Origanum majorana L. extract exhibit positive cooperative effects on the main mechanisms involved in acute infectious diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L. (Lamiaceae) is commonly used in Moroccan folk medicine to treat infantile colic, abdominal discomfort and diarrhea. Liquid stools and abdominal discomfort observed in acute infectious diarrhea are the consequences of imbalance between intestinal water secretion and absorption in the lumen, and relaxation of smooth muscle surrounding the intestinal mucosa. AIM OF THE STUDY: The objective of our study was to see if aqueous extract of Origanum majorana L. (AEOM) may exhibit an effect on those deleterious mechanisms. MATERIALS AND METHODS: The effect of AEOM on electrogenic Cl- secretion and Na+ absorption, the two main mechanisms underlying water movement in the intestine, was assessed on intestinal pieces of mice intestine mounted, in vitro, in Ussing chambers. AEOM effect on muscle relaxation was measured on rat intestinal smooth muscle mounted in an isotonic transducer. RESULTS: 1) AEOM placed on the serosal (i.e. blood) side of the piece of jejunum entirely inhibited in a concentration-dependent manner the Forskolin-induced electrogenic chloride secretion, with an IC50 = 654 ±â€¯8 µg/mL. 2) AEOM placed on the mucosal (i.e. luminal) side stimulated in a concentration-dependent manner an electrogenic Na+ absorption, with an IC50 = 476.9 ±â€¯1 µg/mL. 3) AEOM (1 mg/mL) inhibition of Forskolin-induced electrogenic secretion was almost entirely prevented by prior exposure to Ca++ channels or neurotransmitters inhibitors. 4) AEOM (1 mg/mL) proabsorptive effect was greater in the ileum and progressively declined in the jejunum, distal colon and proximal colon (minimal). 5) AEOM inhibited in a concentration-dependent manner smooth muscle Carbachol or KCl induced contraction, with an IC50 = 1.64 ±â€¯0.2 mg/mL or 1.92 ±â€¯0.8 mg/mL, respectively. CONCLUSION: the present results indicate that aqueous extract of Origanum majorana L. exhibit positive cooperative effects on the main mechanisms that are involved in acute infectious diarrhea.

Cytotoxicity of the Aqueous Extract and Organic Fractions from Origanum majorana on Human Breast Cell Line MDA-MB-231 and Human Colon Cell Line HT-29.

The toxicity of the aqueous extract of Origanum majorana was tested (5 and 10 g/kg) in albino mice. No symptoms of toxicity or mortality were observed. The mice survived being active and healthy during all 14 days of observation. In addition, the weight measurement of the left and right kidneys, heart, and liver shows no significant difference between the control, 5 g/kg, and 10 g/kg. All extracts (aqueous, petroleum ether, dichloromethane, ethyl acetate, methanolic, and depleted aqueous extracts) of Origanum majorana tested against both types of cancer cells showed a more pronounced cytotoxic effect against breast cell line MDA-MB-231 than colon cells line HT-29 cells. The most marked effect is that of the ethyl acetate extract with IC50 30.90 ± 1.39 and 50.11 ± 1.44 (µg/ml), respectively. HPLC analysis of extracts from Origanum majorana showed that this plant contained polyphenols and flavonoids, which may be responsible for the biological activities found.

Relaxant Effect of Essential Oil of Artemisia herba-alba Asso. on Rodent Jejunum Contractions.

Artemisia herba-alba Asso. is a shrub commonly encountered in Morocco. It is used in traditional medicine for treating intestinal disorders. The essential oil extracted from the plant's aerial parts reversibly relaxed the spontaneous tonus of the rabbit jejunum in a reversible concentration dependent manner with an IC(50) value of 97.33 ± 2.59 ng/ml and reversed the tonic contraction of rat jejunum induced by 75 mM KCl and 10(-6) M carbachol with IC(50) values of 115.5 ± 3.05 and 119.4 ± 20.86 ng/ml, respectively. The pre-treatment of the latter isolated intestine with this essential oil produced a dose-dependent shift of the Ca(++) and CCh dose-response curve to the right, with suppression of the maximal effect, similar to the non-competitive antagonist effect on muscarinic receptors and calcium channel, respectively.

The Budding Yeast "Saccharomyces cerevisiae" as a Drug Discovery Tool to Identify Plant-Derived Natural Products with Anti-Proliferative Properties.

The budding yeast Saccharomyces cerevisiae is a valuable system to study cell-cycle regulation, which is defective in cancer cells. Due to the highly conserved nature of the cell-cycle machinery between yeast and humans, yeast studies are directly relevant to anticancer-drug discovery. The budding yeast is also an excellent model system for identifying and studying antifungal compounds because of the functional conservation of fungal genes. Moreover, yeast studies have also contributed greatly to our understanding of the biological targets and modes of action of bioactive compounds. Understanding the mechanism of action of clinically relevant compounds is essential for the design of improved second-generation molecules. Here we describe our methodology for screening a library of plant-derived natural products in yeast in order to identify and characterize new compounds with anti-proliferative properties.

Anti-diarrhoeal activity of crude aqueous extract of Rubia tinctorum L. roots in rodents.

The anti-diarrhoeal effect of aqueous extract of Rubia tinctorum L. (Rubiaceae) roots in rodents was examined. At doses 300, 600 and 800 mg/kg aqueous extract protected rats, in a dose-dependent fashion, against castor oil-induced diarrhoeal dropping by 37, 59 and 64% respectively. Furthermore, it has significantly inhibited by 41% the gastrointestinal transit of charcoal in mice at 800 mg/kg dose of extract. These data suggest that Rubia tinctorum showed antidiarrhoeal activity by inhibiting intestinal motility which was concordant with its use in traditional medicine.

Anti-cancer effect of two alkaloids: 2R and 2S-bgugaine on mastocytoma P815 and carcinoma Hep.

The 2-alkylpyrrolidine R-bgugaine, a natural alkaloid isolated from tubers of Arisarum vulgare Targ. Tozz. (Araceae), and its isomer S-bgugaine, obtained by an asymmetric synthesis, were examined for their cytotoxic activities on two cancerous cellular lines: the murine mastocytoma cell line P815 and the human laryngeal carcinoma cell line Hep. These two alkaloids exhibited an important cytotoxic activity on these two cancerous cellular lines. The concentrations required to induce 50% of lysis (IC(50)) for R-bgugaine and S-bgugaine alkaloids were determined, and are 10 and 5 microg mL(-1), and 5 and 100 microg mL(-1), respectively, for the mastocytoma P815 and carcinoma Hep, compared with those of Adriamycine (5 microg mL(-1) for P815 cell line and 5 microg mL(-1) for Hep cell line), taken as positive controls.

New synthesis of two tridentate bipyrazolic compounds and their cytotoxic activity tumor cell lines.

Two new tripodal compounds - 4-{bis[(3,5-dimethyl-1H-pyrazole-1-yl)methyl]amino}butane-1-ol (1); ethyl 1-[((2-hydroxyethyl){[3-(ethoxycarbonyl)-5-methyl-1H-pyrazole-1-yl]methyl} amino)methyl]-5-methyl-1H-pyrazole-3-carboxylate (2) were reported. The evaluation of the cytotoxic properties in vitro of these ligands, was examined on two tumor cell lines - P815 (mastocytome murine) and Hep (carcinoma of human larynx). The concentration required to induce 50% of lysis (IC(50)) was more pronounced against P815 cell line (IC(50): 39.42 microg mL(-1) for the compound 1 and 97.74 microg mL(-1) for the compound 2) than the Hep cell line (IC(50): 83.49 microg mL(-1) for compound 1 and 185.30 microg mL(-1) for compound 2). Statistical analysis shows that the compound 1 is two to three folds more cytotoxic than the compound 2 (p < 0.05). Interestingly, the cytotoxic activity depends strongly on both the substituents linked to the aminic nitrogen and pyrazolic rings.

New pyrazolic compounds as cytotoxic agents.

The evaluation of the in vitro cytotoxic properties of two pyrazole compounds: 1-(4-nitrophényl)-3,5-diméthylpyrazole (1) and 1,1'-di(4-nitrophényl)-5,5'-diisopropyl-3,3'-bipyrazole (2) was investigated against Hep cell line (Human laryngeal carcinoma). These two compounds showed an important cytotoxic activity on the Hep cell line, with IC(50): 8.25 microg mL(-1) for the compound 1; IC(50): 10.20 microg mL(-1) for the compound 2 while the IC(50) for adriamycine used as positive control was 3.62 microg mL(-1).

Anticancer effect of three pyrazole derivatives.

The evaluation of the cytotoxic properties in vitro of three synthetic tripods containing pyrazole: N,N-bis[(3,5-dimethylpyrazol-1-yl)methyl]aniline (1); N,N-tetrakis[(3,5-dimethylpyrazol-1-yl)methyl]-para-phenylenediamine (2); and N,N-tetrakis-[(1,5-dimethylpyrazol-3-yl)methyl]-para-phenylenediamine (3), was examined for their cytotoxic activity on two tumor cell lines: P815 (murin mastocytoma) and Hep (human laryngeal carcinome). While the compound 2 shows a small cytotoxic activity, compounds 1 and 3 are more cytotoxic against both cell lines. However, this cytotoxicity is more pronounced against Hep cell line (IC50: 3.25 microg mL(-1) for compound 1 and 6.92 microg mL(-1) for compound 3) than P815 cell line (IC50: 17.82 microg mL(-1) for compound 1 and 37.21 microg mL(-1) for compound 3). Statistical analysis shows that the compound 1 is two- to threefold more cytotoxic than compound 3 (P < 0.05). Interestingly, the cytotoxicity induced by compound 1 against Hep cell line is more important than that induced by adriamycin used as a positive control.

Relaxant effect of aqueous extract of Cistus ladaniferus on rodent intestinal contractions.

The effects of the aqueous extract of Cistus ladaniferus leaves and stems were studied on the rodent isolated jejunum. The extract produced a reversible concentration dose-dependent (0.1-3 mg/ml) inhibition of the spontaneous motility of the rabbit jejunum. The inhibitory effects of the extract were not affected by pretreatment with the inhibitors of the alpha and beta adrenergic receptors yohimbine, prazosin or propranolol. The extract also inhibited K(+)-induced contractions in rabbit and rat jejunum at a similar concentration range. This result suggests that the antispasmodic action of the extract is mediated through calcium channel blockade. The results confirm the traditional use of C. ladaniferus in treating intestinal ache.

Cytotoxic effect and electrophysiological activity of S-irniine, a synthesised isomer of the natural R-irniine, on human MRC-5 fibroblasts.

Numerous original alkaloids are present in tubers of Arisarum vulgare Targ. a species belonging to the Araceae family known in Morocco for its toxicity. Some previous works deal with the activity of these natural compounds as R-irniine. As the enantioselective total synthesis of irniine has been realised, the R- and S-forms were obtained and this last one could be tested. Thus, a study of the cytotoxicity and the electrophysiological activity of S-irniine was carried out on human MRC-5 fibroblasts. A cytotoxic effect of S-irniine at 40 microg/mL was detected on MRC-5 fibroblasts. An electrophysiological study was also carried out on the MRC-5 cells by using the patch-clamp technique and no effect of this compound at this concentration on the outward potassium current of MRC-5 fibroblasts was observed. Thus, this study showed, as it was for R-irniine, that the cytotoxicity of S-irniine was not explained by an effect on the potassium currents.

Cytotoxic effect and electrophysiological study on human MRC-5 fibroblasts of R-irniine, a natural alkylpyrrolidine alkaloid.

R-irniine is a natural 2-alkylpyrrolidine alkaloid extracted from Arisarum vulgare Targ., a species belonging to the Araceae family known in Morocco for its toxicity. Cytotoxic and electrophysiological studies of this compound on human MRC-5 fibroblasts were carried out. Cytotoxic potential of R-irniine was detected on MRC-5 fibroblasts at 40 microg/mL. We carried out the electrophysiological study of this compound on MRC-5 cells by using the technique of patch-clamp in "Whole cell" configuration. R-irniine showed no effect on the outward potassium current of the MRC-5 fibroblasts.