Antinociceptive and antiedema effects produced in rats by Brassica oleracea var. italica sprouts involving sulforaphane.

Natural products are recognized as potential analgesics since many of them are part of modern medicine to relieve pain without serious adverse effects. The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of an aqueous extract of Brassica oleracea var. italica sprouts (AEBS) and one of its main reported bioactive metabolites sulforaphane (SFN). Antinociceptive activity of the AEBS (30, 100, and 300 mg/kg, i.p. or 1000 and 2000 mg/kg, p.o.) and SFN (0.1 mg/kg, i.p.) was evaluated in the plantar test in rats to reinforce its analgesic-like activity at central level using the reference drug tramadol (TR, 50 mg/kg, i.p.). The anti-inflammatory-like response was determined in the carrageenan-induced oedema at the same dosages for comparison with ketorolac (KET, 20 mg/kg, i.p.) or indomethacin (INDO, 20 mg/kg, p.o.). A histological analysis of the swollen paw was included to complement the anti-inflammatory response. Additionally, acute toxicity observed in clinical analgesics as the most common adverse effects, such as sedation and/or gastric damage, was also explored. As a result, central and peripheral action of the AEBS was confirmed using enteral and parenteral administration, in which significant reduction of the nociceptive and inflammatory responses resembled the effects of TR, KET, or INDO, respectively, involving the presence of SFN. No adverse or toxic effects were observed in the presence of the AEBS or SFN. In conclusion, this study supports that Brassica oleracea var. italica sprouts are a potential source of antinociceptive natural products such as SFN for therapy of pain alone and associated to an inflammation condition.

ZnO Nanoparticles Induce Dyslipidemia and Atherosclerotic Lesions Leading to Changes in Vascular Contractility and Cannabinoid Receptors Expression as Well as Increased Blood Pressure.

ZnO nanoparticles (ZnONPs) have been shown to have therapeutic potential in some diseases such as diabetes and cancer. However, concentration-dependent adverse effects have also been reported. Studies which evaluate the effects of ZnONPs on the cardiovascular system are scarce. This study aimed to evaluate the cardiovascular effects of a low dose of ZnONPs administered chronically in healthy rats. Changes in dyslipidemia biomarkers, blood pressure, aortic wall structure, vascular contractility, and expression of cannabinoid receptors in the aorta wall were evaluated. Healthy rats were divided into two groups: control or treated (one, two, and three months). The treated rats received an oral dose of 10 mg/kg/day. The results showed that treatment with ZnONPs induced dyslipidemia from the first month, increasing atherosclerosis risk, which was confirmed by presence of atherosclerotic alterations revealed by aorta histological analysis. In in vitro assays, ZnONPs modified the aorta contractile activity in response to the activation of cannabinoid receptors (CB1 and CB2). The expression of CB1 and CB2 was modified as well. Moreover, ZnONPs elicited an increase in blood pressure. In conclusion, long-time oral administration of ZnONPs induce dyslipidemia and atherosclerosis eliciting alterations in aorta contractility, CB1 and CB2 receptors expression, and an increase in blood pressure in healthy rats.

Zinc Oxide Nanoparticles Induce an Adverse Effect on Blood Glucose Levels Depending On the Dose and Route of Administration in Healthy and Diabetic Rats.

Different studies in experimental diabetes models suggest that zinc oxide nanoparticles (ZnONPs) are useful as antidiabetic agents. However, this evidence was performed and measured in long-term treatments and with repeated doses of ZnONPs. This work aimed to evaluate the ZnONPs acute effects on glycemia during the next six h after an oral or intraperitoneal administration of the treatment in healthy and diabetic rats. In this study, the streptozotocin-nicotinamide intraperitoneal administration in male Wistar rats were used as a diabetes model. 10 mg/kg ZnONPs did not modify the baseline glucose in any group. Nevertheless, the ZnONPs short-term administration (100 mg/kg) induced a hyperglycemic response in a dose and route-dependent administration in healthy (130 ± 2 and 165 ± 10 mg/dL with oral and intraperitoneal, respectively) and diabetic rats (155 ± 2 and 240 ± 20 mg/dL with oral, and intraperitoneal, respectively). The diabetic rats were 1.5 fold more sensitive to ZnONPs effect by the intraperitoneal route. In conclusion, this study provides new information about the acute response of ZnONPs on fasting glycemia in diabetic and healthy rat models; these data are essential for possible future clinical approaches.

Moringa oleifera, a species with potential analgesic and anti-inflammatory activities.

Moringa oleifera has long been used in large demand in folk medicine to treat pain. The present study was undertaken to examine the antinociceptive and anti-inflammatory spectrum of M. oleifera leaf extracts discriminating the constituents' nature by using different kind of experimental models in rats. Pharmacological evaluation of a non-polar and/or polar extracts at several doses (30-300mg/kg, p.o.) was explored through experimental nociception using formalin test, carrageenan-induced paw edema and arthritis with subcutaneous injection of collagen in rats. Basic morphology characterization was done by scanning electronic microscopy and laser scanning confocal microscopy. Not only polar (from 30 or 100mg/kg, p.o.) but also non-polar extract produced significant inhibition of the nociceptive behavior with major efficacy in the inflammatory response in different assessed experimental models. This antinociceptive activity involved constituents of different nature and depended on the intensity of the induced painful stimulus. Phytochemical analysis showed the presence of kaempferol-3-glucoside in the polar extract and fatty acids like chlorogenic acid, among others, in the non-polar extract. Data obtained with M. oleifera leaf extracts give evidence of its potential for pain treatment.

Isobolographic analysis of the antinociceptive interaction between ursolic acid and diclofenac or tramadol in mice.

It is considered that natural products used in folk medicine can potentiate the effect of drugs. The aim of this study was to evaluate the pharmacological interaction between ursolic acid, a triterpene isolated from herbal medicines to treat pain, and the analgesics diclofenac or tramadol. Individual dose-response curves of the antinociceptive effect of these compounds were built to calculate the ED50, as well as the pharmacological interaction, by using isobolographic analysis. All treatments decreased significantly and in a dose-dependent manner the writhing behavior with ED50 values of 103.50 ± 19.66, 20.54 ± 6.05, and 9.60 ± 1.69 mg/kg, for ursolic acid, diclofenac, and tramadol, respectively. An isobolographic analysis allowed the characterization of the pharmacological interaction produced by a fixed ratio combination of 1 : 1 and 1 : 3 of equi-effective doses of these compounds. Theoretical antinociceptive ED50 values of ursolic acid-diclofenac were 62.12 ± 10.28 and 41.43 ± 6.69 mg/kg, respectively, not statistically different from those obtained experimentally (44.52 ± 5.25 and 44.89 ± 49.05 mg/kg, respectively), reporting an additive interaction. Theoretical antinociceptive ED50 values of ursolic acid-tramadol (56.56 ± 9.87 and 33.08 ± 5.07 mg/kg, respectively) were significantly lower than those observed experimentally (138.36 ± 49.05 and 67.34 ± 18.98 mg/kg, respectively) reporting antagonism in this interaction. Antinociceptive response obtained from isobolograms in the writhing test was corroborated by using formalin test in mice. Adverse effects such as gastric damage in the ursolic acid-diclofenac combination did not increase in an additive form similarly as with antinociception. Conversely, sedative response was significantly increased in the ursolic acid-tramadol combination. As observed in the formalin test, the antagonism on the antinociceptive response between ursolic acid and tramadol (1 : 1) was not reverted in the presence of the opioid antagonist naltrexone (1 mg/kg, i. p.). These results provide evidence for a differential pharmacological interaction, in which ursolic acid does not interfere with the antinociceptive effect of diclofenac but antagonizes that obtained with tramadol in an independent opioid mechanism. Therefore, medicinal plants containing abundant presence of ursolic acid may also modify efficacy in the alternative combinations for the pain therapy.

Spasmolytic and antinociceptive activities of ursolic acid and acacetin identified in Agastache mexicana.

Agastache mexicana is a plant in high demand that has long been used in Mexican folk medicine to treat anxiety, insomnia, and stomachache, among other afflictions. Ursolic acid and acacetin were isolated and identified as two possible active compounds of A. mexicana aerial parts. An antinociceptive response was demonstrated in a significant and dose-dependent manner with ursolic acid and acacetin (i. p. and p. o.) in comparison to the analgesic diclofenac by using the writhing test in mice. Moreover, acacetin also produced a significant concentration-dependent spasmolytic response with major efficacy compared to ursolic acid and papaverine by using rings from the isolated guinea pig ileum. These results provide evidence of the presence of two active constituents of Agastache mexicana reinforcing its utility as a therapy for visceral pain as used in traditional medicine.