Effect of the proportion of curcuminoids on the gastroprotective action of Curcuma longa L. in rats.

The gastroprotective effect of a turmeric acetone extract (TAE) (Curcuma longa L. [Zingiberaceae]) was evaluated and compared against its major curcuminoids; curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC). Additionally, to demonstrate the importance of the metabolites' ratio in the extract on the synergistic effect, different mixtures were evaluated. An ethanol-induced gastric injury model was used to evaluate the gastroprotection activity in Wistar rats. The pharmacologic interaction analysis was performed using the Combination Index (CI)-Isobologram Equation method. The CI calculated at 0.5 of affected fraction (fa) for the TAE indicated a synergistic interaction between its components. However, when the proportion of curcuminoids changed from 3.7:1:10 in TAE to a 1:1:1 ratio, the CI implied an antagonistic effect. The binary combinations of curcuminoids (1:1) also showed an antagonistic interaction. The results of this work suggest that the proportion of curcuminoids in the TAE is crucial for the gastroprotective effect against ethanol-induced damage.

Mucoadhesive effect of Curcuma longa extract and curcumin decreases the ranitidine effect, but not bismuth subsalicylate on ethanol-induced ulcer model.

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.

Pharmacodynamic interaction of 3α-hydroxymasticadienonic acid and diligustilide against indomethacin-induced gastric damage in rats.

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 indomethacin-induced 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 (mm2 ) was determined. 3α-hydroxymasticadienonic acid and DLG as individual compounds showed a gastroprotective effect against indomethacin-induced gastric damage (p < .05). The effective dose (ED50 ) 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 ED50 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).

The detection and quantification, in vivo and in real time, of hydrogen sulfide in ethanol-induced lesions in rat stomachs using an ion sensitive electrode.

INTRODUCTION: The development of electrochemical sensors for the detection of small molecules has already had a significant effect on the study of biology because of their selectivity and ability to measure low concentrations of small molecules that regulate various functions in living organisms. Hydrogen sulfide (H2S) is a gasotransmitter produced at low levels in several tissues including the stomach. Here, we propose a new method for detecting low concentrations of this transmitter in the rat stomach, in-vivo and in real time, with applications in pharmacology and physiology. METHODS: Wistar rats fasted for 12h. Then, the control group was given an intragastrical dose of saline. l-Cysteine (50mg/kg) or dl-propargylglycine (50mg/kg) were administered to the test groups to modify the H2S levels. Ranitidine (50mg/kg), omeprazole (40mg/kg) or carbenoxolone (30mg/kg) were used as reference anti-ulcer drugs. Thirty minutes later, the electrode was inserted in the middle of the stomach cavity of the anesthetized animals. The basal levels of H2S were recorded every 5min for 30min. Next, gastric lesions were induced with pure ethanol, and the recording continued for 30 additional minutes. RESULTS: The exogenous administration of an H2S precursor (l-cysteine) increased the level of this gasotransmitter whereas dl-propargylglycine, a selective inhibitor of the enzyme cystathionine γ lyase, reduced the total concentration of H2S. The administration of carbenoxolone, a gastroprotective, increased the total amount of H2S. However, the administration of the anti-secretors omeprazole and ranitidine did not modify the total concentration of H2S. DISCUSSION: This work provides the basis for a real-time analysis of the changes in-vivo of the gasotransmitter H2S in the normal and injured stomach and the exploration of the effect of drugs on the regulation of H2S.

Effect of N-Benzylpiperazine, Its Metabolite N-Benzylethylenediamine, and Its Disubstituted Analogue N,N'-Dibenzylpiperazine on the Acquisition, Formation, and Consolidation of Memory in Mice.

BACKGROUND: N-benzylpiperazine (BZP) belongs to a class of piperazine derivatives (PZDs) that have emerged as recreational drugs. These compounds increase the release of dopamine and serotonin. BZP mimics the psychoactive effects of 3,4-methylenedioxymethylamphetamine. BZP is metabolized to N-benzylethylenediamine (BEDA) and benzylamine. The compound N,N'-dibenzylpiperazine (DBZP) is obtained as a byproduct during the synthesis of BZP. Some PZDs have shown effects on memory; however, there are no previous reports on the activity of BZP, BEDA, and DBZP on memory or on a description of their neuropharmacological profile. We evaluated the effects of these compounds on acquisition, formation, and consolidation memory and explored their neuropharmacological profile in mice. METHODS: We used the passive avoidance test to evaluate the nootropic effect and for memory experiments. We also evaluated the sedative, myo-relaxant, motor coordination, anxiogenic, and locomotor activity of these compounds. RESULTS: We showed that BZP, its metabolite BEDA, and the disubstituted analogue DBZP enhance the memory and show anxiogenic effects. BZP, as well as DBZP but not BEDA, showed a strong myo-relaxant effect without impairing motor coordination. CONCLUSIONS: BZP and BEDA enhanced the acquisition and consolidation of memory, whereas DBZP only enhances the acquisition of the memory. BEDA and DBZP have an anxiogenic profile similar to that of BZP. BEDA and DBZP represent new psychoactive compounds with the potential to be new BZP-like recreational entities.

Gastroprotective effect of diligustilide isolated from roots of Ligusticum porteri coulter & rose (Apiaceae) on ethanol-induced lesions in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Ligusticum porteri Coulter& Rose (LP) has been traditionally used by the ethnic group Raramuri in the North of México for treatment of diabetes, tuberculosis, stomachaches, diarrhea and ritual healing ceremonies. It is use as antiulcer remedy has been extended to all Mexico. AIM OF THE STUDY: To evaluate the gastroprotective activity of LP organic extracts and the major natural product diligustilide (DLG),using as experimental model the inhibition of the ethanol-induced lesions in rats. MATERIALS AND METHODS: Gastric ulcers were induced by intragastric instillation of absolute ethanol (1 mL). We tested the gastroprotective activity of the organic extracts of LP and the pure compound DLG. The ulcer index (UI) was determined to measure the activity. In order to elucidate the action mechanism of DLG the animals were treated with L-NAME, N-ethylmalemide, Forskolin, 2',5'-dideoxyadenosine, Indomethacin, Glibenclameide, Diazoxide, NaHS and DL-Propargylglycine. The pylorus-ligated rat model was used to measure gastric secretion. RESULTS: The oral administration of organic extracts of Ligusticum porteri showed gastroprotective effect at 30 mg/Kg on ethanol induced gastric lesions; hexane and dichloromethane extracts were the most active. DLG was the major compound in the hexane extract. This compound at 10 mg/kg prevented significantly the gastric injuries induced by ethanol. The alkylation of endogenous non-protein-SH groups with N-ethylmaleimide abolished the gastroprotective effect of DLG and blocking the formation of endogenous prostaglandins by the pretreatment with indomethacin attenuated the gastroprotective effect of DLG. CONCLUSION: The gastroprotective activity demonstrated in this study tends to support the ethnomedical use of Ligusticum porteri roots. DLG, isolated as major compound of this medicinal plant has a clear gastroprotective effect on the ethanol-induced gastric lesions. The results suggest that the antiulcer activity of DLG depends on the participation of the endogenous non-protein -SH groups and prostaglandins.