Antispasmodic, Bronchodilator and Blood Pressure Lowering Properties of Hypericum oblongifolium - Possible Mechanism of Action

The crude extract of Hypericum oblongifolium (Ho.Cr), which tested positive for flavonoids, saponins and tannins caused concentration-dependent (0.1-1.0 mg/mL) relaxation of spontaneous and high K(+) (80 mM)-induced contractions in isolated rabbit jejunum preparations, suggesting a Ca(++) antagonistic effect, which was confirmed when pretreatment of the tissue with Ho.Cr produced a rightward shift in the Ca(++) concentration-response curves, like that caused by verapamil. Ho.Cr relaxed carbachol (1 mu M) and high K(+)-induced contractions in guinea pig tracheal preparations. It caused a dose-dependent (3-100 mg/kg) fall in arterial blood pressure of rats under anesthesia. In isolated guinea pig atria, Ho.Cr caused inhibition of both atrial force and rate of spontaneous contractions. When tested in rabbit aortic rings, Ho.Cr exhibited a vasodilator effect against phenylephrine (1 mu M) and high K(+)-induced contractions. These results indicate that Ho.Cr possesses gastrointestinal, respiratory and cardiovascular inhibitory effects, mediated via a Ca(++) antagonist mechanism

Synthetically modified bioisosteres of salicyl alcohol and their gastroulcerogenic assessment versus aspirin: biochemical and histological correlates

The present study was conducted to synthesize nitrogen containing derivatives of salicyl alcohol and to investigate in vivo their ulcerogenic potential in comparison with aspirin in rats. The compounds [4-(2-hydroxybenzyl) morpholin-4-iumchloride (I)] and [1,4-bis(2-hydroxybenzyl) piperazine-1,4-diium chloride (II)] were synthesized and their chemical structures were characterized using spectral data. In our previous study (Ali et al., Afr J Pharm Pharmacol 7:585–596, 2013), both compounds showed anti-inflammatory, antinociceptive, and antipyretic properties in standard animal models and a greater binding affinity for cyclooxygenase-2 versus cyclooxygenase-1 in molecular docking and dynamics analysis. For in vivo studies, animals were randomly divided into four groups. The synthetic compounds (both at 100 or 150 mg/kg), aspirin (150 mg/kg), or saline vehicle was administered orally, once daily for 6 days and then tested for ulcerogenic activity. At the end of the procedure, gastric juice and tissues were collected and subjected to biochemical and histological analyses. The results of the study revealed that in the case of the aspirin-treated group, there was a significant increase in gastric juice volume, free acidity, total acidity, and ulcer score and a decrease in gastric pH. Moreover, histological examination of the gastric mucosa of the aspirin-treated group indicated morphological changes while neither of the synthetic compounds showed any significant ulcerogenic or cytotoxic properties. The results of the present study suggest that both compounds are free from ulcerogenic side effects and may represent a better alternative to aspirin

Short-term oral administration of risperidone induces pancreatic damage and hyperamylasemia in Sprague-dawley rats

Risperidone is an atypical antipsychotic acting mainly as a dopamine D2 and serotonin 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various affective disorders. Risperidone has been reported to be associated with weight gain, panreatitis and type 2 diabetes mellitus. Various mechanisms of risperidone-induced toxicities have been reported but the histology of tissues especially pancreas has never been studied. Therefore, the current study was designed to elucidate the toxic effects of chronic administration of risperidone on pancreas, liver and kidneys. Animals (rats) of either gender were divided into two groups, the risperidone and control groups. Risperidone was administered in a dose of 2.5 mg/kg/d for three weeks. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase and amylase were determined at the conclusion of the experiment. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Risperidone showed no weight gain, hyperglycemia or rise in the level of lipase (P> 0.05); however, the level of amylase was raised (***P<0.05). Histological examination under light microscope showed no hepatotoxicity, nephrotoxicity but did show damage to the pancreas. The findings of this study indicated that the incidence of adverse effects associated with risperidone could be prevented/alleviated/delayed by allowing restricted diet

Performance Evaluation of UK Acquiring Companies in the Pre and Post-Acquisitions Periods

This paper has two objectives: first, it examines the financial performance of twenty UK based acquiring companies over the period of five years (2009-2013) using financial ratios of Liquidity, Profitability and Solvency in order to empirically determine whether there is any significant financial performance changes in the operation of the underlying companies as a result of acquisitions. Both average ratio and paired t-test analysis have been conducted. The analysis concludes that none of the ratios proved statistical significance which shows that the underlying acquisitions did not influence changes in the financial performance of the acquiring companies. The paper also examines whether shareholders make short-term gain while opting for acquisitions by analyzing stocks return over 58 days window period i.e. 29 days prior to acquisition announcement and 29 days after acquisition announcement by applying CAPM model and AAR and CAAR analysis. The analysis concludes that none of the results show statistical significance which further asserts that UK shareholders do not make gain in the short-term as a result of the acquisition activities they have undertaken

Pharmacological explanation for medicinal use of St. John's wort in the hypo-motility disorder of gut

St. John's wort (Hypericum perforatum) is widely used in traditional medical system as a laxative agent against gastrointestinal hypo-motility disorders, such as constipation. The present research was carried out to rationalize its therapeutic potential in constipation. St. John's wort aqueous extract (Sw.Aq), which tested positive for presence of flavonoids, saponins and tannins caused concentration-dependent (1.0-10 mg/mL) contractile effect in the isolated rabbit jejunum preparations. Pretreatment of tissues with atropine (0.1 µM) abolished the stimulatory effect of Sw.Aq, suggesting that the spasmogenic effect of St. John's wort is mediated possibly through muscarinic receptor activation. In the in-vivo studies, Sw.Aq exhibited laxative effect, reflected by increase in number of mice feces. These results indicate that Sw.Aq causes gut stimulation, via cholinergic mechanism and thus provides pharmacological basis for its medicinal use in gut hypo-motility disease, constipation.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Effects of probiotic on the intestinal morphology with special reference to the growth of broilers.

The probiotic (Protexin)® increases the growth rate in broilers. It must interfere with the intestinal cell morphology and absorption. The intestinal epithelium is one of the most rapidly renewed tissues in the body and is renewed by a process of continuous cell division. This study was carried out with an aim to establish a link between the use of probiotic doses, growth rate, and intestinal cell proliferation by measuring the length and weight of the intestine and intestinal crypt cell proliferation (CCP) of broiler chicks. The results revealed significant increase in intestinal CCP but no effect was observed on the intestinal weight and length. The increase in CCP has also no significant influence towards growth factor. The increased weight gain in this study is associated with more feed consumption which is observed with Protexin® dose 1.0 g / 10 kg of feed. Furthermore, feed consumption reduced beyond this dose may lead to reduced weight gain

Novel hydroquinone derivatives alleviate algesia, inflammation and pyrexia in the absence of gastric ulcerogenicity

Purpose: To synthesize and characterize novel hydroquinone compounds that exhibit an aspirin-like pharmacological profile devoid of ulcerogenic side effects.Methods: Two novel hydroquinone derivatives, viz, 2,5-bis(piperidinomethyl)hydroquinone and 2,5- bis(pyrrolidinomet hyl)hydroquinone, were synthesized by refluxing hydroquinone, paraformaldehyde and secondary amines (piperidine or pyrrolidine) in ethanol. The structures were authenticated by infrared (IR) spectroscopy, elemental analysis, mass spectrometry (MS) and 1H and 13C nuclear magnetic resonance (NMR) spectroscopic techniques. The synthesized derivatives were evaluated for antinociceptive, anti-inflammatory and antipyretic activities along with gastric-ulcerogenicity using wellknown testing paradigms. Aspirin served as reference standard.Results: The newly synthesized hydroquinone derivatives, significantly attenuated tonic visceral chemically-induced nociception at 10 mg/kg (p < 0.01, p < 0.001), 20 and 40 mg/kg (p < 0.001), inhibited the temporal-inflammatory reaction at 50 mg/kg (2 - 5 h, p < 0.05, p < 0.001), 100 and 150 mg/kg (1 - 5 h, p < 0.05, p < 0.01, p < 0.001) in addition to alleviating the febrile-response at test doses during 0.5 h (p < 0.05, p < 0.01, p < 0.001), 1 and 1.5 h (p < 0.001) of the study period. The synthesized compounds exhibited improved gastric tolerability profile since they were devoid of aspirin-associated biochemical and ulcerative changes. The in silico studies predicted high binding affinity of the hydroquinone derivatives to the active site of the cyclooxygenase 2 (COX-2) enzyme.Conclusion: The synthesized hydroquinone compounds possess analgesic, antipyretic and antiinflammatory properties with low gastric-ulcerogenic potential. This may be credited to preferential inhibition of the COX-2 enzyme and the beneficial basic rather than acidic chemical nature of the compounds. However, further molecular studies are required to substantiate these findings.Keywords: 2,5-Bis(piperidinomethyl)hydroquinone], 2,5- is(pyrrolidinomethyl)hydroquinone, Antiinflammatory, Antinociceptive, Antipyretic, Gastric-ulcerogenicity, Algesi