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ABSTRACT: The ethanolic extract of seeds of Cuminum cyminum (C.c) was found to improve glucose tolerance to the tune of around 18.3% (P \ 0.01) in normal rats and shows around 17.7% (P \ 0.01) and 17.1% fall on blood glucose levels at 0–300 and 0–1440 min, respectively, on streptozotocin-induced diabetic rats at an oral dose of 250 mg/Kg body weight. The extract has also been found to improve around 26.7% (P \ 0.01) glucose intolerance on 14th day post treatment in high fructose fed streptozotocin-induced diabetic rats. The extract was also found to have antidyslipidemic activity as evident by 21.04% (P \ 0.01) decline in serum triglycerides, 22.7% (P \ 0.01) decline in total serum cholesterol, and 16.9% of decline in serum LDL-C, respectively, along with 12.2% (P \ 0.05) increase in serum HDL-C on high fat diet fed male Syrian golden hamster. The extract was also found inhibitory to eye lens aldose reductase (EC 1.1.1.21) with IC 50 value of 7.07 lg/ml as compared to the standard AR inhibiting compound Quercetin which showed IC 50 2.35 lg/ml. The extract was also found inhibitory to a-glucosidase with IC 50 value of 100 lg/ml as compared to known drug Acarbose which showed IC 50 of around 25 lg/ml.
Medicinal Chemistry Research 04/2013; · 1.27 Impact Factor
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ABSTRACT: The diastereomeric mixture of calophyllic acid and isocalophyllic acid (F015) isolated from the leaves of Calophyllum inophyllum was investigated for the metabolic effect on glucose transport in skeletal muscle cells. In L6 myotubes, F015 dose-dependently stimulated glucose uptake by increasing translocation of glucose transporter4 (GLUT4) to plasma membrane without affecting their gene expression. The effects on glucose uptake were additive to insulin. Inhibitors analyses revealed that F015-induced glucose uptake was dependent on the activation of phosphatidylinositol-3-kinase (PI-3-K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), while independent to the activation of 5'AMP-activated kinase (AMPK). F015 significantly increased the phosphorylation of AKT, AS160 and ERK1/2, account for the augmented glucose transport capacity in L6 myotubes. Furthermore, F015 improved glucose tolerance and enhanced insulin sensitivity in skeletal muscle of dexamethasone-induced insulin resistant mice. Our findings demonstrate that F015 activates glucose uptake in skeletal muscle cells through PI-3-K- and EKR1/2-dependent mechanisms and can be a potential lead for the management of diabetes and obesity.
Molecular and Cellular Endocrinology 02/2013; · 4.19 Impact Factor
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ABSTRACT: A new class of N-substituted piperazine analogues of imbricatolic acid have been designed and synthesized by using the appropriate synthetic routes in excellent yield. All synthesised compounds were screened for their in vitro glucose uptake stimulatory activity. Among them compounds 4b, 4e, 8b, and 8e triggered L6 skeletal muscle cells for glucose uptake at 54.73%, 40.79%, 40.90%, and 39.55% stimulation, respectively. Compound 4b has emerged as important lead compound showing potential antidiabetic activity. Illustration about their synthesis and in vitro glucose uptake activity is described.
Bioorganic & medicinal chemistry letters 06/2012; 22(14):4636-9. · 2.65 Impact Factor
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Alok K Verma,
Himanshu Singh,
Mavurapu Satyanarayana,
Swayam P Srivastava,
Priti Tiwari,
Amar B Singh,
Anil K Dwivedi,
Shio K Singh,
Mukesh Srivastava,
Chandishwar Nath,
Ram Raghubir, Arvind K Srivastava,
Ram Pratap
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ABSTRACT: The hybrid congeners 62-90 of 6- and 7-hydroxyflavones with aminopropanol have been synthesized and evaluated for their antidiabetic activity in sucrose-challenged low-dosed streptozotocin (STZ)-induced diabetic rats and db/db mice. The optical enantiomers 70a, 70b, 90a, and 90b of two congeners 70 and 90 exhibiting consistent antidiabetic and antidyslipidemic activities were also prepared, and their antidiabetic activity results indicate its association mainly with S isomers. These compounds also lower cholesterol and TG profiles while improving high-density lipoprotein cholesterol to CHOL ratio in db/db mice. The bioavailability of compound 70 and its isomer varies between 27 and 29% whereas that of the more polar compound 90a is poor as determined in rat by oral and intraperitoneal administrations.
Journal of Medicinal Chemistry 04/2012; 55(10):4551-67. · 4.80 Impact Factor
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ABSTRACT: The root of Glycyrrhiza glabra is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, pulmonary
and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties
such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective
and cardioprotective effects. Glycyrrhizinic acid, a major component of licorice, has antiulcer effect by raising the local
concentration of prostaglandins that promote mucous secretion and cell proliferation in the stomach. Glycyrrhizin shows hepatoprotective
effect by preventing changes in cell membrane permeability, inhibiting phospholipase A2 (PLA2) and increasing survival rate of hepatocytes. Glabridin has effect in melanogenesis and inflammation by inhibiting the tyrosinase
activity of melanocytes. α-glycyhrritinic acid exhibits anti-inflammatory activity by inhibiting glucocorticoid metabolism.
In present study ethanolic (95%) extract of root of Glycyrrhiza glabra and its fractions were investigated for its antidyslipidaemic
activity on HFD induced dyslipidaemic hamsters. Ethanolic extract and its ethyl acetate soluble, water soluble and hexane
soluble fractions decreased serum level of total cholesterol by 25.9, 38.0, 39.0 and 26.3%, respectively. On the other hand
ethanolic extract, ethyl acetate soluble, water soluble and hexane soluble fraction increased the serum HDL-cholesterol level
by 14.8, 34.3, 27.3 and 17.2%, respectively. Ethanolic extract, ethyl acetate fraction, aqueous fraction and hexane fraction
decreased triglyceride level by 31.3, 37.2, 41.2 and 28.9%, respectively. The reduction in LDL-cholesterol level by ethanolic
extract, ethyl acetate soluble fraction and water soluble fraction were 43.9, 31.0, 33.4 and 24.6%, respectively.
Indian Journal of Clinical Biochemistry 04/2012; 24(4):404-409.
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ABSTRACT: The antidiabetic effect of the ethanolic extract of Eclipta alba (EEA) on hyperglycaemia and diabetic nephropathy was investigated in streptozotocin-induced diabetic rats. Single-dose treatment of EEA to streptozotocin-induced diabetic rats lowered the blood glucose level by 17.6% (p < 0.05) at 250 mg kg(-1) dose after 5 h post oral administration. Treatment of animals after 10 weeks of STZ-treatment with EEA (250 mg kg(-1)) for 21 days significantly reduced the elevated levels of blood glucose, %HbA1C, urea, uric acid and creatinine, and significantly increased the depressed serum insulin level. The extract exerted a significant inhibitory effect on alpha-glucosidase in a noncompetitive manner with an IC(50) value of around 54 µg mL(-1) and was found inhibitory to eye lens aldose reductase with an IC(50) value of around 4.5 µg mL(-1). The results suggest that EEA possesses antidiabetic effect associated with alpha-glucosidase and aldose reductase inhibition.
Natural product research 02/2012; · 1.01 Impact Factor
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ABSTRACT: Phytochemical investigation of the ethanolic extract of twigs of Kigelia pinnata DC. afforded one new iridoid 7-hydroxy eucommiol (1), and nine known compounds (2-10). The structure of compounds was elucidated by extensive spectroscopic methods, including 1D, 2D NMR experiments and MS analysis. All these compounds were evaluated for GLUT4 translocation modulatory effect in skeletal muscle cells. Four of the tested compounds 1, 5, 6 and 7 showed significant stimulation of GLUT4 translocation to cell surface in skeletal muscle cells without any adverse effect on cell viability. Effect of these four compounds was concentration-dependent and comparable to standard drug rosiglitazone. These findings indicate that constituents of K. pinnata may provide leads for the therapeutics for insulin resistance and diabetes.
Fitoterapia 01/2012; 83(1):125-9. · 1.85 Impact Factor
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Nimisha Singh,
Sarvesh Kumar Pandey,
Namrata Anand,
Richa Dwivedi,
Shyam Singh,
Sudhir Kumar Sinha,
Vinita Chaturvedi,
Natasa Jaiswal, Arvind Kumar Srivastava,
Priyanka Shah,
M Imran Siddiqui,
Rama Pati Tripathi
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ABSTRACT: An economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines and 9-(arylidene)-4-(aryl)-6,7,8,9-tetrahydro-5H-cycloheptapyrimidin-2-ylamines by the reaction of bis-benzylidene cycloalkanones and guanidine hydrochloride in presence of NaH has been developed. All the synthesized compounds were evaluated against Mycobacterium tuberculosis H(37)Rv strain and the α-glucosidase and glycogen phosphorylase enzymes. Few of the compounds have shown interesting in vitro activity with MIC up to 3.12 μg/mL against M. tuberculosis and very good inhibition of α-glucosidase and glycogen phosphorylase enzymes. The most potent non toxic compound 40 exhibited about 58% ex vivo activity at MIC of 3.12 μg/mL. The present study opens a new gate to synthesize antitubercular agents for diabetic TB patients. In silico docking studies indicate that mycobacterial dihydrofolate reductase is the possible target of these compounds.
Bioorganic & medicinal chemistry letters 08/2011; 21(15):4404-8. · 2.65 Impact Factor
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ABSTRACT: 16-Dehydropregnenolone undergoes a smooth annulation with propan-1-amine and aromatic aldehydes. Several amine derivatives of 16- dehydropregnenolone were synthesized and evaluated as inhibitors of DPP-IV. The structures of compounds were confirmed by (1)H, (13)C, NMR and mass spectral analysis. Among 17 compounds evaluated only five compounds 1, 9, 13, 15 and 16 demonstrated significant inhibition of DPP. This study suggest that introduction of appropriate substituents in the 16-dehydropregnenolone plays an important role in DPP-IV inhibitory activity.
Bioorganic & medicinal chemistry letters 03/2011; 21(8):2232-7. · 2.65 Impact Factor
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ABSTRACT: Various phenolic C-glycosides were evaluated for their in vitro and in vivo antihyperglycemic activity employing glucose uptake by rat muscle cell lines (L-6) and low dosed-streptozotocin-induced diabetic rats, respectively. Some of phenolic C-glycosides were isolated from Pterocarpus marsupium and Ulmus wallichiana and other were synthesized by unprotected sugar and phloroacetophenone using Sc(OTf)(3) in aqueous ethanol. Eight among tested compounds showed significant lowering of blood glucose level on low dosed-streptozotocin-induced diabetic rats. The compound 24 lowered the blood glucose levels by 34.9% and 33.6% during 0-5h and 0-24h, respectively, at the dose of 25mg/kg body weight which is comparable to standard antidiabetic drug metformin.
Bioorganic & medicinal chemistry letters 01/2011; 21(1):228-33. · 2.65 Impact Factor
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ABSTRACT: A series of 2,4-disubstituted polyhydroquinoline were synthesized and evaluated for their in vivo antihyperglycemic as well as antidyslipidemic activities. Several synthesized compounds have exhibited promising in vivo antihyperglycemic in SLM, STZ-S, and db/db mice model along with significant lipid and TG modulating activity. All these compounds were evaluated in various in vitro models of diabetes to know the possible mechanism of their antihyperglycemic action. Interestingly, compounds 3a-r (diaryl substitution) have exhibited promising protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity whereas, compounds 5a-d (acid substituted) have shown significant glycogen phosphorylase activity.
Bioorganic & medicinal chemistry 06/2010; 18(11):4138-48. · 2.82 Impact Factor
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ABSTRACT: The present report confirms the anti-hyperglycaemic and anti-dyslipidemic properties of 4-hydroxyisoleucine, an unusual amino acid isolated from Trigonella foenum-graecum seeds, for the first time in a well-characterised model of type II diabetes, i.e. db/db mice. 4-Hydroxyisoleucine, when given orally to these mice at 50 mg kg(-1) dose level, significantly (p < 0.05) declined their elevated blood glucose, plasma insulin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol levels and raised their declined plasma high-density lipoprotein-cholesterol level. These results indicate that 4-hydroxyisoleucine exhibits significant potential as an anti-diabetic agent by suppressing progression of type II diabetic states that is suggested by enhancement of insulin sensitivity and glucose uptake in peripheral tissue.
Natural product research 02/2010; 24(3):258-65. · 1.01 Impact Factor
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ABSTRACT: A sharp increase in the incidence of type-2 diabetes especially in the developed and fast developing countries is a matter of serious concern. Peroxisome proliferator-activated receptors (PPARs) are important targets for drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type 2 diabetes mellitus (T2DM), and other diseases characterized by abnormal regulation of the glucose and lipid metabolism. Many molecules targeting the PPARγ receptor have come out as drugs in T2DM and established themselves in prescriptions and have gained a widespread acceptance with the physicians and patients. Despite the recent clinical success, the discovery of novel agonists for PPAR remains to be active area of research for medicinal chemist. In conjunction with the efforts to discover novel and potent PPARγ agonists, the present research work aims to explore newer binding groups as replacement of well established cyclic acidic head group eg. thiazolidine-diones for designing novel series of PPARγ ligands employing de novo design protocols.
International conference on Recent Advances in Cardiovascular Sciences (RACS 4th); New Delhi., New Delhi; 01/2010
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ABSTRACT: Bioactivity-guided separation of an antihyperglycemic extract from the leaves of Dodecadenia grandiflora afforded two phenylpropanoyl esters of catechol glycosides (1 and 4) and two lignane bis(catecol glycoside)esters (2 and 3). Their structures were established on the basis of extensive spectroscopic analysis (1D and 2D-NMR, MS). Compounds 2 and 3 are believed to be derived from dimerization via the two phenylpropanoid units of 1. Compounds 1-4 showed significant antihyperglycemic activity in streptozotocin-induced (STZ) diabetic rats, which is comparable to the standard drug metformin. Our results provide support to explain the use of D. grandiflora as antihyperglycemic agent by the traditional medical practitioners.
Phytochemistry 09/2009; 70(11-12):1448-55. · 3.35 Impact Factor
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ABSTRACT: The db/+ mice, which represent the heterozygous counterpart of diabetic db/db mice, are carriers of the mutated gene of the leptin receptor but do not become diabetic at any stage during their lifespan. These mice are being used only for the production of db/db mice. Attempts were made to develop these mice as an alternate in vivo model for antidiabetic drug screening.
Diabetes was induced by injecting streptozotocin, and establishment of diabetic condition was confirmed by measuring blood glucose level, insulin level, body weight, lipid profile, and activity of the key enzymes of carbohydrate metabolism.
Animals showed the characteristics of diabetes throughout the study period and also showed the beneficial effect of the treatment of the gold standard antidiabetic drug metformin that validates these mice as a screening model.
Results showed that streptozotocin-treated db/+ mice can be used as an alternate model in antidiabetic drug discovery research.
Archives of medical research 03/2009; 40(2):73-8. · 1.88 Impact Factor
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ABSTRACT: A new steroidal saponin, chloragin (1), was isolated and characterised from the aerial part of Chlorophytum nimonii. The structure of chloragin (1) was established as tigogenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 4)-beta-D-xyloopyranoside on the basis of detailed chemical and spectral evidence. The saponin showed potent antihyperglycaemic and antidyslipidaemic activities in albino rats.
Natural product research 02/2009; 23(10):963-72. · 1.01 Impact Factor
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ABSTRACT: A number of O-alkylated xanthone, carbazoles and coumarins have been synthesised and screened for their in vitro anti-diabetic activity, such as glucose-6-phosphatase, glycogen phosphorylase and alpha glucosidase inhibitors. Compounds which were showing significant percentage inhibition were also tested for in vivo anti-hyperglycemic activity in sucrose loaded normal and streptozotocin (STZ)-induced diabetic rats. These compounds show 22.1, 24.4 and 26.7% and 20.8, 25.0, 20.5% lowering in sucrose loaded normal rats and STZ-induced diabetic rats at a dose of 100 mg kg(-1).
Natural product research 02/2009; 23(1):60-9. · 1.01 Impact Factor
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ABSTRACT: The ethanolic extracts of a mangrove plant Ceriops tagal (Family Rhizophoraceae) and its sequential fractions thereof were studied for their effect on 3H-2-deoxyglucose uptake by L6 rat muscle cells cultured to the myotube stage. Among these, the n-hexane soluble fraction of ethanolic extract of the leaves of C. tagal enhanced 3H-2-deoxyglucose uptake even at 2 microg mL(-1) concentration with half maximum activity at 10 microg mL(-1), comparable with insulin (1 microM) and metformin (400 microM). This enhancement in glucose uptake was found to be insulin independent and in contrast to insulin, its effect was also prevalent in undifferentiated myoblasts. It may be concluded from the results that n-hexane soluble fraction of ethanolic extract of C. tagal have the property to stimulate the glucose uptake, which might be a useful source for the isolation of new antihyperglycemic compounds.
Natural Product Research 06/2008; 22(7):592-9. · 1.01 Impact Factor
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ABSTRACT: Antihyperglycaemic effect of the crude extract (1) and four fractions (2, 3, 4, and 5) of Ceriops tagal (Perr.) C.B. Rob. (Rhizophoraceae) were evaluated in normal healthy sucrose-loaded and STZ-induced diabetic rats. The crude
extract improved the glucose tolerance of the sucrose-loaded rats significantly (p<0.05) with 33.2% activity, while in STZ-induced diabetic rats the extract caused a fall of 10.9% in hyperglycaemia. All
of the four isolated fractions improved the glucose tolerance of normal rats post sucrose load, albeit to varying degree.
Fraction 4 exerted the strongest effect of 37.2% (p<0.05) in sucrose-loaded rats while in STZ-induced diabetic rats it caused a fall of 17% (p<0.05) in hyperglycaemia. The fasting blood glucose levels of STZ-induced diabetic rats were normalized and the glucose
tolerance of these animals was significantly improved after 20 days of daily oral administration of fraction 4 at a 100 mg/kg
dose.
Medicinal Chemistry Research 05/2008; 17(2):74-84. · 1.27 Impact Factor
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ABSTRACT: A series of chalcone based aryloxypropanolamines were synthesized and evaluated for their antihyperglycemic activity in SLM and STZ rat models. Most of the compounds exhibited moderate to good activity ranging from 6.5% to 31.1% in SLM and 8.3% to 22.6% in STZ models, respectively. The most potent compound 5 g exhibited glucose lowering of 26.7% in SLM and 22.6% in STZ models. A definite structure-activity relationship was observed while varying the nature as well as the position of the amine in ring B.
Bioorganic & Medicinal Chemistry Letters 03/2007; 17(3):799-802. · 2.55 Impact Factor
