Shyam Chatterjee - Academia.edu (original) (raw)

Papers by Shyam Chatterjee

PubMed, Nov 6, 2003

We have previously found that a 7-hydroxycoumarin derivative has potent anti-Helicobacter pylori ... more We have previously found that a 7-hydroxycoumarin derivative has potent anti-Helicobacter pylori (H. pylori) activity, comparable with metronidazole. In this report, we describe the structural requirement for the anti-H. pylori activity of several hydroxylated coumarins (1-23). It was found that 7-hydroxy-4-methylcoumarin (6), 6,7-dihydroxy-4-methylcoumarin (8), 6-hydroxy-7-methoxy-4-methylcoumarin (10) and 5,7-dihydroxycyclopentanocoumarin (21) showed comparable anti-H. pylori activity with metronidazole. The presence of 7- and/or 6-hydroxyl groups seems to be essential to display higher anti-H. pylori activity. Their activities depended on the number and position of the hydroxyl group on the benzenoid ring of the coumarin system. Methylation of the hydroxy group generally diminished the activity. In hydroxylated coumarins, the methyl group at C-4 position enhanced the activity. The inhibitory activity of coumarins (1-23) against jack bean urease was examined, but no coumarins showed any inhibition at 160 micrograms/mL.

Intrinsic activity, Oct 16, 2017

European Journal of Pharmacology, Jul 1, 1990

noradrenaline and to selective alpha-1 (phenylephrine) and alpha-2 (UK-14304) adrenoceptor agonis... more noradrenaline and to selective alpha-1 (phenylephrine) and alpha-2 (UK-14304) adrenoceptor agonists in pithed rats. Electrical stimulation (0.25-8 I-D.) of the spinal sympathetic outflow, noradrenaline (0.1-10/tg/kg i.v.), phenylephrine (1-300/xg/kg i.v.) and UK-14304 (1-300 ~g/kg i.v.) produced increases in diastolic blood pressure in pithed rats. Oral administration of MPC-1304 (0.3-3 mg/kg) shifted the frequency-response curve for sympathetic nerve stimulation and the dose-response curves for noradrenaline and phenylephrine to the right. MPC-1304 (1-3 mg/kg p.o.) shifted the dose-response curve for UK-14304 to the right with a.marked suppression of maximum pressor response. Moreover, MPC-1304 (3 mg/kg p.o.) depressed the pressor response induced by UK-14304 (10/tg/kg i.v.) during more than 6 hr. The inhibitory effects of MPC-1304 on these pressor responses were about 3 times more potent than those of nifedipine. These results indicate that MPC-1304 possesses the greater ability to inhibit vasoconstrictor responses to ~teurogenically released noradrenalhie and to circulating catecholamines compared with nifedipine, which may be correlated with the difference of antihypertensive potency between MPC-1304 and nifedipine. In vitro study, it was found that the inhibitory effect of MPC-1304 on the calcium-induced contraction of guinea pig aorta was abolished ~ore slowly after drug washout compared with nifedipine. This finding may, in part, contribute to the long ~ction of Mt~C-1304 in vivo.

Hamostaseologie, 1993

ZusammenfassungMonoextrakte aus den Blättern des Ginkgobaumes (Ginkgo biloba L.) werden zur Behan... more ZusammenfassungMonoextrakte aus den Blättern des Ginkgobaumes (Ginkgo biloba L.) werden zur Behandlung von peripheren und zentralen Durchblutungsstörungen sowie bei nachlassender intellektueller Leistungsfähigkeit eingesetzt. Der Spezialextrakt EGb 761 wird in einem standardisierten, vielstufigen Produktionsverfahren gewonnen. Ziel des Herstellungsprozesses ist neben der Anreicherung aktiver Inhaltsstoffe die weitgehende Entfernung von Substanzen mit unerwünschten Eigenschaften. Die experimentellen Befunde zeigen, daß dieser Extrakt pharmakologische Effekte auf alle wesentlichen, an der Blutversorgung beteiligten Komponenten ausübt. Auf der Gefäßebene bewirkt EGb 761 eine Steigerung der lokalen Durchblutung, beeinflußt den Arterienund Venentonus, vermindert eine erhöhte Kapillarpermeabilität und stimuliert die endotheliale Prostazyklinsynthese. Die Wirkungen auf das Blut umfassen unter anderem eine Verbesserung der rheologischen Eigenschaften, eine Stabilisierung der Erythrozytenmembran und die Hemmung PAF-vermittelter Reaktionen. Im Gewebe erhöht EGb 761 die Hypoxietoleranz, besitzt antiischämische Eigenschaften, verbessert den Energiemetabolismus und schützt vor Radikalinduzierten Schädigungen durch Hemmung und Neutralisierung von freien Radikalen.

Science of Ashwagandha: Preventive and Therapeutic Potentials, 2017

Ashwagandha (Withania somnifera) extracts and several pharmaceutical formulations containing them... more Ashwagandha (Withania somnifera) extracts and several pharmaceutical formulations containing them are currently often used as tonics useful for prevention and cure of mental health problems, including sleep disturbances, accompanying or caused by diverse slowly progressing chronic diseases. The possibility that W. somnifera could be used for treatments of diabetes and associated metabolic disturbances were first suggested by the results of an exploratory clinical study conducted with its root powdered in diabetic patients and published in 2000. Since then, numerous preclinical and a randomized, double blind and placebo controlled clinical study with extracts of the plant have continued to add experimental evidences in favor of the convictions of the scholars and practitioners of Ayurvedic and other traditionally known systems of medicine that the plant could also be used for prevention and cure of diabetes and other metabolic disorders associated physical and mental health problems. Currently available information suggesting such possibilities are summarized and critically analyzed in this chapter. Potential uses of our current knowledge on phytopharmaclogy and medicinal phytochemistry of the plant and its bioactive constituents for obtaining more sustainable and reproducible health benefits from the plant in patients suffering from, or at risk to, metabolic disorders associated mental health problems, or for discovering novel therapeutic lead against such health problems of the twenty-first century are also discussed.

Oriental Pharmacy and Experimental Medicine, 2016

Withania somnifera is an important Ayurvedic Rasayana herb, the roots of which are often used in ... more Withania somnifera is an important Ayurvedic Rasayana herb, the roots of which are often used in traditionally known systems of medicine as tonic or for rejuvenation purposes. Effects of a single and ten daily oral doses (10, 20 and 40 mg/kg) of an analytically well standardized Withania somnifera root extract against foot shock stress triggered transient hyperthermia and hotplate test for analgesics in male mice were quantified. Body weights and basal rectal temperatures of animals were recorded on all observational days and on the 11th and 12th day of the experiment, all animals were subjected to tail suspension and pentobarbital hypnosis tests respectively. Daily dose dependent efficacy of the tested extract in stress induced hyperthermia test and in hot plate test increased with increasing number of treatment days, and its dose dependent inhibitory effect on immobility time in tail suspension were observed after its 11 daily oral doses. Daily handling and intermittent foot shock stress triggered body weight losses and elevations in basal core temperatures were almost completely prevented even by its lowest daily dose (10 mg/kg/day) tested. Repeated daily low oral doses of the Withania somnifera extract is effective in suppressing diverse stress responses, and its centrally acting analgesics and anxiolytics or antidepressants like efficacies increase with increasing numbers of treatment days. These observations reaffirm that Withania somnifera is an adaptogenic herb, and suggest that its effective therapeutic doses has to be adjusted according to the pre-existing allostatic load of patients.

Pharmacy & Pharmacology International Journal, 2015

Objective: To compare physiological stress response modulating potentials of triethylene glycol a... more Objective: To compare physiological stress response modulating potentials of triethylene glycol and quercetin in mice. Methods: Effects of single and 10 daily oral doses (5, 20, 100 and 400 mg/kg/ day) of quercetin and triethylene glycol (TEG) to male mice on foot shock stress induces transient hyperthermia and on basal rectal temperatures and body weight changes and of their 11 daily doses in tail suspension test and on pentobarbital induced sedation were compared. In further experiments, the effects of their 11 and 12 daily minimally effective stress response suppressing doses (5 mg/kg/ day) in two versions of the marble burying test for anxiolytics were assessed. Results: Dose dependant efficacies of quercetin and TEG for suppressing transient hyperthermia triggered by 1 min duration of foot shock stress increased with increasing numbers of their daily dose and body weight losses and slight elevation of basal core temperatures triggered by daily handling and occasional foot shocks were also antagonized by both of them. Significant effects of even the lowest tested (5 mg/kg/day) doses of both of them were observed after their 11 daily doses in tail suspension test in mildly stressed mice, bur after such treatments only quercetin had statistically significant effects in one of the two versions of the marble burying tests in stressed mice. Conclusion: Fairly low daily, but not single, oral doses of quercetin and TEG desensitize physiological stress responses of male mice triggered by occasional exposures to short duration of foot shocks. Both of them possess daily dose dependant antidepressant like activities and after their low stress response suppressing doses only quercetin possess some anxiolytics like activity in stressed mice.

Pharmacopsychiatry, 2001

Despite almost forty years of widespread use of antidepressant drugs, their mode of action is sti... more Despite almost forty years of widespread use of antidepressant drugs, their mode of action is still unknown. Hyperforin, a phloroglucinol derivative, is a major pharmacologically and therapeutically active constituent of Hypericum perforatum extract that is widely used as an herbal antidepressant drug. However, the mechanism or mechanisms of action of these naturally abundant, non-toxic extracts remain unclear. Enzymatically isolated patch-clamped rat central and peripheral neurons exposed to rapid changes in the composition of external medium (concentration clamp) were used in our experiments to investigate the modulation of the various voltage- and ligand-gated channels by hyperforin, as well as by other constituents of Hypericum perforatum. At nanomolar concentrations, hyperforin induced significant inhibition of various ion channels. In the case of P-type Ca2+ channels, we established that hyperforin acts via interaction with calmodulin or through calmodulin-activated pathways involving at least one second messenger. The results presented here indicate that multiple mechanisms and extract constituents may be involved in the antidepressant action of Hypericum extracts, and that they could also possess neuroprotective and analgesic effects.

Drug Designing: Open Access, 2017

Fumaric acid esters, now often used for treatment of psoriasis and multiple sclerosis, have been ... more Fumaric acid esters, now often used for treatment of psoriasis and multiple sclerosis, have been identified as bioactive constituents of Fumaria indica used in traditionally known system of medicine as a liver tonicor for treatments of diverse inflammatory conditions, itches and pain. Observations made during efforts to quantify their roles in therapeutically interesting bioactivity profiles of its extracts strongly suggest that their hydrolysis inside the digestive tract to fumaric acid are involved in their protective effects stress triggered alteration in growth rates and behavior of laboratory rodents. They also reaffirm that repeated daily low oral dose studies is necessary for deciphering the roles of fumaric acid or other food chemicals with bactericidal activities, in quantitative systems phytopharmacology of therapeutically used herbal extracts. Our current knowledge on low dose pharmacology of some such phytochemicals commonly consumed with every day meals, or with herbal remedies, is summarized in this report. Aim of this overview is to point out the necessity of better understanding of quantitative systems pharmacology of food phytochemical not only for more rational medicinal uses of traditionally known herbal remedies, but also for increasing the possibility of success in drug discovery and development ventures. Potential uses of bioassays procedures evolving from efforts to better understand quantitative systems pharmacology of fumarates and other food phytochemicals for such purposes are also suggested.

Journal of Medicinal Chemistry, 1971

Molecular Pharmacology, 2009

The naturally occurring acylated phloroglucinol derivative hyperforin was recently identified as ... more The naturally occurring acylated phloroglucinol derivative hyperforin was recently identified as the first specific canonical transient receptor potential-6 (TRPC6) activator. Hyperforin is the major antidepressant component of St. John's wort, which mediates its antidepressant-like properties via TRPC6 channel activation. However, its pharmacophore moiety for activating TRPC6 channels is unknown. We hypothesized that the phloroglucinol moiety could be the essential pharmacophore of hyperforin and that its activity profile could be due to structural similarities with diacylglycerol (DAG), an endogenous nonselective activator of TRPC3, TRPC6, and TRPC7. Accordingly, a few 2-acyl and 2,4-diacylphloroglucinols were tested for their hyperforin-like activity profiles. We used a battery of experimental models to investigate all functional aspects of TRPC6 activation, including ion channel recordings, Ca 2ϩ imaging,

Journal of Ethnopharmacology, 2003

The antidiabetic activity of an extract from the leaves of Lagerstroemia speciosa standardized to... more The antidiabetic activity of an extract from the leaves of Lagerstroemia speciosa standardized to 1% corosolic acid (Glucosol TM) has been demonstrated in a randomized clinical trial involving Type II diabetics (non-insulin-dependent diabetes mellitus, NIDDM). Subjects received a daily oral dose of Glucosol TM and blood glucose levels were measured. Glucosol TM at daily dosages of 32 and 48 mg for 2 weeks showed a significant reduction in the blood glucose levels. Glucosol TM in a soft gel capsule formulation showed a 30% decrease in blood glucose levels compared to a 20% drop seen with dry-powder filled hard gelatin capsule formulation (P < 0.001), suggesting that the soft gel formulation has a better bioavailability than a dry-powder formulation.

Pharmacopsychiatry, 2003

We have previously shown that hypoxia and N-methyl-D-aspartate (NMDA) receptor activation induce ... more We have previously shown that hypoxia and N-methyl-D-aspartate (NMDA) receptor activation induce breakdown of choline-containing phospholipids in rat hippocampus, a process which is mediated by calcium influx and phospholipase A (2) activation. Bilobalide, a constituent of Ginkgo biloba, inhibited this process in a potent manner (Weichel et al., Naunyn-Schmiedeberg's Arch. Pharmacol. 360, 609-615, 1999). In this study, we used fluorescence microscopy and radioactive flux measurements to show that bilobalide does not interfere with NMDA-induced calcium influx. Instead, bilobalide seems to inhibit NMDA-induced fluxes of chloride ions through ligand-operated chloride channels. In our experiments, substitution of chloride in the superfusion medium fully blocked the effect of NMDA on choline release from hippocampal slices, while the presence of chloride transport inhibitors (furosemide, DIDS) was partially antagonistic. The inhibitory effect of bilobalide and of HA-966, a glycine B receptor antagonist, on NMDA-induced choline release was attenuated in the presence of glycine. The inhibitory effect of bilobalide, but not that of HA-966, was also antagonized by GABA. The inhibitory effect of MK-801, an NMDA channel blocker, on choline release was insensitive to glycine. We conclude from our findings that bilobalide inhibits an NMDA-induced chloride flux through glycine/GABA-operated channels, thereby preventing NMDA-induced breakdown of membrane phospholipids. This effect is expected to contribute to the neuroprotective effects of ginkgo biloba extracts.

Neuroscience letters, 1999

Hyperforin is the main antidepressant component of hypericum perforatum (St. John's Wort). U... more Hyperforin is the main antidepressant component of hypericum perforatum (St. John's Wort). Using the push-pull superfusion technique we tested whether hyperforin influences extracellular concentrations of neurotransmitters in the rat locus coeruleus. Hyperforin (10 mg/kg, ip) ...

… archives of pharmacology, 1999

In rat hippocampal slices superfused with magnesium-free buffer, glutamate (1 mM) caused the rele... more In rat hippocampal slices superfused with magnesium-free buffer, glutamate (1 mM) caused the release of large amounts of choline due to phospholipid breakdown. This phenomenon was mimicked by N-methyl-D-aspartate (NMDA) in a calcium-sensitive manner and was blocked by NMDA receptor antagonists such as MK-801 and 7-chlorokynurenate. The NMDA-induced release of choline was not caused by activation of phospholipase D but was mediated by phospholipase A2 (PLA2) activation as the release of choline was accompanied by the formation of lyso-phosphatidylcholine (lyso-PC) and glycerophospho-choline (GPCh) and was blocked by 5-[2-(2-carboxyethyl)-4-dodecanoyl-3,5-dimethylpyrrol-1-yl]pentano ic acid, a PLA2 inhibitor. Bilobalide, a constituent of Ginkgo biloba, inhibited the NMDA-induced efflux of choline with an IC50 value of 2.3 microM and also prevented the formation of lyso-PC and GPCh. NMDA also caused a release of choline in vivo when infused into the hippocampus of freely moving rats by...