Methods: The blood glucose levels were determined during 6 hours and 15 days during this treatment. In addition the oral glucose tolerance test as well as the analysis of histopathological changes of liver was performed. The antioxidant activity of aqueous A. Leucotrichus extract was also valuated by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH). Results: A. Leucotrichus fruit aqueous extract (ALFAE) reduced the blood glucose levels in both normal and diabetic rats. In addition, a remarkable influence on glucose tolerance was also noticed after ALFAE treatment. Moreover, ALFAE was able to exhibit a beneficial effect on histologlogical structure of liver. Finally a potential antioxidant effect has been shown in vitro. Conclusion: In conclusion, this study demonstrates the antihyperglycemic and hypoglycemic effects of A. Leucotrichus in rats supporting then its traditional use for the management of diabetes.

Background Xyloglucan (XyG) is a ubiquitous polysaccharide that possesses hypoglycemic effects, antihyperlipidemia effects, gut barrier protective properties, and positive effects on coronary heart disease. As a nonstarch polysaccharide, XyG cannot be processed directly by enzymes encoded on the human genome. After being ingested, XyG transits the large intestine where it becomes food for the intestinal microbial community. The species within the intestinal microbiota use various strategies to recognize and degrade XyG. However, most current studies focus on the industrial application of XyG. We must examine the beneficial effects of XyG on human health and the roles that the gut microbiota play in XyG degradation. Scope and approach The current review summarizes the relationship between XyG and intestinal microbiota, including the degradation process of XyG by gut Bacteroidetes and the influence of XyG on the intestinal microbiota. In addition, the possible effects of XyG or its microbial degradation products on human health are presented. Key findings and conclusions XyG breakdown in the large intestine is mediated by several proteins encoded on XyG utilization loci. Surface glycan-binding proteins and glycan-degrading enzymes encoded on XyG utilization loci are the main components that utilize XyGs in the large intestine. Secondary metabolites and fermentation end products that are generated in XyG degradation by gut microbiota can improve human health. The beneficial effects of XyG on human health may be realized through its microbial degradation.

Bitter gourd (Momordica charantia L.) is a fruit that traditionally believe to have benefits on health. It is a widely used traditional remedy for the treatment of diabetes. Bitter gourd is suggested for hyperglycemia treatment due to its ability to reduce glucose levels in the body. Some of the bioactive compounds present in it possess anti diabetic effects. It contains phytochemicals with anti-diabetic properties such as charantin, p-insulin and vicine. Hypoglycemic effects of bitter gourd have been shown in clinical studies. This review will focus on the hyperglycemic properties of bitter gourd.

Pomegranate juice (PJ) has gained popularity attributed to its phenolic compounds and their medicinal properties. Its potential hypoglycemic effect has been related to enzymatic inhibition, insulin release, and the protection of pancreatic tissue. These effects depend on several aspects, such as the content and composition of phenols in pomegranate and characteristics of the organism that consumes the juice. The objective of this study was to systematically review scientific evidence investigating the hypoglycemic effect of PJ; the factors that affect bioactive compounds; and the mechanisms of action attributed to this effect. Human and rodent in vivo and in vitro studies were retrieved from PubMed, Scopus, and ScienceDirect databases. After reviewing the articles, it was identified that the methodologies and results among the scientific evidence were quite heterogeneous. Despite these limitations, many of the in vivo and in vitro studies found important hypoglycemic effects from PJ, as well as an increase in the function of β-cell, insulin secretion, a significantly lower activity of α-amylase enzyme, an inhibition of the enzyme α-glucosidase and dipeptidyl peptidase-4 (DPP-4), and the protection against DNA damage. Determining the potential health benefits of polyphenols contained in the pomegranate is limited for multiple factors that could affect the efficacy of PJ. Overall, the results of this review suggest the need for further experimentation, using controlled variable factors and testing the effect of PJ under similar experimental conditions.

The inhibition of porcine pancreatic α-amylase (PPA) by 9 galloyl-based polyphenols was evaluated via initial digestion velocity, IC50, inhibition kinetics, fluorescence quenching and molecular docking studies. The results show that the polyphenols with free galloyl moieties (GMs) exhibited a much higher inhibition effect than that with bound GMs. The inhibition was competitive mode and increased with an increase in the number of free GMs. Interestingly, all the constants that indicate the binding affinity of polyphenols to PPA, including the reciprocal of the competitive inhibition constant (1/Kic), fluorescence quenching constant (KFQ) and binding energy (Eb), increased with an increase in the number of free GMs. Besides, the respective order of 1/Kic, KFQ and Eb for the galloyl-based polyphenols was contrary to that of IC50, indicating that the polyphenol-PPA binding interactions resulted in enzyme inhibition. In addition, the binding interactions were suggested to result from the hydrogen bonding and π-π conjugation forces between the free GMs and amino acid residues at the active sites of PPA, whereas the chemical linkage of the GMs with additional polyphenol groups limited these interactions. Furthermore, the hypoglycemic effects of two polyphenols with 5 free GMs indicate that GMs may be considered a functional fragment involved in the alleviation of the symptoms of type II diabetes through α-amylase inhibition.

As emerging woody oil crops, the tree peony seeds recently have been attracting great attention for their metabolites and bioactivities. In this research, the phytochemical profiles of the seed coats of tree peonies from different production regions were investigated systematically. Twelve phytochemicals were separated and prepared, mainly belonging to stilbenes. A great variation in stilbene content was detected in the three Paeonia plants, and Paeonia ostii seed coats (POSC) had significantly higher contents of the stilbene compounds than other species. There were nineteen significant correlations between ecogeographical factors and the predominant compounds. A clear discrimination among the species was observed in their HPLC fingerprint and chemometric analysis. Furthermore, POSC extracts could significantly reduce the starch mediated PBG (postprandial blood glucose) levels in normal/diabetic mice. Meanwhile, in vitro enzyme tests revealed that the predominant compounds, suffruticosol B and ampelopsin D, could effectively and competitively inhibit α-glucosidase, indicating that POSC could be a natural source of hypoglycemics in the food and drug fields.

Proso millets are eco-friendly smart grains rich in minerals and phytochemical compounds that preserve the health of the individuals. The bioactives present in proso millet gives protection against metabolic syndromes and lifestyle diseases. Hypoglycemic effects of millets, in general are much appreciated and currently millets are used in valorizing the food products due to its functional key elements. In spite of its health benefits and agronomical and economical prospective, millets lost its fame especially in developing countries and it has not reached the massive population may be due to processing difficulty and reduction in production area. This article presents reviews and research investigations about agronomical advantages, post harvest handling protocols, nutraceutical and functional properties and methods of valorizing the proso millet.

In the study, the structural features and hypoglycemic effects of a polysaccharide Pan from the root of Panax notoginseng were investigated. The molecular weight of Pan was 8.27 kDa. Structural analysis indicated that Pan mainly consisted of →3)-β-L-Rhap-(1→, →3,6)-β-D-Galf-(1→ and →6)-β-D-Galf-(1→ residues with acetyl groups. Pan exhibited good antioxidant activity. Pan could slow down the body weight and the content of blood glucose in the high-fat diet-induced mice, further suppress GLUT-2 and SGLT-1 expression in the intestines, and enhance p-IRS and p-AMPK expression in the livers, finally exhibiting hypoglycemic effects. The results could supply a direction for further research on polysaccharides as components for the control of hyperglycemia induced by obesity and diabetes.

Purpose Non-communicable diseases such as type 2 diabetes, hypertension, cancers and cardiovascular diseases have become a major health concern globally. As literature claims that frequent consumption of fruits and vegetables can delay the onset of type 2 diabetes and its complications, this paper aims to evaluate the potential hypoglycemic properties in five types of non-leafy vegetables (pumpkin, sweet potato, bitter gourd, onion and lady’s finger), which are commonly available in Malaysia. Design/methodology/approach Articles were identified through several main search engines, including Pubmed, Google Scholar, Taylor and Francis Online, EDS, Wiley, ScienceDirect and Scopus. The search was limited to selected keywords to refine the outcome. Findings All the five types of non-leafy vegetables demonstrate hypoglycemic properties to some extent. Emerging findings indicate that there are several phytonutrients in the non-leafy vegetables contributing to the hypoglycemic effects. To date, the underlying mechanism of action remains to be elucidated, although a number of potential mechanisms of action have been proposed in the literature. Originality/value This review provides some insights into the hypoglycemic properties in non-leafy vegetables. In addition, phytonutrients that are responsible for the hypoglycemic effects and their mechanism of action are also highlighted.

Antidesma bunius (L.) Spreng and Mollugo oppositifolia L., also known as “bignay” and “malagoso” respectively, are commonly used medicinal plants in the Philippines to treat diabetes. However, the hypoglycemic effect of A. bunius (L.) Spreng and M. oppositifolia L. has not been reported to date. Therefore, this study was undertaken to investigate the hypoglycemic effects of the fresh and ethanolic extracts of the plants in db/db diabetic male mice. Fresh and ethanolic extracts (12.5 ml/kg and 250 mg/kg, respectively) were administered by gavage in db/db mouse, an animal model of diabetes. Blood from the tail snip was used to measure blood sugar levels on days 1 (D1), 8 (D8), 15 (D15), 22 (D22) and 29 (D29). Fresh extract of M. oppositifolia L. caused a significant reduction of blood glucose levels on D22 compared to untreated db/db mice (P < 0.05). On D29, fresh extract of A. bunius (L.) Spreng (P < 0.01), and fresh (P < 0.01) and ethanolic leaf extracts (P < 0.05) of M. oppossitifolia L. caused a significant reduction of blood glucose compared to untreated db/db mice. Fresh and ethanolic extracts of A. bunius (L.) Spreng and M. oppositifolia L. exhibited a significant hypoglycemic activity in db/db mice. Key words: Antidesma bunius L, Spreng, Mollugo oppositifolia L., diabetes, mouse, hypoglycemic.

This present study was to evaluate the protein tyrosine phosphatase 1B (PTP1B) inhibitory activity of nine diterpenes isolated from seeds of Phalaris canariensis, as well as their effect on strepto...

Diabetes mellitus (DM) is a chronic progressive systemic disease caused by a metabolic disorder. In recent years, a large number of studies have shown that certain traditional Chinese medicines and their bioactive ingredients have obvious hypoglycemic effects. This literature review focuses on medicine food homology (MFH) and medicinal health food (MHF) species used in China with a hypoglycemic function and emphasizes the bioactive ingredients and their pharmacological effects. The bioactive ingredients of MFH and MHF have been divided into six categories: saponins, flavonoids, terpenoids, alkaloids, polysaccharides, and others; and their sources, models, efficacy, and mechanisms of action have been described. It is noteworthy that the mechanisms of the bioactive ingredients of MFH and MHF with hypoglycemic effects have been summarized as follows: a) insulin-mimetic effects and restoration of the damaged pancreas; b) effect on glucose metabolism; c) increased insulin sensitivity and improved insulin resistance; and d) regulation of intestinal flora. We conclude that this review provides useful data and information to support the further investigation and application of MFH and MHF to treat DM.

The present study was undertaken to examine the antidiabetic potential of naturally occurring peptides and hydrolysate fractions from easy-to-cook (ETC) and hard-to-cook (HTC) beans. All fractions were tested regarding their in vitro inhibitory activities against α-amylase and α-glucosidase as well as in vivo anti-hyperglycemic and hypoglycemic effects. Results evidenced that the peptide fractions with the lowest molecular weight (3 kDa) have the highest inhibitory activities, and a 16.9%-89.1% inhibition of α-amylase and 34.4%-89.2% inhibition of α-glucosidase were observed. Regarding the antihyperglycemic activity, the fraction ETCNO3-10 showed a better performance than the positive control (acarbose). In addition, results from hypoglycemic activity evidenced that the tested peptide fractions were able to decrease the glucose levels at the same extension of glibenclamide, maintaining a constant basal glucose level without a postprandial hyperglycemia peak. Finally, it is possible to suggest that the naturally occurring peptides and hydrolysate fractions obtained from ETC and HTC common beans could be used in functional food production or pharmaceutical formulations to prevent diabetes.

Recently, there has an increased focus on the isolation, chemical properties and bioactivities of polysaccharides from buckwheat (Fagopyrum Mill), which is a member of the Polygonaceae family. Phytochemical and pharmacological studies have shown that polysaccharides are important biologically-active components of buckwheat, with numerous biological activities, including antioxidant, antitumor, immunomodulatory, antihypertensive and hypoglycemic effects. The purpose of this mini-review is to appraise available literature describing the extraction, separation, purification, structural characterization and biological activities of polysaccharides isolated from buckwheat. This mini-review also provides a foundation for the further investigation, production and application of buckwheat polysaccharides as functional foods and therapeutic agents.

Introduction: The aim of the current analysis was to judge the hypoglycemic action of the phyto-extracts of Lagenaria siceraria, Cynodon dactylon and Stevia rebaudiana using suitable in vitro approaches. Methods: The hypoglycemic activity of the phyto-material extracts was evaluated by employing various in-vitro methods namely glucose diffusion, amylolysis kinetics and glucose adsorption capacity. Results: The extracts of L. siceraria, C. dactylon and S. rebaudiana exhibited glucose dialysis retardation indices (GDRI) of 48.14%, 37.03% and 29.62%, respectively at 60 minutes which were reduced to 15.78%, 10.52% and 18.42%, respectively at 120 minutes. All the plant extracts used in the study adsorbed glucose and their adsorptions markedly enhanced with increase in sugar concentration. Conclusion: From the outcome of the assay it can be concluded that the extracts of L. siceraria, C. dactylon and S. rebaudiana have hypoglycemic activity as observed in various in-vitro assays. However, the beneficial actions require to be verified by adopting various in vivo techniques along with clinical trials for their efficient use as potential remedial moiety.

Dietary intervention in type 2 diabetes mellitus (T2DM) is a hotspot in international research because of potential threats to human health. Phellinus baumii, a wild fungus traditionally used as a food and medicine source, is now cultivated in certain East Asian countries, and is rich in polyphenols, which are effective anti-inflammatory ingredients useful in treatment of T2DM, with fewer side effects than drugs. To examine the hypoglycaemic effects of Phellinus baumii phenolics (PPE), the metabolite profiles of T2DM mice induced by streptozotocin after PPE intervention were systematically analyzed. Here, 10 normal mice were given normal saline as control group, and 50 model mice were randomly assigned to five groups and daily intragastric administrated with saline, metformin (100 mg/kg), and PPE (50, 100, 150 mg/kg of body weight), for 60 days. The pro-inflammatory factor contents of lipopolysaccharide stimulation of RAW 264.7 cells were decreased in a dose-dependent manner after PPE treatment, we propose that PPE could exert anti-inflammatory properties. PPE could also effectively reduce blood glucose levels, increased insulin sensitivity, and improved other glucolipid metabolism. Q-PCR results suggested that the hypoglycemic effects of PPE might be through activating IRS1/PI3K/AKT pathway in diabetic mice. These results suggest that PPE has strong potential as dietary components in the prevention or management of T2DM.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause various health damages. However, some PAH derivatives are still used as agents, and some of them have hypoglycemic effects. Till now, few studies explored the relationship between urinary PAH metabolites and fasting plasma glucose (FPG). In this study, A total of 2682 non-smokers in the second follow-up of the Wuhan-Zhuhai cohort were included to explore the relationship between urinary PAH metabolites and FPG. FPG related epigenome-wide association study (EWAS) was conducted among 212 never smokers, and the mediation analysis was performed to find potential mediator cytosine-phosphoguanine (CpG) sites in the above relationship. The concentration of total urinary PAH metabolites was 3.60 (2.37, 5.85) μg/mmol Cr. The urinary PAH metabolites were negatively associated with FPG. Each 1-U increase in ln-transformed levels of 1-hydroxynaphthalene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, or 2- hydroxyphenanthrene was associated with 0.008-, 0.007-, 0.010-, or 0.010- unit decreased in ln-transformed levels of FPG, respectively (all p 0.05). We found 28 new CpG sites related to FPG (FDR0.05) through EWAS. Mediation analysis found that cg11350141 on AMER3 mediated 41.91% of the negative association of total urinary PAH metabolites with FPG. These results provide a new clue for the development of hypoglycemic agents.

The incidence rate of diabetes has been increasing every year in nearly all nations and regions. The traditional control of diabetes using transdermal insulin delivery by metal needles is generally associated with pain and potential infections. While microneedle arrays (MAs) have emerged as painless delivery techniques, the integration of MA systems with electronic devices to precisely control drug delivery has rarely been realized. In this study, we developed an iontophoresis-microneedle array patch (IMAP) powered by a portable smartphone for the active and controllable transdermal delivery of insulin. The IMAP in situ integrates iontophoresis and charged nanovesicles into one patch, achieving a one-step drug administration strategy of “penetration, diffusion and iontophoresis”. The MA of the IMAP is first pressed on the skin to create microholes and then is retracted, followed by the iontophoresis delivery of insulin-loaded nanovesicles through these microholes in an electrically controlled manner. This method has synergistically and remarkably enhanced controlled insulin delivery. The amount of insulin can be effectively regulated by the IMAP by applying different current intensities. This in vivo study has demonstrated that the IMAP effectively delivers insulin and produces robust hypoglycemic effects in a type-1 diabetic rat model, with more advanced controllability and efficiency than delivery by a pristine microneedle or iontophoresis. The IMAP system shows high potential for diabetes therapy and the capacity to provide active as well as long-term glycemic regulation without medical staff care. A device developed by researchers in China uses a microneedle array to efficiently and painlessly deliver precise doses of insulin and can be used by patients without help from medical staff. The new system was developed by a team led by Xi Xie and Lelun Jiang of Sun Yat-Sen University. The array of microneedles is pressed against the skin to create micro-holes and then automatically retracted. A mild electric current then drives charged nanovesicles carrying insulin through the holes. The circuit is powered and controlled via a smartphone, which can alter the intensity of the current to determine the dosage of insulin delivered. The team showed that the device effectively delivered insulin to a diabetic rat model with no obvious harmful effects. It thus offers a powerful tool for efficient, controllable, and convenient delivery of macromolecular drugs.

Medicinal plants have been known as a rich source of natural products (NPs). Due to their diverse chemical structures and remarkable pharmacological activities, NPs are regarded as important repertoires for drug discovery and development. Biebersteinia plant species belong to the Biebersteiniaceae family, and have been used in folk medicines in China and Iran for ages. However, the chemical properties, bioactivities and modes of action of the NPs produced by medicinal Biebersteinia species are poorly understood despite the fact that there are only four known Biebersteinia species worldwide. Here, we reviewed the chemical classifications and diversity of the various NPs found in the four known Biebersteinia species. We found that the major chemical categories in these plants include flavonoids, alkaloids, phenylpropanoids, terpenoids, essential oils and fatty acids. We also discussed the anti-inflammatory, analgesic, antibacterial, antioxidant, antihypertensive and hypoglycemic effects of the four Biebersteinia species. We believe that the present review will facilitate the exploration of traditional uses and pharmacological properties of Biebersteinia species, extraction of the NPs and elucidation of their molecular mechanisms, as well as the development of novel drugs based on the reported properties and mode-of-action.

The rhizome of Polygonatum kingianum has been used as a traditional medicine in China. In this study, a novel polysaccharides (PKPs-1) was isolated from P. kingianum and characterized by its molecular weight, primary structure. The hypoglycemic activity of PKPs-1was investigated by in vitro assay with the HepG2 cell line and in vivo test using STZ-induced diabetic mice. Results showed that the average molecular weight of PKPs-1 was 14.05 kDa and is composed mainly of glucose and mannose. Methylation analysis indicated that this polysaccharides fraction consisted mainly of β1,2-link glucose. Besides, PKPs-1 exhibited significant anti-hyperglycemic activity on STZ-induced mice, improved insulin tolerance, and affected the metabolism of serum lipids. Results of real-time quantitative PCR (RT-PCR) showed that PKPs-1 significantly increased the expression of insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), indicating that PKPs-1 regulates glucose metabolism by activating the PI3K/AKT signaling pathway. This study provides new insights for investigating the hypoglycemic effects of PKPs-1 and suggests that PKPs-1 could be a promising functional food or medicine for treating T2DM.

Qingzhuan tea (QZT), a post-fermented tea, has been reported to have anti-obesity and anti-hyperglycemic effects, perhaps due to bioactive compounds that inhibit lipase and α-amylase. It is unknown what chemical constituents’ changes and what bioactive compounds occur during the manufacture of QZT. The aim of this study was to determine the secondary metabolites changes that occur during post-fermentation and how these changes affect the ability of QZT to inhibit the activities of lipase and α-amylase. During the processing steps, metabolites levels and their inhibitory effects on lipase and α-amylase were assessed. Changes in content and activities suggested that the first turn over or the second turn over was critical for the formation and conversion of bioactive compounds responsible for the anti-obesity and hypoglycemic effects. The relationship between constituents and activities was further evaluated by correlation analysis, which showed that amino acids and flavonoids might be responsible for the anti-obesity and anti-hyperglycemic effects of QZT. This study clarified that compounds were altered during pile fermentation of QZT and tentatively identified the bioactive compounds formed during QZT manufacture.

Quinoa (Chenopodium quinoa Willd.) is native to the Andean region and has attracted a global growing interest due its unique nutritional value. The protein content of quinoa grains is higher than other cereals while it has better distribution of essential amino acids. It can be used as an alternative to milk proteins. Additionally, quinoa contains a high amount of essential fatty acids, minerals, vitamins, dietary fibers, and carbohydrates with beneficial hypoglycemic effects while being gluten-free. Furthermore, the quinoa plant is resistant to cold, salt, and drought, which leaves no doubt as to why it has been called the “golden grain”. On that account, production of quinoa and its products followed an increasing trend that gained attraction in 2013, as it was proclaimed to be the international year of quinoa. In this respect, this review provides an overview of the published results regarding the nutritional and biological properties of quinoa that have been cultivated in different parts of the world during the last two decades. This review sheds light on how traditional quinoa processing and products evolved and are being adopted into novel food processing and modern food products, as well as noting the potential of side stream processing of quinoa by-products in various industrial sectors. Furthermore, this review moves beyond the technological aspects of quinoa production by addressing the socio-economic and environmental challenges of its production, consumption, and marketizations to reflect a holistic view of promoting the production and consumption of quinoa., We acknowledge the EIT Food education program which provided the funds for an open access publication in the context of the winning prize for top students of the summer school “Food Tech Transitions: reconnecting agri-food, technology, and society” (project number 19162)., info:eu-repo/semantics/publishedVersion

The purpose of this study was to evaluate the effects of oral administration of cinnamon extract (CE) in rats fed on high fat diet (HFD). Thirty two adult male albino rats were divided into four groups; control group, HFD group, HFD group treated by cinnamon and the last group was treated with cinnamon extract. In HFD group, rats were fed on HFD for two months. In HFD group treated by cinnamon, rats fed on HFD for two months then CE was orally administered for a period of 4 weeks at a dose of 200 mg/kg body weight. In CE treated group, rats were fed on standard diet for two months then orally administered CE for a period of 4 weeks at a dose of 200 mg/kg body weight. The obtained results indicated that the oral administration of cinnamon extract has antihyperlipidemic effect that improving the lipid profile. There were reductions in the levels of serum triglycerides, LDL-C, VLDL-C (P≤ 0.01) and total cholesterol (P

The present investigation was undertaken to assess the hypoglycemic potential of Caesalpinia bonducella (C.bonducella) and Myristica fragrans (M.fragrans), employing various in vitro techniques. The extracts of seeds of C. bonducella and M. fragrans were studied for their effects on glucose adsorption capacity, in vitro glucose diffusion, in vitro amylolysis kinetics and glucose transport across the yeast cells. It was observed that the plant extracts under study adsorbed glucose and the adsorption of glucose increased remarkably with an increase in glucose concentration. There were no significant (p≤0.05) differences between their adsorption capacities. The results of amylolysis kinetic experimental model revealed that the rate of glucose diffusion was found to be increased with time from 30 to 180 min and both the plant extracts demonstrated significant inhibitory effects on movement of glucose into external solution across dialysis membrane as compared to control. Also, the plant extracts promoted glucose uptake by the yeast cells. It was observed that the enhancement of glucose uptake was dependent on both the sample and glucose concentration. C. bonducella extract exhibited significantly higher (p≤0.05) activity than the extract of M. fragrans at all concentrations. The results of the study verified the hypoglycemic activity of the extracts of C. bonducella and M. fragrans. However, the observed effects exhibited by the extracts of seeds of C. bonducella and M. fragrans need to be confirmed by using different in vivo models and clinical trials for their effective utilization as therapeutic agents in better management of diabetes mellitus.

To improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w emulsion-solvent evaporation method. The particle size of the NPs-Fc was approximately 30 nm larger than that of the unmodified NPs with polydispersity indices in a narrow range (PDIs; PDI in vivo imaging in live mice. Therefore, Fc-targeted nano-delivery systems show great promise for oral peptide/protein drug delivery.

The prevalence of natural health product (NHP) use in Canada is extensive. Patients with chronic diseases, including diabetes, use NHPs at a higher rate than the general population. Many NHPs exert hypoglycemic effects, among other effects relevant to diabetes management. To provide a practical, clinical review of NHPs with such effects targeted to pharmacists, a literature search was performed to collect data on the efficacy and safety profiles of 10 commonly used NHPs that exert antidiabetic properties. The following NHPs are included in this clinical review: alpha-lipoic acid, chromium, magnesium, bitter melon, cinnamon, fenugreek, gymnema, milk thistle, Reishi mushroom and white mulberry. Given the potential of NHPs to additively cause hypoglycemia when used concurrently with conventional medications, pharmacists should be up to date with current evidence around NHPs that may affect diabetes care to prevent adverse reactions and interactions. In addition, effective and respectful communication with patients around NHP use and collaboration with various health-care providers are essential in the patient care process.

Aim The aim of this study was to investigate the immediate effect of bitter gourd, Knol-khol, and ash gourd juices on blood glucose level among Type II diabetes mellitus patients. Methods In 2015, pilot study was conducted randomly enrolling 30 patients with type 2 diabetes mellitus into three groups in SRK college, India. The first group received bitter gourd juice at FBS range between 120 to 300 mg per dl. The second, third group received Knol-khol, ash gourd juice respectively in the same range of fasting blood sugar level. Blood sugar level was evaluated ½ hour interval till 2 h after received respective juices. Data were collected for statistical analysis. Results The mean blood glucose concentration in bitter gourd group was not statistically significant between time points, (P = .176). However, 90 min after the intake of bitter gourd juice shows statistical significant reduction of blood glucose level when compare with fasting level, (p = .049). After Knol khol juice the mean blood glucose level differed statistically significant between time points, shown in (p = .029). But no statistical changes seen in ash gourd group. As a result bitter gourd juice is immediately reducing the blood glucose level, while Knol khol juice reduces the blood sugar level gradually for longer period of 120 min. Conclusion This study shows the significance of hypoglycemic effects of bitter gourd and Knol khol juices among the type 2 Diabetic patients. Hence Bitter gourd juice, Knol khol juices may be beneficial in Diabetes patients to reduce the blood glucose level., Graphical abstract

Thiazolo[2, 3-f]purine derivatives and their analogs – dihydrothiazolo[2, 3-f]purine, 7-(thietan-3-yl)purine, and 8-(2-hydroxypropylthio)purine derivatives – were synthesized. The compounds synthesized here had no effects on protein glycation reactions using glucose; they gave weak inhibition of glycogen phosphorylase; they had no hemorheological activity. Substances with hypotensive activity greater than that of Dibazol were found. A number of substances had hypoglycemic effects greater than those of chlorpropamide and Adebit. Two compounds inhibited dipeptidylpeptidase-4, but were less active than reference agent vildagliptin.

Aim: A semisynthetic primary bile acid (PBA) has exerted hypoglycemic effects in Type 1 diabetic animals, which were hypothesized to be due to its anti-inflammatory and cellular glucose-regulatory effects. Thus, the research purpose aimed to examine antidiabetic effects of a PBA, in terms of cellular inflammation and survival and insulin release, in the context of supporting β-cell delivery and Type 1 diabetic treatment. Materials & methods: 10 formulations were prepared, five without PBA (control) and five with PBA (test). Formulations were used to microencapsulate pancreatic β cells and the microcapsules were examined for morphology, cell viability, insulin release and inflammation. Results & conclusion: PBA improved cell viability, insulin release and reduced inflammation in a formulation-dependent manner, which suggests potential use in cell delivery and diabetes treatment. [Formula: see text]

Graphical abstract, The recent discoveries in the fields of pathogenesis and management of diabetic nephropathy have revolutionized the knowledge about this disease. Little was added to the management of diabetic nephropathy after the introduction of renin angiotensin system blockers. The ineffective role of the renin- angiotensin system blockers in primary prevention of diabetic nephropathy in type 1 diabetes mellitus necessitated the search for other early therapeutic interventions that target alternative pathogenic mechanisms. Among the different classes of oral hypoglycemic agents, recent studies highlighted the distinguished mechanisms of sodium glucose transporter 2 blockers and dipeptidyl peptidase-4 inhibitors that settle their renoprotective actions beyond the hypoglycemic effects. The introduction of antioxidant and anti-inflammatory agents to this field had also added wealth of knowledge. However, many of these agents are still waiting well-designed clinical studies in order to prove their beneficial therapeutic role. The aim of this review of literature is to highlight the recent advances in understanding the pathogenesis, diagnosis, the established and the potential renoprotective therapeutic agents that would prevent the development or the progression of diabetic nephropathy.

Polygonum multiflorum (PM) has been used as a tonic edible plant and is a popular anti-ageing dietary supplement. Trans-2,3,5,4′-tetrahydroxystilbene 2-O-β-glucopyranoside (trans-THSG) is the major active compound in PM. It was found to have potent anti-inflammatory effects in RAW 264.7 macrophage cells and in TPA-induced mouse ear edema model. Research in the significance and rational of traditional process of post-harvested PM has been neglected. With the aid of modern analytical technology, we studied the major phytochemical transformation of PM solution from trans- to cis-THSG under UV light, reminiscent of traditional process, and further evaluated the hypoglycemic effects of the processed PM extract. In a high fat diet-induced type 2 diabetic mice model, processed PM extract containing cis- and trans-THSG (ratio = 2:3) exhibited significant hypoglycemic capacity, while pure trans-THSG and unprocessed PM extract (cis-/trans-THSG ratio = 1:20) did not, suggesting the importance of anti-diabetic effect of cis-THSG and PM natural process.

Objective The objective of the present investigation was to evaluate the hypoglycemic potential of Berberis aristata and Tamarindus indica using various in vitro techniques. Methods The selected plant extracts were studied for their effects on glucose adsorption capacity, in vitro glucose diffusion, in vitro amylolysis kinetics and glucose transport across the yeast cells. Results It was observed that both the plant extracts adsorbed glucose and the adsorption of glucose increased remarkably with an increase in glucose concentration. No significant (p ⩽ 0.05) differences were observed between the adsorption capacities of B. aristata and T. indica. The results of amylolysis kinetic experimental model exhibited that the rate of glucose diffusion was increased with time from 30 to 180 min and both the plant extracts demonstrated significant inhibitory effects on movement of glucose into external solution across dialysis membrane as compared to control. It was observed that the plant extracts also promoted glucose uptake by the yeast cells. Enhancement of glucose uptake was dependent on both the sample and glucose concentration. B. aristata extract exhibited significantly higher (p ⩽ 0.05) activity than the extract of T. indica at all concentrations. Conclusion The results of the study verified the hypoglycemic activity of the extracts of B. aristata and T. indica. However, the observed effects need to be confirmed using different in vivo models and clinical trials for their effective utilization as therapeutic agents.

To summarize current hotspots and predict the potential trends in traditional drugs of diabetes treatment for further research. Publications on the application of traditional drugs in diabetes treatment were searched from PubMed without language limits. Highly frequent MeSH terms were identified through Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). Biclustering analysis results were visualized utilizing the gCLUTO software. Finally, a strategic diagram was generated. Totally 2,386 relevant publications were obtained from PubMed on November 9th, 2018, and 69 highly frequent MeSH terms were identified. Biclustering analysis revealed that these highly frequent MeSH terms were classified into 7 clusters. After calculating the density and centrality of each cluster, strategy diagram was presented. Cluster 0 “Chinese medicine monomers such as antioxidant and hypoglycemic effects” was considered as the most potential research hotspot. In this study, we found 7 topics related to the application of traditional drugs in diabetes treatment. The molecular mechanisms of Chinese medicine monomers in diabetes could become a potential hotspot with high centricity and low density.

Morus alba L. is an edible fruit with multiple medical function. To reveal the geographic variation pattern of polysaccharide content in the mulberry fruits and its antioxidant and hypoglycemic activities, the fruit samples were collected and analyzed from seven geographic locations throughout the distribution areas in China. The polysaccharide content in the mulberry fruits ranged from 4.13 ± 0.04% to 1.07 ± 0.07%. All the polysaccharides derived from mulberry fruit showed certain antioxidant and hypoglycemic activities with a significant variation. Significant differences were observed among polysaccharide content, antioxidant activity, and sunshine hours, but no clear geographical or polysaccharide content variation patterns were observed for hypoglycemic activity. Pearson correlation analysis indicated that the annual average sunshine hours was significantly correlated to the polysaccharide content and antioxidant activity. According to the polysaccharide contents and bioactivities, certain natural populations of M. alba L. such as Xinjiang, Hunan, and Anhui were recommended for food and medical use in future. PRACTICAL APPLICATIONS: Morus alba L. belonging to the family Moraceae, is cultivated across an extensive range of geographical, climatic, and soil conditions. Polysaccharides from mulberry fruit have been proved to have the function of enhancing immunity, antiaging, anti‐inflammatory, antioxidant, hypolipidemic, and hypoglycemic effects with no toxic record in clinic. It has been reported that the phytochemicals accumulation in plants is greatly affected by genetic, climatic, and harvesting factors during the growing period. We revealed the geographic variation pattern of polysaccharide content in the mulberry fruits and its antioxidant activity. Based on the polysaccharide contents and bioactivities, certain natural populations of M. alba L. such as Xinjiang, Hunan, and Anhui were recommended for food and medical use in future. The information obtained by this study could be useful for the selection of natural populations with adequate polysaccharide content, as well as high food and medical use for M. alba L.

Hepatic-directed insulin utilizes a hepatocyte-targeting moiety passively attaching free insulin, improving subcutaneous insulin’s hepatic biodistribution. We assessed injections of HDV-insulin lispro (HDV-L) vs. insulin lispro (LIS) in T1DM in a 26-week, multicenter, randomized, double-blind trial of 176 subjects (randomized 2:1 HDV-L:LIS) with A1C 7.0-10.5% treated with basal insulin glargine or degludec. Primary objective was HDV-L A1C non-inferiority (prespecified margin 0.4%). Mean A1C change to week 26 was -0.09% (HDV-L) and -0.16% (LIS), (estimated treatment difference, HDV-L - LIS: +0.09% [95% CI -0.18 to 0.35]), confirming HDV-L non-inferiority. A1C status modified treatment group effect on “severe” hypoglycemia (subjectively categorized by investigators as “mild,” “moderate,” “severe,” or “life threatening”) incidence (interaction p-value Disclosure D.C. Klonoff: Consultant; Self; EOFlow, Lifecare, Inc., Merck & Co., Inc., Novo Nordisk A/S, Roche Diagnostic USA, Voluntis USA. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. N.J. Cohen: None. W. Geho: Board Member; Self; Diasome Pharmaceuticals, Inc. D.B. Muchmore: Consultant; Self; ADOCIA, Capillary Biomedical, Inc., Diasome Pharmaceuticals, Inc., Zucara Therapeutics Inc. Stock/Shareholder; Self; Capillary Biomedical, Inc., Diasome Pharmaceuticals, Inc. Funding JDRF