Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action.

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO's effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC50 = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC50 = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.

Selective extraction of galactomannan from fenugreek (Trigonella foenum-graecum L.) seed husk and its enzyme inhibitory potential associated with hyperglycaemia.

BACKGROUND: Fenugreek seeds host various bioactive compounds, and galactomannan (GM) is a significant soluble fibre. In this study, selective extraction is adapted to extract fenugreek seed GM to improvise the yield recovery. The seeds are fractionated, separated and classified as husk and cotyledons. Comparative studies have been performed to evaluate the crude and pure GM yield between different groups such as the whole seed, and the classified fractions. Characterization is done using Fourier transform infrared, differential scanning calorimetry, scanning electron microscopy, monosaccharide composition and optical density, and the structure is elucidated through nuclear magnetic resonance. The GM obtained through extraction is used to study its enzyme inhibitory property associated with hyperglycaemia. RESULTS: GM yield extracted from the husk is highly significant compared to other groups. Crude GM and pure GM yield was 2 and 3.25 times higher than that obtained through whole seed samples. The characterization of the pure GM is on a par with the existing reports. The purified GM inhibited α-amylase and α-glucosidase enzymes in vitro, with an IC50 of 21.08 ± 0.085 and 67.17 ± 5.15 µg mL-1 , respectively. CONCLUSION: Selective extraction prompts enhancement in the recovery of the bioactive compound, minimal use of resources, and promotes industrial viability. Characterization of the compound confirms the structure. Its enzyme inhibitory property makes GM a valuable compound in diabetic prevention/treatment. © 2021 Society of Chemical Industry.

Ameliorative effect of phosphodiesterase 4 and 5 inhibitors in deoxycorticosterone acetate-salt hypertensive uni-nephrectomized KKAy mice.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). Hypertension increases kidney stress, which deteriorates function, and leads to peripheral renal vascular resistance. Long-term hypoperfusion promotes interstitial fibrosis and glomerular sclerosis, resulting in nephrosclerosis. Although hypertension and DN are frequent ESRD complications, relevant animal models remain unavailable. We generated a deoxycorticosterone acetate (DOCA)-salt hypertensive uni-nephrectomized (UNx) KKAy mouse model demonstrating hypertension, hyperglycemia, cardiac hypertrophy, kidney failure, increased urinary albumin creatinine ratio (UACR), and increased renal PDE4D and cardiac PDE5A mRNA levels. We hypothesized that the novel PDE4 selective inhibitor, compound A, and PDE5 inhibitor, sildenafil, exhibit nephroprotective, and cardioprotective effects in this new model. Compound A, sildenafil, and the angiotensin II receptor blocker, irbesartan, significantly reduced ventricular hypertrophy and pleural effusion volume. Meanwhile, compound A and sildenafil significantly suppressed the UACR, urinary kidney injury molecule-1, and monocyte chemoattractant protein-1 levels, as well as that of renal pro-fibrotic marker mRNAs, including collagen 1A1, fibronectin, and transforming growth factor-beta (TGF-ß). Moreover, compound A significantly suppressed TGF-ß-induced pro-fibrotic mRNA expression in vitro in all major kidney lesions, including within the glomerular mesangial region, podocytes, and epithelial region. Hence, PDE4 and PDE5 inhibitors may be promising treatments, in combination with irbesartan, for DN with hypertension as they demonstrate complementary mechanisms.

Proinflammatory cytokines trigger biochemical and neurochemical changes in mouse retinal explants exposed to hyperglycemic conditions.

Purpose: Diabetic retinopathy (DR) is one of the most frequent complications of diabetes affecting the retina and eventually causing vision impairment. Emerging evidence suggests that inflammation plays a vital role in DR progression. In this study, we evaluated the early biochemical and neurochemical changes in mouse retinal explants to understand the contribution of proinflammatory cytokines to disease progression. Methods: DR was modeled in vitro by incubating mouse retinal explants in a physiological buffer supplemented with high glucose and the proinflammatory cytokines TNF-α and IL-1ß. Key metabolites of retinal energy metabolism, including glucose, lactate, ATP, glutamate, glutamine, and enzymes supporting retinal ATP levels were assessed 40 min after the application of high glucose and proinflammatory cytokines. As retinal energy metabolism is tightly coupled to retinal neurochemistry, we also determined the short-term effect on the amino acid distribution of glutamate, gamma aminobutyric acid (GABA), glutamine, and glycine. Results: The results indicated that the combined application of high glucose and proinflammatory cytokines increased retinal glucose, lactate, and ATP levels, and decreased retinal glutamate, without affecting glutamine levels or the enzymes supporting ATP levels. Moreover, we observed a statistically significant increase in ATP and glutamate release. Correspondingly, statistically significant alterations in amino acid distribution were observed in retinal explants coexposed to high glucose and proinflammatory cytokines. Conclusions: These data suggest that short-term exposure to proinflammatory cytokines contributes to the early biochemical and neurochemical changes caused by hyperglycemia, by affecting retinal energy metabolism and amino acid distribution. These data are consistent with the idea that early intervention to prevent inflammation-triggered loss of metabolic homeostasis in patients with diabetes is necessary to prevent DR progression.

Identification of α-glucosidase inhibitors from cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking.

Leaves of Cyclocarya paliurus (CP) have a potential antihyperglycemic effect, but its active compositions responsible for the beneficial properties remain unclear. The CP extract exhibited remarkable α-glucosidase inhibitory activity with an IC50 value of 31.5 ± 1.05 µg mL-1, much lower than that of the positive control acarbose (IC50 = 296.6 ± 1.06 µg mL-1). To identify the specific α-glucosidase inhibitors from the CP extract, affinity ultrafiltration coupled with ultra-performance liquid chromatography and quadrupole-time-of-flight mass spectrometry (UF-UPLC-Q/TOF-MS/MS) was developed and 11 potential α-glucosidase inhibitors from CP extract were identified. In vitro α-glucosidase inhibitory assay verified that quercetin-3-O-glucuronide, kaempferol-3-O-rhamnoside, quercetin, kaempferol, asiatic acid and genistein were primarily responsible for the α-glucosidase inhibitory activity of the CP extract. Further, a hypoglycemia test also verified that these α-glucosidase inhibitors had the potential to reduce post-prandial hyperglycaemia in C57BL/6 mice. Moreover, the molecular docking study revealed that these identified α-glucosidase inhibitors more easily occupy the active sites of α-glucosidase than does the positive control acarbose. These findings suggest the CP tea leaves are the potential source of a hypoglycaemic agent.

Resveratroloside Alleviates Postprandial Hyperglycemia in Diabetic Mice by Competitively Inhibiting α-Glucosidase.

The regulation of postprandial blood glucose (PBG) levels is an effective therapeutic method to treat diabetes and prevent diabetes-related complications. Resveratroloside is a monoglucosylated form of stilbene that is present in red wine, grapes, and several traditional medicinal plants. In our study, the effect of resveratroloside on reducing PBG was studied in vitro and in vivo. In comparison to the starch treatment alone, the oral administration of resveratroloside-starch complexes significantly inhibited the PBG increase in a dose-dependent pattern in normal and diabetic mice. The PBG level treated with resveratrol (30 mg/kg) was not lower than that of resveratroloside. Further analyses demonstrated that resveratroloside strongly and effectively inhibited α-glucosidase, with an 50% inhibitory concentration value of 22.9 ± 0.17 µM, and its inhibition was significantly stronger than those of acarbose and resveratrol (264 ± 3.27 and 108 ± 2.13 µM). Moreover, a competitive inhibition mechanism of resveratroloside on α-glucosidase was determined by enzyme kinetic assays and molecular docking experiments. The molecular docking of resveratroloside with α-glucosidase demostrated the competitive inhibitory effect of resveratroloside, which occupies the catalytic site and forms strong hydrogen bonds with the residues of α-glucosidase. Resveratrol was also determined to be a competitive inhibition mechanism on α-glucosidase by enzyme kinetic assays and molecular docking experiments. This study suggested that resveratroloside had the ability to regulate PBG levels and can be considered a potential agent for the treatment of diabetes mellitus.

Secondary metabolite profiling, cytotoxicity, anti-inflammatory potential and in vitro inhibitory activities of Nardostachys jatamansi on key enzymes linked to hyperglycemia, hypertension and cognitive disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Nardostachys jatamansi (D. Don) DC., 'Spikenard' or 'Jatamansi', a highly valued, aromatic herb from alpine Himalayas has a long history of use as ethnomedicine and dietary supplements in Ayurveda, Unani and Chinese system of medicine since Vedic ages (1000-800 BC). In Ayurveda and traditional system of medicine, the species is used as stimulant, sedative, brain tonic or mind rejuvenator, antidiabetic, cardio tonic, and in the treatment of various neurological disorders such as insomnia, epilepsy, hysteria, anxiety and depression. It is considered as Sattvic herb in Ayurveda and is now commercially marketed either as single or poly-herbal formulations by many companies in national and international markets. AIM OF THE STUDY: The species has become threatened in its natural habitats due to over exploitation and illegal trade of its rhizomes for drug preparation in herbal and pharmaceutical industries. Considering the increasing demand and tremendous medicinal importance of this threatened plant species, a detailed study was undertaken to evaluate its antioxidant potential, secondary metabolite profiling, cytotoxicity, anti-inflammatory potential and in vitro enzyme inhibitory activities on key enzymes linked to hyperglycemia, hypertension and cognitive disorders in different plant parts of wild and in vitro-raised plants with respect to different solvent systems for its sustainable utilization. MATERIALS AND METHODS: Anti-cholinesterase activity of leaves and rhizome of wild and cultured plant extracts was investigated against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. In vitro anti-hyperglycemic (α-amylase and PTP1B), anti-hypertensive (angiotensin-converting enzyme), anti-tyrosinase and anti-inflammatory potential (5-lipoxygenase and hyaluronidase) of different plant parts of wild and in vitro-raised plants with respect to different solvent systems were also evaluated. In vitro cytotoxic effect of rootstock extracts of wild and in vitro-derived plants were against cancer (HCT-116, MCF-7 and OE33) and two normal (HEK and MEF) cell lines. Secondary metabolite profiling of rhizome segments of wild and in vitro-derived plants was carried out by quantitative gas chromatography-mass spectrometry (GC-MS). RESULTS: In vitro-raised plantlets showed comparative higher yield of various secondary metabolites with a significantly high antioxidant activity as compared to the wild plants. Methanolic rootstock extracts of both wild and in vitro-derived plants of N. jatamansi exhibited significant AChE (IC50 36.46 ±â€¯2.1 and 31.18 ±â€¯2.6 µg/ml, respectively) and BuChE (IC50 64.6 ±â€¯3.5 and 60.12 ±â€¯3.6 µg/ml, respectively) inhibitory potential as compared to standard inhibitor galanthamine (IC50 0.94 ±â€¯0.03 and 4.45 ±â€¯0.5 µg/ml). Methanolic rootstock extract of in vitro-derived plants showed significant α-amylase (IC50 90.69 ±â€¯2.1 µg/ml), PTP1B (IC50 24.56 ±â€¯0.8 µg/ml), angiotensin-converting enzyme (IC50 42.5 ±â€¯3.6 µg/ml) and tyrosinase (IC50 168.12 ±â€¯3.6 µg/ml) inhibitory potential as compared to standard acarbose (IC50 52.36 ±â€¯3.1 µg/ml), ursolic acid (IC50 5.24 ±â€¯0.8 µg/ml), captopril (IC50 32.36 ±â€¯2.5 µg/ml) and kojic acid (IC50 = 54.44 ±â€¯2.3 µg/ml). Both the methanolic rootstock and leaf extracts of tissue culture-derived plants exhibited promising anti-5-LOX and anti-hyaluronidase activities against the known inhibitor of 5-LOX and hyaluronidase. Furthermore, methanolic rootstock extracts of both wild and in vitro-derived plants exhibited promising cytotoxic effects to HCT-116, MCF-7 and OE33 cell lines as compared to the normal HEK and MEF after 12 h of treatment. Secondary metabolite profiling of wild and in vitro-derived plants by quantitative GC-MS analysis revealed the presence of different classes of terpenoids and phenolic acids might be responsible for its effective biological activities. CONCLUSION: In vitro-derived plants revealed a substantial anti-cholinesterases, anti-hyperglycemic anti-inflammatory, anti-hypertensive and anti-tyrosinase potential with higher yield of various bioactive metabolites and significantly higher antioxidant activity which substantially explain medicinal importance of N. jatamansi in traditional medicine, used for centuries in different Ayurvedic formulations. The present findings suggest that cultured plants could be a promising alternative for the production of bioactive metabolites with comparative biological activities to the wild plants.

Inhibitory Effects of Siegesbeckia orientalis Extracts on Advanced Glycation End Product Formation and Key Enzymes Related to Metabolic Syndrome.

Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase, pancreatic lipase and angiotensin I-converting enzyme (ACE). This study used an in vitro approach to assess the potential of four extracts of Siegesbeckia orientalis linne on key enzymes relevant to metabolic syndrome. In this research, S. orientailis was firstly extracted by ethanol. The ethanol extract (SE) was then partitioned sequentially with hexane, ethyl acetate and methanol, and these extracts were named SE-Hex, SE-EA and SE-MeOH, respectively. The experimental results showed that SE-EA had the highest total phenolic content (TPC, 76.9 ± 1.8 mg/g) and the total flavonoids content (TFC, 5.3 ± 0.3 mg/g). This extract exhibited the most significant antioxidant activities, including DPPH radical-scavenging capacity (IC50 = 161.8 ± 2.4 µg/mL), ABTS radical-scavenging capacity (IC50 = 13.9 ± 1.5 µg/mL) and reducing power. For anti-glycation activities, SE-EA showed the best results in the inhibition of AGEs, as well as inhibitory activities against α-glucosidase (IC50 = 362.3 ± 9.2 µg/mL) and α-amylase (IC50 = 119.0 ± 17.7 µg/mL). For anti-obesity activities, SE-EA indicated the highest suppression effect on pancreatic lipase (IC50 = 3.67 ± 0.52 mg/mL). Finally, for anti-hypertension activity, SE-EA also demonstrated the strongest inhibitory activity on ACE (IC50 = 626.6 ± 15.0 µg/mL). Close relationships were observed among the parameters of TPC, antioxidant activities, inhibitory activities on α-amylase, α-glucosidase, lipase and ACE (R > 0.9). Moderate correlations were found among the parameters of TFC, antioxidant activities, and suppression of dicarbonyl compounds formation (R = 0.5-0.9). Taken together these in vitro studies reveal the therapeutic potential of SE-EA extract in the prevention and treatment of metabolic disorders.

Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation.

Hyperglycemia leads to diabetes and its diabetic complications. In this study, we investigated the synergistic effects of luteolin and fisetin on proinflammatory cytokine secretion and its underlying epigenetic regulation in human monocytes exposed to hyperglycemic (HG) concentrations. Human monocytic cells (THP-1) were cultured under controlled (14.5 mM mannitol), normoglycemic (5.5 mM glucose), or HG (20 mM glucose) conditions in the absence or presence of the two phytochemicals for 48 h. Whereas HG conditions significantly induced histone acetylation, nuclear factor-kappa B (NF-κB) activation, interleukin 6, and tumor necrosis factor-α release from THP-1 cells; combination treatments with the two phytochemicals (500 nM fisetin, and l µM and 500 nM luteolin) suppressed NF-κB activity and inflammatory cytokine release. Fisetin, luteolin, and their combination treatments also significantly decreased the activity of histone acetyltransferase, a known NF-κB coactivator; inhibited reactive oxygen species production; and activated sirtuin (SIRT)1 and forkhead box O3a (FOXO3a) expressions (P < .05). Thus, combination treatments with the two phytochemicals inhibited HG condition-induced cytokine production in monocytes, through epigenetic changes involving NF-κB activation. We, therefore, suggest that combination treatments with luteolin and fisetin may be a potential candidate for the treatment and prevention of diabetes and its complications.

Effect of solvents extraction on phytochemical components and biological activities of Tunisian date seeds (var. Korkobbi and Arechti).

BACKGROUND: The interest in natural antioxidants, especially polyphenols, is growing more and more thanks to their positive contribution to human health. Thus, the prevention from the harmful action of oxidative stress which has been involved in many diseases such as cancer, inflammation diabetes, and cardiovascular illness. Recent research proved the bioactive compounds richness of date seeds which could be a good biological matrix of natural antioxidants. Unfortunately, an important quantity of Tunisian dates seed is discarded yearly. METHODS: In this study, different solvents extraction (water, methanol, absolute acetone and aqueous acetone 80%) were used and the evaluation of its effect on phytochemical level, in vitro antioxidant activities, in vitro hyperglycemia key enzymes inhibition and in vivo anti-inflammatory proprieties were established for Tunisian date seeds. RESULTS: The result revealed that the polar solvent exhibited the highest amount of bioactive compounds. The correlation between polyphenol compounds and the antioxidant potentiality explains the powerful effect of used polar solvents on inflammation, TBARS and hyperglycemia inhibition. Furthermore, it showed its higher capacity to scavenge radicals. CONCLUSIONS: Therefore, this big waste of Tunisian seeds could be used as cheap source of natural antioxidant compounds which are considered as a health challenge for the poor countries.

The chemical profiling of loquat leaf extract by HPLC-DAD-ESI-MS and its effects on hyperlipidemia and hyperglycemia in rats induced by a high-fat and fructose diet.

In this study, the inhibitory effects of loquat leaf extract (LLE) on pancreatic α-amylase and α-glucosidase, and the preventative effects of LLE on hyperlipidemia and hyperglycemia in rats induced by a high fat and fructose diet have been evaluated. The LLE was chemically described using a high performance liquid chromatography-diode array detector coupled with a mass spectrometer (HPLC-DAD-MS/MS). 20 compounds including phenolic acids, flavonoids and triterpene acids were tentatively identified with authentic compounds or by referring to published articles and accessible databases (e.g. MassBank, METLIN). Enzyme activity measurements showed that the IC50 values of the LLE on α-amylase and α-glucosidase were 11.34 ± 1.04 mg mL-1 and 50.77 ± 1.04 µg mL-1, respectively. The calculated Michaelis-Menten constants indicated that the LLE is an effective inhibitor against α-glucosidase in a mixed-model competitive mode. The fluorescence data revealed that the LLE binds with α-amylase and α-glucosidase. The animal experiment results indicated that the LLE significantly decreased the levels of fasting blood glucose, and hepatic and serum triglycerides.

Natural Prenylchalconaringenins and Prenylnaringenins as Antidiabetic Agents: α-Glucosidase and α-Amylase Inhibition and in Vivo Antihyperglycemic and Antihyperlipidemic Effects.

Inhibition of α-glucosidase and α-amylase decreases postprandial blood glucose levels and delays glucose absorption, making it a treatment strategy for type 2 diabetes. This study examined in vivo and in vitro antidiabetic activities of natural prenylchalconaringenins 1 and 2 and prenylnaringenins 3 and 4, found in hops and beer. 3'-Geranylchalconaringenin (2) competitively and irreversibly inhibited α-glucosidase (IC50 = 1.08 µM) with activity 50-fold higher than that of acarbose (IC50 = 51.30 µM) and showed moderate inhibitory activity against α-amylase (IC50 = 20.46 µM). Docking analysis substantiated these findings. In addition, compound 2 suppressed the increase in postprandial blood glucose levels and serum levels of total cholesterol and triglycerides in streptozotocin-induced diabetic mice. Taken together, these results suggest that 2 has dual inhibitory activity against α-glucosidase and α-amylase and alleviates diabetic hyperglycemia and hyperlipidemia, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

Germinated Pigmented Rice (Oryza Sativa L. cv. Superhongmi) Improves Glucose and Bone Metabolisms in Ovariectomized Rats.

The effect of germinated Superhongmi, a reddish brown pigmented rice cultivar, on the glucose profile and bone turnover in the postmenopausal-like model of ovariectomized rats was determined. The ovariectomized Sprague-Dawley rats were randomly divided into three dietary groups (n = 10): normal control diet (NC) and normal diet supplemented with non-germinated Superhongmi (SH) or germinated Superhongmi (GSH) rice powder. After eight weeks, the SH and GSH groups showed significantly lower body weight, glucose and insulin concentrations, levels of bone resorption markers and higher glycogen and 17-ß-estradiol contents than the NC group. The glucose metabolism improved through modulation of adipokine production and glucose-regulating enzyme activities. The GSH rats exhibited a greater hypoglycemic effect and lower bone resorption than SH rats. These results demonstrate that germinated Superhongmi rice may potentially be useful in the prevention and management of postmenopausal hyperglycemia and bone turnover imbalance.

Russelioside B, a pregnane glycoside ameliorates hyperglycemia in streptozotocin induced diabetic rats by regulating key enzymes of glucose metabolism.

An alternative strategy to treat diabetes mellitus is the use of various natural agents possessing hypoglycemic effect. Caralluma quadrangula has been used in Saudi traditional medicine in cases of thirst and hunger and for the treatment of diabetes. The present study was designed to evaluate the improving effect of russelioside B, a pregnane glycoside isolated from Caralluma quadrangula on glucose metabolism in the liver of streptozotocin-induced diabetic rats. Diabetes mellitus was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Experimental rats were administered russelioside B at a dose of 50 mg/kg body weight once a day for 30 days. The results showed that RB improved the fasting serum glucose level, glycated hemoglobin percent, serum insulin level and lipid profile. A significant improvement was observed upon the administration of russelioside B on the activities of the key enzymes of carbohydrate metabolism (glucokinase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and glycogen phosphorylase) in the liver of diabetic rats. Further, russelioside B administration to diabetic rats reverted gene expression of glucokinase, glucose-6-phosphatase, glycogen synthase and glycogen synthase kinase-3ß to near normal levels. In conclusion, russelioside B possess antidiabetic and antihyperlipidemic effect in streptozotocin induced diabetic rats. Hence, administration of russelioside B may represent a potentially useful strategy for the management of diabetes.

Trans-anethole, a terpenoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats.

Trans-anethole (TA), a terpenoid and a principle constituent of many essential oils from medicinal plants possess hypoglycemic and antioxidant activities. This study was undertaken to explore beneficial effects of TA on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced type 2 diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg BW). TA was administered to diabetic rats at a dose of 20, 40 and 80 mg/kg BW for 45 days. However, the dose at 80 mg/kg BW, resulted in a significant reduction in the levels of plasma glucose, glycosylated haemoglobin (HbA1c) and increase in the levels of insulin and haemoglobin (Hb). Upon administration of TA, the altered levels of liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase) and gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) in the liver and kidney of diabetic rats significantly reverted to near normal levels. In addition to this, TA also improved the hepatic and muscle glycogen content in diabetic rats. The histological studies showed the ameliorative effect of TA on the ß-cells of pancreas in diabetic rats. The results were compared with glibenclamide, a standard oral hypoglycemic drug. These encouraging findings suggest that TA may be used as a propitious bioactive compound in the development of therapeutic agents against type 2 diabetes mellitus.

X-3, a mangiferin derivative, stimulates AMP-activated protein kinase and reduces hyperglycemia and obesity in db/db mice.

Diabetes mellitus is a major health concern, affecting nearly 10% of the population. Here we describe a potential novel therapeutic agent for this disease, X-3, a derivative of mangiferin. Therapeutic administration of X-3 significantly and dose-dependently reduced plasma glucose and triglycerides in db/db mice following 8 week-treatments. Treatment with X-3 dose-dependently increased the number of insulin-positive ß-cell mass. Importantly, X-3 did not cause any death or signs of toxicity in acute toxicity studies. Study of mechanism of action revealed that X-3 increased glucose uptake in parallel with increased phosphorylation of AMP-activated protein kinase (AMPK) in 3T3-L1 cells. It activates AMPK in both LKB1-dependent and -independent manner. Furthermore, administration of X-3 resulted in activation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in the hypothalamus, liver, muscle and adipose tissues of C57BL/6 mice. An 80 mg/kg X-3 was more potent than metformin at 500 mg/kg in the hypothalamus, and interscapular fat tissues, potent than MF at the same dose in the liver. Thus, we conclude that X-3 is a promising new class of AMPK activating drug, and can potentially be used in the treatment of type 2 diabetes.

Phytochemical profile, antioxidative and anti-inflammatory potentials of Gynura bicolor DC.

BACKGROUND: The phytochemical composition of aqueous and ethanol extracts from Gynura bicolor DC., a vegetable, was determined. Human umbilical vein endothelial (HUVE) cells were used to examine the antioxidative and anti-inflammatory potentials of these extracts at 1, 2 or 4% (v/v) against high-glucose-induced injury. RESULTS: Both aqueous and ethanol extracts contained phenolic acids, flavonoids, carotenoids and anthocyanins in the ranges 1428-1569, 1934-2175, 921-1007 and 2135-2407 mg per 100 g dry weight respectively. Both extracts were rich in quercetin, lutein, malvidin and pelargonidin. Addition of these extracts at test doses decreased reactive oxygen species formation, preserved glutathione content and retained glutathione peroxide and catalase activities in high-glucose-treated HUVE cells (P < 0.05). Treatments with these extracts at 2 and 4% lowered interleukin-6, tumor necrosis factor-alpha and prostaglandin E2 production and reduced cyclooxygenase-2 activity (P < 0.05). CONCLUSION: These findings suggest that this vegetable could be considered as a functional food and might provide antioxidative and anti-inflammatory protection.

Effect of walnut oil on hyperglycemia-induced oxidative stress and pro-inflammatory cytokines production.

PURPOSE: In this study, we focused on the effect of hyperglycemia on the generation of reactive oxygen species and on the release of pro-inflammatory cytokines in the human monocytic cell line (U937). We also monitored potential anti-inflammatory effects of walnut oil as well as its protective effect against oxidative damage to biopolymers (DNA and proteins). METHODS: We cultured U937 cells under normoglycemic or hyperglycemic conditions for 72 h, in the absence or presence of walnut oil. We detected cell proliferation by the MTT test. To determine the antioxidant status of cells, we used the trolox equivalent antioxidant capacity method. We determined the activity of superoxide dismutase (SOD) spectrophotometrically, the oxidative damage to DNA by an enzyme-modified comet assay, and the oxidative damage to proteins by the marker-protein carbonyls and the levels of pro-inflammatory cytokines by the ELISA method. RESULTS: Hyperglycemia reduced the antioxidant capacity of cells, induced oxidative damage to DNA, and increased the release of pro-inflammatory cytokines. It had no effect on cell proliferation, SOD activity, nor oxidative damage to proteins. Walnut oil significantly increased the antioxidant capacity of cells as well as SOD activity on the second and third day of incubation, but had no effect on cell proliferation and showed no protective effect against oxidative damage to DNA and proteins. The walnut oil showed both anti-inflammatory and pro-inflammatory properties depending on its concentration and time of its incubation with the monocytic cell line. CONCLUSION: Our in vitro results indicate that walnut oil can diminish oxidative stress with its antioxidant properties. However, we could not confirm its protective effect against oxidative damage to DNA and proteins.

Impact of processing on the phenolic profiles of small millets: evaluation of their antioxidant and enzyme inhibitory properties associated with hyperglycemia.

The effects of germination, steaming and microwave treatments of whole grain millets (barnyard, foxtail and proso) on their phenolic composition, antioxidant activities and inhibitory properties against α-amylase and α-glucosidase were investigated. Compositional analysis of phenolics by HPLC revealed that vanillic and ferulic acids were the principal phenolic acids and kaempferol was the predominant flavonoid found in raw millets. Different processing treatments brought about relevant changes in the composition and content of certain phenolic acids and flavonoids in processed millets. Phenolic extracts of raw and processed millets exhibited multiple antioxidant activities and are also potent inhibitors of α-amylase and α-glucosidase. In general, germinated millets showed highest phenolic content as well as superior antioxidant and enzyme inhibitory activities. These results suggest that germinated millet grains are potential source of phenolic antioxidants and also great sources of strong natural inhibitors for α-amylase and α-glucosidase.

Aqueous extract of Annona macroprophyllata: a potential α-glucosidase inhibitor.

Annona genus contains plants used in folk medicine for the treatment of diabetes. In the present study, an aqueous extract prepared from Annona macroprophyllata (Annonaceae, also known as A. diversifolia) leaves was evaluated on both the activity of yeast α -glucosidase (an in vitro assay) and sucrose tolerance in Wistar rats. The results have shown that the aqueous extract from A. macroprophyllata inhibits the yeast α -glucosidase with an IC50 = 1.18 mg/mL, in a competitive manner with a K(i) = 0.97 mg/mL, a similar value to that of acarbose (K(i) = 0.79 mg/mL). The inhibitory activity of A. macroprophyllata was reinforced by its antihyperglycemic effect, at doses of 100, 300, and 500 mg/kg in rats. Chromatographic analysis identified the flavonoids rutin and isoquercitrin in the most polar fractions of A. macroprophyllata crude extract, suggesting that these flavonoids are part of the active constituents in the plant. Our results support the use of A. macroprophyllata in Mexican folk medicine to control postprandial glycemia in people with diabetes mellitus, involving active constituents of flavonoid nature.