No abstract

Our results suggest that the acute administration of the HELSm in the scototaxis and NTDT tests in a zebrafish model (Danio rerio) produced anxiolytic and antidepressant effects, devoid of hypnotic and sedative actions by immersion, and this action was improved when administered by oral via. Possibly, the presence of isoquercitrin in the leaves of Spondias mombin participates in the anxiolytic and antidepressant effects.

No abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs due to their antipyretic, anti-inflammatory, and analgesic properties. However, NSAIDs can cause adverse reactions, mainly gastrointestinal damage. Omeprazole (OMP) exhibits gastroprotective activity, but its protection is limited at the intestinal level. For this reason, it is essential to utilize a combination of therapies that provide fewer adverse effects, such as the combined treatment of OMP and docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-inflammatory, analgesic, and gastroprotective activities. The objective of this study was to evaluate the pharmacological interaction between DHA and OMP in a murine model of indomethacin-induced gastrointestinal damage. The gastroprotective and enteroprotective effects of DHA (0.3-10 mg/kg, p.o.), OMP (1-30 mg/kg, p.o.), or the combination treatment of both compounds (3-56.23 mg/kg, p.o.) were evaluated in the indomethacin-induced gastrointestinal damage model (30 mg/kg, p.o.). Since DHA and OMP exhibited a protective effect in a dose-responsive fashion, the ED 30 for each individual compound was determined and a 1:1 combination of DHA and OMP was tested. Isobolographic analysis was used to determine any pharmacodynamic interactions. Since the effective experimental dose ED 30 (Zexp) of the combined treatment of DHA and OMP was lower than the theoretical additive dose (Zadd; p < .05) in both the stomach and small intestine their protective effects were considered synergistic. These results indicate that the synergistic protective effects from combined treatment of DHA and OMP could be ideal for mitigating damage generated by NSAIDs at the gastrointestinal level.

The aims of the study were to evaluate the pharmacodynamic interaction between 3α-hydroxymasticadienonic acid and diligustilide (DLG), isolated from the plants Amphiptherygium adstringens and Ligusticum porteri, respectively, using the indomethacininduced gastric injury model, as well as their individual gastroprotective efficacy in this model. Male Wistar rats were orally administered with 3α-hydroxymasticadienonic acid, DLG or the mixture of 3α-hydroxymasticadienonic acid-DLG (at a fixed-ratio combination of 1:1, 1:3, and 3:1). Thirty minutes later, the gastric damage was induced by a single oral dose of indomethacin (30 mg/kg). Three hours later, the gastric injury (mm 2 ) was determined. 3α-hydroxymasticadienonic acid and DLG as individual compounds showed a gastroprotective effect against indomethacin-induced gastric damage (p < .05).The effective dose (ED 50 ) values for each compound were 6.96 ± 1.25 mg/kg for 3α-hydroxymasticadienonic acid and 2.63 ± 0.37 mg/kg for DLG. The isobolographic analysis performed showed that the combination exhibited super-additive interaction as the experimental ED 50 values (Zexp) were lower than theoretical additive dose values (Zadd; p < .05). Our results identify the super-additive (synergist) interaction between 3α-hydroxymasticadienonic acid and DLG and the gastric safety of both compounds in the indomethacin-induced gastric injury model, suggesting their potential in the future as a strategy to decrease the gastric damage associated to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). K E Y W O R D S3α-hydroxymasticadienonic acid, diligustilide, gastric injury, isobolographic analysis, NSAIDs

(Z,Z')-Diligustilide (DLG) or levistolide A is a dimeric phthalide isolated from Ligusticum porteri (Osha), the roots of which are used in the traditional treatment of many diseases including gastric aches. However, its action has not been completely elucidated. We analyzed the contributions of hydrogen sulfide and S-nitrosothiols to the action of DLG. Animals were pretreated with freshly formed in vitro nitrosothiol using NaS and sodium nitroprusside to elucidate participation in the action of DLG. We also evaluated the production of HS in vivo and in real time on the stomach via a specific electrode introduced into the stomachs of anaesthetized animals pretreated with DLG. Treatment with 10 mg/kg DLG increases gastric HS production in vivo from 7.8 ± 0.81 ppm to 13.1 ± 3.01 ppm and prevents the decrease in gastric injury caused by absolute ethanol. In addition, it maintains endogenous concentrations of GSH and NO. Exogenous S-nitrosothiols protect the gastric mucosa from damage, suggesting that the action of DLG might be associated with S-nitrosothiol and HS formation.

No abstract

The study of pharmacological interactions between herbal remedies and conventional drugs is important because consuming traditional herbal remedies as supplements or alternative medicine is fairly common and their concomitant administration with prescribed drugs could either have a favorable or unfavorable effect. Therefore, this work aims to determine the pharmacological interactions of a turmeric acetone extract (TAE) and its main metabolite (curcumin) with common anti-ulcer drugs (ranitidine and bismuth subsalicylate), using an ethanol-induced ulcer model in Wistar rats. The analysis of the interactions was carried out via the Combination Index-Isobologram Equation method. The combination index (CI) calculated at 0.5 of the affected fraction (fa) indicated that the TAE or curcumin in combination with ranitidine had a subadditive interaction. The results suggest that this antagonistic mechanism is associated to the mucoadhesion of curcumin and the TAE, determined by rheological measurements. Contrastingly, both the TAE and curcumin combined with bismuth subsalicylate had an additive relationship, which means that there is no pharmacological interaction. This agrees with the normalized isobolograms obtained for each combination. The results of this study suggest that mucoadhesion of curcumin and the TAE could interfere in the effectiveness of ranitidine, and even other drugs.