Research in Pharmaceutical Sciences
Volume:9 Issue: 2, Apr 2014

Isovanillin and iso-acetovanillon are two phenolic components isolated from a number of plants including Pycnocycla spinosa. P. spinosa extract has antispasmodic and antidiarrheal activities. However, no comparative study has been done on antidiarrheal action of isovanillin and iso- acetovanillon, so far. The aim of this study was to investigate antidiarrheal action of isovanillin and iso-acetovanillon and their effects on small intestinal transit, for comparison with propantheline. Male mice (25-30 g), fasted over night with free access to water, were treated with test compounds or control (p.o.). Thirty min later castor oil (0.5 ml) was given orally to the animals. In another groups of animals MgSO4 (0.5 ml of 10% solution) was given first and half an hour later the test drugs were administered. Onset and number of wet defecations were recorded for each animal over 3.5 h after treatment with diarrhoea inducing agents. In another groups, intestinal transit of charcoal meal was determined following administration of the compounds. Isovanillin (2 mg/kg & 5 mg/kg), iso-acetovanillon (2 mg/kg & 5 mg/kg) and P. spinosa extract (5 mg/kg) delayed onset of diarrhoea and significantly reduced wet defecation induced by castor oil and MgSO4. They all had antidiarrheal effect similar to propantheline (5 mg/kg). Isovanillin, iso-acetovanillon and P. spinosa extract compared to control groups, significantly reduced small intestinal transit of charcoal meal. This study shows that antidiarrheal effect of P. spinosa extract is at least partially due to presence of two active compounds isovanillin and iso-acetovanillon.

The present study was carried out to investigate cytotoxic activity of flower, leaf, stem and root extracts of five Artemisia species against breast cancer cell line (MCF7) and human embryonic kidney normal cell line (HEK293). The studied Artemisia species were A. absinthium, A. vulgaris, A. incana, A. fragrans and A. spicigera. The cytotoxic activity was measured by MTT assay at different concentrations (62.5, 125, 250, 500 μg/ml). Among these five species, methanol extracts of flower, leaf, stem and root of A. absinthium and A. vulgaris exhibited considerable cytotoxic activity. The flower extracts of these two species were found to have higher cytotoxic effect on MCF7 cell with an IC50 value of 221.5 and >500 μg/ml, respectively. Leaf methanol extract of A. incana also showed cytotoxic activity. Cytotoxic activity of different extracts of A. absinthium, A. vulgaris and A. incana against MCF7 was 10%-40% more than HEK293 cells. Not only the extracts of A. spicigera andA. fragrans did not show any cytotoxic effect against both cell lines, but also increased the number of cells. This study revealed that A. absinthium and A. vulgaris may have a great potential to explore new anticancer drugs.

Amodiaquine is an antimalarial drug used in the prophylaxis and treatment of this disease. However, hepatotoxicity as a life‑threatening adverse effect is associated with its clinical use. We evaluated amodiaquine-induced toxicity in isolated rat hepatocytes as an in vitro model for studying drug‑induced hepatotoxicity. This study attempts to investigate the protective effects of taurine and N-acetyl cysteine against the cytotoxicity induced by amodiaquine. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. This technique is based on liver perfusion with collagenase after removal of calcium ion (Ca2+) with a chelator (ethylene glycol tetraacetic acid (EGTA) 0.5 mM). Cells were treated with different concentrations of amodiaquine, taurine and N‑acetyl cysteine. Cell death, protein carbonylation, reactive oxygen species formation, lipid peroxidation, and mitochondrial depolarization were assessed as toxicity markers. Amodiaquine cytotoxic mechanism involved protein carbonylation as well as reactive oxygen species formation and lipid peroxidation. In addition, mitochondria seem to be a target for amodiaquine to induce cellular damage. Administration of taurine (200 µM) and/or N-acetyl cysteine (200 µM) reduced oxidative stress, lipid peroxidation and protein carbonylation caused by amodiaquine. Furthermore, amodiaquine‑induced mitochondrial injury was significantly mitigated by taurine and/or N-acetyl cysteine. In glutathione‑depleted cells, only N‑acetyl cysteine protected hepatocytes against amodiaquine, and taurine showed no protective properties in this situation. Taurine and N-acetyl cysteine protect hepatocytes against amodiaquine probably via their antioxidant properties and counteracting oxidative stress.

Melissa officinalis L. (Labiatae) traditionally used in treating neurological disorders has also been identified as a memory-enhancing herb. The extract of M. officinalis has a cholinergic property. The role of basal forebrain cholinergic neurons, the neurons that are destroyed in Alzheimer’s disease (AD), in learning and memory, is also well known. The aim of this study is to investigate the role of cholinergic system on the memory improving activity of M. officinalis extract. The leaves of M. officinalis were extracted with ethanol 80% using the maceration method. Rats received intra-peritoneal injections of M. officinalis extract in different doses (50–400 mg/kg) alone or in combination with scopolamine (1 mg/kg) before being trained in a Morris water maze (MWM) in a single-day training protocol. After training, the acetylcholinesterase enzyme (AChE) activity was measured in the hippocampus. Administration of M. officinalis extract (200 mg/kg) could significantly enhance learning and memory of naïve rats (p<0.001) and significantly ameliorate scopolamine-induced learning deficit, but the effect of the extract was not dose dependent, and doses above 200 mg/kg could neither enhance memory in naïve rats nor reverse scopolamine-induced memory impairment. Also, inhibition of AChE activity was observed in both naïve and scopolamine-induced memory-impaired rats. These results suggest that M. officinalis can improve memory and that the cholinergic property of the extract may contribute to the memory-improving effects observed in this study. Then M. officinalis extract has potential therapeutic value in alleviating certain memory impairment observed in AD.

Previous studies have indicated that some species of Cuscuta possess anticancer activity on various cell lines. Due to the lack of detailed researches on the cytotoxic effects of Cuscuta chinensis and Cuscuta epithymum, the aim of the present study was to evaluate cytotoxic effects of chloroform and hydroalcoholic extracts of these plants on the human breast carcinoma cell line (MDA-MB-468), human colorectal adenocarcinoma cell line (HT29) and human uterine cervical carcinoma (Hela). Using maceration method, different extracts of aerial parts of C. chinensis and C. epithymum were prepared. Extraction was performed using chloroform and ethanol/water (70/30). Total phenolic contents of the extracts were determined according to the Folin-Ciocalteu method. Using MTT assay, the cytotoxic activity of the extracts against HT29, Hela and MDA-MB-468 tumor cells was evaluated. Extracts were considered cytotoxic when more than 50% reduction on cell survival was observed. The poly-phenolic content of the hydroalcoholic and chloroform extracts of C. chinensis and C. epithymum were 56.08 ± 4.11, 21.49 ± 2.00, 10.64 ± 0.86 and 4.81 ± 0.38, respectively. Our findings showed that the chloroform extracts of C. chinensis and C. epithyum significantly reduced the viability of Hela, HT-29 and MDA-MB-468 cells. Also, hydroalcoholic extracts of C. chinensis significantly decreased the viability of HT29, Hela and MDA-MB-468 cells. However, in the case of hydroalcoholic extracts of C. epithymum only significant decrease in the viability of MDA-MB-468 cells was observed (IC50 = 340 µg/ml). From these findings it can be concluded that C. chinensis and C. epithymum are good candidates for further study to find new possible cytotoxic agents.

The aim of this work was to develop and evaluate a minoxidil foamable emu oil emulsion with the purpose of improving minoxidil permeation into the skin, increasing hair growth, reducing skin irritation, and increasing consumer compliance. Minoxidil was dissolved in a solvent system comprising ethanol: glycerin: lactic acid: water (10:20:5:65). The foamable emulsion was prepared by mixing the oil phase with minoxidil solution using different amount of various emulsifiers. Seventeen formulations were prepared and the most stable foamable emulsion was selected and evaluated for various pharmaceutical parameters such as homogeneity, pH, stability to centrifugal stress, freeze-thaw and foamability. The adopted formulation showed good pharmaceutical characteristics. In vitro release rate of the formulations were evaluated using Franz diffusion cell using phosphate buffer pH 7.4 and ethanol as the receiver medium at sink condition. The release rate of formulations was found to obey Higuchi kinetic model. Experimental animal study was performed to evaluate hair growth potential of the formulation. Different cyclic phases of hair follicles, like anagen, and telogen phases, were determined at one month period. Histological study after treatment with adopted formulation exhibited greater number of hair follicles in anagenic phase (96%) which were higher as compared to marketed 5% minoxidil solution (Pakdaru® 70%) and the control group (42%). From animal study it was concluded that the selected formulation exhibited a significant potency in promoting hair growth in comparison with marketed 5% minoxidil solution Pakdaru®.

One of the most important and serious disorders of gastrointestinal tract is acute pancreatitis which in severe form is associated with high mortality rate particularly in the presence of systemic inflammatory response and multiple organ failure. Apoptosis linked to oxidative stress has been shown in the pancreas of the patients with acute pancreatitis. Lithium, one of the most effective drugs for the treatment of bipolar disorder, also has dramatic effects on preventing cell damage and apoptosis. Also lithium has shown anti-inflammatory effects in some animal studies. This study was designed to investigate the possible effect of lithium chloride in acute pancreatitis. Induction of acute pancreatitis was performed in male mice (25-30 g) by five intraperitoneal (i.p.) injection of cerulein (50 μg/kg) with 1 h intervals. Lithium chloride (10, 20 and 30 mg/kg) was administered i.p. 15 min before the induction of pancreatitis. Six h after the last injection of cerulein, the animals were sacrificed and biochemical as well as histopathological analysis was performed. Pretreatment with 20 mg/kg i.p. of lithium chloride reduced significantly the inflammatory response in cerulein-induced acute pancreatitis by ameliorating pancreatic edema and leukocyte infiltration, attenuating amylase and lipase serum levels, and myeloperoxidase activity compared to control group (p<0.05). Two other administered doses namely 10 and 30 mg/kg were found ineffective. In this study our findings demonstrate that lithium can dose dependently exhibit protective effect against cerulein-induced acute pancreatitis.

A quantiatative structure property relationship (QSPR) treatment was used to a data set consisting of diverse 3-hydroxypyridine-4-one derivatives to relate the logarithmic function of octanol:water partition coefficients (denoted by log po/w) with theoretical molecular descriptors. Evaluation of a test set of 6 compounds with the developed partial least squares (PLS) model revealed that this model is reliable with a good predictability. Since the QSPR study was performed on the basis of theoretical descriptors calculated completely from the molecular structures, the proposed model could potentially provide useful information about the activity of the studied compounds. Various tests and criteria such as leave-one-out cross validation, leave-many-out cross validation, and also criteria suggested by Tropsha were employed to examine the predictability and robustness of the developed model.

Essential oils obtained from aerial parts of Artemisia persica and Artemisia turcomanica were analyzed by GC/MS. While 28 components representing 91.01 % of A. persica were identified, the identity of 50 components, constituting 81.93 % of the total oil, was confirmed in A. turcomanica. β- thujone was the main compound (75.23%) in A. persica while the major identified phytochemicals in A. turcomanica were 1,8-cineol (19.23%), camphor (15.55%) and filifolone (15.53%). Both of the essential oils were predominantly made up of monoterpenes. Time- and dose-dependent cytotoxic effects of A. persica and A. turcomanica on MCF-7 cell line evaluated by MTT assay at 24, 48 and 72 h, showed that the highest cytotoxic effect of A. persica and A. turcomanica were appeared at 72 h incubation. At that incubation period, CI50 of A. persica was found to be 0.15 µg/ml, while that of A. turcomanica was 0.1 µg/ml. Thus, cytotoxicity of A. turcomanica was slightly higher than A. persica which could be attributed to the higher content of sesquiterpene present in A. turcomanica. As a conclusion, these volatile oils could have chemotherapeutic potentials.