Srinivas Nammi | Western Sydney University (original) (raw)

Papers by Srinivas Nammi

Research paper thumbnail of Polysaccharide Peptide Extract From Coriolus versicolor Increased Tmax of Tamoxifen and Maintained Biochemical Serum Parameters, With No Change in the Metabolism of Tamoxifen in the Rat

Frontiers in Pharmacology, Apr 1, 2022

Background: Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Tramet... more Background: Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Trametes; Polyporaceae) is increasingly used in cancer to support the immune system. However, its interaction with tamoxifen is unknown. Aim of the study: To investigate the effect of a PSP extract on the pharmacokinetics, biochemical parameters, and depletion of tamoxifen. Methods: The pharmacokinetic and biochemical parameters of tamoxifen (20 mg/mL oral single dose and repeated dosing for 12 days) was investigated in female Sprague Dawley rats with or without PSP (340 mg/kg orally for 7 days) (n = 5 per group). Tamoxifen (5 µM) depletion rate with PSP (10-100 μg/mL) was measured in female rat hepatic microsomes in vitro. Results: Compared to tamoxifen alone, the time to reach maximum concentration (T max) significantly increased by 228% (4.15 ± 1.15 versus 13.6 ± 2.71 h) in the single tamoxifen dose with PSP and 93% (6 ± 2.17 versus 11.6 ± 0.4 h) in the repeated tamoxifen dosing with PSP (p < 0.05). No significant changes in the area-under-curve and maximum concentration were observed in the single dose and repeated tamoxifen dosing plus PSP compared to tamoxifen alone. Pharmacodynamically, the repeated tamoxifen dosing with PSP maintained 19 out of 23 hepatic, renal and cardiac biochemical serum parameters in rats compared to untreated rats (p > 0.05). PSP extract did not significantly alter in vitro intrinsic clearance of tamoxifen compared to tamoxifen control. Conclusion: With the increased use of PSP as an adjunct therapy, this study highlights the importance of clinician's knowledge of its interaction with tamoxifen to avoid compromising clinical actions and enhancing clinical therapy.

Research paper thumbnail of Evaluation of biological activity in quality control of herbal medicines

Evaluation of biological activity is a fundamental step in evaluating the quality, safety and eff... more Evaluation of biological activity is a fundamental step in evaluating the quality, safety and efficacy of herbal medicines. To determine the complex biological activities caused by multiple chemical components in herbal medicines, new scientific research methods and comprehensive documentation are required. This review covers the significance and methodology of the biological evaluation in relation to quality control of herbal medicines. Vigorous and validated in vitro, in vivo and clinical studies of herbal medicines will need to be applied in order to ascertain active extracts or compounds, their potential pharmacological activity and synergistic effect of active compounds. This systematic biological evaluation and quality standardisation research platform concept is related to the bioequivalence theory in pharmaceutical science. The concept is further discussed in reviewing the development in the assessment of anti-inflammatory and anti-diabetic activities of herbal medicines

Research paper thumbnail of Studies on the Antimicrobial Activity of Heliotropium indicum Linn

Journal of Natural Remedies, 2002

Objective: To investigate the antimicrobial activity of alcoholic extract of Heliotropium indicum... more Objective: To investigate the antimicrobial activity of alcoholic extract of Heliotropium indicum . Materials and method: Antimicrobial activity was studied at concentrations of 1 μg/ml, 100μg/ml, 1 mg/ml, 50 mg/ml and 100 mg/ml of the extract dissolved in propylene glycol against four strains each of Gram positive and Gram negative bacteria, three strains of fungi and two yeast by agar cup plate diffusion method. Results: The alcoholic extract of Heliotropium indicum was found to possess dose dependent antimicrobial activity in all the test organisms. Conclusion: The study lends support for the use of the plant as folklore medicine for the treatment of infectious diseases.

Research paper thumbnail of Evaluation of synergistic effects of a multi-herb combination used for the treatment of osteoarthritis

Advances in Integrative Medicine, 2019

S37 groups. All 40 pathologically-confirmed UC patients initiated prescribed 1 gr. damask rose oi... more S37 groups. All 40 pathologically-confirmed UC patients initiated prescribed 1 gr. damask rose oil (in dosage form of capsule) TID for two months. The evaluation items (measurement tool) were: clinical symptoms (partial Mayo clinic score), quality of life (inflammatory bowel disease questionnaire or IBDQ-9), and calprotectin level (laboratory kit). Results: The demographic data and assigned clinical items showed no statistically significant differences before the trial between groups. Partial Mayo clinic scores declined in both groups at the end of the trial, although between groups difference was not statistically significant (P = 0.99). Quality of life, based on IBDQ-9 scores, improved within groups (P = 0.012), while the differences between groups were not statistically significant (P = 0.61) after the treatment period. Comparing an objective tool for better judgment, calprotectin level mean demonstrated insignificant discrepancy between the intervention and placebo groups (P = 0.219). Conclusion: This study revealed that Rosa damascena Mill L. may mitigate UC clinical symptoms, but performing high-standard superior quality clinical trials seems crucial in order to confirm the practicality of damask rose for UC patients.

Research paper thumbnail of Erratum to “Nonpharmacologic Interventions in Prevention and Treatment of Hypertension”

International Journal of Hypertension, 2019

Research paper thumbnail of Variability of the Polyphenolic Content and Antioxidant Capacity of Methanolic Extracts of Pomegranate Peel

Natural Product Communications, 2013

Pomegranate is a popular food due to its high polyphenolic content and antioxidant capacities. Po... more Pomegranate is a popular food due to its high polyphenolic content and antioxidant capacities. Pomegranate peel is used in traditional medicine and has greater antioxidant capacity compared with other parts of pomegranate. This study elucidated the differences in the polyphenolic content and antioxidant capacities of the methanolic extracts of pomegranate peel from different geographical localities including Australia, China and USA. The results showed that pomegranate peel from China generally had higher polyphenolic contents and antioxidant capacities than those from Australia and USA. The total contents of polyphenols and flavonoids, but not condensed tannins, were closely correlated with their total antioxidant activities. Differentiation of extracts from Chinese pomegranate peel to those extracts originating from Australia and USA were achieved by multivariate analyses based on their polyphenolic content and antioxidant capacities. The results indicate that polyphenols are usef...

Research paper thumbnail of Pharmacological Evaluation of the Recuperative Effect of Morusin Against Aluminium Trichloride (AlCl3) - Induced Memory Impairment in Rats

Central nervous system agents in medicinal chemistry, Jan 10, 2016

Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory defici... more Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action. Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acidreactive species (TBARS) and glutathione (GSH) levels. AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also prod...

Research paper thumbnail of Natural Products: Biochemical-Chemical Characterization, and Evidence for Therapeutic Potential

Journal of Pharmacy & Pharmaceutical Sciences, 2015

This Special Issue follows from a previous Issue entitled “Mechanism-Based Development of Natural... more This Special Issue follows from a previous Issue entitled “Mechanism-Based Development of Natural Products for Human Health” arising from an inaugural conference on Natural Products Development held at Whistler Mountain, Canada from September 21-22, 2012. The timeliness of this issue reflects the continued growth in Natural Product research and the success of the First Issue, as judged from feedback we received and citations received. We were also encouraged by the interest in natural products research in recent years, as exemplified by the recent publication on Traditional Medicine in the prestigious journal Science (1, 2).

Research paper thumbnail of Indirect biochemical evidence that reserpine methiodide produces selective depletion of peripheral biogenic amines in rats

Die Pharmazie, 2005

Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action ... more Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. In the present investigation, reserpine methiodide (RMI), a quaternary analogue of reserpine was synthesised and evaluated biochemically for its central and peripheral amine depleting actions in rats and compared with reserpine. The 24 h urinary excretion of vanillylmandelic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the respective metabolites of noradrenaline, serotonin and dopamine were estimated and considered as indirect biochemical indices for the amine depleting action of reserpine and RMI. The results indicate that RMI at doses of equal to and double the equimolar doses of reserpine was found to deplete the peripheral amines without affecting the central stores of the amines. The results further suggest that the quaternization of reserpine might restrict its transfer across the blood-brain barrier and could be the reason for its selec...

Research paper thumbnail of PINSA B65 No 5 pp 245-256 (1999)

Research paper thumbnail of Hypoglycemic effect of Aegle Marmelos leaf extract on normal and diabetic model rabbits

Research paper thumbnail of Antimicrobial activity of alcoholic extract of Heliotropium Indicum in vitro

Research paper thumbnail of Hypoglycemic and insulin release effects of Hugonia mystax leaves in rabbits

The ethanolic extract of Hugonia mystax leaves was tested for its hypoglycemic and insulin releas... more The ethanolic extract of Hugonia mystax leaves was tested for its hypoglycemic and insulin releasing properties in normal and diabetic rabbits. Blood glucose levels were determined after treatment with the extract at doses of 100, 200 and 300 mg/kg. Significant reductions in blood levels were observed in both normal and diabetic rabbits while an appreciable rise in serum insulin was also observed in diabetic rabbits compared to control animals. These results suggest that the reduction in blood glucose produced by the extract is through insulin secretion.

Research paper thumbnail of Pharmacological evidence for lack of central effects of reserpine methonitrate: a novel quaternary analog of reserpine

Research paper thumbnail of Evaluation of Herbal Preparations for Hypoglycemic Activity in Normal and Diabetic Rabbits

Pharmaceutical Biology, 2003

ABSTRACT The leaf juice of Catharanthus roseus and the seed powder of fenugreek were tested for t... more ABSTRACT The leaf juice of Catharanthus roseus and the seed powder of fenugreek were tested for their hypoglycemic action individually and in combination in normal and alloxan-induced diabetic rabbits. Blood glucose was determined in all the groups before and after treatment with Catharanthus roseus and fenugreek at doses of 0.5, 0.75 and 1.0ml/kg and 50, 100 and 150 mg/kg, respectively, at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 h after being fasted for 18 h. The effect was found to be dose-dependent with both the treatments at the doses administered. The percentage blood glucose reduction produced by the combination of Catharanthus roseus (0.5 ml/kg) and fenugreek (50mg/kg) was more than the sum of their individual percent blood glucose reduction in both normal and diabetic rabbits, suggesting that the combination produced a synergistic action.

Research paper thumbnail of Reserpine methonitrate, a novel quaternary analogue of reserpine augments urinary excretion of VMA and 5-HIAA without affecting HVA in rats

BMC pharmacology, 2004

Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action ... more Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. In later years, its use has been reduced because of precipitation of depression and extra pyramidal symptoms due to its central action. In the present investigation, reserpine methonitrate (RMN), a novel quaternary analogue of reserpine was synthesised and evaluated biochemically for its central and peripheral amine depleting actions in rats while its influence on the blood pressure was measured in anaesthetized rats in comparison with reserpine

Research paper thumbnail of Reduced intestinal and renal amino acid transport in PDK1 hypomorphic mice

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2006

The phosphoinositide-dependent kinase PDK1 activates the serum- and glucocorticoid-inducible kina... more The phosphoinositide-dependent kinase PDK1 activates the serum- and glucocorticoid-inducible kinase isoforms SGK1, SGK2, and SGK3 and protein kinase B, which in turn are known to up-regulate a variety of sodium-coupled transporters. The present study was performed to explore the role of PDK1 in amino acid transport. As mice completely lacking functional PDK1 are not viable, mice expressing 10-25% of PDK1 (pdk1(hm)) were compared with their wild-type (WT) littermates (pdk1(wt)). Body weight was significantly less in pdk1(hm) than in pdk1(wt) mice. Despite lower body weight of pdk1(hm) mice, food and water intake were similar in pdk1(hm) and pdk1(wt) mice. According to Ussing chamber experiments, electrogenic transport of phenylalanine, cysteine, glutamine, proline, leucine, and tryptophan was significantly smaller in jejunum of pdk1(hm) mice than in pdk1(wt) mice. Similarly, electrogenic transport of phenylalanine, glutamine, and proline was significantly decreased in isolated perfus...

Research paper thumbnail of Gallic acid protects against endothelial injury by restoring the depletion of DNA methyltransferase 1 and inhibiting proteasome activities

International Journal of Cardiology, 2014

Background: The aim of this study was to investigate the protective effects of gallic acid, a com... more Background: The aim of this study was to investigate the protective effects of gallic acid, a common phenolic compound naturally present in food and nutraceuticals, on endothelial cell death and the mechanisms involved. Methods: Endothelial cell death was induced by the combination of homocysteine, adenosine and tumour necrosis factor (TNF) in human vascular endothelial cells (EAhy926 and HBEC-5i cells). The protective effects of gallic acid were evaluated against cytotoxicity, apoptosis and microparticle release. Underlying mechanisms were further investigated focusing on the involvement of DNA methyltransferase 1 (DNMT1) and proteasome activities. Results: Our results showed that gallic acid dose-dependently arrested cytotoxicity in EAhy926 and HBEC-5i cells induced by the combination. Gallic acid showed anti-apoptotic effects and reduced the formation of microparticles. Notably, gallic acid reversed DNMT1 depletions at the protein level. The cytoprotective and anti-apoptotic effects of gallic acid were counteracted by the pre-treatment with DNMT1 inhibitor, 5-aza-2-deoxycytidine (5aza-dC). Treatment with gallic acid led to the accumulation of ubiquitinated protein aggregates and the reduction in chymotrypsin-like proteasome activities indicating proteasome inhibition. Conclusion: Our results demonstrate for the first time that gallic acid is capable of protecting endothelial cells from injury induced by the combination of homocysteine, adenosine and TNF, at least in part, by restoring the depletion of DNMT1 and inhibiting proteasome activities.

Research paper thumbnail of Reserpine-induced central effects: pharmacological evidence for the lack of central effects of reserpine methiodide

Canadian Journal of Physiology and Pharmacology, 2005

Reserpine, an alkaloid from Rauwolfia serpentina, was widely used for its antihypertensive action... more Reserpine, an alkaloid from Rauwolfia serpentina, was widely used for its antihypertensive action. However, its use has been reduced because of its sedative and extra pyramidal symptoms. In the present investigation, reserpine methiodide (RMI), a quaternary analogue of reserpine, was synthesized and pharmacologically evaluated in rats and mice for its central (barbiturate hypnosis, spontaneous motor activity, body temperature, and avoidance of conditioned response) and peripheral actions (blood pressure) in comparison with reserpine. The results indicate that reserpine produced a dose-dependent depression of the central nervous system. RMI at doses equal to and double the equimolar doses of reserpine did not produce any behavioural changes compared with control animals. Nevertheless, both reserpine and RMI were found to produce dose-dependent reduction in the blood pressure of anaesthetized rats, although only at higher doses of RMI, indicating that quaternization of reserpine not o...

Research paper thumbnail of The discovery of novel isoflavone pan peroxisome proliferator-activated receptor agonists

Bioorganic & Medicinal Chemistry, 2013

Twenty three dual PPARα and γ molecules of natural product origin, previously reported by our gro... more Twenty three dual PPARα and γ molecules of natural product origin, previously reported by our group, were further investigated for pan PPAR transactivation against PPARδ. The in vitro cell toxicity profile, as well as, in silico study of the most active molecules within this new class of pan PPAR agonists are also described. 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;,5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; Dimethoxy-7 hydroxyisoflavone 6, Ψ-baptigenin 7, 4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; fluoro-7 hydroxyisoflavone 8, and 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; methoxy-7 hydroxyisoflavone 9 were identified as the most potent molecules studied within the set compared to the commercially available pan PPAR agonist, bezafibrate 1. These novel active molecules may thus be useful as future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome.

Research paper thumbnail of Polysaccharide Peptide Extract From Coriolus versicolor Increased Tmax of Tamoxifen and Maintained Biochemical Serum Parameters, With No Change in the Metabolism of Tamoxifen in the Rat

Frontiers in Pharmacology, Apr 1, 2022

Background: Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Tramet... more Background: Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Trametes; Polyporaceae) is increasingly used in cancer to support the immune system. However, its interaction with tamoxifen is unknown. Aim of the study: To investigate the effect of a PSP extract on the pharmacokinetics, biochemical parameters, and depletion of tamoxifen. Methods: The pharmacokinetic and biochemical parameters of tamoxifen (20 mg/mL oral single dose and repeated dosing for 12 days) was investigated in female Sprague Dawley rats with or without PSP (340 mg/kg orally for 7 days) (n = 5 per group). Tamoxifen (5 µM) depletion rate with PSP (10-100 μg/mL) was measured in female rat hepatic microsomes in vitro. Results: Compared to tamoxifen alone, the time to reach maximum concentration (T max) significantly increased by 228% (4.15 ± 1.15 versus 13.6 ± 2.71 h) in the single tamoxifen dose with PSP and 93% (6 ± 2.17 versus 11.6 ± 0.4 h) in the repeated tamoxifen dosing with PSP (p < 0.05). No significant changes in the area-under-curve and maximum concentration were observed in the single dose and repeated tamoxifen dosing plus PSP compared to tamoxifen alone. Pharmacodynamically, the repeated tamoxifen dosing with PSP maintained 19 out of 23 hepatic, renal and cardiac biochemical serum parameters in rats compared to untreated rats (p > 0.05). PSP extract did not significantly alter in vitro intrinsic clearance of tamoxifen compared to tamoxifen control. Conclusion: With the increased use of PSP as an adjunct therapy, this study highlights the importance of clinician's knowledge of its interaction with tamoxifen to avoid compromising clinical actions and enhancing clinical therapy.

Research paper thumbnail of Evaluation of biological activity in quality control of herbal medicines

Evaluation of biological activity is a fundamental step in evaluating the quality, safety and eff... more Evaluation of biological activity is a fundamental step in evaluating the quality, safety and efficacy of herbal medicines. To determine the complex biological activities caused by multiple chemical components in herbal medicines, new scientific research methods and comprehensive documentation are required. This review covers the significance and methodology of the biological evaluation in relation to quality control of herbal medicines. Vigorous and validated in vitro, in vivo and clinical studies of herbal medicines will need to be applied in order to ascertain active extracts or compounds, their potential pharmacological activity and synergistic effect of active compounds. This systematic biological evaluation and quality standardisation research platform concept is related to the bioequivalence theory in pharmaceutical science. The concept is further discussed in reviewing the development in the assessment of anti-inflammatory and anti-diabetic activities of herbal medicines

Research paper thumbnail of Studies on the Antimicrobial Activity of Heliotropium indicum Linn

Journal of Natural Remedies, 2002

Objective: To investigate the antimicrobial activity of alcoholic extract of Heliotropium indicum... more Objective: To investigate the antimicrobial activity of alcoholic extract of Heliotropium indicum . Materials and method: Antimicrobial activity was studied at concentrations of 1 μg/ml, 100μg/ml, 1 mg/ml, 50 mg/ml and 100 mg/ml of the extract dissolved in propylene glycol against four strains each of Gram positive and Gram negative bacteria, three strains of fungi and two yeast by agar cup plate diffusion method. Results: The alcoholic extract of Heliotropium indicum was found to possess dose dependent antimicrobial activity in all the test organisms. Conclusion: The study lends support for the use of the plant as folklore medicine for the treatment of infectious diseases.

Research paper thumbnail of Evaluation of synergistic effects of a multi-herb combination used for the treatment of osteoarthritis

Advances in Integrative Medicine, 2019

S37 groups. All 40 pathologically-confirmed UC patients initiated prescribed 1 gr. damask rose oi... more S37 groups. All 40 pathologically-confirmed UC patients initiated prescribed 1 gr. damask rose oil (in dosage form of capsule) TID for two months. The evaluation items (measurement tool) were: clinical symptoms (partial Mayo clinic score), quality of life (inflammatory bowel disease questionnaire or IBDQ-9), and calprotectin level (laboratory kit). Results: The demographic data and assigned clinical items showed no statistically significant differences before the trial between groups. Partial Mayo clinic scores declined in both groups at the end of the trial, although between groups difference was not statistically significant (P = 0.99). Quality of life, based on IBDQ-9 scores, improved within groups (P = 0.012), while the differences between groups were not statistically significant (P = 0.61) after the treatment period. Comparing an objective tool for better judgment, calprotectin level mean demonstrated insignificant discrepancy between the intervention and placebo groups (P = 0.219). Conclusion: This study revealed that Rosa damascena Mill L. may mitigate UC clinical symptoms, but performing high-standard superior quality clinical trials seems crucial in order to confirm the practicality of damask rose for UC patients.

Research paper thumbnail of Erratum to “Nonpharmacologic Interventions in Prevention and Treatment of Hypertension”

International Journal of Hypertension, 2019

Research paper thumbnail of Variability of the Polyphenolic Content and Antioxidant Capacity of Methanolic Extracts of Pomegranate Peel

Natural Product Communications, 2013

Pomegranate is a popular food due to its high polyphenolic content and antioxidant capacities. Po... more Pomegranate is a popular food due to its high polyphenolic content and antioxidant capacities. Pomegranate peel is used in traditional medicine and has greater antioxidant capacity compared with other parts of pomegranate. This study elucidated the differences in the polyphenolic content and antioxidant capacities of the methanolic extracts of pomegranate peel from different geographical localities including Australia, China and USA. The results showed that pomegranate peel from China generally had higher polyphenolic contents and antioxidant capacities than those from Australia and USA. The total contents of polyphenols and flavonoids, but not condensed tannins, were closely correlated with their total antioxidant activities. Differentiation of extracts from Chinese pomegranate peel to those extracts originating from Australia and USA were achieved by multivariate analyses based on their polyphenolic content and antioxidant capacities. The results indicate that polyphenols are usef...

Research paper thumbnail of Pharmacological Evaluation of the Recuperative Effect of Morusin Against Aluminium Trichloride (AlCl3) - Induced Memory Impairment in Rats

Central nervous system agents in medicinal chemistry, Jan 10, 2016

Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory defici... more Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action. Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acidreactive species (TBARS) and glutathione (GSH) levels. AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also prod...

Research paper thumbnail of Natural Products: Biochemical-Chemical Characterization, and Evidence for Therapeutic Potential

Journal of Pharmacy & Pharmaceutical Sciences, 2015

This Special Issue follows from a previous Issue entitled “Mechanism-Based Development of Natural... more This Special Issue follows from a previous Issue entitled “Mechanism-Based Development of Natural Products for Human Health” arising from an inaugural conference on Natural Products Development held at Whistler Mountain, Canada from September 21-22, 2012. The timeliness of this issue reflects the continued growth in Natural Product research and the success of the First Issue, as judged from feedback we received and citations received. We were also encouraged by the interest in natural products research in recent years, as exemplified by the recent publication on Traditional Medicine in the prestigious journal Science (1, 2).

Research paper thumbnail of Indirect biochemical evidence that reserpine methiodide produces selective depletion of peripheral biogenic amines in rats

Die Pharmazie, 2005

Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action ... more Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. In the present investigation, reserpine methiodide (RMI), a quaternary analogue of reserpine was synthesised and evaluated biochemically for its central and peripheral amine depleting actions in rats and compared with reserpine. The 24 h urinary excretion of vanillylmandelic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the respective metabolites of noradrenaline, serotonin and dopamine were estimated and considered as indirect biochemical indices for the amine depleting action of reserpine and RMI. The results indicate that RMI at doses of equal to and double the equimolar doses of reserpine was found to deplete the peripheral amines without affecting the central stores of the amines. The results further suggest that the quaternization of reserpine might restrict its transfer across the blood-brain barrier and could be the reason for its selec...

Research paper thumbnail of PINSA B65 No 5 pp 245-256 (1999)

Research paper thumbnail of Hypoglycemic effect of Aegle Marmelos leaf extract on normal and diabetic model rabbits

Research paper thumbnail of Antimicrobial activity of alcoholic extract of Heliotropium Indicum in vitro

Research paper thumbnail of Hypoglycemic and insulin release effects of Hugonia mystax leaves in rabbits

The ethanolic extract of Hugonia mystax leaves was tested for its hypoglycemic and insulin releas... more The ethanolic extract of Hugonia mystax leaves was tested for its hypoglycemic and insulin releasing properties in normal and diabetic rabbits. Blood glucose levels were determined after treatment with the extract at doses of 100, 200 and 300 mg/kg. Significant reductions in blood levels were observed in both normal and diabetic rabbits while an appreciable rise in serum insulin was also observed in diabetic rabbits compared to control animals. These results suggest that the reduction in blood glucose produced by the extract is through insulin secretion.

Research paper thumbnail of Pharmacological evidence for lack of central effects of reserpine methonitrate: a novel quaternary analog of reserpine

Research paper thumbnail of Evaluation of Herbal Preparations for Hypoglycemic Activity in Normal and Diabetic Rabbits

Pharmaceutical Biology, 2003

ABSTRACT The leaf juice of Catharanthus roseus and the seed powder of fenugreek were tested for t... more ABSTRACT The leaf juice of Catharanthus roseus and the seed powder of fenugreek were tested for their hypoglycemic action individually and in combination in normal and alloxan-induced diabetic rabbits. Blood glucose was determined in all the groups before and after treatment with Catharanthus roseus and fenugreek at doses of 0.5, 0.75 and 1.0ml/kg and 50, 100 and 150 mg/kg, respectively, at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 h after being fasted for 18 h. The effect was found to be dose-dependent with both the treatments at the doses administered. The percentage blood glucose reduction produced by the combination of Catharanthus roseus (0.5 ml/kg) and fenugreek (50mg/kg) was more than the sum of their individual percent blood glucose reduction in both normal and diabetic rabbits, suggesting that the combination produced a synergistic action.

Research paper thumbnail of Reserpine methonitrate, a novel quaternary analogue of reserpine augments urinary excretion of VMA and 5-HIAA without affecting HVA in rats

BMC pharmacology, 2004

Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action ... more Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. In later years, its use has been reduced because of precipitation of depression and extra pyramidal symptoms due to its central action. In the present investigation, reserpine methonitrate (RMN), a novel quaternary analogue of reserpine was synthesised and evaluated biochemically for its central and peripheral amine depleting actions in rats while its influence on the blood pressure was measured in anaesthetized rats in comparison with reserpine

Research paper thumbnail of Reduced intestinal and renal amino acid transport in PDK1 hypomorphic mice

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2006

The phosphoinositide-dependent kinase PDK1 activates the serum- and glucocorticoid-inducible kina... more The phosphoinositide-dependent kinase PDK1 activates the serum- and glucocorticoid-inducible kinase isoforms SGK1, SGK2, and SGK3 and protein kinase B, which in turn are known to up-regulate a variety of sodium-coupled transporters. The present study was performed to explore the role of PDK1 in amino acid transport. As mice completely lacking functional PDK1 are not viable, mice expressing 10-25% of PDK1 (pdk1(hm)) were compared with their wild-type (WT) littermates (pdk1(wt)). Body weight was significantly less in pdk1(hm) than in pdk1(wt) mice. Despite lower body weight of pdk1(hm) mice, food and water intake were similar in pdk1(hm) and pdk1(wt) mice. According to Ussing chamber experiments, electrogenic transport of phenylalanine, cysteine, glutamine, proline, leucine, and tryptophan was significantly smaller in jejunum of pdk1(hm) mice than in pdk1(wt) mice. Similarly, electrogenic transport of phenylalanine, glutamine, and proline was significantly decreased in isolated perfus...

Research paper thumbnail of Gallic acid protects against endothelial injury by restoring the depletion of DNA methyltransferase 1 and inhibiting proteasome activities

International Journal of Cardiology, 2014

Background: The aim of this study was to investigate the protective effects of gallic acid, a com... more Background: The aim of this study was to investigate the protective effects of gallic acid, a common phenolic compound naturally present in food and nutraceuticals, on endothelial cell death and the mechanisms involved. Methods: Endothelial cell death was induced by the combination of homocysteine, adenosine and tumour necrosis factor (TNF) in human vascular endothelial cells (EAhy926 and HBEC-5i cells). The protective effects of gallic acid were evaluated against cytotoxicity, apoptosis and microparticle release. Underlying mechanisms were further investigated focusing on the involvement of DNA methyltransferase 1 (DNMT1) and proteasome activities. Results: Our results showed that gallic acid dose-dependently arrested cytotoxicity in EAhy926 and HBEC-5i cells induced by the combination. Gallic acid showed anti-apoptotic effects and reduced the formation of microparticles. Notably, gallic acid reversed DNMT1 depletions at the protein level. The cytoprotective and anti-apoptotic effects of gallic acid were counteracted by the pre-treatment with DNMT1 inhibitor, 5-aza-2-deoxycytidine (5aza-dC). Treatment with gallic acid led to the accumulation of ubiquitinated protein aggregates and the reduction in chymotrypsin-like proteasome activities indicating proteasome inhibition. Conclusion: Our results demonstrate for the first time that gallic acid is capable of protecting endothelial cells from injury induced by the combination of homocysteine, adenosine and TNF, at least in part, by restoring the depletion of DNMT1 and inhibiting proteasome activities.

Research paper thumbnail of Reserpine-induced central effects: pharmacological evidence for the lack of central effects of reserpine methiodide

Canadian Journal of Physiology and Pharmacology, 2005

Reserpine, an alkaloid from Rauwolfia serpentina, was widely used for its antihypertensive action... more Reserpine, an alkaloid from Rauwolfia serpentina, was widely used for its antihypertensive action. However, its use has been reduced because of its sedative and extra pyramidal symptoms. In the present investigation, reserpine methiodide (RMI), a quaternary analogue of reserpine, was synthesized and pharmacologically evaluated in rats and mice for its central (barbiturate hypnosis, spontaneous motor activity, body temperature, and avoidance of conditioned response) and peripheral actions (blood pressure) in comparison with reserpine. The results indicate that reserpine produced a dose-dependent depression of the central nervous system. RMI at doses equal to and double the equimolar doses of reserpine did not produce any behavioural changes compared with control animals. Nevertheless, both reserpine and RMI were found to produce dose-dependent reduction in the blood pressure of anaesthetized rats, although only at higher doses of RMI, indicating that quaternization of reserpine not o...

Research paper thumbnail of The discovery of novel isoflavone pan peroxisome proliferator-activated receptor agonists

Bioorganic & Medicinal Chemistry, 2013

Twenty three dual PPARα and γ molecules of natural product origin, previously reported by our gro... more Twenty three dual PPARα and γ molecules of natural product origin, previously reported by our group, were further investigated for pan PPAR transactivation against PPARδ. The in vitro cell toxicity profile, as well as, in silico study of the most active molecules within this new class of pan PPAR agonists are also described. 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;,5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; Dimethoxy-7 hydroxyisoflavone 6, Ψ-baptigenin 7, 4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; fluoro-7 hydroxyisoflavone 8, and 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; methoxy-7 hydroxyisoflavone 9 were identified as the most potent molecules studied within the set compared to the commercially available pan PPAR agonist, bezafibrate 1. These novel active molecules may thus be useful as future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome.