D.K. Ganguly

Anti-hyperglycemic effect of black tea (Camellia sinensis) in rat

Investigations were carried out to evaluate the effect of the hot water extract of black tea (Camellia sinensis (L.) O. Kuntze (Theaceae) on streptozotocin (STZ)-induced diabetes in rats. The extract significantly reduced the blood glucose level and was found to possess both preventive and curative effects on experimentally produced diabetes in rats. The study reveals that, like green tea, black tea also possesses antidiabetic activity.

Anti-ulcer effect of the hot water extract of black tea (Camellia sinensis)

The effect of the hot water extract of black tea (Camellia sinensis (L.) O. Kuntze, Theaceae) on ulceration induced by various ulcerogens and by cold restraint stress (CRS) was investigated in albino rats. While prior administration of tea extract for 7 days significantly reduced the incidence of ulcer, ulcer number and ulcer index produced by aspirin, indomethacin, ethanol, reserpine and CRS, it failed to inhibit the ulcers induced by serotonin and histamine. Tea extract also favourably altered the changes in acid and peptic activity of gastric secretion induced by aspirin, indomethacin, ethanol, reserpine and CRS. The observations suggest that the hot water extract of black tea possesses anti-ulcer activity, probably mediated through prostaglandins.

Resistance of Golden Hamster to l‐Methyl‐4‐Phenyl‐1,2,3,6 Tetrahydropyridine: Relationship with Low Levels of Regional Monoamine Oxidase B

Abstract: Effects of acute and chronic administration of 1 ‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) were investigated for dopamine (DA) and its metabolites, 3,4‐dihydroxyphenylacetic acid and 4‐hydroxy‐3‐methoxyphenylacetic acid, in nucleus caudatus putamen (NCP), limbic system, and substantia nigra (SN) of golden hamster and BALB/c and C57/BL mice to obtain a clue for the variance of MPTP toxicity between the strains and species. Regional differences in the levels of monoamine oxidase (MAO) and the in vitro effects of MAO inhibitors were also determined and correlated with MPTP neurotoxicity. Concentrations of MPTP in the brains of mice and golden hamster at 10 min were comparable. Golden hamster was found to be resistant to the administration of MPTP as indicated by a lack of any alteration from the normal content of DA in NCP, limbic system, and SN. Both strains of mice exhibited >50% and >75% depletion of DA (C57/BL and BALB/c, respectively). The metabolites‐to‐DA ratios were decreased and increased in golden hamster and mouse strains, respectively, after acute or chronic treatment. Whereas the content of total MAO in golden hamster was one‐third to one‐sixth of any nuclei or mitochondria of both strains of mice, the ratio of MAO A to B was significantly higher in the former species. A possible involvement of discrete regional MAO activity in determining the extent of susceptibility of a species to MPTP toxicity is indicated from the study because (1) susceptibility as evidenced by DA depletion of a species coincided with high levels of MAO activity in SN and NCP, and (2) a highly positive correlation existed with total MAO and MAO B activity, there was a lack of correlation with MAO A activity, and a negative correlation existed with MAO A‐to‐B ratio and DA depletion. Hence, we propose that the resistance of a species to MPTP toxicity may depend on the content as well as the ratios of the two forms of MAO in NCP and SN. In other words, a higher MAO activity and a relative dominance of MAO B in these nuclei are critical in determining the susceptibility of a species to MPTP neurotoxicity.

Dissociation of serotoninergic and dopaminergic components in acute effects of 1-methy 1-4-pheny 1-1,2,3,6-tetrahydropyridine in mice

Behavioural and neurochemical effects of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in mice have been studied in order to determine the change in the neurotransmitter profile of the following areas of the brain: substantia nigra (SN), nucleus caudatus putamen (NCP), limbic system (LS; tuberculum olfactorium and nucleus accumbens), medulla oblongata (MO) and cerebellum (CER). Subcutaneous administration of MPTP (40 mg/kg) caused behavioural syndromes including restlessness, straub tail, hindlimb abduction, tremor, jumping, bradykinesia and akinesia in Balb/c mice. There existed a well-defined biphasic profile of motor activity comprising of an initial excitatory phase followed by an inhibitory phase lasting about two and a half and five hours, respectively. A significant rise in 5-hydroxytryptamine (5-HT) content together with a decreased 5-HT utilization as evidenced by lower 5-hydroxyindole acetic acid (5-HIAA) to 5-HT ratio in the above brain areas demarcated the excitatory phase, whereas the inhibitory phase was distinguished by a significant decrease in dopamine (DA) content along with an increased turnover of the amine as shown by a higher homovanillic acid (HVA) to DA ratio in the functionally important nuclei of the extrapyramidal system like SN, NCP and LS. Methysergide, a nonspecific 5-HT receptor blocker, but not ketanserin, a specific 5-HT2 antagonist, prevented the occurrence of the initial excitatory phase without affecting the depressive phase. Administration of apomorphine, a dopamine agonist, 30 minutes prior to MPTP was ineffective, whereas its application 90 minutes after MPTP prevented the occurrence of bradykinesia and akinesia. Interestingly, treatment with haloperidol, the dopamine (D1/D2) antagonist, before and after MPTP administration caused an early onset and prolongation of the inhibitory phase without affecting the initial hyperexcitement. The results provide direct evidence for the involvement of serotoninergic and dopaminergic mechanisms in the genesis of the early and late syndromes of acute MPTP poisoning respectively.

Anticlastogenic effects of black tea (World blend) and its two active polyphenols theaflavins and thearubigins in vivo in Swiss albino mice

This study investigated the inhibition of cyclophosphamide (CP) and dimethylbenz(a)anthracene (DMBA) induced genetic damage by black tea (World blend) and its two active polyphenols theaflavins (TF) and thearubigins (TR) in Swiss albino mice as measured by chromosome aberrations (CA) and sister chromatid exchanges (SCE). Three different concentrations (5, 10 and 20%) of tea and a single dose of TF and TR were tested for their anticlastogenic effects against DMBA (50 mg/kg body weight) and CP (20 mg/kg for CA and 10 mg/kg for SCE). A significant decrease in CA was observed in all the three concentrations of tea extract plus DMBA treated groups when compared with the respective DMBA treated group alone. Similarly a significant decrease in CA was observed in all the three concentrations of tea extracts plus CP treated series when compared with the group treated with CP alone. In SCE assay, a significant decrease in SCE was observed in 5, 10 and 20% black tea extract plus CP and 10 and 20% tea extracts plus DMBA treated groups when compared with the CP or DMBA treated group alone. In the single dose of TF and TR treated groups a significant decrease in both CA and SCE was observed in both the TF and TR plus both the carcinogen treated groups when compared with their positive controls. The protective effects of black tea extracts were more significant than that of its two polyphenols. This study indicates that both black tea and its active polyphenols TF and TR have significant anticlastogenic effects in bone marrow cells of mice.

Involvement of the presynaptic dopamine D2 receptor in the depression of spinal reflex by apomorphine.

THE relative roles of Dl and D2 dopamine (DA) receptors in mediating apomorphine (APO)-induced changes in the spinal reflex was investigated. Low doses of APO, a DA receptor agonist (0.2 mg kg−1, i.v.), depressed the monosynaptic mass reflex (MMR) in spinalized rats. Pretreatment with the D2-specific antagonist, spiperone, 10 min before APO prevented the APO-induced MMR depression. Pretreatment with the Dl antagonist SCH 23390 failed to prevent the APO-induced depression. Interestingly, SCH 23390 pretreatment preferentially antagonized the depression induced by a high dose of APO (3 mg kg−1, i.v.). Pretreatment with SKF 38393, a selective Dl agonist, completely prevented the APO-induced MMR depression. These results suggest that inhibition of spinal transmission by low dose of APO may be mediated through its action on presynaptic D2 receptors and that Dl and D2 receptors are functionally coupled at the spinal level in modulating the spinal motor output.

Presynaptic dopaminergic inhibition of the spinal reflex in rats.

Dopaminergic influence on spinal monosynaptic transmission was examined in rats. Monosynaptic mass reflex (MMR) was recorded from the ventral root L6 following supramaximal stimulation (0.2 Hz; 0.1 ms) to the ipsilateral dorsal root L6 in spinalized rat under pentobarbitone sodium (40 mg/kg, i.p.) anaesthesia. MMR was inhibited by intravenous administration of the dopaminergic agonist, apomorphine (50-200 ug/kg) in a dose-dependent manner. The attenuatory effect of apomorphine (200 ug/kg i.v.) on the reflex could be reversed by the dopaminergic antagonist haloperidol (0.5 mg/kg, i.v.). Under tetanic stimulation (200 Hz; 15s), the pretetanic relative inhibition induced by apomorphine (200 ug/kg, i.v.) was increased only for a short period immediately after the cessation of tetanic stimulation. The results indicate existence of presynaptic dopamine receptors on the afferent terminals converging on the motoneurone which may functionally modulate the spinal motor output.

Tremorogenesis by physostigmine is unrelated to acetylcholinesterase inhibition: Evidence for serotoninergic involvement

Studies were performed to bring out a serotoninergic involvement in physostigmine tremor, hitherto known to be working via the cholinergic system. 5-Hydroxytryptamine (5-HT) was estimated fluorimetrically after isolation on Sephadex G-10 and acetylcholinesterase (AChE) was assayed spectrophotometrically. The dose-dependent tremor was quantified by a double-blind study. No correlation (r = 0.01) existed between tremor and AChE inhibition since the non-tremoring dose of physostigmine caused the same degree of enzyme inhibition. An increase of 5-HT was found to be correlated (r = 0.59) with the duration and intensity of tremor. Cholinergic antagonists atropine (2 and 5 mg/kg, i.p.), scopolamine (0.5, 1.0, 2.0 mg/kg, i.p.) and mecamylamine (1 mg/kg, i.p.) failed to block the tremor while the 5-HT antagonists methysergide (5 mg/kg, i.v.) and cyproheptadine (10 and 30 mg/kg, s.c.) could afford more than 60% protection. These results suggest a serotoninergic rather than a cholinergic component in the genesis of physostigmine tremor.

Involvement of gamma-aminobutyric acid in the stimulatory effect of metoclopramide on gastrointestinal motility

The involvement of gamma-aminobutyric acid (GABA) in the mechanism of action of metoclopramide (MCP) on gastrointestinal (GI) tract was investigated employing guinea-pig myenteric plexus longitudinal muscle preparations. MCP induced a concentration dependent enhancement of electrically induced twitch responses of the myenteric plexus and this effect was further intensified by arecaidine and L-2, 4-diaminobutyric acid (L-DABA; GABA uptake inhibitors) and ethylenediamine (EDA; GABA releasing agent). The facilitatory effect of MCP was reduced by 3-mercaptopropionic acid (3-MPA; GABA synthesis and release inhibitor) and after GABA desensitization but remained unchanged after bicuculline methiodide, a specific GABA receptor antagonist. The MCP induced contraction of the unstimulated preparation was also reduced after GABA desensitization and EDA without affecting responses to exogenous acetylcholine (ACh). The study indicates that GABA plays a role in the facilitatory effect of MCP on both stimulated and unstimulated preparations of guinea pig myenteric plexus.

Desensitization of spinal 5-HT1A receptors to 8-OH-DPAT: an in vivo spinal reflex study.

SEROTONERGIC influence on spinal monosynaptic transmission and the desensitization of spinal 5-HT1A receptors following a single pretreatment with a 5-HT1A ligand were examined in vivo in acutely spinalized adult rats. Administration of a selective 5-HT1A agonist, 8-OH-DPAT (0.1 mg kg−1) significantly depressed the monosynaptic mass reflex (MMR) amplitude, which was prevented effectively by S(−)-propranolol, a 5-HT1A antagonist. The inhibitory effect of 8-OH-DPAT on MMR amplitude was significantly attenuated with a single dose of 8-OH-DPAT (1 mg kg−1, s.c.) administered 24 h before the experiments, indicating a marked desensitization of spinal 5-HT1A receptors. Desensitization of 5-HT1A receptors could be reversed by treatment of spiperone (1 mg kg−1, i.p.) 3 h before 8-OH-DPAT pretreatment. These results demonstrate that 5-HT1A receptor functionally modulates the spinal motor output and confirms the ability of 8-OH-DPAT to desensitize presynaptic 5-HT1A receptors as observed for the first time in rat spinal cord.