Carvacrol-Loaded Nanoemulsion Promotes Tocolytic and Anti-Dysmenorrhea Effects in Rodents.

INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

Lippia origanoides essential oil induces tocolytic effect in virgin rat uterus and inhibits writhing in a dysmenorrhea mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The species Lippia origanoides Kunth, popularly known as "salva-de-marajó", is used in Brazilian traditional "quilombola" communities to treat menstrual cramps and uterine inflammation. AIM OF THE STUDY: Evaluate the spasmolytic activity of Lippia origanoides essential oil (LOO) on experimental models of uterine conditions related to menstrual cramps and investigate its mechanism of action. MATERIALS AND METHODS: Virgin rat-isolated uterus was mounted in the organ bath apparatus to evaluate the spasmolytic effect of LOO on basal tonus and contractions induced by carbachol, KCl, or oxytocin. We used pharmacological agents to verify the relaxation mechanism of LOO. The evaluation of uterine contractility in virgin rats, after treatment with LOO for three consecutive days, was carried out by the construction of a concentration-response curve with oxytocin or carbachol. The primary dysmenorrhea animal model was replicated with an injection of estradiol cypionate in female mice for three consecutive days, followed by intraperitoneal application of oxytocin. RESULTS: LOO relaxed the rat uterus precontracted with 10-2 IU/mL oxytocin (logEC50 = 1.98 ± 0.07), 1 µM carbachol (logEC50 = 1.42 ± 0.07) or 60 mM KCl (logEC50 = 1.53 ± 0.05). It was also able relax uterus on spontaneous contractions (logEC50 = 0.41 ± 0.05). Preincubation with glibenclamide, propranolol, phentolamine or L-NAME in contractions induced by carbachol did not alter significantly the relaxing effect of LOO. However, in the presence of 4-aminopyridine, CsCl or tetraethylammonium there was a reduction of LOO potency, whereas the blockers methylene blue, ODQ, aminophylline and heparin potentiated the LOO relaxing effect. Preincubation with LOO in a Ca2+ free medium at concentrations of 27 µg/mL or 81 µg/mL reduced the contraction induced by carbachol. The administration of LOO for 3 days did not alter uterus contractility. The treatment with LOO at 30 or 100 mg/kg intraperitoneally, or 100 mg/kg orally, inhibited writhing in female mice. The association of LOO at 10 mg/kg with nifedipine or mefenamic acid potentiated writhing inhibition in mice. CONCLUSIONS: The essential oil of L. origanoides has tocolytic activity in rat isolated uterus pre-contracted with KCl, oxytocin, or carbachol. This effect is possibly related to the opening of potassium channels (Kir, KV, and KCa), cAMP increase, and diminution of intracellular Ca2+. This relaxant effect, probably, contributed to reduce the number of writhings in an animal model of dysmenorrhea being potentiated by nifedipine or mefenamic acid. Taken together, the results here presented indicate that this species has a pharmacological potential for the treatment of primary dysmenorrhea, supporting its use in folk medicine.

Ethanolic extract of the aerial parts of Passiflora cincinnata Mast. (Passifloraceae) reduces nociceptive and inflammatory events in mice.

BACKGROUND: Passiflora cincinnata Mast. is described as a native species from the Caatinga biome, and used by traditional medicine for several pharmacological purposes, such as inflammatory disorders. However, studies that prove its biological activities are scarce. HYPOTHESIS/PURPOSE: This paper aims to evaluate the antinociceptive and anti-inflammatory activities of the aerial parts of Passiflora cincinnata (Pc-EtOH) in mice. METHODS: The chemical composition of Pc-EtOH was assessed by high-performance liquid chromatography coupled to diode array detector (HPLC-DAD). The antinociceptive profile of the extract (given orally: 100, 200 and 400 mg/kg) was established using the in vivo chemical models (acetic acid-induced abdominal constriction and formalin-induced paw licking test) and thermal (hot plate test) of nociception. The role of opioid, potassium channels, TRPV-1, muscarinic, serotoninergic (5-HT3) receptors and the participation of the nitric oxide pathway also was determined. The rota-rod test was used to verify the possible interference of the extract treatment in motor performance. Paw edema induced by carrageenan or histamine, and leukocyte migration, determination of total protein and nitric oxide to the peritoneal cavity were used for anti-inflammatory profile. RESULTS: The presence of flavonoids in the extract was confirmed using HPLC-DAD. At all doses tested the Pc-EtOH significantly reduced the number of writhing and decreased the paw licking time in both phases of the formalin test (p < 0.05). In the hot plate test, the extract increased the reaction time, reducing painful behavior. The antinociceptive mechanism probably involves central and peripheral pathways, involving the pathway of opioid and muscarinic receptors with influence of potassium channels and the nitric oxide pathway. However, the motor coordination test indicated that in the time of 120 min the extract decreases the stay time of the animal in the rota-rod. Pc-EtOH inhibited significantly (p < 0.05) the increase of the edema volume after administration of carrageenan and histamine. In the peritonitis test, acute pre-treatment with Pc-EtOH inhibited leukocyte migration, with a reduction in the number of neutrophils and concentration of total proteins and nitric oxide. CONCLUSION: The present study suggests that Pc-EtOH possesses peripheral and central antinociceptive action, and showed potential in inhibition of release of mediators of the inflammatory process.

The role of flavonoids on oxidative stress in epilepsy.

BACKGROUNDS: Oxidative stress can result from excessive free-radical production and it is likely implicated as a possible mechanism involved in the initiation and progression of epileptogenesis. Flavonoids can protect the brain from oxidative stress. In the central nervous system (CNS) several flavonoids bind to the benzodiazepine site on the GABAA-receptor resulting in anticonvulsive effects. OBJECTIVE: This review provides an overview about the role of flavonoids in oxidative stress in epilepsy. The mechanism of action of flavonoids and its relation to the chemical structure is also discussed. RESULTS/CONCLUSIONS: There is evidence that suggests that flavonoids have potential for neuroprotection in epilepsy.