Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence

Midbrain dopaminergic(DA)neurons are governed by an endogenous cholinergic system,originated in the mesopontine nuclei.Nicotine hijacks nicotinic acetylcholine receptors(nAChRs)and interferes with physiological function of the cholinergic system.In this review,we describe the anatomical organization of the cholinergic system and the key nAChR subtypes mediating cholinergic regulation of DA transmission and nicotine reward and dependence,in an effort to identify potential targets for smoking intervention.Cholinergic modulation of midbrain DA systems relies on topographic organization of mesopontine cholinergic projections,and activation of nAChRs in midbrain DA neurons.Previous studies have revealed thatα4,α6,andβ2 subunit-containing nAChRs expressed in midbrain DA neurons and their terminals in the striatum regulatefirings of midbrain DA neurons and activity-dependent dopamine release in the striatum.These nAChRs undergo modification upon chronic nicotine exposure.Clinical investigation has demonstrated that partial agonists of these receptors elevate the success rate of smoking cessation relative to placebo.However,further investigations are required to refine the drug targets to mitigate unpleasant side-effects.     

Electrophysiological and pharmacological properties of nucleus basalis magnocellularis neurons in rats

INTRODUCTION The nucleus basalis magnocellularis (nbM), alsotermed nucleus basalis of Meynert in primate, includescells located in the ventral and medial globus pallidus(GP) and substantia innominate (SI). The nbM con-tains a heterogeneous population of neurons, in thatmost large neurons are cholinergic. These neurons aremultipolar and have large dendritic fields. In addition tocholinergic neurons, some of the large neurons areGABAergic[1,2]. The smaller neurons intermixed with…     

Idebenone protects hippocampal neurons against amyloid β-peptide-induced neurotoxicity in rat primary cultures

The application of amyloid β-peptide (Aβ) 1–40 (10 μM) caused neurodegeneration of hippocampal neuronal cells, as indicated by the release of lactate dehydrogenase (LDH) into the culture medium. Treatment with idebenone (10–1000 nM), a potent antioxidant in mitochondria, protected the hippocampal neurons against the Aβ1–40 (10 μM)-induced neurotoxicity. To determine the morphological change in neurons during the Aβ1–40-induced cytotoxicity, the cells were immunostained with anti-MAP2 antibodies. After 4-day exposure to 10 μM Aβ1–40, the number of neurons was reduced, and the surviving neurons had an apparently reduced number of neurites which were shorter than those of control neurons. When idebenone was added to the culture medium with Aβ1–40, the number of surviving neurons was significantly increased, and their neurites were as long as seen in control culture. These results suggest that reactive oxygen species mediate neurotoxicity of Aβ1–40, and idebenone protects neurons against the Aβ1–40-induced neurotoxicity. Received: 5 June 1998 / Accepted: 25 August 1998     

Huntingtin processing in pathogenesis of Huntington disease

Huntington‘s disease (HD) is caused by an expansion of the polyglutamine tract in the protein named huntingtin. The expansion of polyglutamine tract induces selective degeneration of striatal projection neurons and cortical pyramidal neurons. The bio-hallmark of HD is the formation of intranuclear inclusions and cytoplasmic aggregates in association with other cellular proteins in vulnerable neurons. Accumulation of N-terminal mutant huntingtin in HD brains is prominent. These pathological features are related to protein misfolding and impairments in protein processing and degradation in neurons. This review focused on the role of proteases in huntingtin cleavage and degradation and the contribution of altered processing of mutant huntingtin to HD pathogenesis.     

Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with DA receptor subtypes

AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antagonist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was recorded in the nucleus accumbens (NAc) neurons of naive and unilateral-6-hydroxydopamine (6-OHDA)-lesioned Sprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by thechange of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB- 18 was capable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on NAc firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which wasreversed by the D1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited byiontophoretically applied THPB- 18 in 90 % of 6-OHDA-lesioned rats, while THPB- 18 caused variable effects on thefiring of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked byiontophoretic application of SCH23390, but not D2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine,THPB-18 also possesses the “D1 agonistic-D2 antagonistic“ dual action on the VTA-NAc DA system.AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antago-nist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was re-corded in the nucleus accumbens (NAc) neurons of naive and unilateral-6-hydroxydopamine (6-OHDA)-lesionedSprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by thechange of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced adecrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB- 18 wascapable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on NAc firingactivity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which wasreversed by the D1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited byiontophoreticaUy applied THPB- 18 in 90 % of 6-OHDA-lesioned rats, while THPB- 18 caused variable effects on thefiring of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked byiontophoretic application of SCH23390, but not D2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine,THPB-18 also possesses the “D1 agonistic-D2 antagonistic“ dual action on the VTA-NAc DA system.     

Expression manner of 5-lipoxygenase in human traumatic brain injury and astrocytoma

5-lipoxygenase (5-LO) is a key enzyme of arachidonic acid metabolism. The metabolites, leuklotrienes, are important mediators in asthma, inflammatory and allergic disorders. The activation of 5-LO includes the gathering of 5-LO,adhering onto the membranes of nuclei and entrance to the nuclei. In the central nervous system, 5-LO is widely expressed     

Mechanism of regulation of CaCC by the Mas-related G protein-coupled receptor D

MrgD is expressed almost exclusively in dorsal root ganglion(DRG) neurons.And its activation inhibited KCNQ/M-currents that contributes to an increase in excitability of DRG neurons and thus may enhance the signaling of primary afferent nociceptive neurons.Ca2+-activated chloride channels(CaCCs) are found in DRG neurons and regulate neuronal cell excitability as well.But the interaction between CaCCS and MrgD is still unknown.We here found that β-alanine-induced activation of MrgD resulted in eliciting Ca2+-activated chloride currents.The currents were inhibited by flufenamic acid(FFA) and by inhibition of phospholipase C and Ca2+ chelating agent EGTA.However,calphostin C,a PKC inhibitor,had no effect on the currents.These present data show that the inward currents induced by activation of MrgD were mediated through Gq-phospholipase C-IP3-Ca2+ release pathway,but not via Gi pathway.     

Injections of muscimol into the median raphe nucleus produce hippocampal theta rhythm in the urethane anesthetized rat

It has previously been shown that serotonergic [5-hydroxytryptamine (5-HT)] neurons of the median raphe nucleus (MR) are critically involved in the control of the hippocampal electroencephalogram (EEG). Activation of MR 5-HT neurons desynchronizes the hippocampal EEG, whereas inhibition of MR 5-HT activity produces hippocampal theta rhythm. The MR contains an intrinsic population of gamma-aminobutyric acid (GABA) containing neurons that synapse on 5-HT cells of the MR. The present study examined the effects on the hippocampal EEG of injections of the GABA_A agonist muscimol hydrobromide into the MR. Low doses of muscimol (0.5 μg) produced hippocampal theta rhythm at a mean latency of 6.81 min and for a mean duration of 23.6 min. Higher doses (1.0 μg and 3.0 μg, respectively) produced theta at mean latencies of 2.24 min and 3.2 min and for mean durations of 31.84 min and 24.88 min. Injections of muscimol into regions adjacent to the MR generated theta at significantly longer latencies or were without effect. The present results indicate that MR injections of muscimol produce theta by inhibiting the activity of MR 5-HT neurons. It is concluded that MR GABAergic systems, via their influence on MR 5-HT cells, serve an important role in the control of the hippocampal EEG.     

Histamine modulation of acute nociception involves regulation of Nav1.8 in primary afferent neurons in mice

OBJECTIVE To explore the role of histamine in acute pain perception.METHODS We studied the sensitivity to acute pain in histidine decarboxylase knockout mice(HDC-/-),wild-type mice treated with α-fluoromethylhistidine(α-FMH),a specific HDC inhibitor,and mice feed a low-histamine diet.Morphological,Western blotting and Electrophysiology studies were taken to explore the involvement of sodium channel 1.8(Nav 1.8) in the pathological process.RESULTS Behavioral tests revealed that HDC-/-mice had lower nociceptive thresholds for acute thermal(hot-plate),mechanical(tail-pressure) and chemical(acetic acid and formalin) stimulation than the wild-type.The low-histamine diet elevated the sensitivity to all these noxious stimuli in the wild-type,and to heat and formalin stimuli in the HDC-/-mice.α-FMH treatment also augmented acute thermal nociception in the wild-type.Morphological and Western blotting studies showed that both HDC knockout and α-FMH treatment increased the expression of Nav1.8 in nociceptive primary afferent neurons.The higher Nav1.8 current density in nociception-related small DRG neurons of HDC-/-mice verified this upregulation.Moreover,the current required to evoke action potentials was significantly lower,and the firing rate in response to suprathreshold stimulation was higher in neurons from HDC-/-mice.The hyperexcitability of DRG neurons in HDC-/-mice was diminished by a Nav1.8 inhibitor,but not TTX.CONCLUSION Our results indicate that histamine participates in acute pain modulation,which may be related to the regulation of Nav1.8 in,as well as the excitability of,nociceptive primary afferent neurons.     

Comparison of effects of hypotension and handling stress on the release of noradrenaline and dopamine in the locus coeruleus and medial prefrontal cortex of the rat

The effects of two different types of stress (hypotension and handling) on the release of dopamine, noradrenaline and DOPAC in the locus coeruleus (LC) and medial prefrontal cortex (mPFC) was studied by means of the dual-probe microdialysis technique. One probe was implanted in the vicinity of the LC and a second probe was implanted in the mPFC. Both probes were used to record simultaneously noradrenaline, dopamine and DOPAC. Samples from the LC were collected in the presence of nomifensine, which was added to the perfusion fluid in a concentration of 50 μM. Hypotension (20 min) induced by intravenous administration of nitroprusside stimulated the release of noradrenaline in the LC and mPFC to about 190% and 150% of control values, respectively. Hypotension also strongly stimulated the release of dopamine in the mPFC (to 320% of control) and DOPAC in the LC (to 270% of control). The effect of hypotension on extracellular dopamine, noradrenaline and DOPAC was decreased by halothane anaesthesia, and was blocked by chloral hydrate anaesthesia. Handling stress (10 min) stimulated the release of noradrenaline in the LC and mPFC to 180% and 160% of control values, respectively. Handling stimulated the release of dopamine in the mPFC to about 160% of control. The effect of hypotension or handling stress was further evaluated in animals in which the LC was lesioned by an infusion of 6-OH-dopamine. Lesioning of the noradrenergic LC neurons did not the prevent the hypotension-related stimulation of dopamine release, but shortened the time course of the effect dramatically. Lesioning of the noradrenergic neurons had no effect on the stimulatory effect of handling on the release of dopamine in the mPFC. This study shows that mesocortical dopamine neurons, in contrast to noradrenaline neurons, respond much stronger to hemodynamic stress than to an emotional stress. During certain conditions like hypotension stress, but not during handling stress, the LC activity is able to modulate the release of dopamine from mesocortical neurons. Received: 23 November 1998 / Accepted: 23 April 1999 / Published online: 21 June 1999     

Effect of hyperprolactinaemia as induced by pituitary homografts under kidney capsule on gastric and duodenal ulcers in rats.

The effect of hyperprolactinaemia, induced by two or four pituitary homografts under the kidney capsule, on gastric and duodenal ulcers has been studied. The acute gastric ulcer models used were pylorus ligation, indometacin-induced and ethanol-induced gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by mercaptamine hydrochloride. After pylorus ligation, there was an approximate 30-40% increase in gastric secretion, a significant increase in total acidity (P < 0.01) and in the ulcer index (P < 0.01) in rats bearing pituitary homografts under the kidney capsule when compared with the sham-operated control. Hyperprolactinaemia did not affect the formation of ethanol-induced gastric ulcers but showed a 40% reduction in the development of indometacin-induced gastric ulcers. It also produced a 20% increase in the ulcer index in acetic acid-induced chronic gastric ulcers and a 30% increase in ulcer area in mercaptamine-induced duodenal ulcers. Our results showed that hyperprolactinaemia induced gastric acid secretion and thereby aggravated gastric and duodenal ulcers in rats. Hyperprolactinaemia did not affect gastric cytoprotection.     

Effects of the novel anti-ulcer agent 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine on experimental ulcers and gastric secretion in rats

The effects of 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285) on various experimentally induced ulcers and gastric acid secretion were investigated in rats. HWA 285 (10-50 mg/kg, p.o.) inhibited restraint and water-immersion-induced stress, ulcers, indometacin- and absolute ethanol-induced gastric ulcers and mepirizole-induced duodenal ulcers in rats in a dose-dependent manner. HWA 285 (10-25 mg/kg i.d.) had inhibitory effects on acetylsalicylic acid-induced ulcers. The healing of acetic acid-induced chronic ulcers was significantly accelerated by HWA 285 (25 mg/kg p.o.) when it was given twice daily for 7 consecutive days. When given orally (twice a day, 11 doses in total) before the induction of gastric ulcers by stress, cimetidine at 100 mg/kg aggravated the ulcers, whereas, HWA 285 at 25 mg/kg had not such an effect. In conscious pylorus-ligated rats, HWA 285 (10-100 mg/kg i.p.) showed a dose-dependent inhibition on basal and desglugastrin- and 2-deoxy-D-glucose (2-DG)-stimulated gastric acid secretion. In stomach-lumen perfused rats, HWA 285 (30 mg/kg i.v.) inhibited 2-DG-stimulated gastric acid secretion but not carbachol-stimulated gastric acid secretion. These results suggest that the anti-ulcer effects of HWA 285 are produced by cytoprotective and central anti-secretory activity without peripheral anti-cholinergic properties. Whether the central anti-secretory effects of HWA 285 play thereby the key role, have to be clarified in further investigation.     

Effects of 5-acetylspiro[benzofuran-2(3H),1'-cyclopropan]-3-one, a new anti-ulcer agent, on experimental acute and chronic ulcers

The effects of 5-acetylspiro[benzofuran-2(3H),1'-cyclopropan]-3-one (AG 629), a newly synthesized compound, on various experimentally induced ulcers were investigated. Oral or intraduodenal administration of AG 629 in a dose range of 25-100 mg/kg inhibited water-immersion stress ulcer, exertion ulcer, Shay ulcer, indometacin- and acetylsalicylic acid (ASA)-induced gastric ulcer, and indomethacin-induced small intestinal ulcer in rats, histamine-induced gastric ulcer in guinea pigs, and ASA-induced gastric ulcer in dogs, though it was not effective against cysteamine-induced duodenal ulcer in rats. AG 629 in doses of 6.3-25 mg/kg p.o. twice a day significantly promoted the healing of acetic acid- or thermal-cortisone-induced gastric ulcers and acetic acid-induced duodenal ulcers in rats. AG 629 (25-100 mg/kg i.d.) inhibited the secretion of gastric acid and pepsin in pylorus-ligated rats and the acid secretion stimulated by distension of the rat stomach with air, whereas this compound did not affect acid secretion stimulated by histamine, pentagastrin, carbachol or 2-deoxy-D-glucose. This study shows that AG 629 has both prophylactic and curative effects on various ulcers. The anti-ulcer effect of this agent seems to be mediated primarily by increasing mucosal resistance and secondarily by an antisecretory activity.     

Antiulcer activity of cod liver oil in rats

Objective:

Cod liver oil is used widely as a dietary supplement. The present study was carried out to evaluate the effect of cod liver oil (0.5 g/kg, p.o. and 1 g/kg, p.o.) on gastric and duodenal ulcers.

Materials and Methods:

The study was carried out on different gastric ulcer models such as acetic acid induced chronic gastric ulcers, pylorus ligation, indomethacin induced ulcers, stress induced ulcers and ethanol induced ulcers. The duodenal ulcers were induced using cysteamine hydrochloride (HCl). Ranitidine (50 mg/kg p.o.) and misoprostol (100 µg/kg, p.o.) were used as standard drugs.

Results:

Both doses of cod liver oil showed gastric ulcer healing effect in acetic acid induced chronic gastric ulcers, produced gastric antisecretory effect in pylorus-ligated rats and also showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced ulcer. Cod liver oil also produced a significant reduction in the development of stress induced gastric ulcers and cysteamine induced duodenal ulcer. The high dose of cod liver oil (1 g/kg, p.o.) was more effective compared to the low dose (0.5 g/kg, p.o.).

Conclusion:

Cod liver oil increases healing of gastric ulcers and prevents the development of experimentally induced gastric and duodenal ulcers in rats.     

胃散对胃溃疡模型大鼠胃黏膜保护作用的研究

目的 研究胃散对胃溃疡大鼠胃黏膜的保护作用。方法 采用乙酸烧灼型胃溃疡模型、幽门结扎型胃溃疡模型、乙醇损伤型胃溃疡模型,检测溃疡指数、胃酸总酸度、胃酸分泌速度和胃蛋白酶活性,综合考察胃散对胃溃疡模型大鼠胃黏膜的保护作用。结果 胃散在1、0.5、0.25 g/kg剂量下,对乙酸烧灼型胃溃疡有非常显著的促愈合作用;对幽门结扎型胃溃疡的形成有显著的抑制作用;对乙醇损伤的胃黏膜也有显著的保护作用;对胃液总酸度、胃酸分泌速度和胃蛋白酶活性有明显抑制作用,显著增加胃液分泌量。结论 胃散具有增加胃液分泌、抑制胃酸分泌、抑制胃蛋白酶活性、保护胃黏膜和防止胃溃疡的作用。     

Effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various gastric lesions induced in rats

We studied the effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various acute and chronic gastric lesions produced in rats. Arbaprostil significantly inhibited gastric secretion in 4 hr-pylorus-ligated preparations when given intraduodenally in a dose of 30 or 100 micrograms/kg. The agent, however, significantly stimulated gastric secretion of rats with either a ligated or intact pylorus when given orally in doses of 3-100 micrograms/kg. Orally administered arbaprostil dose-dependently prevented the development of HCI-ethanol-, histamine-, water-immersion stress-, or indomethacin-induced gastric erosions. Intraduodenally administered arbaprostil also dose-dependently prevented the development of aspirin-induced gastric erosions in pylorus-ligated rats. Arbaprostil, given orally in doses of 1-100 micrograms/kg twice daily for 2 weeks, had little or no effect on the healing of acetic acid-induced gastric ulcers. However, oral administration of the agent in a dose of 3 or 10 micrograms/kg twice daily for 4 weeks significantly accelerated the healing of acetic acid-induced gastric ulcers. The increase in doses up to 100 micrograms/kg twice daily for 4 weeks had no effect on ulcer healing. These results indicate that arbaprostil, at either antisecretory or even acid stimulating doses, is effective in preventing the development of acute gastric erosions and in accelerating the healing of chronic gastric ulcers.     

Effect of an H+, K+-ATPase inhibitor, omeprazole (OPZ), on gastric acid secretion and gastric or duodenal lesion. Comparison with an H2-receptor antagonist, famotidine (FMD)

In pylorus ligated rats, OPZ inhibited gastric acid secretion dose-dependently, with a potency greater than that of FMD. At the same time, OPZ increased gastric K+ secretion and inhibited pepsin and Na+ secretions at the highest dose. In Heidenhain pouch dogs, single injection of OPZ inhibited gastric acid secretion induced by histamine to a degree almost equal to that by FMD. In the case of repeated administration, anti-secretory activity of OPZ was enhanced by up to several days and then remained constant. After several days, the inhibitory activity of OPZ was more potent and longer than that of FMD, and it still had not ceased 22hr after administration. In pylorus ligated rats, OPZ prevented gastric ulceration, and the potency was greater than that of FMD. OPZ promoted healing of gastric and duodenal ulcers induced by acetic acid in rats. At the same doses, FMD failed to promote the healing of both ulcers. In water-immersion stressed rats, OPZ prevented formation of gastric erosions, with a potency greater than that of FMD. In addition, OPZ prevented formation of gastric erosions induced by ethanol in rats. These results indicate that the anti-secretory and anti-ulcer activities of OPZ are superior to those of FMD, so that OPZ should have excellent therapeutic application for peptic ulcers.     

Gastroprotective activity of α-terpineol in two experimental models of gastric ulcer in rats

BACKGROUND AND THE PURPOSE OF THE STUDY: Several plant essential oils, as well as terpenes present in essential oils, have shown gastroprotective activity. The aim of the present work was to evaluate the gastroprotective activity of α-terpineol, a monoterpene alcohol which is present in essential oils of various plants. METHODS: The gastroprotective activity of α-terpineol was evaluated in rats by assessing the changes in ethanol and indomethacin-induced gastric ulcer scores and on gastric secretory volume and total acidity in pylorus-ligated rats. Alpha-terpineol was administrated orally at the doses of 10, 30, and 50 mg/kg one hour before administration of the ulcer inducing agents by the pylorus ligation procedure. The involvement of endogenous prostaglandins in the protective effect of α-terpineol in ethanol-induced gastric lesions test was assessed by administration of indomethacin (10 mg/kg, s.c.) 30 min before oral administration of α-terpineol at the dose of 50 mg/kg. RESULTS: α-terpineol presented gastroprotective activity against ethanol-induced ulcers at the doses of 10, 30, and 50 mg/kg. Epoxy-carvone at the dose of 10 mg/kg did not present gastroprotective activity against ulcer induced by indomethacin, but at the doses of 30 and 50 mg/kg it attenuated the gastric damages induced by this agent significantly. Pretreatment with indomethacin did not prevent the gastroprotective effect of α-terpineol on ethanol-induced ulcers. Alpha-terpineol also did not affect the gastric secretion in pylorus-ligated rats. MAJOR CONCLUSION: The results suggest that α-terpineol presents gastroprotective action which does not involve either an increase in the synthesis of endogenous prostaglandin or a decrease in the gastric acid secretion.     

胃甘胶囊对实验性胃溃疡的保护作用

目的:研究胃甘胶囊对实验性胃溃疡的作用.方法:采用水浸应激性、利血平型、幽门结扎型及乙酸型胃溃疡模型研究胃甘胶囊抗胃溃疡作用;以幽门结扎收集胃液观察对胃液分泌的影响.结果:胃甘胶囊对小鼠水浸应激性、利血平型及大鼠幽门结扎型胃溃疡均有明显的保护作用;对大鼠乙酸型胃溃疡有明显的促进愈合作用;能抑制大鼠胃酸的分泌并促进胃粘液分泌.结论:胃甘胶囊有抑制实验性胃溃疡的作用,该作用可能与其抑制胃酸分泌、促进胃粘液分泌有关.     

Proulcerogenic effect of water extract of Boswellia sacra oleo gum resin in rats

Context: The water extract of Boswellia sacra Flueck. (Burseraceae) is used in the treatment of gastric and hepatic disorders in the Arab countries.

Objective: The effect of Boswellia sacra water extract on gastric secretion and experimentally induced gastric ulcers in rats was studied.

Materials and methods: Acetic acid-induced chronic gastric ulcers, pylorus ligation, aspirin-induced, ethanol-induced, and restraint plus cold stress-induced gastric ulcer models were employed. The effect on normal rats was also studied. The water extract of B. sacra was administered orally at doses of 2 and 5?ml/kg once daily ranging from single dose to 30?d treatment depending on the model. The extract was subjected to GC-MS analysis to determine the presence of various phytoconstituents.

Results: Boswellia sacra water extract (5?ml/kg, p.o (per os)) aggravated acetic acid-induced chronic ulcers, wherein an increase in ulcer index (p?<?0.01) and ulcer score (p?<?0.05) was observed. In pylorus-ligated rats, the extract increased gastric content volume (p?<?0.01), free acidity (p?<?0.01), total acidity (p?<?0.01), ulcer index (p?<?0.01), and pepsin activity (p?<?0.05). There was no significant effect on the development of ethanol-induced and aspirin-induced ulcers while an increase in the development of stress-induced ulcers was observed (p?<?0.01). The extract did not produce any ulcers when administered to normal rats. The dose of 2?ml/kg was less proulcerogenic compared with 5?ml/kg. The GC-MS analysis revealed the presence of several phytoconstituents that included menthol, 3-cyclohexen-1-ol, and octanoic acid.

Conclusion: Boswellia sacra water extract has proulcerogenic activity due to its gastric hypersecretory effect.