Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Phytochemical and biological attributes of Bauhinia variegata L. (Caesalpiniaceae) / Atributos fitoquímicos e biológicos de Bauhinia variegata L. (Caesalpiniaceae)

Bauhinia variegata plant is a very popular and traditionally potent ethnomedicine. Therefore, it is need of hour to study ameliorative characteristics of B. variegata for novel secondary metabolites. The current study was designed to explore antiproliferative potential of B. variegata due to scant reports on this aspect. Extracts of various parts (flowers, leaves, bark, stem, and roots) were prepared by successive maceration using organic solvents in increasing order of polarity (n-hexane, ethyl acetate, methanol, and water). The determination of polyphenolic contents was done by using colorimetric methods while antioxidant potential was measured using reducing power assay. Brine shrimp lethality assay was performed for determining preliminary cytotoxicity and antiproliferative activity against breast cancer MCF-7 cell line using MTT protocols. Moreover, antimicrobial activities were detected by using disc diffusion assay. The alpha-amylase assay was performed to monitor the antidiabetic potential of the plant. In case of phytochemical analysis methanolic extract of leaves and bark showed highest phenolic and flavonoids contents. n-Hexane and ethyl acetate extracts of stem and roots exhibited more than 90% mortality with LD50 ranges between 1-25 µg/mL when studied by brine shrimp lethality assay. n-Hexane and ethyl acetate extracts of roots and stem also showed antiproliferative activity against human breast cancer MCF-7 cell line with IC50 values ranges between 12.10-14.20 µg/mL. Most of the extracts displayed moderately high antibacterial and antifungal activities. The n-hexane extract of roots showed antidiabetic activity with 60.80 ± 0.20% inhibition of alpha-amylase. In sum, these preliminary results will be useful for further compound isolation from selected plant parts for the discovery of antibacterial, antidiabetic, and anticancer lead candidates.

A planta Bauhinia variegata é uma etnomedicina muito popular e tradicionalmente potente. Portanto, as características de melhoria de B. variegata foram estudadas. Foi avaliada a determinação dos teores antioxidantes e polifenólicos. O ensaio de letalidade do camarão de salmoura foi realizado para determinar a citotoxicidade preliminar e a atividade antiproliferativa contra linhas de células de câncer de mama MCF-7 usando protocolos de MTT. Além disso, foram detectadas atividades antimicrobianas. O ensaio da alfa-amilase foi realizado para monitorar o potencial antidiabético da planta. Dentre vinte amostras diferentes, o extrato metanólico (EM) da casca apresentou os maiores teores fenólicos totais. A EM das folhas apresentou excelente conteúdo de flavonoides, atividade antioxidante significativa foi exibida pelo extrato hexânico do caule. O extrato do caule de hexano exibe 77,40% como citotóxico em DL50 10,50 µg/mL quando avaliado através do ensaio de letalidade de artêmia. Extratos de hexano e acetato de etila de raiz e caule mostraram atividade antiproliferativa contra a linhagem celular MCF7 de câncer de mama humano (IC50 12,10-14,20 µg/mL). Para potencial antimicrobiano importante, vários extratos exibiram excelentes atividades antibacteriana e antifúngica, enquanto o extrato de n-hexano da raiz mostrou atividade antidiabética (60,80 ± 0,20% na concentração de 200 µg/mL). Em suma, estes resultados preliminares serão úteis para isolamento adicional de compostos a partir de partes de plantas selecionadas para a descoberta de candidatos a antibacterianos, antidiabéticos e anticâncer.

Phytochemical and biological attributes of Bauhinia variegata L. (Caesalpiniaceae)

Abstract Bauhinia variegata plant is a very popular and traditionally potent ethnomedicine. Therefore, it is need of hour to study ameliorative characteristics of B. variegata for novel secondary metabolites. The current study was designed to explore antiproliferative potential of B. variegata due to scant reports on this aspect. Extracts of various parts (flowers, leaves, bark, stem, and roots) were prepared by successive maceration using organic solvents in increasing order of polarity (n-hexane, ethyl acetate, methanol, and water). The determination of polyphenolic contents was done by using colorimetric methods while antioxidant potential was measured using reducing power assay. Brine shrimp lethality assay was performed for determining preliminary cytotoxicity and antiproliferative activity against breast cancer MCF-7 cell line using MTT protocols. Moreover, antimicrobial activities were detected by using disc diffusion assay. The alpha-amylase assay was performed to monitor the antidiabetic potential of the plant. In case of phytochemical analysis methanolic extract of leaves and bark showed highest phenolic and flavonoids contents. n-Hexane and ethyl acetate extracts of stem and roots exhibited more than 90% mortality with LD50 ranges between 1-25 µg/mL when studied by brine shrimp lethality assay. n-Hexane and ethyl acetate extracts of roots and stem also showed antiproliferative activity against human breast cancer MCF-7 cell line with IC50 values ranges between 12.10-14.20 µg/mL. Most of the extracts displayed moderately high antibacterial and antifungal activities. The n-hexane extract of roots showed antidiabetic activity with 60.80 ± 0.20% inhibition of alpha-amylase. In sum, these preliminary results will be useful for further compound isolation from selected plant parts for the discovery of antibacterial, antidiabetic, and anticancer lead candidates.

Resumo A planta Bauhinia variegata é uma etnomedicina muito popular e tradicionalmente potente. Portanto, as características de melhoria de B. variegata foram estudadas. Foi avaliada a determinação dos teores antioxidantes e polifenólicos. O ensaio de letalidade do camarão de salmoura foi realizado para determinar a citotoxicidade preliminar e a atividade antiproliferativa contra linhas de células de câncer de mama MCF-7 usando protocolos de MTT. Além disso, foram detectadas atividades antimicrobianas. O ensaio da alfa-amilase foi realizado para monitorar o potencial antidiabético da planta. Dentre vinte amostras diferentes, o extrato metanólico (EM) da casca apresentou os maiores teores fenólicos totais. A EM das folhas apresentou excelente conteúdo de flavonoides, atividade antioxidante significativa foi exibida pelo extrato hexânico do caule. O extrato do caule de hexano exibe 77,40% como citotóxico em DL50 10,50 µg/mL quando avaliado através do ensaio de letalidade de artêmia. Extratos de hexano e acetato de etila de raiz e caule mostraram atividade antiproliferativa contra a linhagem celular MCF7 de câncer de mama humano (IC50 12,10-14,20 µg/mL). Para potencial antimicrobiano importante, vários extratos exibiram excelentes atividades antibacteriana e antifúngica, enquanto o extrato de n-hexano da raiz mostrou atividade antidiabética (60,80 ± 0,20% na concentração de 200 µg/mL). Em suma, estes resultados preliminares serão úteis para isolamento adicional de compostos a partir de partes de plantas selecionadas para a descoberta de candidatos a antibacterianos, antidiabéticos e anticâncer.

Improved performance of naringenin herbosomes over naringenin in streptozotocin-induced diabetic rats: In vitro and in vivo evaluation

Objective: To prepare naringenin herbosome and evaluate its antidiabetic activity. Methods: Herbosomes were prepared by the solvent evaporation method. In vitro parameters like particle size, polydispersity index, zeta potential, and entrapment efficiency were estimated and in vitro diffusion study was performed. The in vivo studies were also performed in streptozotocin-induced diabetic male Sprague Dawley rats to evaluate blood glucose, total cholesterol, triglyceride, blood urea nitrogen, total protein, albumin level, aspartate aminotransferase, and alanine aminotransferase levels. Results: The optimized herbosome batch showed a particle size of 564.4 nm, a polydispersity index of 0.412, and zeta potential of-39.3 mV. The percentage entrapment of this formulation was 84.04%, with complete drug release within 8 h. Treatment of diabetic rats with naringenin herbosomes for 28 d significantly reduced the elevated level of plasma glucose as compared to plain naringenin. In biochemical parameters, the treatment showed a significant decrease in total cholesterol, triglyceride, and blood urea nitrogen; while elevated levels of aspartate aminotransferase and alanine aminotransferase were returned to normal. Pure naringenin and herbosome formulation at high dose increased the total protein whereas albumin level significantly increased in naringenin herbosomes at the highest dose but not in the pure naringenin treatment group. Conclusions: Naringenin herbosomes could improve the metabolic profile of diabetic rats, indicating enhanced antidiabetic activity of herbosome formulation.

Evaluation of antidiabetic activities of Etlingera elatior flower aqueous extract in vitro and in vivo

Diabetes mellitus (DM) is a global health problem for millions of people worldwide. Nowadays, medicinal plantshave started gaining more attention in diabetes management due to the minimal side effects and cost-effectiveness.This study aims to ascertain the antidiabetic potential of the Etlingera elatior flowers aqueous extract on the in vitroinhibition of carbohydrate digestive enzymes and in vivo type 2 DM rat model. The findings demonstrate that E.elatior flower has a high percentage of inhibitory activity against α-amylase (99.70 ± 2.88%) and moderate activityfor the α-glucosidase enzyme (52.39 ± 1.50%). In addition, E. elatior flower has also exhibited an antihyperglycemiceffect that is dose-dependent and has significantly decreased the elevated total cholesterol, triglycerides, and lowdensity lipoprotein levels in the in vivo study. Furthermore, serum creatinine, aspartate aminotransferase, and alkalinephosphatase also were significantly decreased when compared to untreated DM. The high contents of total phenolic(39.06 ± 1.59 mg GAE/g), total flavonoid (39.00 ± 2.42 mg QE/g extract), and potent antioxidant activity weresuggested to contribute to the antidiabetic activity of the extract. In conclusion, E. elatior flower could potentially bedeveloped as a natural source of antioxidants that can be used for the prevention or treatment of diabetes.

Antihyperglycemic and antihyperlipidemic activities of wild musk melon (Cucumis melo var. agrestis) in streptozotocin-nicotinamide induced diabetic rats / 中草药·英文版

Objective: Wild musk melon (Cucumis melo var. agrestis, CMA) is one of the edible plants form Tamil Nadu. Traditionally, this plant was used as diabetic diet (leaves of CMA with Momordica charantia leaves), but there is no scientific report on antidiabetic action of this plant material. Hence, the current research work was designed to evaluate the antihyperglycemic and antihyperlipidemic effect of hydroalcoholic extract of CMA leaves (HALEC) in streptozotocin (STZ)-nicotinamide (NIC)-induced diabetic rats. Methods: Diabetes was induced by administration of STZ (60 mg/kg, i.p.) after 15 min of NIC (120 mg/kg i.p.) administration. The diabetic rats were treated with HALEC (300 and 600 mg/kg, p.o., respectively) for 21 d. Results: After the management with HALEC, blood glucose, HbA1c levels, total cholesterol, LDL cholesterol, triglycerides levels, glycogen phosphorylase and glucose-6-phosphatase levels were significantly diminished in diabetic rats. However, haemoglobin level, HDL cholesterol, liver glycogen, total protein, hexokinase, glucose-6-phosphate dehydrogenase levels were significantly increased in HALEC treated diabetic rats. The histopathological studies of the pancreas in HALEC-treated diabetic rats showed almost normal appearance. L6 cell line study revealed the increased glucose uptake activity of HALEC. High performance thin layer chromatography (HPTLC) analysis confirms the presence of active principles such as rutin, gallic acid and quercetin in HALEC. Conclusion: The results indicated that HALEC possess significant antihyperglycemic and antihyperlipidemic activity in STZ-NIC-induced type II diabetic rats with protective effect. This research work will be useful for the isolation of active principles and development of herbal formulation in phytopharmaceuticals.

Phytochemical Composition, In Vitro Studies On Α-Amylase And Α-Glucosidase Inhibitory Activity Of Selected Mangrove Plants

The purpose of this study is to show the phytochemical composition and in vitro antidiabetic potential in the leaves of Ceriops tagal, Bruguiera cylindrica, and Salvadora persica mangrove plants. The phytochemical composition was studied by qualitative analysis. To determine in vitro antidiabetic activity leaves were subjected to solvent extraction by the Soxhlet method using methanol, ethanol, ethyl acetate, and pet ether and α-amylase, α-glucosidase inhibition assays were performed. The findings indicates that alkaloid, steroid, flavonoid, terpenoid, glycosides, tannin, saponin, phenol, quinones and coumarin principles are present in the leaves of selected mangrove species. Among the selected mangrove species C. tagal leaves recorded the highest antidiabetic activity for both the assay followed by B. cylidrica and S. persica. Overall C. tagal was found highly potent in the antidiabetic activity.

Effect Ofco-Administration Of Emblica Officinalis And Aegle Marmelos Extracts For Antioxidant And Antidiabetic Activity

Objective: The objective of the present study was to develop an HPLC analytical method and to perform in vivo study of Emblica officinalis and Aegle marmelos extracts for antioxidant and antidiabetic activity. Methods: The phytochemical analyses, total phenolic content (TPC), TLC, DPPH assay were performed for freeze-dried Emblica officinalis fruits aqueous extract (EOFAE) and Aegle marmelos leaves ethyl acetate extract (AMLEAE). The active constituents present in both extracts were estimated by using HPLC system having Hibar® C18 column [250 x4.6 mm, 5 µm] and UV detector (264 nm). A gradient mobile phase (acetonitrile and water with 0.1% trifluoroacetic acid) was used at a flow rate of 0.8 ml/min. In vivo antioxidant, antidiabetic activity of both extracts was conducted on male albino Wistar rats for 21 d in streptozotocin-induced diabetic rats (42 rats; n=6). The antidiabetic activity was measured by blood glucose level and biochemical parameters i.e. total cholesterol, triglycerides and total protein. Oxidative stress was measured by antioxidant biomarkers i.e. SOD, GSH, lipid peroxidation by thiobarbituric acid reactive substances method on the liver of the experimental rat. Results: Tannins, saponins, carbohydrate, glycosides are found in EOFAE; coumarins and flavonoids are found in AMLEAE and quinones, phenols are present in both extracts. The values of TPC present in standard gallic acid, EOFAE and AMLEAE were found to be 485.7, 315.6, 300.7 mgGAE/g, respectively. Rf values obtained by TLC of EOFAE and AMLEAE were found to be 0.41 and 0.50, respectively. The values of % inhibition shown by EOFAE and AMLEAE in DPPH assay were found to be 97.8%±2 and 95.2%±2, respectively. The values of retention time of EOFAE and AMLEAE by HPLC analysis were found to be 4.59 and 5.28 min, respectively. Histopathological examination of the liver was revealed that low dose EOAM (containing of EOFAE 250+AMLEAE 250 mg/kg body weight) administered once a daily for 21 d showed significant activity (P˂0.001) with biochemical parameters and antioxidant biomarkers. Conclusion: The present study showed that the EOFAE and AMLEAE treated group III with (EOAM) low dose of 500 mg/kg body weight has potent antioxidant and antidiabetic activity.

Antidiabetic activity evaluation of Onobrychis species on alloxan-induced diabetic mice

In the current study, four Onobrychis species, O. albiflora Hub.-Mor., O. argyrea Boiss. subsp. argyrea Boiss., O. galegifolia Boiss., and O. tournefortii (Willd.) Desv. were collected from Anatolia to be evaluated for their antidiabetic activities. Methanol water extracts of the aerial parts were used for experiments. An alloxan-induced diabetic mice test model was used. Phytochemical analysis of the tested extracts was investigated using the HPLC method. The highest activity was observed with treatment of O. albiflora aerial part extract. Significant decrements were detected in the blood glucose levels as follows: 180.83±47.48 and 252.83±50.47mg/dL at 100 mg/kg and 200 mg/kg doses of O. albiflora, respectively, when compared to the isotonic saline solution control group, eliciting a blood glucose level of 494.20±27.32. Among the tested standard compounds, rutin and isoquercetin were detected in the examined species. The highest amount of rutin (1.1981±0.0017%) and isoquercetin (0.7318±0.0197%) were found in O. albiflora and O. argyrea subsp. argyrea, respectively. Antidiabetic activities of the tested Onobrychis species seem to indicate a possible correlation with their rutin and isoquercetin contents. Therefore, rutin and isoquercetin may be the antidiabetic compounds that contribute to the antidiabetic activity of the tested Onobrychis species.

Hypoglycemic and antioxidant activities of Clerodendrum inerme leaf extract on streptozotocin-induced diabetic models in mice / 中草药·英文版

Objective: Recently, much attention has been paid to natural product-derived compounds for antidiabetic drug discovery. More recent studies are being focused on clarifying the bioactivity of plants and derived products. The aim of the present study was to investigate the anti-oxidant and antidiabetic activities of Clerodendrum inerme leaf extract (CILE) in streptozotocin-induced diabetic mice. Methods: C. inerme leaves were analyzed for preliminary phytochemical properties and the content of total phenolic and flavonoid were determined. In vitro anti-oxidant activity was measured using DPPH assay. Streptozotocin-induced diabetic model in mice was applied for in vivo study by the effect of CILE at two dose levels (343 and 686 mg/kg b.w.). Results: The results showed that C. inerme leaves contained the major constituents of flavonoids, alkaloids, tannins, triterpenes, and saponins. CILE exhibited the total polyphenol and flavonoid content with 120.458 mg gallic acid equivalent/g dry weight and 4.494 mg hispidulin equivalent/g dry weight, respectively. The anti-oxidant activity of CILE was expressed with IC50 = 25.28 µg/mL. CILE at the doses of 343 mg/kg and 686 mg/kg after 7 d administration exerted a decrease in plasma glucose, protected the liver, kidneys against oxidation stress via increasing glutathione content in the liver, and reduced malondialdehyde content in the liver and kidneys. Pancreatic histological analysis in diabetic mice treated with CILE also showed the pancreatic β-cells regeneration via increasing the size and number of pancreatic islets. Conclusion: These findings suggested that C. inerme leaves had potent antidiabetic and anti-oxidant activities. The results provide reliable scientific base, which is the premise for further research and development of CILE as supplements.

Antidiabetic, antihyperlipidemic and antioxidant influences of the spice cinnamon ( Cinnamomum zeylanicumon ) in experimental rats

ABSTRACT The present study investigates the effect of cinnamon (Cinnamomum zeylanicumon) powder supplementation on glucose levels, lipid profiles, and oxidative stress parameters in alloxan-induced diabetic rats. Diabetes was induced in adult male Wistar rats via a single subcutaneous alloxan injection (15 mg/kg). Cinnamon powder was mixed with the standard feed of the rats in an amount of 5% for 28 consecutive days. Serum concentrations of total cholesterol (TC) and triglycerides (TG) were assayed at the end of the experimental period in all investigated groups. Anti-oxidative enzymes such as glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) were sought in the serum and pancreas. Alloxan caused the fasting blood sugar level to increase. The administration of cinnamon blocked the increase of blood glucose. There was also a significant difference in the TG and TC levels between control and treated diabetic rats. In diabetic rats, cinnamon treatment restored the activities of SOD, CAT and GPx. These findings suggested that cinnamon has an anti-hyperglycemic effect, improves lipid profiles, and protect against damage induced by oxidative stress in the diabetic state.

Preparation and therapeutic evaluation of rutin-phospholipid complex for antidiabetic activity.

The objective of the present work to prepare Rutin-phospholipid complex (RPC), a phytoformulation and characterization, evaluation for its antidiabetic activity in streptozotocin induced diabetic model. Prepared RPC was characterized and screened for antidiabetic activity by OGTT in normoglycemic and diabetic rats for RT and RPC at different time intervals. Effect of RT and RPC (50 and 100 mg/kg b.w. p.o. respectively) in STZ induced diabetic rats for one day and fifteen days was studied. This is followed by estimation of Estimation of SG, and lipid parameters. Histopathology studies of pancreatic tissue and bioavailability studies of RT & RPC were also carried out. SEM data showed that RPC has irregular size vesicles consisting of phosphatidylcholine. RPC showed a single endothermal peak at 147.68°C in DSC studies. OH group has shifted to lower frequency in phytosome compared to rutin phospholipid in FTIR spectra. Treatment with RPC (50 and 100 mg/kg b.w. p.o.) significantly reduced the blood glucose levels and restored the altered lipid parameters as compared to RT. Histopathological studies revealed that RPC also restored back the size of pancreatic islets and maintained the normal β-cells. A higher serum concentration of RT (13.20 μg/mL) in RPC treated group was observed in bioavailability studies as compared to RT. RPC maintained effective concentration of rutin for a longer period in rat serum.

In vitro inhibitory effects on α-glucosidase and α-amylase level and antioxidant potential of seeds of Phoenix dactylifera L

Objective: To evaluate and compare the antioxidant activity, total phenolic contents (TPCs) and in vitro antidiabetic activity of various pits extracts obtained from five Omani date cultivars. Methods: Sun-dried mature fruits of five Omani date varieties, namely, Fardh, Naghal, Khalas, Khinazi and Khasab were purchased from the local market in Muscat, Oman in the month of September 2014. Four seed extracts viz. water, ethanol, methanol and acetone were prepared for each date variety and their antioxidant activities were investigated by 1,1-diphenyl-2-picrylhydrazyl, hydrogen peroxide scavenging method and reducing power assay method, respectively. In vitro antidiabetic activity of the date pit extracts was evaluated by measuring their inhibitory effect on α-glucosidase and α-amylase level. TPCs were also quantified colorimetrically. Results: The results indicated that TPC of date seeds was solvent dependent. Acetone, ethanol and methanol were found to be significantly better solvents than water in extracting phenolic compounds from the date seeds. Pit extracts exhibited moderate to good in vitro antioxidant activity and increased reducing power. Among all date pit extracts, water extract exhibited significant in vitro antidiabetic activity in comparison to standard drug, acarbose. Conclusions: The present study confirms that disposed waste of Omani dates is a rich source of dietary antioxidant because of its high TPC. The pits due to their inhibitory effects on α-glucosidase and α-amylase level could be used as a monotherapy along with an appropriate diabetic diet and exercise or might be in conjunction with antidiabetic therapy to manage and prevent progression of diabetes.

Evaluation of hypoglycemic and hypolipidemic activities of aqueous extract of Cistus ladaniferus in streptozotocin-induced diabetic rats

Objective To evaluate the effect of aqueous leaf extract of Cistus ladaniferus (C. ladaniferus) on glycemic and lipidemic status in diabetic rats. Methods Overnight fasted rats were injected intraperitoneally with streptozotocin (45 mg/kg) to induce experimental diabetes. The aqueous extract of the leaves of C. ladaniferus was administered orally at the dose of 500 mg/kg body weight to diabetic rats for a period of 28 days. Hypoglycemic effect, body weight, oral glucose tolerance, change in lipid parameters, urea, creatinine, aspartate aminotransferase and alanine aminotransferase levels of diabetic rats treated with aqueous extract were evaluated in experimental animals. Results Administration of 500 mg/kg of C. ladaniferus extract to diabetic rats for 28 days resulted in a significant reduction in the levels of blood glucose, alanine aminotransferase, aspartate aminotransferase, urea and creatinine. Furthermore, the extract of C. ladaniferus improved glucose tolerance in diabetic rats, and its antidiabetic effect was similar to the one obtained with glibenclamide. The hypolipidemic effect was demonstrated by an important decrease in plasma total cholesterol, triglycerides and low density lipoprotein-cholesterol levels. Conclusions It is concluded that C. ladaniferus leaf extract showed an antidiabetic activity in experimental diabetes which was similar to the one obtained with glibenclamide.

Antidiabetic Potential of Potentilla fulgens Roots in Validated Animal Models of Diabetes

The present study was undertaken to investigate the antidiabetic potential of tap roots of Potentilla fulgens in streptozotocin induced diabetic rat models. The crude powder, ethanolic, ethanolic: aqueous and aqueous extracts of tap roots were administered to normoglycemic- and streptozotocin (STZ)-induced diabetic rats in a single dose study. The ethanolic extract showed significant improvement in oral glucose tolerance and antihyperglycemic effect on sucrose loaded normal rats and STZ-induced diabetic rats. Of the isolated aqueous, n-butanol, chloroform and n-hexane soluble fractions of the active ethanolic extract of the roots, the aqueous fraction (100 mg/kg body weight) showed significant blood glucose lowering effect on STZ-induced diabetic rats. In a multiple dose study, aqueous fraction of ethanolic extract of P. fulgens roots significantly improved the body weight, percent glycated hemoglobin (%HbA1c), fasting blood glucose, oral glucose tolerance (OGTT), serum insulin, lipid profile, liver and kidney parameters in STZ-induced diabetic rats. The aqueous fraction also showed marked improvement in OGTT and serum insulin level in neonatal STZ-induced diabetic rats for 30 consecutive days. The aqueous fraction of the roots also inhibited the activity of alpha (α)-glucosidase enzyme in a dose dependent manner. In conclusion, the finding suggested that an aqueous fraction of tap roots of P. fulgens possessed potential antidiabetic activity.

HPTLC finger printing profile and evaluation of in vitro antidiabetic potential of medicinally important plant Cassia obtusa L. (Caesalpiniaceae).

The aim of the study was to establish the finger printing profile and evaluation of in vitro antidiabetic potential of C. obtusa. In vitro antidiabetic activity was carried out according to the method adopted by Miller, 1959. HPTLC studies were carried out using CAMAG HPTLC system equipped with Linomat 5 applicator, TLC scanner 3 and Win cats-4 software for the active fractionation of aqueous-methanolic leaf extracts of C. obtusa. Among the various plant parts analyzed, leaf exhibited efficient inhibitory activity against α-amylase and α-glucosidase enzymes. Therefore, the leaf extract was further fractionated using various solvent systems petroleum ether, chloroform, ethylacetate, butanol and water and were subjected to in vitro antidiabetic activity. Among the fractions analyzed chloroform fraction exhibited remarkable antidiabetic activity by inhibiting α-amylase and α- glucosidase enzymes. Furthermore, the active leaf fractions were analyzed with HPTLC to develop fingerprint profiles and these fractions revealed the presence of 13 and 22 major spots of alkaloids and flavonoids respectively with different Rf values. The results of the present study thus claim the folkloric usage of the plant in diabetic related maladies.

Efecto inhibitorio de un extracto acuoso de las hojas de Allophylus cominia (L) Sw sobre las proteínas tirosina fosfatasa 1B y dipeptidil peptidasa IV / Inhibitory effect of Allophylus cominia (L) Sw leaves aqueous extract on tyrosine phosphatase 1B and dipeptidyl peptidase IV proteins

Introducción: Allophylus cominia (L.) Sw es una planta medicinal cubana usada por la medicina tradicional para el tratamiento de la diabetes, cuyo mecanismo de acción es desconocido. Objetivo: evaluar el efecto del extracto acuoso de hojas de A. cominia (L.) Sw y sus fracciones sobre la proteína tirosina fosfatasa 1B (PTP1B) y dipeptidil peptidasa IV (DPPIV) como diana terapéuticas para el tratamiento de la diabetes tipo 2. Métodos: el extracto acuoso de hojas de A. cominia fue fraccionado sucesivamente con mezclas de solventes orgánicos, incrementando la polaridad, para obtener diez fracciones. El extracto y sus fracciones fueron evaluados para su posible actividad antidiabética sobre diana terapéuticas de diabetes tipo 2: PTP1B y DPPIV. Se realizaron ensayos de inhibición enzimática y la actividad inhibitoria se calculó a partir de los valores de fluorescencia, empleando longitudes de onda de excitación y de emisión de 360 nm y 460 nm respectivamente. Resultados: el extracto acuoso de A. cominia inhibió la actividad enzimática de PTP1B y DPPIV de manera dependiente de la concentración, con valores de CI50 de 0,69 µg/mL y 344,3 µg/mL respectivamente. Varias fracciones se detectaron como potentes inhibidores de PTP1B. Las fracciones más polares AcF9 y AcF10 fueron las más activas, y mostraron valores de CI50 de 4,4 µg/mL y 3,8 µg/mL respectivamente. Las fracciones mostraron una ligera inhibición de DPPIV, y las más activas resultaron AcF6, AcF9 y AcF10, con valores de porcentajes de inhibición de 52,0 por ciento, 39,0 por ciento y 40,0 por ciento respectivamente. Conclusiones: el extracto acuoso de A. cominia y sus fracciones polares (AcF9 y AcF10) tienen propiedades antidiabéticas in vitro y son candidatos promisorios para el desarrollo de nuevos medicamentos con actividad inhibidora de PTP1B y DPPIV para el tratamiento de la diabetes tipo 2(AU)

INTRODUCTION: Allophylus cominia (L.) Sw is a Cuban medicinal plant used by traditional medicine for the treatment of diabetes with unknown mechanisms of action. OBJECTIVE: to evaluate the effect of Allophylus cominia (L.) Sw leaves aqueous extract and its fractions on protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase IV (DPPIV) enzymatic activity, as therapeutic targets of type 2 diabetes. METHODS: the aqueous extract of A. cominia leaves was successively partitioned with organic solvents mixtures, thus increasing polarity in order to obtain ten fractions. The extract and its fractions were tested for their possible antidiabetic activity on therapeutic targets of type 2 diabetes: PTP1B and DPPIV. The enzymatic inhibition assays were performed and the inhibitory activity was calculated with the fluorescence values using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. RESULTS: the aqueous extract from A. cominia inhibited the enzymatic activity of PTP1B and DPPIV according to the concentration, being IC50 values equal to 0.69 µg/mL and 344.3 µg/mL, respectively. Several fractions were detected as potent PTP1B inhibitors. The most polar fractions AcF9 and AcF10 were more active, showing IC50values of 4.4 µg/mL and 3.8 µg/mL respectively. The fractions showed a slight DPPIV inhibition, being fractions AcF6, AcF9 and AcF10 the most active, exhibiting inhibition percentages of 52.0 percent, 39.0 percent and 40.0 percent respectively. CONCLUSIONS: A. cominia aqueous extract and its polar fractions (AcF9 and AcF10) have antidiabetic properties in vitro and are promissory candidates for development of new drugs with inhibitory activity of PTP1B and DPPIV for type 2 diabetes treatment(AU)

Bioassay Guided Isolation and Evaluation of the Antidiabetic Principles of Combretum dolichopetalum Root.

Aims: The present study was aimed at investigating the antidiabetic potentials of Combretum dolichopetalum root in alloxan-induced animals with the hope of isolating its antidiabetic principles. Study Design: Sixty four Wistar albino rats of either sexes were randomly segregated into 16 groups (n=4). Also, thirty two albino mice were segregated into 8 groups. These received various doses of the plant sample, vehicle or glibenclamide for the antidiabetic study. Place and Duration of Study: This study was done in the laboratory of the Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka between March and October, 2013. Methodology: The root of C. dolichopetalum was extracted with methanol (ME) and fractionated successively with various solvents (n-hexane, chloroform, ethylacetate, methanol and water) to afford the respective fractions: HF, CF, EF, MF and AF. CF was further fractionated to afford six sub-fractions: C1-C6. Acute toxicity study was done using ME. Antidiabetic activity of various doses (p.o.) of ME (100, 200, 400 and 600 mg/kg body weight), its fractions (200 and 400 mg/kg) and sub-fractions (200 mg/kg), glibenclamide (0.2 mg/kg) and vehicle (control) were investigated in alloxan-induced (i.p.) diabetic animals for 9 h. Phytochemical analysis was also carried on ME and fractions. Results: The extract was considered safe with LD50 greater than 5000 mg/kg. ME (400 mg/kg), CF (400 mg/kg) and C3 (200 mg/kg) produced maximum reduction (36.78%, 72.43% and 83.17% respectively) in fasting blood glucose of animals after 9 h which were significantly (P < .01, P < .001) different from the control and better than glibenclamide (48.18%). Phytochemical analysis showed alkaloids, flavonoids, terpens and steroids as the likely antidiabetic agent(s). Conclusion: The root of C. dolichopetalum possesses potent antidiabetic activity which increases as the extract is purified. The antidiabetic effect of the plant may likely be due to the presence of alkaloids, flavonoids, terpens or steroids.

Anti-hyperglycemic activity of Rutin in streptozotocin-induced diabetic rats: An effect mediated through cytokines, antioxidants and lipid biomarkers.

Administration of rutin (50 and 100 mg/kg) and pioglitazone (10 mg/kg) orally for 3 weeks treatment significantly improved body weight, reduced plasma glucose and glycosylated hemoglobin, pro-inflammatory cytokines (IL-6 and TNF-α), restored the depleted liver antioxidant status and serum lipid profile in high fat diet + streptozotocin induced type 2 diabetic rats. Rutin treatment also improved histo-architecture of ß islets and reversed hypertrophy of hepatocytes. Rutin exhibited significant antidiabetic activity, presumably by inhibiting inflammatory cytokines, improving antioxidant and plasma lipid profiles in High fat diet + streptozotocin induced type 2 diabetic model and may be useful as a diabetic modulator along with standard antidiabetic drugs. However, such effects need to be confirmed on human subjects in clinical condition.

Inhibitory effect of Persea americana Mill leaf aqueous extract and itsfractions on PTP1B as therapeutic target for type 2 diabetes / Efecto inhibidor del extracto acuoso de hojas de Persea americana Mill y sus fracciones sobre PTP1Bcomo diana terapéutica para la diabetes tipo 2

Persea Americana Mill (Lauraceae), is a popular plant in Cuba due to its nutritional and medicinal properties. The fruit of the plant is commonly known as avocado. The leaves of Persea americana Mill have been popularly used in the treatment of diabetes incountries in Latin America and Africa. The present study is aimed to explore one of the underlying mechanisms that mediate the antidiabeticefficacy of Persea americana Mill. The aqueous extract from the leaves of the plant and its fractions were evaluated on the inhibitory activity of the protein tyrosine phosphatase 1B (PTP1B) as target of type 2 diabetes. The results revealed that aqueous extract from Pamericana inhibited the enzymatic activity of PTP1B in an extract concentration dependent manner, resulting mainly active the most polarfraction. The present research demonstrated that aqueous extract from P americana and polar fraction (PaF10) have promissory antidiabetic properties mediated by PTP1B, which is a relevant mechanism involved on insulin resistance in type 2 diabetes.

Persea americana Mill. (Lauraceae), es una planta popular en Cuba, debido a sus propiedades nutricionales y medicinales. El fruto de la planta se conoce comúnmente como aguacate. En la etnomedicina las hojas de Persea americana Mill. se han utilizadopopularmente en el tratamiento de la diabetes en varios países en Latinoamérica y África. El presente estudio tuvo el objetivo de explorar laeficacia antidiabética y el mecanismo subyacente, de las hojas de Persea americana. El extracto acuoso de las hojas de la planta y sus fracciones, se evaluaron en un blanco terapéutico de interés en la de diabetes tipo 2: actividad enzimática de la proteína tirosina fosfatasa 1B (PTP1B). Los resultados revelaron que el extracto acuoso de P americana inhibe la actividad enzimática de la enzima PTP1B en una manera dependiente de la concentración, resultando más activa la fracción de mayor polaridad. La presente investigación demostró que elextracto acuoso de P americana y su fracción polar (PaF10), poseen efecto antidiabético promisorio, debido al efecto inhibitorio de PTP1B, mecanismo relevante en la insulino resistencia en la diabetes tipo2.