The antidiarrheal effects of the aqueous extract of Punica granatum L. (Punicaceae) peels were evaluated in rats. Studies were carried out on the isolated rat ileum, gastrointestinal motility in vivo, and on castor oil-induced diarrhea in rats. The results revealed that the extract exhibited a concentration-dependent inhibition of the spontaneous movement of the isolated rat ileum and attenuated acetylcholine-induced contractions. The extract (100, 200, 300, and 400 mg=kg) also caused a dose-dependent decrease of gastrointestinal transit and markedly protected rats against castor oil-induced diarrhea enteropooling. The intraperitoneal injection LD 50 of the extract was found to be 1321AE15 mg=kg in mice. A preliminary phytochemical screening of the aqueous extract of Punica granatum peels gave positive tests for tannins, flavonoids, and alkaloids. The results obtained showed that the aqueous extract of Punica granatum peels may contain some biologically active principles that may be active against diarrhea, and this may be the basis for its traditional use for gastrointestinal disorders.

No abstract

The perturbation in plasma free amino acid metabolome has been observed previously in diabetes mellitus, and is associated with insulin resistance as well as the onset of cardiovascular disease in this population. In this study, we investigated, for the first time, changes in the amino acid profile in a group of people with and without type 2 diabetes (T2D) with normal BMI, from Jordan, who were only managed on metformin. Twenty one amino acids were evaluated in plasma samples from 124 people with T2D and 67 healthy controls, matched for age, gender and BMI, using amino acids analyser. Total amino acids, essential amino acids, non-essential amino acids and semi-essential amino acids were similar in T2D compared to healthy controls. Plasma concentrations of four essential amino acids were increased in the presence of T2D (Leucine, p < 0.01, Lysine, p < 0.001, Phenylalanine, p < 0.01, Tryptophan, p < 0.05). On the other hand, in relation to non-essential amino acids, Alanine and Serine were reduced in T2D (p < 0.01, p < 0.001, respectively), whereas Aspartate and Glutamate were increased in T2D compared to healthy controls (p < 0.001, p < 0.01, respectively). A semi-essential amino acid, Cystine, was also increased in T2D compared to healthy controls (p < 0.01). Citrulline, a metabolic indicator amino acid, demonstrated lower plasma concentration in T2D compared to healthy controls (p < 0.01). These amino acids were also correlated with fasting blood glucose and HbA1c (p < 0.05). Glutamate, glycine and arginine were correlated with the duration of metformin treatment (p < 0.05). No amino acid was correlated with lipid profiles. Disturbances in the metabolism of these amino acids are closely implicated in the pathogenesis of T2D and associated cardiovascular disease. Therefore, these perturbed amino acids could be explored as therapeutic targets to improve T2D management and prevent associated cardiovascular complications.

In Jordan, the leaves of Laurus nobilis (Family Lauraceae) have been used in folk medicine for the treatment of diarrhea, among other ailments. However, the ethnopharmacology of this plant needs to be scientifically validated. The present work was carried out to evaluate the scientific basis of the antidiarrheal effect of the aqueous extract of L. nobilis leaf. L. nobilis leaf extract significantly inhibited castor oil-induced diarrhea (effective concentration producing 50% of the maximum response [EC(50)]=150±6.4 mg/kg) and reduced castor oil-induced enteropooling in rats (EC(50)=162±5.9 mg/kg). The extract also significantly inhibited intestinal transit of a charcoal meal and exerted a significant dose-dependent relaxation (EC(50)=71±5.3 mg/mL) on rat ileal smooth muscle. The aqueous extract tested positive for flavonoids, alkaloids, and tannins. These results established the efficacy of L. nobilis leaf aqueous extract as an antidiarrheal agent and are consistent with the popular use of the plant in the treatment of gastrointestinal disorders, particularly diarrhea.

Insulin resistance in skeletal muscle is a feature associated with exposure to an excess of saturated fatty acids such as palmitate. Oleic acid has been shown to blunt palmitate-induced insulin resistance in muscle cells. However, there is no literature available regarding the effect of oleic acid on palmitate-induced insulin resistance in intact muscle. Therefore, this study investigated the effect of oleic acid on palmitate-induced insulin resistance in rat soleus muscle and its underlying mechanisms. For these purposes, oleic acid (1 mM) was administered for 12 h in the absence or presence of palmitate (2 mM). At the end of the experiment, plasmalemmal GLUT4, the phosphorylation of AS160 and Akt-2, and the total expression of these signaling proteins were examined. We found that treatment with palmitate for 12 h reduced insulin-stimulated GLUT4 translocation and the phosphorylation of AS160 and Akt-2. However, the administration of oleic acid fully restored insulin-stimulated GLUT4 translocation (P < 0.05), as well as AS160 and Akt-2 phosphorylation (P < 0.05) despite the continuous presence of palmitate. Wortmannin, an inhibitor of PI3-K, only slightly prevented the oleic acid-induced improvements in insulin-stimulated GLUT4 translocation, and AS160 phosphorylation. However, this treatment completely inhibited the oleic acid-induced improvement in insulin-stimulated Akt-2 phosphorylation. In contrast, the oleic acid-induced improvement in insulin signaling was not affected by compound C, an AMPK specific inhibitor. In conclusion, the results clearly indicate that oleic acid administration alleviates palmitate-induced insulin resistance by promoting GLUT4 translocation in muscle, at least in part, by activating the PI3K pathway.

Oleuropein, the main constituents of leaves and fruits of the olive tree, has been demonstrated to exert various therapeutic and pharmacological properties including antidiabetic effect. However, the effectiveness of oleuropein on glucose homeostasis in intact rat skeletal muscle ex vivo has never been explored. Therefore, our current study was carried out to investigate and confirm the beneficial effect of oleuropein (1.5 mM) on glucose uptake and on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle. For this purpose, soleus muscles were incubated for 12 hr without (control) or with oleuropein, in the presence or absence of AMP-activated protein kinase (AMPK) inhibitor, compound C, or wortmannin, an inhibitor of phosphatidylinositol kinase. Oleuropein-stimulated glucose transport, plasmalemmal glucose transporter 4 (GLUT4), and phosphorylation of phosphatidylinositol kinase and AMPK were examined. We observed that oleuropein treatment enhanced glucose transport, GLUT4 translocation, and AMPK phosphorylation. The oleuropein-stimulated glucose uptake and GLUT4 translocation were inhibited by compound C and were not affected by wortmannin. These results suggest that increased glucose uptake induced by oleuropein might be mediated through activation of AMPK and the subsequent increase in GLUT4 translocation in skeletal muscles.

Artemisia herba-alba (A. h.-a.) has wide use in traditional medicine for the relief of coughing, healing external wounds, and treatment of pain associated with gastrointestinal disturbances. We investigated in vivo antinociceptive and anti-inflammatory activities of an aqueous extract (aq. ex.) and two isolated compounds obtained from aerial parts of A. h.-a. The analgesic effects of aq. ex. (10, 31.6, 100, 316, and 1000 mg/kg), astragalin, and eupatilin (both, 0.316, 1, 3.16, 10, 31.6, and 100 mg/kg) were studied using the hot-plate test in mice and formalin test in rats. The effects were compared with those of 5 mg/kg morphine. Dosedependent analgesic effects of aq. ex., astragalin, and eupatilin were clearly manifested in both hot-plate assay and early and late phases of formalin-induced paw licking. These effects were significantly but partly reduced by the opioid receptor antagonist naloxone (5 mg/kg). The same range of doses of aq. ex., astragalin, and eupatilin caused dose-dependent suppression of carrageenan-induced paw edema in rats. Thus, we demonstrated that A. h.-a. possesses noticeable antinociceptive and anti-inflammatory activities; our data support the reasons for using this plant as a remedy for treatment of pain and inflammation. Antinociceptive and anti-inflammatory actions of A. h.-a. are considerably related to the presence of astragalin and eupatilin.

Purpose: To investigate the antinociceptive effect of the essential oil from the aerial parts of Gundelia. tournefortii (EOGT) in various experimental models