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Viswanatha G.L.,Industrial Research Ltd. | Venkataranganna M.V.,Connexios Life science Pvt. Ltd. | Prasad N.B.L.,Andhra University | Ashok G.,Industrial Research Ltd.
Journal of Intercultural Ethnopharmacology | Year: 2016

Objectives: This study was aimed to examine the anti-epileptic activity of leaf extracts of Punica granatum in experimental models of epilepsy in Swiss albino mice. Materials and Methods: Petroleum ether leaf extract of P. granatum (PLPG), methanolic LPG (MLPG), and aqueous LPG (ALPG) extracts of P. granatum leaves was initially evaluated against 6-Hz-induced seizure model; the potent extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Further, the potent extract was evaluated for its influence on Gamma amino butyric acid (GABA) levels in brain, to explore the possible mechanism of action. In addition, the potent extract was subjected to actophotometer test to assess its possible locomotor activity deficit inducing action. Results: In 6-Hz seizure test, the MLPG has alleviated 6-Hz-induced seizures significantly and dose dependently at doses 50, 100, 200, and 400 mg/kg. In contrast, PLPG and ALPG did not show any protection, only high dose of ALPG (400 and 800 mg/kg, p.o.) showed very slight inhibition. Based on these observations, only MLPG was tested in MES and PTZ models. Interestingly, the MLPG (50, 100, 200 and 400 mg/kg) has offered significant and dose-dependent protection against MES (P < 0.01) and PTZ-induced (P < 0.01) seizures in mice. Further, MLPG showed a significant increase in brain GABA levels (P < 0.01) compared to control and showed insignificant change in locomotor activity in all tested doses (100, 200 and 400 mg/kg). Interestingly, higher dose of MLPG (400 mg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) have completely abolished the convulsions in all the anticonvulsant tests. Conclusion: These findings suggest that MLPG possesses significant anticonvulsant property, and one of the possible mechanisms behind the anticonvulsant activity of MLPG may be through enhanced GABA levels in the brain. © SAGEYA.


Viswanatha G.L.,Industrial Research Ltd. | Venkataranganna M.V.,Connexios Life science Pvt Ltd | Prasad N.B.L.,Jawaharlal Nehru Technological University Anantapur | Godavarthi A.,Industrial Research Ltd.
Metabolic Brain Disease | Year: 2017

The present study was aimed to examine the possible anticonvulsant property of aerial parts of Achyranthes aspera using various experimental models of epilepsy in mice. Petroleum ether extract of aerial parts of A. aspera (PeAA), methanolic eAA (MeAA) and aqueous eAA (AeAA) was initially evaluated against six-hertz seizure model in mice, based on the outcomes the effective extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) models in mice. In addition, the potent extract was evaluated against the PTZ model by co-administering with flumazenil (FMZ), and also evaluated for its effect on GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the probable locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice. In results, only MeAA showed protection against six-hertz-induced seizures in mice, based on these outcomes only MeAA was evaluated in MES and PTZ models. Notably, the MeAA (200, 400 and 800 mg/kg) has offered mild and dose dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeAA (400 mg/kg) showed a significant increase in GABA levels in the brain compared to control, and in line with these findings the anti-PTZ effect of MeAA (400 mg/kg, p.o.) was blocked when co-administered with flumazenil (5 mg/kg, i.p.). However, the MeAA has not shown significant protection against NMDA-induced mortality and also did not cause significant change in locomotor activity compared to before treatment. These findings suggest that MeAA possess mild anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanism behind the anticonvulsant activity of MeAA. © 2017 Springer Science+Business Media New York


Baliga M.S.,Father Muller Hospital Road | Joseph N.,Father Muller Hospital Road | Venkataranganna M.V.,Connexios Life science Pvt Ltd | Saxena A.,University of South Carolina | And 2 more authors.
Food and Function | Year: 2012

Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD. This journal is © The Royal Society of Chemistry.


Venkatarangana M.,Connexios Life science Pvt Ltd
Journal of Functional Foods | Year: 2015

Standardization is an essential step in the development of nutraceutical based formulations or products. The objective of the present study was to exemplify screening standardization of the potent antioxidant nutraceuticals (generic), namely curcumin, quercetin, hesperidin, gallic acid, citric acid, L-ascorbic acid, phytic acid and α-tocopherol based on ferric reducing antioxidant power (FRAP) value and also tried to justify the reliability of two different designs of experiments i.e. Plackett-Burman fold-over design and Taguchi L18 in screening related experiments. First screening of antioxidant nutraceutical was performed by Plackett-Burman fold-over design (resolution IV) and the outcome was analysed based on Pareto chart of standardized effect where the quercetin, gallic acid and curcumin have shown p value of <0.05 and the same factors were found to be positive outliner in half normal probability analysis. Further, the results were validated using factorial Taguchi orthogonal array, based on SN ratio (maximum the best response). Both statistical designs have given the same order of potency based on FRAP value as: quercetin > gallic acid > curcumin. Therefore it can be concluded that the statistical design of experiments is reliable in screening related experiments for development of nutraceutical formulations or products. © 2015 Elsevier Ltd.


The present invention relates to certain amide derivatives that have the ability to inhibit 11--hydroxysteroid dehydrogenase type 1 (11-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions.


Patent
Connexios Life science Pvt. Ltd. | Date: 2013-06-19

The embodiments disclosed here in relates to use of activators of ADSL for the production of pharmaceutical agents to achieve glycemic control in mammals and which are therefore useful in the treatment of certain disorders that can be prevented or treated by activation of this enzyme.


Gogna N.,Indian Institute of Science | Krishna M.,Connexios Life science Pvt. Ltd. | Oommen A.M.,Connexios Life science Pvt. Ltd. | Dorai K.,Indian Institute of Science
Molecular BioSystems | Year: 2015

It is well known that obesity/high body mass index (BMI) plays a key role in the evolution of insulin resistance and type-2 diabetes mellitus (T2DM). However, the exact mechanism underlying its contribution is still not fully understood. This work focuses on an NMR-based metabolomic investigation of the serum profiles of diabetic, obese South Indian Asian subjects. 1H 1D and 2D NMR experiments were performed to profile the altered metabolic patterns of obese diabetic subjects and multivariate statistical methods were used to identify metabolites that contributed significantly to the differences in the samples of four different subject groups: diabetic and non-diabetic with low and high BMIs. Our analysis revealed that the T2DM-high BMI group has higher concentrations of saturated fatty acids, certain amino acids (leucine, isoleucine, lysine, proline, threonine, valine, glutamine, phenylalanine, histidine), lactic acid, 3-hydroxybutyric acid, choline, 3,7-dimethyluric acid, pantothenic acid, myoinositol, sorbitol, glycerol, and glucose, as compared to the non-diabetic-low BMI (control) group. Of these 19 identified significant metabolites, the levels of saturated fatty acids, lactate, valine, isoleucine, and phenylalanine are also higher in obese non-diabetic subjects as compared to control subjects, implying that this set of metabolites could be identified as potential biomarkers for the onset of diabetes in subjects with a high BMI. Our work validates the utility of NMR-based metabolomics in conjunction with multivariate statistical analysis to provide insights into the underlying metabolic pathways that are perturbed in diabetic subjects with a high BMI. © The Royal Society of Chemistry 2015.


Patent
Connexios Life science Pvt. Ltd. | Date: 2013-12-05

The present invention relates to use of inhibitors of TAK-1 for the production of pharmaceutical agents to achieve glycemic control in mammals and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme.


Patent
CONNEXIOS LIFE science PVT. LTD. | Date: 2012-12-21

The present invention relates to certain amide derivatives that have the ability to inhibit 11--hydroxysteroid dehydrogenase type 1 (11-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions.


Patent
CONNEXIOS LIFE science PVT. LTD. | Date: 2015-01-09

The present invention relates to certain substituted bicyclic compounds that are agonists of RXR and which are therefore useful in the treatment of certain disorders that can be prevented or treated by activation of this receptor. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders.

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