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The roots of Ligusticum porteri J.M. Coult. & Rose, Apiaceae, are used in Mexican traditional medicine for the treatment of gastrointestinal disorders. The dimeric phthalide (Z´)-diligustilide found in their organic extracts is associated with the gastroprotective properties. In this study, the gastroprotective effect of nanoemulsion of the volatile oil from the roots of L. porteri (at doses of 1, 3, 10, and 30 mg/kg) in the indomethacin-induced gastric damage model was tested, and nitric oxide (NO) and hydrogen sulfide (H2S) gastric levels were determinate. The volatile oil obtained by steam distillation (0.63% yield) contained 37 constituents, as assessed by GC-MS analysis, where the significant compounds were 4-phenyl-3-buten-2-ol (20.54%) and (Z)-3-butylidenephthalide (20.54%) that correspond to phthalide monomers. These results demonstrate that nanoemulsion of the volatile oil from L. porteri (at 10 and 30 mg/kg) shows a significant gastroprotective effect (72 and 92% respectively) against indomethacin-induced gastric damage, which is not different from the gastroprotective effect of omeprazole (69%) (p

(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 Na2S and sodium nitroprusside to elucidate participation in the action of DLG. We also evaluated the production of H2S 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 H2S 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 H2S formation.

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.

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).

Ethnopharmacological relevance The rhizome of Ligusticum porteri Coulter& Rose (LP) has been traditionally used by the ethnic group Raramuri in the North of Mexico 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.

Introduction: Perillyl alcohol (POH) is a hydroxylated monocyclic monoterpene found in lemon and lavender essential oils, among others. It’s widely recognized by antitumoral activity. Despite the great potential of nanoformulations for pharmaceutics, to the date the obtainment a perillyl alcohol-nanoemulsion (NPOH) and its toxicity investigation were not previously reported. On this context, the present study aim to evaluate the toxicity of NPOH on zebrafish (Danio rerio). Lethal concentration (LC50), effects on behaviour and acute administrations effects (48h) on histopathological parameters of the gills, liver and kidneys were performed. Results: Exposure to different concentrations of NPOH (25, 35, 50 e 125 µg/L - expressed as POH content) allowed determination of LC50= 33.4 µg/L. Moreover, NPOH at 50 and 125 µg/L induced 100% of mortality, in addition the alterations of behavior. NPOH at 25 and 35 µg/L induced higher damage to gills tissue when compared to remaining concentrations and control group (surfactant at 125 µg/L) (p < 0.001, p < 0.01 and p < 0.05, Anova, Tukey-Kramer test). NPOH at 25, 35 e 50 µg/L induced significative damage to liver tissue, when compared to control (p < 0.01 and p < 0.05). No significant histopathological alterations were observed in kidneys. Thus, our results suggest that NPOH present toxicity pattern in accordance to nanoformulations and xenobiotics.