Molecular mechanisms that underlie the sexual stimulant actions of Avicennia marina [Forssk.] Vierh. and Crocus sativus L

The effects of extracts and sub-fractions of Avicennia marina, Crocus sativus and sildenafil on the sexual behavior of male rats and their effects on the intracavernosal pressure [I.CV], intracavernosal cyclic GMP and dihydrotestosterone plasma level were examined. The sexual behavior was followed for four hours using infra-red video cameras to quantify the effects on various male sexual behaviors. The results revealed that the active sub-fraction in case of A. marina was the hexane fraction of the chloroform extracts [C/H] whereas that of C. sativus was the hexane fraction of the alcoholic extract [A/H]. [C/H], [A/H] and sildenafil significantly increased the total sexual stimulation index from 53.8 +/- 2.7 [control] to 406 +/- 7.8, 225 +/- 4 and 401 +/- 30.1, respectively [P<0.001, N=6]. They significantly increased the index of successful mounting and ejaculation from 2.6 +/- 0.5 [control] to 40 +/- 2.7, 21 +/- 2.3 and 18 +/- 1.7, respectively [P<0.01, N=6]. They significantly increased the cyclic GMP level from 0.94 +/- 0.07 [control] to 3.1 +/- 0.13, 1.59 +/- 0.11 and 3.66 +/- 0.19 ng/mg wet tissue, respectively [P<0.05, N=7]. They did not affect dihydrotestosterone plasma level. [C/H], [A/H] and sildenafil increased the [I.CV] pressure by 4.8 +/- 0.3, 1.4 +/- 0.8 and 4.2 +/- 0.9 mmHg. The [C/H] seemed to be more active than sildenafil and twice active than [A/H]. Both extracts and sildenafil acted via an increase in cyclic GMP

[CNS, cytotoxicity and antimicrobial activities of [+]-dihydroperfamine and its derivatives]

In this work [+]-dihydroperfamine was isolated from Haplophyllum tuberculatum and several derivatives, namely, anhydroperforine, dihydroperfaminole, haplophyllidine, [-]-perforine and [+]-perforine were prepared. Dihydroperfamine and its derivatives were investigated for prolongation of sleeping time of pentobarbitone. Their cytotoxic activity was performed using a mechanism-based bioassay utilizing genetically engineered mutants of the yeast Saccharomyces cerevisiae. In addition, their antimicrobial activity was also tested using agar dilution method. The results showed that dihydroperfamine and its derivatives except haplophyllidine prolonged the hypnotic duration of pentobarbital. Dihydroperfamine was the only compound that possessed cytotoxic activity against strain I. On the other hand, all compounds were antimicrobially inactive

Evaluation of the hepatoprotective effect of ecbalium elaterium, convolvulus pilosellifolius, cyperus bulbosus and echinacea angustifolia against experimentally induced liver injury in rats

Ecbalium elaterium, Convolvulus piosellifollus, Cyperus bulbosus and Echinacea angustifolia were selected for studying their hepatoprotective effects against induced liver toxicity by CCI4 in rats. The extent of liver protection is reflected by measuring the biochemical parameters: serum glutamate oxaloacetate transaminase [SGOT], serum glutamate pyruvate transaminase [SGPT], alkaline phosphatase [ALP] and total bilirubin that indicate the condition of liver cells. Extracts that showed good reduction in the biomarker levels were further subjected for histopathological study to explore the extent of protection of hapatocytes. Only the extract of Ecbalium elaterium was effective in reducing the elevated enzyme levels at the 500 mg/kg dose. However, in the histopathological study the extract failed to restore the normal appearance of hepatocytes. All the results were compared with silymarin, as a reference hepatoprotective drug

Kynurenic acid as an additional endogenous anti-aggregatory factor

Kynurenic acid [KNA] is an endogenous metabolite of tryptophan that has been characterized both in the brain and various peripheral organs that included blood vessels, kidneys, hearts, intestine and the eye. Its release from the vascular tissues which also release prostacyclin and nitric oxide directed us to investigate its influence on platelets aggregation. Exposure of guinea-pig platelets to KNA in concentrations ranging from 0.1 to 2mM inhibited adenosine diphosphate [ADP] and arachidonic acid [AA] induced aggregations in a dose-dependent manner.The inhibitory dose 50 values against ADP and AA were found to be 1.1 +/- 0.06 and 0.9 +/- 0.08 mM respectively. [N=8]. The anti-aggregatory effect was significantly reversed in presence of exogenous Ca[2+]. Elevation of the level of the plasma by 0.5mM Ca[2+] reversed the anti-aggregatory effect KNA by 60 +/- 4.5 and 71.5 +/- 6.3% against ADP and AA, respectively [P<0.01, N=8]. It is suggested that KNA may be considered as an additional endogenous anti-aggregatory factor

Conventional drugs and herbal medicines-induced hepatotoxicity

This review deals mainly with enlightening physicians, pharmacists and all those who are involved in the medical field with the abilities of various synthetic drugs and medicinal plants-that are formulated in various elegant pharmaceutical forms-that are circulating in both our own countries and abroad. It initially gives an idea about the prevalence of drugs-induced hepatotoxicity in some countries and then it describes the various physiological functions of the liver. It also discusses the various mechanisms through which chemicals induce toxic and allergic hepatotoxicity and other disturbances such as cholestasis, granulomatous hepatitis, phospholipidosis, steatohepatitis, fibrosis, cirrhosis and tumors. For each of these diseases numerous examples of synthetic drugs and medicinal plants arc given. With regard to medicinal plants. the Latin and Trade names, botanical families, uses and active constituents responsible for the induction of the hepatotoxicity are also given. The possible methods available for diagnosis and treatment of such diseases are given. The review then draws the attention to the fact that withdrawal of these drugs and medicinal plants from the pharmaceutical register does not limit the effective treatments of the various diseases for which these chemicals arc indicated

Recent advances in the roles of calcium ions [Ca2+] and their antagonism in various body functions

This review deals mainly with the importance and the various roles played by Ca[2+] ions [Ca[2+]] in mammalian body functions and the various implications following the prevention of release from. the intracellular stores or the influx from the extracellular fluids. It discusses the molecular mechanisms through which Ca[2+] mediate muscular contractility, secretion of hormones, release of autacoids, neurotransmitters, cytokines and bone formation. Furthermore, the reveiw points out the various disturbances and diseases that follow inappropriate and excessive Ca[2+] release in various organs and the available pharmacological means to normalise it. The review also deals with the various means that regulate the intracellular and the extracellular levels of Ca[2+]. Special emphasis was given to the various types of Ca[2+] channels so far discovered in the mammalian organs. The review concluded by pointing out the shortcomings of the existing organic Ca[2+] channel blockers and the importance of discovery of organ and channel selective Ca[2+] channel blockers with the ultimate goal of decreasing the multiple side effects observed following the use of the existing Ca[2+] channel blockers

pharmacology of honey bee products: 1. Actions of Propolis on rat arterial blood pressure, respiratory systems and some smooth muscles

The influence of the honey bee propolis was examined on the cardiovascular system the respiratory system and the in vivo uterine activity in rats together with its effects on the isolated rabbit jejunum. Administration of propolis in doses of [2.5-10 mg kg -1 i.v.] decreased the arterial blood pressure and the heart rate increased the respiratory rate and the intra tracheal and the intra-uterine pressures in a dose dependent manner. The cardiovascular depressant effects were antagonized by cyproheptadine and atropine. They were not antagonized by hexamethonium mepyramine, ranitidine indomethacin cutting of the vagus to the heart or by spinal pithing of the animals. The induced respiratory and uterine effects were antagonized by treatment of the animals with atropine and cyproheptadine respectively, suggesting mediation via muscarinic and serotoninergic mechanisms. Exposure of the isolated rabbit jejunum to propolis extract in concentrations of [5-20 micro gml-1] induced dose dependent contractions that were antagonized by pretreatment of the tissue with hexamethonium and atropine, suggesting propolis induced activation of the parasympathetic ganglia with concomitant release of Ach from the terminals of the postganglionic parasympathetic fibers. It was concluded that propolis contains constituents that directly or indirectly activate muscarinic and/or serotoninergic mechanisms in both rats and rabbits

Flumazenil: a novel and potent benzodiazepine competitive receptor blocker

One of the most rewarding outcomes in the recent research in the field of benzodiazepines [BNZs] is the discovery of BNZ receptors and their association with GABA receptors, together with the discovery of some synthetic BNZ agonists andas antagonists. To the latter group belongs the 1,4-imidazodiazepine derivative-flumazenil which was introduced in 1981. It is shown to be competitive blocker for both types of BNZ receptors, namely, BNZ type-1 which are involved in the anxiolytic effects and BNZ type-2 which are involved in sedation and sleep. Administration of flumazenil [10 micro g/kgi.v] is shown to rapidly antagonize [within minutes] BNZ-induced anxiolytic, sedative,hypnotic, ataxic, anticonvulsant, amnestic and respiratory depressant effects. The major disadvantage of flumazenil is its rapid hepatic metabolism that curtails its oral use. Beside helping in reversal of BNZ- induced intoxication,the drug has been proven to be of value in the diagnosis of unconsciousness of unknown origin, to test for BNZs- involvement and in the improving of consciousness in some cases of hepatic coma. The introduction of flumazenil is expected to give an extended margin of safety to the use of BNZs, but it is hoped that it would not encourage the overwhelming use of these drugs

Effect of the volatile oil of Nigella sativa on the arterial blood pressure and heart rate of the Guinea-Pig

The effects of the volatile oil [V.O.] of the black seed-Nigella sativa Linn, and its constituent thymoquinon [T.Q.] were examined on the arterial blood pressure and the heart rate of urethane-anaesthetized guinea-pigs. Intravenous administration of the V.O. [30-120 micro 1 kg-1] decreased the arterial blood pressure and the heart rate in a dose-depended manner. Similarly, administration of T.Q.[6-24mg kg -1] decreased the arterial blood pressure and the heart rate. Pretreatment of the animals with atropine or cyproheptadine [2 mg kg -1 for 5 min] or with hexamethonium [10 mg kg -1 for 10 min] antagonized V.O. and T.Q.- induced cardiovscular depressant effects. V.O-induced cardiovascular depressant effects were also significantly antagonized by spinal pithing.it was concluded that V.O.-induced effects were probably due to its constituent T.Q. and were probably mediated centrally within the medulla ablongata via activation of 5-hydroxytrptaminergic and muscarinic mechanisms