Limonene from Agastache mexicana essential oil produces antinociceptive effects, gastrointestinal protection and improves experimental ulcerative colitis.

ETHNOPHARMACOLOGY RELEVANCE: Agastache mexicana is a popular plant of great demand in folk medicine, essentially due to its calming properties and for alleviating arthritic, muscular and abdominal pain. Despite its spectrum for pain relief, pharmacological studies of its bioactive constituents have been barely investigated. AIM OF THE STUDY: To evaluate protective properties of the A. mexicana and bioactive compounds improving pathological gastrointestinal conditions in rodents. MATERIAL AND METHODS: Different doses of the essential oil of A. mexicana ssp. mexicana and ssp. xolocotziana (30-562.2 mg/kg, i.p.) and individual monoterpenes (3-300 mg/kg, i.p.) were evaluated in an abdominal pain model. The most active monoterpene limonene and sulfasalazine (reference drug, 100 mg/kg, p.o.) were also evaluated in the oxazolone-induced colitis model using an oral gavage, where some inflammatory cytokines were analyzed by enzyme-linked immunosorbent assays. Finally, colonic histological assessment and gastroprotection in the absolute ethanol-induced ulcer model were explored. RESULTS: Our results demonstrated that the essential oil of both subspecies produced a significant reduction in the abdominal writhes, where monoterpenes limonene and pulegone were partially responsible bioactive metabolites. Limonene showed the major antinociceptive efficacy in the writhing test. It also significantly decreased hyperalgesia, pathological biomarkers, and colonic inflammatory cytokines in the oxazolone-induced colitis model, as well as prevention in gastric damage. CONCLUSIONS: Present results provide scientific evidence to reinforce the use of A. mexicana in the traditional medicine for gastrointestinal conditions, mainly related to pain and inflammation, demonstrating the potential of monoterpenes as natural products in the therapeutics of gastrointestinal affections such as ulcer, colitis, and abdominal pain.

Neo-clerodane diterpenic influence in the antinociceptive and anti-inflammatory properties of Salvia circinnata Cav.

ETHNOPHARMACOLOGICAL RELEVANCE: Mexico is considered an ancestral center of diversity of Salvia species, however many of them lack scientific information. Salvia circinnata Cav. (syn. Salvia amarissima Ortega) is an endemic species used in traditional medicine to treat disorders attributed to a cold state like anxiety in the central nervous system, as well as gastrointestinal ailments and pain relief. AIM OF THE STUDY: To give preclinical evidence about the pharmacological properties of this species by investigating its antinociceptive and anti-inflammatory effects, the chemical nature of at least one metabolite, and a possible mechanism of action and adverse effects, using different experimental models of pain. MATERIAL AND METHODS: Different crude extracts of Salvia circinnata Cav. aerial parts were prepared using increasing polarity and evaluated in the formalin test in mice. This screening allowed to select and evaluate an ethyl acetate extract (EtOAc), as the most bioactive extract, and a metabolite. Antinociceptive and anti-inflammatory activities were confirmed using the plantar test and carrageenan-induced edema. The antinociceptive effects of the extracts were compared to that observed with morphine (1 mg/kg), tramadol (20 mg/kg) or indomethacin (20 mg/kg) as reference drugs. Participation of opioids and TRPV1 receptors was investigated, as well as acute toxicity and adverse effects of sedation and gastric damage. RESULTS: EtOAc (0.1-10 mg/kg) of S. circinnata Cav. showed a dose-dependent and significant antinociceptive activity, associated in part with the presence of a neo-clerodane glycoside amarisolide A (0.01-1 mg/kg), in the neurogenic and inflammatory phases of the formalin test. Central action of both treatments was corroborated in the plantar test, whereas anti-inflammatory effects were confirmed with the extract (1 and 10 mg/kg) and amarisolide A (1 mg/kg) in the carrageenan-induced edema test. An opioid mechanism in both treatments, and the TRPV1 receptor modulation in the extract were involved. No acute toxicity and adverse effects were noticed with the extract and pure compound in comparison to the reference drugs. CONCLUSION: These results provide preclinical evidence of the ethnopharmacological antinociceptive S. circinnata Cav. properties, in which the neo-clerodane diterpene glycoside amarisolide A was partially responsible involving the participation of the opioid receptors, while TRPV1 receptor modulation was implicated in the anti-inflammatory activity may be because of the presence of other constituents. This information supports the use of this species in folk medicine for pain therapy.

Depressant effects of Agastache mexicana methanol extract and one of major metabolites tilianin

OBJECTIVE@#To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana (A. mexicana). Also, to establish the pharmacophoric requirements of tilianin, as a possible ligand of GABAA/BZD receptor, by the alignment of diazepam, CGS-9896 and diindole, using a previously described pharmacophoric model.@*METHODS@#Tilianin (30 to 300 mg/kg, ip. and 300 mg/kg, po.) and methanol crude extract (10 to 300 mg/kg, ip. and 300 mg/kg po.) from A. mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field, hole-board, cylinder of exploration, plus-maze and sodium pentobarbital-induced hypnosis mice methods.@*RESULTS@#Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg, ip. or 300 mg/kg, po. and were less potent than diazepam 0.1 mg/kg, a reference anxiolytic drug used. Moreover, depressant activity of both potentiates sodium pentobarbital (SP)-induced sleeping time. The anxiolytic-like effect of 30 mg/kg ip. observed for the extract and tilianin, by using the plus-maze model, was partially prevented in the presence of flumazenil (a GABAA/BZD antagonist, 5 mg/kg ip.) but not in the presence of WAY 100635 (a selective 5-HT1A receptor antagonist, 0.32 mg/kg, ip.). Pharmacophoric modeling alignments of three agonist of GABAA/BZD allow identify seven chemical features. Tilianin contains six of the seven features previously determined.@*CONCLUSIONS@#Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity of A. mexicana, reinforcing its central nervous system uses, where GABAA/BZD, but not 5-HT1A, receptors are partially involved.

Depressant effects of Agastache mexicana methanol extract and one of major metabolites tilianin

Objective: To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana (A. mexicana). Also, to establish the pharmacophoric requirements of tilianin, as a possible ligand of GABAA/BZD receptor, by the alignment of diazepam, CGS-9896 and diindole, using a previously described pharmacophoric model. Methods: Tilianin (30 to 300 mg/kg, ip. and 300 mg/kg, po.) and methanol crude extract (10 to 300 mg/kg, ip. and 300 mg/kg po.) from A. mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field, hole-board, cylinder of exploration, plus-maze and sodium pentobarbital-induced hypnosis mice methods. Results: Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg, ip. or 300 mg/kg, po. and were less potent than diazepam 0.1 mg/kg, a reference anxiolytic drug used. Moreover, depressant activity of both potentiates sodium pentobarbital (SP)-induced sleeping time. The anxiolytic-like effect of 30 mg/kg ip. observed for the extract and tilianin, by using the plus-maze model, was partially prevented in the presence of flumazenil (a GABAA/BZD antagonist, 5 mg/kg ip.) but not in the presence of WAY 100635 (a selective 5-HT1A receptor antagonist, 0.32 mg/kg, ip.). Pharmacophoric modeling alignments of three agonist of GABAA/BZD allow identify seven chemical features. Tilianin contains six of the seven features previously determined. Conclusions: Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity of A. mexicana, reinforcing its central nervous system uses, where GABAA/BZD, but not 5-HT1A, receptors are partially involved.