Hypokinetic Activity of Menthofuran on the Gastrointestinal Tract in Rodents.

The acute toxicity and hypokinetic activity induced by menthofuran on the gastrointestinal tract of rodents were investigated in the present study. An absence of acute toxicity was observed. Menthofuran delayed gastric emptying at oral doses of 25, 50, and 100 mg/kg in the experimental model of phenol red, as well as it reduced the intestinal transit at oral doses of 50 and 100 mg/kg. Interestingly, a scopolamine-similar hypokinetic effect was observed for menthofuran. In the experimental model of castor oil-induced intestinal hypermotility, menthofuran (50 and 100 mg/kg) reduced the number of loose stools as observed for the normal group. Additionally, menthofuran induced a marked concentration-dependent relaxation in rat ileum segments precontracted with KCl (EC50 = 0.059 ± 0.008 µg/mL) or carbachol (EC50 = 0.068 ± 0.007 µg/mL). These results suggest the possible decrease of calcium influx underlying the effects of menthofuran on the gastrointestinal tract, which opens the door for further study regarding this potential application for the treatment of gastrointestinal disorders, noting possible limitations of its use due to adverse effects in children.

Gastroprotective effect of the crude ethanolic extract from the stem barks of Piptadenia viridiflora (Kunth) Benth. (Fabaceae) / Efecto gastroprotector del extracto etanólico crudo de la corteza de Piptadenia viridiflora (Kunth) Benth. (Fabaceae)

The objective of this work was to evaluate the gastroprotective activity of the crude ethanolic extract (CEE) from the stem barks of Piptadenia viridiflora using the acute models of inducing gastric ulcers by ethanol, ethanol-acidified, and ischemia-reperfusion, and correlating this response with the antioxidant activity, as well as, analyze the chemical profile of the extract by high-performance liquid chromatography coupled to diode array detector (HPLC-DAD). For this purpose, mice and rats were used. The ethanol ulcer induction test showed that CEE at doses of 100 and 200 mg/kg promoted 70% and 80% of gastroprotection, respectively. In the gastric ulcer induction test by acidified-ethanol and ischemia-reperfusion, CEE (200 mg/kg) promoted 66% and 90% of gastroprotection in animals, respectively. In conclusion, this species has gastroprotective activity, and this response is possibly related to the antioxidant activity, as well as the presence of flavonoids detected in CEE of P. viridiflora.

El objetivo de este trabajo fue evaluar la actividad gastroprotectora del extracto etanólico crudo (CEE) de Piptadenia viridiflora, utilizando los métodos de inducción de úlceras gástricas agudas por etanol, etanol acidificado y de isquemia-reperfusión, y correlacionando esta respuesta, con la actividad antioxidante, así como, perfil químico de la muestra. Para ello se utilizaron ratones (Swiss) y ratas (Wistar). Como resultado, la prueba de inducción de úlceras por etanol mostró que la CEE a dosis de 100 y 200 mg/kg promovió 70% y 80% de gastroprotección, respectivamente. En la prueba de inducción de úlcera gástrica por etanol acidificado e isquemia-reperfusión, la CEE (200 mg/kg) promovió 66% y 90% de gastroprotección en animales, respectivamente. Concluimos que la especie tiene una acción gastroprotectora y que esta respuesta posiblemente esté relacionada con la actividad antioxidante, así como con la presencia de flavonoides detectados en la CEE de P. viridiflora.

Antioxidant Mechanisms Underlying the Gastroprotective Effect of Menthofuran on Experimentally Induced Gastric Lesions in Rodents.

Menthofuran is a monoterpene present in various essential oils derived from species from Mentha genus, and in Brazil, those species are widely used in treating gastrointestinal and respiratory disorders. Considering the wide pharmacological potential of monoterpenes, including their antioxidant activity, this study aimed to evaluate menthofuran-gastroprotective activity, as well as the involvement of antioxidant mechanisms in this effect. The acute toxicity was evaluated according to the fixed dose method. The antiulcerogenic activity was investigated by using experimental models of gastric ulcers induced by ethanol, indomethacin, and ischemia/reperfusion in rats. The antisecretory gastric activity, the catalase activity, and the gastric wall mucus were determined in pylorus ligated rats. Gastric wall nonprotein sulfhydryl (NPSH) group content, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) content were evaluated in ethanol-induced the gastric ulcer model. Menthofuran (2 g/kg) presented low acute toxicity and showed gastroprotective activity against ethanol-, indomethacin-, and ischemia/reperfusion-induced ulcers. Moreover, menthofuran presented antisecretory activity, reduced the total acidity, and increased pH of gastric secretion. On the other hand, a decrease in mucus content of gastric wall without alteration of gastric juice volume and catalase activity was observed. Interestingly, menthofuran increased NPSH levels and reduced MDA levels and MPO activity. Gastroprotective effects of menthofuran appear to be mediated, at least in part, by the NOS pathway, endogenous prostaglandins, reduced gastric juice acidity, increased concentration of the NPSH groups, and reduced lipidic peroxidation. These findings support the menthofuran as an effective gastroprotective agent, as well as the marked participation of antioxidant mechanisms in this response.

Gastroprotective Activity of Neoglaziovia variegata (Arruda) Mez. (Bromeliaceae) in Rats and Mice.

Neoglaziovia variegata (Arruda) Mez (Bromeliaceae) is a medicinal plant popularly known as "caroá." The leaves are made up of highly resistant fibers, which is of great commercial value to the handicraft and textile industry. Some studies have demonstrated that ethanolic extract of N. variegata have gastroprotective properties. This study aimed to investigate the gastroprotective activity and cytoprotective mechanisms of ethyl acetate (Nv-AcOEt), hexane (Nv-Hex), and chloroform (Nv-CHCl3) fractions of N. variegata leaves. The gastroprotective activity of Nv-AcOEt, Nv-Hex, and Nv-CHCl3 was evaluated using the ethanol and ethanol/HCl-induced gastric injury model. To elucidate the gastroprotective mechanisms, the functions of prostaglandins (PGs), nitric oxide (NO), and KATP channels were evaluated. In addition, the nonprotein sulfhydryl groups and the mucus content in the gastric tissues were analyzed. All fractions of N. variegata leaves at oral doses of 100, 200, and 400 mg/kg significantly decreased ethanol and ethanol/HCl-induced gastric lesions, leading to gastroprotection, accompanied by an increase in reduced glutathione (GSH) and gastric mucus. Gastroprotective activity of Nv-AcOEt was inhibited after pretreatment with ibuprofen and N(G)-nitro-L-arginine (L-NOARG). Gastroprotective effect of Nv-Hex and Nv-CHCl3 was also inhibited after pretreatment with L-NOARG and with glibenclamide. The results indicate that N. variegata (Arruda) Mez exhibits promising gastroprotective activity with the possible participation of NO, PGs, mucus, sulfhydryl groups, and KATP.

Antidiarrheal activity of farnesol in rodents: Pharmacological actions and molecular docking.

Diarrhea is a condition in which the individual has about three or more daily bowel movements, followed by changes in stool consistency. It is currently considered as one of the worst public health problems due to the number of cases and deaths involved and difficulty of treatment. Thus, the use of natural products is an alternative for new treatments. Among these possibilities is Farnesol (C15H26O), a sesquiterpene found in different herbal species that has known biological activities. The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE2. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests with castor oil and PGE2, being considered as the standard dose, reducing motility by anticholinergic mechanisms. There was a reduction in fluid secretion when FOH interacted directly with GM1 receptors; cholera toxin and molecular docking showed strong interaction between farnesol and these targets. In view of the results presented, the antidiarrheal activity occurs through anticholinergic, anti-inflammatory and anti-secretory action, making farnesol a potential candidate for the development of a new drug to treat diarrheal diseases.

Cardiovascular Effect of Diosgenin in Ovariectomized Rats.

Diosgenin is a phytoestrogen and a constituent of Dioscorea. It has several biological effects, and some of them are anti-inflammatory, antidiabetic, antitumor, and vasodilatory. The present study investigated both the vasorelaxing and antioxidant mechanisms of diosgenin in isolated rat aortic rings. Female rats weighing 200-220 g were subjected to sham or OVX operations at 8 weeks of age. Ovariectomy was performed for menopause induction after anesthesia. Diosgenin (10-9 M-3 × 10-4 M) produced a concentration-dependent relaxation in aortic rings precontracted with phenylephrine (1 µM), exhibiting Emax value of 55.34% ± 7.7% (in endothelium-intact rings) and Emax value of 30.30% ± 5.7% (in endothelium-denuded rings). In the endothelium-intact rings, the vasorelaxing effect of diosgenin was reduced by NG-nitro-l-arginine methyl ester (L-NAME) (100 µM), atropine (1 µM), indomethacin (10 µM), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (10 µM), 4-aminopyridine (1 mM), tetraethylammonium (3 mM), glibenclamide (10 µM), apamin (10 µM), and Tiron (1 µM). Diosgenin (10-5 M) inhibited the contractions induced by cumulative addition of phenylephrine (10-9-10-5 M). The 28-days treatment with diosgenin (50 mg/kg, v.o.) did not imply changes in the myeloperoxidase parameter, but increased significantly, levels of glutathione, superoxide dismutase, and nitric oxide, as well as reduced the concentration of malondialdehyde related to lipid peroxidation. Our results suggest that diosgenin induced relaxation in aortic rings via an endothelium-dependent pathway, which involves the EDRF, the opening of potassium channels and antioxidant action.

Pharmacological and biotechnological advances with Rosmarinus officinalis L.

INTRODUCTION: Rosmarinus officinalis L. is an aromatic plant with a number of biological properties. Recently, has been studied regarding its therapeutic potential. The objective of this study was to perform a systematic review on R. officinalis essential oil for its pharmacological properties and biotechnological applications. AREAS COVERED: The databases were searched for articles (Science Direct, Pub Med and Web of Science) and patents (INPI, WIPO and EPO) with publications on R. officinalis and associations with essential oil (EO-Ro), cardiovascular system, hypertension and cyclodextrin. We selected 305 articles on EO-Ro in the most diverse subjects and six articles with of R. officinalis associated with hypertension. 59 patents were analyzed. The results demonstrate how extensive the studies are on the biological activities with the extract and EO-Ro. These have shown effects antibacterial, antifungal, anti-inflammatory, antitumor and other. The properties exhibited by EO-Ro reinforce the use of this plant as a phytotherapeutic agent. EXPERT OPINION: Although there are several pharmacological properties, studies on the prevention or treatment of cardiovascular diseases with EO-Ro are scarce, especially to evaluate the antihypertensive activity of EO-Ro. It has also become clear that EO-Ro can be exploited in different commercial products as supplement, cosmetics and new formulations.

Gastroprotective effect of (-)-myrtenol against ethanol-induced acute gastric lesions: possible mechanisms.

OBJECTIVES: (-)-Myrtenol is a natural fragrance monoterpenoid structurally related to α-pinene found in diverse plant essential oils. This study was aimed to assess the anti-ulcerogenic potential of (-)-myrtenol against ethanol-induced gastric lesions and to elucidate the underlying mechanism(s). METHODS: Gastroprotective activity of (-)-myrtenol was evaluated using the mouse model of ethanol-induced gastric damage. To elucidate the gastroprotective mechanism(s), the roles of GABA, prostaglandins, nitric oxide and KATP channels were assessed. Besides, the oxidative stress-related parameters and the mucus content in gastric tissues were analysed. KEY FINDINGS: (-)-Myrtenol at oral doses of 25, 50 and 100 mg/kg significantly decreased the severity of ethanol-induced gastric lesions affording gastroprotection that was accompanied by a decrease in the activity of myeloperoxidase and malondialdehyde, an increase in GPx, SOD, and catalase activity in gastric tissues, and with well-maintained normal levels of nitrite/nitrate, gastric mucus and NP-SHs. Pretreatment with GABA-A receptor antagonist flumazenil, the COX inhibitor indomethacin, and NO synthesis inhibitor L-NAME but not with KATP channel blocker glibenclamide significantly blocked the (-)-myrtenol gastroprotection. CONCLUSION: These results provide first-time evidence for the gastroprotective effect of (-)-myrtenol that could be related to GABAA -receptor activation and antioxidant activity.

Abarema cochliacarpos extract decreases the inflammatory process and skeletal muscle injury induced by Bothrops leucurus venom.

Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation.

Pharmacological evidence of α2-adrenergic receptors in the hypotensive effect of Platonia insignis mart.

Platonia insignis Mart. (Clusiaceae) is a medicinal plant from the Brazilian Amazon region. The present study evaluated the biological potential of the ethanol extract (Pi-EtOH) and ethyl acetate fraction (Pi-EtOAc) of the P. insignis fruit shells on the cardiovascular system of rats. Pi-EtOH or Pi-EtOAc (12.5, 25, and 50 mg/kg) was administered intravenously in normotensive rats (260-300 g), and the mean arterial pressure and the heart rate were monitored. The Pi-EtOH induced hypotension (-11.56±0.89, -7.43±0.85, and -17.56±1.97 mmHg) followed by bradycardia in two highest doses (-8.89±3.62 and -15.79±1.83 beats/min) and Pi-EtOAc, at the same doses, induced hypotension (-11.2±1.03, -14.48±1.13, -29.89±2.67 mmHg) more intensively, followed by tachycardia at the dose 12.5 and 25 mg/kg (15.64±2.06, 19.31±1.92 beats/min) and bradycardia at a dose of 50 mg/kg (-9.98±7.33 beats/min). The hypotensive response from Pi-EtOAc was not attenuated when used in the pretreatment with L-NAME, verapamil, propranolol, and hexamethonium. However, when using yohimbine, the hypotensive effect was inhibited (-4.42±1.28 (P<.05), -3.29±0.99 (P<.05), 2.06±1.18 mmHg (P<.05); Student's t-test). Hence, the Pi-EtOAc seems to act similarly to the α2-adrenergic agonist in this hypotensive effect.

Spasmolytic action of the methanol extract and isojuripidine from Solanum asterophorum Mart. (Solanaceae) leaves in guinea-pig ileum.

Solanum asterophorum Mart. (Solanaceae) is a shrub popularly known as "jurubeba-defogo" in the northeast of Brazil. In the present work, the methanol extract (SA-MeOH, 3750 microg/mL) and isojuripidine (10(-7) - 3 x 10(-4) M), a steroidal alkaloid obtained from S. asterophorum Mart. leaves, inhibited phasic contractions induced by both 1 microM histamine [IC50 = (225.8 +/- 47.4), g/mL and (3.5 +/- 0.8) x 10(-5) M] or 1 microm acetylcholine [IC50 = (112.5 +/- 20.6) microg/mL and (2.3 +/- 0.4) x 10(-5) M] in guinea-pig ileum, respectively. The extract and isojuripidine also relaxed the ileum (SA-MeOH, 1-750 microg/mL, and isojuripidine, 10(-9) - 3 x 10(-4) M) pre-contracted with 1 M histamine [EC50 = (101.1 +/- 17.4) microg/mL and (1.2 +/- 0.3) x 10(-6) M] or 1 microM acetylcholine [EC50 = (136.8 +/- 21.1) microg/mL and (1.9 +/- 0.4) x 10(-6) M] or 40 mm KCl [EC50 = (149.4 +/- 19.5) microg/mL and (1.8 +/- 0.7) x 10(-6) M], respectively, in an equipotent and concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-operated calcium (Ca(v)) channels. To confirm this hypothesis, we evaluated their effect on cumulative CaCl2 curves in depolarizing medium nominally without Ca2+. SA-MeOH (27, 243, 500, and 750 microg/mL) and isojuripidine (3 x 10(-8), 10(-6), 3 x 10(-5), and 3 x 10(-4) M) inhibited the contractions induced by CaCl2, in a concentration-dependent manner. The concentration-response curves to CaCl2, in the presence of SA-MeOH and isojuripidine, were shifted downward in relation to a control curve in a non-parallel manner resulting in reduction of the maximum effect [E(max) = (71.2 +/- 9.2); (57.4 +/- 9.2); (43.8 +/- 3.4); (41.5 +/- 2.4) and (90.6 +/- 4.8); (74.7 +/- 8.7); (66.4 +/- 3.9); (31.3 +/- 4.1)%, respectively]. SA-MeOH and isojuripidine present spasmolytic action in guinea-pig ileum due to a partially blockade of calcium influx through Ca(v) channels.