A phlorotannin constituent of Ecklonia cava alleviates postprandial hyperglycemia in diabetic mice

Context: 2,7″-Phloroglucinol-6,6′-bieckol is a type of phlorotannin isolated from brown algae, Ecklonia cava Kjellman (Phaeophyceae; Laminareaceae). 2,7″-Phloroglucinol-6,6′-bieckol mediates antioxidant activities. However, there has been no research on improving postprandial hyperglycaemia using 2,7″-phloroglucinol-6,6′-bieckol.

Objective: This study investigated the inhibitory effects of 2,7″-phloroglucinol-6,6′-bieckol on activities of α-glucosidase and α-amylase as well as its alleviating effect on postprandial hyperglycaemia in streptozotocin-induced diabetic mice.

Materials and methods: α-Glucosidase and α-amylase inhibitory assays were carried out. The effect of 2,7″-phloroglucinol-6,6′-bieckol on hyperglycaemia after a meal was measured by postprandial blood glucose in streptozotocin-induced diabetic and normal mice. The mice were treated orally with soluble starch (2?g/kg BW) alone (control) or with 2,7″-phloroglucinol-6,6′-bieckol (10?mg/kg bw) or acarbose (10?mg/kg BW) dissolved in 0.2?mL water. Blood samples were taken from tail veins at 0, 30, 60, and 120?min and blood glucose was measured by a glucometer.

Results: 2,7″-Phloroglucinol-6,6′-bieckol showed higher inhibitory activities than acarbose, a positive control against α-glucosidase and α-amylase. The IC₅₀ values of 2,7″-phloroglucinol-6,6′-bieckol against α-glucosidase and α-amylase were 23.35 and 6.94?μM, respectively, which was found more effective than observed with acarbose (α-glucosidase IC₅₀ of 130.04?μM; α-amylase IC₅₀ of 165.12?μM). In normal mice, 2,7″-phloroglucinol-6,6′-bieckol significantly suppressed the postprandial hyperglycaemia caused by starch. The 2,7″-phloroglucinol-6,6′-bieckol administration group (2349.3?mmol·min/L) had a lower area under the curve (AUC) glucose response than the control group (2690.83?mmol·min/L) in diabetic mice.

Discussion and conclusion: 2,7″-Phloroglucinol-6,6′-bieckol might be used as an inhibitor of α-glucosidase and α-amylase as well as to delay absorption of dietary carbohydrates.     

Bioassay-guided fractionation and identification of α-amylase inhibitors from Syzygium cumini leaves

Context: Pancreatic α-amylase and α-glucosidase inhibitors serve as important strategies in the management of blood glucose. Even though Syzygium cumini (L.) Skeels (Myrtaceae) (SC) is used extensively to treat diabetes; scientific evidence on antidiabetic effects of SC leaves is scarce.

Objective: SC leaf extract was investigated for α-amylase inhibitory effect and continued with isolation and identification of α-amylase inhibitors.

Materials and methods: Bioassay-guided fractionation was conducted using in vitro α-amylase inhibitory assay (with 20–1000?μg/mL test material) to isolate the inhibitory compounds from ethyl acetate extract of SC leaves. Structures of the isolated inhibitory compounds were elucidated using ¹H NMR and ¹³C NMR spectroscopic analysis and direct TLC and HPLC comparison with authentic samples. Study period was from October 2013 to October 2015.

Results: An active fraction obtained with chromatographic separation of the extract inhibited porcine pancreatic α-amylase with an IC₅₀ of 39.9?μg/mL. Furthermore, it showed a strong inhibition on α-glucosidase with an IC₅₀ of 28.2?μg/mL. The active fraction was determined to be a 3:1 mixture of ursolic acid and oleanolic acid. Pure ursolic acid and oleanolic acid showed IC₅₀ values of 6.7 and 57.4?μg/mL, respectively, against α-amylase and 3.1 and 44.1?μg/mL respectively, against α-glucosidase.

Discussion and conclusions: The present study revealed strong α-amylase and α-glucosidase inhibitory effects of ursolic acid and oleanolic acid isolated from SC leaves for the first time validating the use of SC leaves in antidiabetic therapy.     

Hypoglycemic activity of C-glycosyl flavonoid from Enicostemma hyssopifolium

Context: Enicostemma hyssopifolium Verdoon (Gentianaceae) has been documented for various therapeutic effects in traditional systems of medicine; the hypoglycemic and hypolipidemic activities are also well reported.

Objective: Bioactivity guided fractionation of methanol extract of E. hyssopifolium to test the hypothesis that E. hyssopifolium and its constituents influence cells and systemic glucose homeostasis.

Materials and methods: Derived fraction and isolated compounds were studied for (1) aldose reductase (AR) inhibition, (2) α-glucosidase inhibition, (3) effect on gluconeogenesis in rat hepatoma, (4) cytoprotection against streptozotocin (STZ)-induced toxicity on RINm5F cells, (5) normalization of glycemic control in acute hyperglycemic rat model, and (6) insulin-releasing effect both in vitro and in vivo.

Results: The results indicated that E. hyssopifolium can modify the glucose homeostasis at the cellular level. Two bioactive constituents were identified. Swertisin was found to inhibit AR (IC₅₀ 1.23?μg/mL) and α-glucosidase (IC₅₀ 1.89?μg/mL). It also possessed a significant cytoprotective action of RINm5F cell line against toxicant STZ. Swertiamarin was found to have hepatic gluconeogenesis inhibiting and insulin-releasing effect on rat hepatoma and RINm5F cells, respectively. The results of the in vivo study showed that swertiamarin, unlike the in vitro effect, produced no significant raise of insulin secretion. Swertisin normalized the serum glucose 60?min after high dose of glucose (2?g/kg, i.p.) in rats.

Discussion and conclusion: These findings demonstrate that the fraction derived from the aerial part of E. hyssopifolium achieve normoglycemic status in hyperglycemic conditions via various mechanisms. The constituents swertiamarin and swertisin are responsible for bioactivity.     

Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water extractable phytochemicals from some tropical spices

Context: Spices have been used as food adjuncts and in folklore for ages. Inhibition of key enzymes (α-amylase and α-glucosidase) involved in the digestion of starch and protection against free radicals and lipid peroxidation in pancreas could be part of the therapeutic approach towards the management of hyperglycemia and dietary phenolics have shown promising potentials.

Objective: This study investigated and compared the inhibitory properties of aqueous extracts of some tropical spices: Xylopia aethiopica [Dun.] A. Rich (Annonaceae), Monodora myristica (Gaertn.) Dunal (Annonaceae), Syzygium aromaticum [L.] Merr. et Perry (Myrtaceae), Piper guineense Schumach. et Thonn (Piperaceae), Aframomum danielli K. Schum (Zingiberaceae) and Aframomum melegueta (Rosc.) K. Schum (Zingiberaceae) against α-amylase, α-glucosidase, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and sodium nitroprusside (SNP)-induced lipid peroxidation in rat pancreas - in vitro using different spectrophotometric method.

Materials and methods: Aqueous extract of the spices was prepared and the ability of the spice extracts to inhibit α-amylase, α-glucosidase, DPPH radicals and SNP-induced lipid peroxidation in rat pancreas - in vitro was investigated using various spectrophotometric methods.

Result: All the spice extracts inhibited α-amylase (IC₅₀?=?2.81–4.83?mg/mL), α-glucosidase (IC₅₀?=?2.02–3.52?mg/mL), DPPH radicals (EC₅₀?=?15.47–17.38?mg/mL) and SNP-induced lipid peroxidation (14.17–94.38%), with the highest α-amylase & α-glucosidase inhibitory actions and DPPH radical scavenging ability exhibited by X. aethiopica, A. danielli and S. aromaticum, respectively. Also, the spices possess high total phenol (0.88–1.3?mg/mL) and flavonoid (0.24–0.52?mg/mL) contents with A. melegueta having the highest total phenolic and flavonoid contents.

Discussion and conclusion: The inhibitory effects of the spice extracts on α-amylase, α-glucosidase, DPPH radicals and SNP-induced lipid peroxidation in pancreas (in vitro) could be attributed to the presence of biologically active phytochemicals such as phenolics and some non-phenolic constituents of the spices. Furthermore, these spices may exert their anti-diabetic properties through the mechanism of enzyme inhibition, free radicals scavenging ability and prevention of lipid peroxidation.     

Effect of Ficus racemosa stem bark on the activities of carbohydrate hydrolyzing enzymes: An in vitro study

Herbal medicines have been used since prehistoric times by different cultures worldwide for the treatment of diabetes. The present investigation evaluated the effect of Ficus racemosa Linn. (Moraceae) stem bark on carbohydrate hydrolyzing enzymes, viz., porcine pancreatic α-amylase, rat intestinal α-glucosidase, sucrase, and almond β-glucosidase, using in vitro model systems. In addition, the effect of heat treatment was also studied. Untreated F. racemosa bark (FRB) significantly inhibited (p?≤?0.05) α-amylase, α-glucosidase, β-glucosidase, and sucrase in a dose-dependent manner. Heat treatment of the sample comparably increased α-amylase, α-glucosidase, and sucrase inhibitory activities, while a marginal decrease in β-glucosidase inhibitory activity was observed; however, no statistical differences were noted. Untreated FRB showed IC₅₀ values of 0.94% and 280, 212, and 367 μg/mL for α-amylase, α-glucosidase, β-glucosidase, and sucrase, respectively, while the IC₅₀ values for heat treated FRB were 0.58% and 259, 223, and 239 μg/mL, respectively. Further, a significant correlation (p?≤?0.01; r?=?0.791) was observed between α-amylase, α-glucosidase, β-glucosidase, and sucrase inhibitory activities of both untreated and heat treated FRB. The results clearly demonstrate that inhibition of carbohydrate hydrolyzing enzymes is one mechanism through which F. racemosa stem bark exerts its hypoglycemic effect in vivo. Therefore, the potential exists to explore the utilization of F. racemosa stem bark in the development of nutraceuticals and functional foods for the management of diabetes and related symptoms/disorders.     

Antidiabetic and antioxidant potency evaluation of different fractions obtained from Cucumis prophetarum fruit

Abstract

Context: Cucumis prophetarum Linn. (Cucurbitaceae) fruit is used for inflammatory-related problems and is proved to be possessing anticancer and hepatoprotective effects.

Objective: The present investigation was to study the effect of different fractions of C. prophetarum on antidiabetic and antioxidant activity.

Materials and methods: Aqueous crude extract (CE) of C. prophetarum fruits was fractionated into water soluble fraction 1 (F1), chloroform fraction 2 (F2), basic fraction 3 (F3), and neutral fraction 4 (F4) by acid–base extraction. CE and its fractions at different doses (0.02–0.1?mg/mL) were subjected to antidiabetic (α-amylase and α-glucosidase inhibition assays) and antioxidant (DPPH, superoxide radical scavenging (SO) and metal chelation) evaluation.

Results: F1 exhibited effective antidiabetic activity (p?<?0.05) with an IC₅₀ value of 20.6 and 59.9?µg/mL. The activity decreased in the order of CE?>?F4?>F3?>?F2, according to α-amylase assay, which were the same, with the exception of the rank order of F4 and CE, as the α-glucosidase assay. Furthermore, F1 (IC₅₀?=?73?µg/mL) showed better reducing ability than CE?>F4?>F2?>?F3 (IC₅₀?=?78–272?µg/mL), according to the DPPH assay. In SO and metal chelation assays, F1 showed the highest activity (IC₅₀?=?101 and 147?µg/mL), respectively; the activity decreased in the order of CE?>F4?>F3?>?F2 (IC₅₀?=?126–469?µg/mL) for SO and 194–944?µg/mL for metal chelation assay.

Conclusion: The results indicate that F1 possesses potent in vitro antidiabetic and antioxidant activities.     

Antiobesity and antihyperglycaemic effects of Adiantum capillus-veneris extracts: in vitro and in vivo evaluations

Context: Adiantum capillus-veneris L. (Adiantaceae) hypocholesterolemic activity is therapeutically praised.

Objectives: Pharmacological modulation of pancreatic triacylglycerol lipase (PL) and α-amylase/α-glucosidase by A. capillus-veneris are evaluated.

Materials and methods: Using positive controls (acarbose, orlistat, guar gum, atorvastatin, glipizide and metformin) as appropriate, crude aqueous extracts (AEs) of A. capillus-veneris aerial parts were tested via a combination of in vitro enzymatic (0.24–100?mg/mL), acute in vivo carbohydrate tolerance tests (125, 250 or 500?mg/kg body weight [b.wt]) and chronic in vivo studies (500?mg/kg b.wt) in high cholesterol diet (HCD) fed Wistar rats.

Results: Like acarbose, A. capillus-veneris as well as chlorogenic acid, with respective IC₅₀ values (mg/mL) of 0.8?±?0.0 and 0.2?±?0.0, were identified as in vitro potent dual inhibitors of α-amylase/α-glucosidase. Unlike guar gum, A. capillus-veneris had no glucose diffusion hindrance capacity. Equivalent to orlistat, A. capillus-veneris and its phytoconstituents inhibited PL in vitro with an ascending order of PL- IC₅₀ values (μg/mL): ferulic acid; 0.48?±?0.06?A. capillus-veneris; 1600?±?100. Incomparable to acarbose or metformin and glipizide, A. capillus-veneris (125, 250 and 500?mg/kg b.wt) lacked antihyperglycaemic efficacies in acute starch- or glucose-evoked postprandial hyperglycaemia increments in normoglycaemic overnight fasting rats. Superior to atorvastatin; A. capillus-veneris exerted significant antiobesity (p?p?Discussion and conclusion: A. capillus-veneris, modulating pancreatic digestive enzymes, may be advocated as a combinatorial diabesity prevention/phytotherapy agent.     

Dieckol isolated from Ecklonia cava inhibits α-glucosidase and α-amylase in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice

This study was designed to investigate whether dieckol may inhibit α-glucosidase and α-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. Dieckol isolated from Ecklonia cava, brown algae, evidenced prominent inhibitory effect against α-glucosidase and α-amylase. The IC₅₀ values of dieckol against α-glucosidase and α-amylase were 0.24 and 0.66 mM, respectively, which evidenced the higher activities than that of acarbose. Dieckol did not exert any cytotoxic effect in human umbilical vein endothelial cells (HUVECs) at various concentrations (from 0.33 to 2.69 mM). The increase of postprandial blood glucose levels were significantly suppressed in the dieckol administered group than those in the streptozotocin-induced diabetic or normal mice. Moreover, the area under curve (AUC) was significantly reduced via dieckol administration (259 versus 483 mmol min/l) in the diabetic mice as well as it delays absorption of dietary carbohydrates. Therefore, these result indicated that dieckol might be a potent inhibitor for α-glucosidase and α-amylase.     

Identification of highly potent α-glucosidase inhibitory and antioxidant constituents from Zizyphus rugosa bark: enzyme kinetic and molecular docking studies with active metabolites

Context: Previous studies have shown that extracts of Zizyphus rugosa Lam. (Rhamnaceae) bark contained phytoconstituents with antidiabetic potential to lower blood glucose levels in diabetic rats. However, there has been no report on the active compounds in this plant as potential antidiabetic inhibitors.

Objective: We evaluated the α-glucosidase inhibitory and antioxidant activities of Z. rugosa extract. Moreover, the active phytochemical constituents were isolated and characterized.

Materials and methods: The α-glucosidase inhibition of crude ethanol extract obtained from the bark of Z. rugosa was assayed as well as the antioxidant activity. Active compounds (1–6) were isolated, the structures were determined, and derivatives (2a–2?l) were prepared. All compounds were tested for their α-glucosidase inhibitory (yeast and rat intestine) and antioxidant (DPPH) activities.

Results: The active α-glucosidase inhibitors (1–6) were isolated from Z. rugosa bark and 12 derivatives (2a–2?l) were prepared. Compound 2 showed the most powerful yeast α-glucosidase inhibitory activity (IC₅₀ 16.3?μM), while compounds 3 and 4 display only weak inhibition toward rat intestinal α-glucosidase. Moreover, compound 6 showed the most potent antioxidant activity (IC₅₀ 42.8?μM). The molecular docking results highlighted the role of the carboxyl moiety of 2 for yeast α-glucosidase inhibition through H-bonding.

Discussion and conclusions: These results suggest the potential of Z. rugosa bark for future application in the treatment of diabetes and active compounds 1 and 2 have emerged as promising molecules for therapy.     

The α-amylase and α-glucosidase inhibitory activities of the dichloromethane extracts and constituents of Ferulago bracteata roots

Context: Ferulago (Apiaceae) species have been used since ancient times for the treatment of intestinal worms, hemorrhoids, and as a tonic, digestive, aphrodisiac, or sedative, as well as in salads or as a spice due to their special odors.

Objectives: This study reports the α-amylase and α-glucosidase inhibitory activities of dichloromethane extract and bioactive compounds isolated from Ferulago bracteata Boiss. &; Hausskn. roots.

Materials and methods: The isolated compounds obtained from dichloromethane extract of Ferulago bracteata roots through bioassay-guided fractionation and isolation process were evaluated for their in vitro α-amylase and α-glucosidase inhibitory activities at 5000–400?µg/mL concentrations. Compound structures were elucidated by detailed analyses (NMR and MS).

Results: A new coumarin, peucedanol-2′-benzoate (1), along with nine known ones, osthole (2), imperatorin (3), bergapten (4), prantschimgin (5), grandivitinol (6), suberosin (7), xanthotoxin (8), felamidin (9), umbelliferone (10), and a sterol mixture consisted of stigmasterol (11), β-sitosterol (12) was isolated from the roots of F. bracteata. Felamidin and suberosin showed significant α-glucosidase inhibitory activity (IC₅₀ 0.42 and 0.89?mg/mL, respectively) when compared to the reference standard acarbose (IC₅₀ 4.95?mg/mL). However, none of the tested extracts were found to be active on α-amylase inhibition.

Discussion and conclusions: The present study demonstrated that among the compounds isolated from CH₂Cl₂ fraction of F. bracteata roots, coumarins were determined as the main chemical constituents of this fraction. This is the first report on isolation and characterization of the bioactive compounds from root extracts of F. bracteata and on their α-amylase and α-glucosidase inhibitory activities.     

Inhibition of key enzymes linked to type 2 diabetes by compounds isolated from Aframomum melegueta fruit

Context: The use of Aframomum melegueta K. Schum. (Zingiberaceae) fruit for treatment of diabetes has recently been established in Nigeria. However, compounds responsible for the antidiabetic action have not been identified.

Objective: The present study carried out the bioassay-guided isolation of possible bioactive compounds responsible for the antidiabetic action of A. melegueta fruit.

Materials and methods: The A. melegueta fruit was sequentially extracted using ethyl acetate (EtOAc), ethanol and water, and the most active extract (EtOAc) was subjected to column chromatography on a silica gel column using solvent gradient systems of hexane (HEX):EtOAc and EtOAc:MeOH and the isolation of compounds was guided by α-glycosidase and α-amylase inhibitory activities at various concentrations (30–240?μg/mL).

Results: According to the results, 3 arylalkanes, 6-paradol (1), 6-shogaol (2) and 6-gingerol (3) and a pentacyclic triterpene, oleanolic acid (4) were isolated from A. melegueta fruit. All the compounds exhibited inhibitory effects against α-amylase and α-glucosidase. 6-Gingerol (3) and oleanolic acid (4) showed higher inhibitory activity against α-amylase (IC₅₀: 6-gingerol: 81.78?±?7.79?μM; oleanolic acid: 91.72?±?1.63?μM) and α-glucosidase (IC₅₀: 6-gingerol: 21.55?±?0.45?μM; oleanolic acid: 17.35?±?0.88?μM) compared to the standard drug, acarbose and other isolated compounds. The kinetics of the enzyme action of the compounds showed a noncompetitive mode of inhibition.

Conclusion: The data of this study suggest that the 6-gingerol (3) and oleanolic acid (4) showed higher α-amylase and α-glucosidase inhibitory action and therefore could be responsible for the antidiabetic activity of A. melegueta fruit.     

Unlocking the in vitro anti-inflammatory and antidiabetic potential of Polygonum maritimum

Context: Several Polygonum species (Polygonaceae) are used in traditional medicine in Asia, Europe and Africa to treat inflammation and diabetes.

Objective: Evaluate the in vitro antioxidant, anti-inflammatory and antidiabetic potential of methanol and dichloromethane extracts of leaves and roots of the halophyte Polygonum maritimum L.

Material and methods: Antioxidant activity was determined (up to 1?mg/mL) as radical-scavenging activity (RSA) of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), copper (CCA) and iron (ICA) chelating activities and iron reducing power (FRAP). NO production was measured in lipopolysaccharide (LPS)-stimulated macrophages for 24?h at concentrations up to 100?μg/mL and antidiabetic potential was assessed by α-amylase and α-glucosidase inhibition (up to 10?mg/mL) assays. The phytochemical composition of the extracts was determined by gas chromatography-mass spectrometry (GC-MS).

Results: The methanol leaf extract had the highest activity against DPPH? (IC₅₀ =?26?μg/mL) and ABTS⁺? (IC₅₀ =?140?μg/mL), FRAP (IC₅₀ =?48?μg/mL) and CCA (IC₅₀ =?770?μg/mL). Only the dichloromethane leaf extract (LDCM) showed anti-inflammatory activity (IC₅₀ =?48?μg/mL). The methanol root (IC₅₀ =?19?μg/mL) and leaf (IC₅₀ =?29?μg/mL) extracts strongly inhibited baker’s yeast α-glucosidase, but LDCM had higher rat’s α-glucosidase inhibition (IC₅₀ =?2527?μg/mL) than acarbose (IC₅₀ =?4638?μg/mL). GC-MS analysis identified β-sitosterol, stigmasterol, 1-octacosanol and linolenic acid as possible molecules responsible for the observed bioactivities.

Conclusions: Our findings suggest P. maritimum as a source of high-value health promoting commodities for alleviating symptoms associated with oxidative and inflammatory diseases, including diabetes.     

Antidiabetic,antioxidant, and TNF-α lowering properties of extract of the traditionally used plant Ixeris gracilis in alloxan-induced diabetic mice

Abstract

Context: Ixeris gracilis DC. Stebbins (Asteraceae) is a plant considered to be medicinal by local communities of Meghalaya, India.

Objective: To evaluate the antidiabetic potential, antioxidant activity, and effect of the 80% methanolic extract of the leaves of Ixeris gracilis on tumor necrosis factor-α (TNF-α) expression.

Materials and methods: Varying doses (250–1000?mg/kg body weight) were administered intraperitoneally to normoglycemic mice and their hypoglycemic properties noted for 24?h; the optimum dose observed was used to evaluate its antihyperglycemic activity and effect on glucose tolerance. In vitro antioxidant activity was analyzed by assessing the DPPH radicals scavenging ability of the extract and the total polyphenols, flavonoid, carbohydrate, and protein contents were determined. Diabetic mice were then subjected to daily intraperitoneal injections of the extract for 12 days after which the antioxidant enzyme activities in the tissues were assayed and serum TNF-α was evaluated by ELISA.

Results: The extract displayed varying hypoglycemic activity. The dose of 250?mg/kg body weight exhibited potent antihyperglycemic activity and improved glucose tolerance. The extract was able to scavenge free radicals (IC₅₀ 57.544?µg/ml) and contained polyphenol (76.269?±?0.204?mg GAE/g dry wt), flavonoid (70.070?±?0.626?mg rutin equivalent/g dry wt), protein (4.368?±?8.916?mg/g dry wt), and carbohydrate (558.189?±?0.002?mg/g dry wt). TNF-α level and overall activity of glutathione peroxidase and superoxide dismutase in the liver, kidney, and brain of extract-treated diabetic mice were improved.

Conclusion: The study supports the inclusion of Ixeris gracilis in the list of plants with antidiabetic potential.     

Effects of Aphloia theiformis on key enzymes related to diabetes mellitus

Context: Aphloia theiformis (Vahl.) Benn. (Flacourtiaceae) (AT) is traditionally used for the management of diabetes mellitus (DM), but there is no scientific data regarding activity against enzymes linked to this condition.

Objective: To evaluate the kinetics of AT on key enzymes inhibition related to DM, and establish the antioxidant profile of AT.

Materials and methods: Dried powdered AT leaves were used to prepare crude methanol extract (70% v/v) (CME). Kinetics of CME (5000 to 156.25?μg/mL) on α-amylase, α-glucosidase, and lipase inhibition were studied. CME was partitioned using solvents of increasing polarity and kinetics of enzyme inhibition of each fraction (1000–31.25?μg/mL) was evaluated. Potent fractions were combined to assess any synergistic effect. Total phenol, flavonoid, tannin, anthocyanin contents, and antioxidant capacity of AT was evaluated using standard spectrophotometric methods.

Results: CME, ethyl acetate, and n-butanol fractions showed potent inhibitory activities against the enzymes with IC₅₀ ranging from 22.94–939.97?μg/mL. Significant (p?50 (15.72 and 157.03?μg/mL against α-amylase and lipase, respectively) was observed when ethyl acetate and n-butanol fractions were combined; showing synergism. The extracts showed noncompetitive inhibition against α-amylase and α-glucosidase. Ethyl acetate, n-butanol fractions, and CME showed highest antioxidant capacities (0.44–1.41?μg GAE/mg sample), and phenol content (211.74-675.53?μg GAE/mg sample).

Conclusion: This study supports the use of AT in the management of DM and provides the rationale for bioactivity guided isolation and characterization of compounds from the ethyl acetate and n-butanol fractions.     

In vitro studies to assess the antidiabetic,antiperoxidative, and radical scavenging potential of Stereospermum colais

Context: Stereospermum colais (Buch.-Ham. ex Dillw.) Mabberley (Bignoniaceae), which has traditional medicinal properties, is distributed all over deciduous forests. In spite of its many uses, the antidiabetic, antiperoxidative and radical scavenging activities of this species have not been assessed, and its chemical composition is scarcely known.

Objective: Antidiabetic, antiperoxidation, xanthine oxidase (XO) inhibition, and radical scavenging activities of acetone and methanol extracts of Stereospermum colais roots were investigated. Protective effects of Stereospermum colais root extract in stabilizing sunflower oil was also examined.

Materials and methods: The protective effect of acetone (ASC) and methanol (MSC) extracts of Stereospermum colais root for the potential inhibition of α-glucosidase and α-amylase enzymes were studied by in vitro method. Glycation inhibitory activity was also studied to inhibit the production of glycated end products.

Results: Compared with acarbose, ASC showed a strong inhibitory activity against α-glucosidase (IC₅₀ 61.21 µg/mL) and a moderate inhibitory activity against α-amylase (IC₅₀ 681.08 µg/mL). Glycation inhibitory activity of Stereospermum colais root extracts by using an in vitro glucose-bovine serum albumin (BSA) assay was also done and compared with standard gallic acid. ASC also shows high XO inhibition potential, free radical scavenging activities, and low p-anisidine value indicates the high medicinal potency of Stereospermum colais root.

Discussion and conclusion: These results suggest that the extract of Stereospermum colais may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia, and or as food additives due to its antiradical efficiency.     

Hypoglycemic activity of Erythrina variegata leaf in streptozotocin-induced diabetic rats

Context: Erythrina variegata Linn. (Fabaceae), commonly known as Tiger’s Claw, is a thorny deciduous tree grown in tropical and subtropical regions of Eastern Africa, Southern Asia, and Northern Australia. In India, its leaves are traditionally used for diabetes mellitus.

Objective: To evaluate the hypoglycemic activity of methanol extract of E. variegata leaf (MEEV) in streptozotocin (STZ)-induced diabetic Wistar rats.

Materials and methods: Hyperglycemia was induced in rats by single intraperitoneal injection of STZ (55?mg/kg body weight). Three days after STZ induction, the hyperglycemic rats were treated with MEEV orally at the doses of 300, 600, and 900?mg/kg body weight daily for 21 days. Glibenclamide (1?mg/kg, orally) was used as reference drug. The fasting blood glucose levels were measured on every 7th day during the 21 days of treatment. Serum biochemical parameters including lipid content were estimated.

Results and discussion: MEEV at the doses of 300, 600, and 900?mg/kg orally significantly (P?<?0.01) and dose-dependently reduced and normalized blood glucose levels as compared to that of STZ control group; the dose 900?mg/kg being the most potent showing complete normalization of blood glucose levels. Serum biochemical parameters including lipid profile were significantly (P?<?0.01) restored toward normal levels in META-treated rats as compared to STZ control animals.

Conclusion: This study concludes that E. variegata leaf demonstrated promising hypoglycemic action in STZ-induced diabetic rats substantiating its ethnomedicinal use.     

Synthesis of some novel orsellinates and lecanoric acid related depsides as α-glucosidase inhibitors

Abstract

Sixteen novel orsellinic esters (6a-l, 7a-d) along with four lecanoric acid related depsides (3a-c, 4) were synthesized and confirmed their structures by spectroscopic data (¹H, ¹³C & HRMS). The synthesized compounds were evaluated for their in vitro α-glucosidase (Saccharomyces cerevisiae) inhibitory potential. Among the tested compounds, 3c (IC₅₀: 140.9 μM) and 6c (IC₅₀: 203.9 μM) displayed potent α-glucosidase inhibitory activity and found more active than the standard drug acarbose (IC₅₀: 686.6 μM). Both the test compounds were subjected to in vivo antihyperglycemic activity using sucrose loaded model in Wistar rats and found compound 3c exhibited significant reduction in glucose levels.     

Xanthones as α-glucosidase inhibitors from the antihyperglycemic extract of Securidaca inappendiculata

Context: Securidaca inappendiculata Hassk. (SI) is used to cure fractures and rheumatoid arthritis in China. Also, it is a potential antidiabetes drug; however, there are no reports on this.

Objective: The study was designed to evaluate the antihyperglycemic activities of fractions and compounds from SI, and attempt to explore the mechanism.

Materials and methods: Antihyperglycemic activities were evaluated by the suppression on serum glucose levels in vivo and α-glucosidase inhibition assays in vitro. Fractions were given to mice by gastric intubation for 8?d. The high, medium, and low doses of fractions were equal to 10, 5, and 2.5?g/kg of the herb [SID (dichloromethane fraction) and SIE (ethyl acetate fraction) were doubled]. The serum glucose was monitored at 1 and 12?h after feeding. The silica gel and LH-20 chromatography were used to isolate active compounds. Structure–activity relationship analysis was based on IC₅₀s and structures.

Results: The IC₅₀s of SID, SIE, SIA (acetone fraction), SIM (methanol fraction), and acarbose were 712, 446, 1123, 1418, and 735?μg/mL. The postprandial and fasting serum glucose levels of SID, SIE, SIA, and SIM (high dose) were 5.5, 5.9, 6.2, 6.3 and 3.7, 3.5, 4.0, 5.0?mmol/L, while those of vehicle control were 7.5 and 5.6?mmol/L. Eleven xanthones isolated all exhibited inhibitory activities, mainly in a non-competitive reversible manner. The IC₅₀s varied from 3.2 to 77.3?μg/mL. Structure–activity relationship analysis exhibited free hydroxyls contributed the most importance to the activity.

Conclusion: The results indicated that xanthones from SI were powerful agents for antidiabetes.     

Salacia chinensis stem extract and its thiosugar sulfonium constituent,neokotalanol, improves HbA1c levels in ob/ob mice

The antidiabetic effects of a hot water extract of the stems of Salacia chinensis (SCE) were evaluated in vivo in ob/ob mice (genetically obese hyperglycemic mice). Administration of dietary feed containing 0.20 and 0.50% of SCE for 23 days to ob/ob mice significantly suppressed the elevation of both blood glucose and HbA1c levels, without significantly changing body weight and food intake. To characterize the antidiabetic effects of the thiosugar sulfonium constituent neokotalanol (1), which has potent α-glucosidase inhibitory activity, we performed a similar in vivo study. HbA1c levels were significantly suppressed in ob/ob mice after the administration of dietary feed containing 0.0003% of neokotalanol (1) for 20 days. These results indicate that SCE and neokotalanol (1) are potential leads for the development of novel antidiabetic agents.