Antinociceptive effects of Laelia anceps Lindl. and Cyrtopodium macrobulbon (Lex.) G.A. Romero & Carnevali, and comparative evaluation of their metabolomic profiles.

ETHNOPHARMACOLOGICAL RELEVANCE: Laelia anceps and Cyrtopodium macrobulbon are two orchids used in Mexican traditional medicine for treating pain. AIM OF THE STUDY: The individual antinociceptive activity of ethanol extracts from the roots of Laelia anceps (LAE) and Cyrtopodium macrobulbon (CME) was evaluated, and their metabolomic profiles were comparatively evaluated. The antinociceptive activity of CME and naproxen combination (1:1) was also addressed. MATERIALS AND METHODS: The antinociceptive actions of LAE and CME were examined using three nociceptive tests. The combination of CME with naproxen was evaluated in the acetic acid test using isobologram analysis. Metabolomic analysis was performed using capillary reversed phase liquid chromatography-electrospray ionization-high resolution mass spectrometry and the MS-DIAL 4.70 software was used for data analysis and statistics. RESULTS: LAE (ED50 = 48.4 mg/kg) and CME (ED50 = 17.8 mg/kg) showed antinociceptive activity in the acetic acid test. Pre-treatment with L-NAME reverted the antinociceptive effects of LAE and CME in the acetic acid test. LAE (ED50 = 97 mg/kg) and CME (ED50 = 29 mg/kg) also induced antinociceptive activity in the second phase of the formalin test. The combination of CME with naproxen induced synergistic (interaction index = 0.434) antinociceptive effects (ED50 = 10.6 mg/kg). Overall, 156 compounds allocated in 97 different ontologies were found to be differentially expressed in the two orchids; among them, 125 compounds corresponded to LAE and 31 to CME. Three phenanthrene derivatives annotated in CME might be associated with its antinociceptive activity. CONCLUSION: LAE and CME induced antinociceptive activity with the possible participation of the nitric oxide pathway. CME in combination with naproxen synergistically produces antinociceptive effects in the acetic acid test. The untargeted metabolomic analysis allowed for annotation of several compounds potentially involved in the therapeutic potential of two plants; among them, three phenanthrene derivatives might contribute to the observed antinociceptive activity.

Pharmacological activities of Asclepias curassavica L. (Apocynaceae) aerial parts.

ETHNOPHARMACOLOGICAL RELEVANCE: Asclepias curassavica L. (Apocynaceae) is a perennial shrub used in the folk treatment of parasitism, pain, and inflammation. AIM OF THE STUDY: This work assessed the antiparasitic, anti-inflammatory, antinociceptive, and sedative effects of an ethanol extract from the aerial parts of Asclepias curassavica (ACE). MATERIALS AND METHODS: The antiparasitic activity against Trichomonas vaginalis was evaluated using the trypan blue exclusion test. The in vitro anti-inflammatory actions of ACE (1-200 µg/ml) were analyzed using LPS-stimulated primary murine macrophages. The in vivo pharmacological activity of ACE (50-200 mg/kg p.o.) was evaluated using animal models of inflammation (TPA-induced ear edema test and carrageenan-induced paw edema test) and nociception (acetic acid-induced writhing test, formalin-induced licking test, and hot plate test). RESULTS: ACE showed poor antiparasitic effects against Trichomonas vaginalis (IC50 = 302 µg/ml). ACE increased the production of IL-10 in both in vitro assays (EC50 = 3.2 pg/ml) and in vivo assays (ED50 = 111 mg/kg). ACE showed good antinociceptive actions (ED50 = 158 mg/kg in phase 1 and ED50 = 83 mg/kg in phase 2) in the formalin test. Pre-treatment with naloxone blocked the antinociceptive response induced by ACE. In addition, ACE did not induce sedative effects or motor coordination deficits in mice. CONCLUSION: Findings showed that the anti-inflammatory activity of ACE is associated with increasing levels of IL-10 in both in vitro and in vivo assays, whereas the antinociceptive effect is associated with the participation of the opioidergic system, without inducing sedation or motor coordination impairment.

In vitro and in vivo anti-inflammatory effects of an ethanol extract from the aerial parts of Eryngium carlinae F. Delaroche (Apiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Eryngium carlinae F. Delaroche (Apiaceae) is an herb used in folk medicine as a diuretic, analgesic, and anti-inflammatory agent. AIM OF THE STUDY: This work assessed the diuretic, antinociceptive, and anti-inflammatory actions of an ethanol extract from the leaves and stems of Eryngium carlinae (ECE). These ethnomedicinal properties of ECE were scientifically validated using in vitro and in vivo assays. MATERIALS AND METHODS: The antinociceptive and diuretic actions of ECE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing test and by using metabolic cages to house mice, respectively. The in vitro anti-inflammatory actions of ECE (1-500 µg/ml) were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed using the TPA-induced ear edema test (2 mg/ear) and carrageenan-induced paw edema test (50-200 mg/kg p.o.). The production of inflammatory mediators was estimated using in vitro and in vivo assays. RESULTS: ECE lacked antinociceptive and diuretic effects. ECE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 37.8 pg/ml) and the carrageenan-induced paw edema test (ED50 = 82.6 mg/kg). ECE showed similar in vivo anti-inflammatory actions compared to those observed with indomethacin. CONCLUSION: ECE exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.

Diuretic activity and neuropharmacological effects of an ethanol extract from Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae).

Ethnopharmacological relevance Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a shrub empirically used as diuretic, and for the treatment of neurological disorders. These pharmacological effects have not been previously evaluated. AIM OF THE STUDY: To evaluate the diuretic and CNS effects of a standardized ethanol extract of Senna septemtrionalis aerial parts (SSE). MATERIALS AND METHODS: Gas chromatography mass spectrometry was used to perform a chemical analysis with SSE. In all tests, SSE was evaluated from 10 to 100 mg/kg p.o. The diuretic activity of SSE was assessed in mice individually placed in metabolic cages. After 6 h, the urine volume and the electrolyte excretion (Na and K) were measured. The role of prostaglandins and nitric oxide was assessed administrating mice with indomethacin and N(ω)-nitro-L-arginine methyl ester (L-NAME), prior the administration of 100 mg/kg SSE. The sedative effects of SSE were analyzed with the pentobarbital-induced sleeping time test. The effects of SSE on motor coordination in mice were evaluated with the rotarod test. The antidepressant-like activity of SSE was analyzed with the forced swimming test (FST) and the tail suspension test (TST). The role of 5-HT2 receptor, α1-and α2-adrenoceptors, or muscarinic receptors was assessed administrating mice with cyproheptadine, prazosin, yohimbine, and atropine, respectively, prior the administration of 100 mg/kg SSE in the FST. The anxiolytic-like activity of SSE (10-100 mg/kg p.o.) was assessed using the light-dark test (LDB), the elevated plus maze test (EPM), the cylinder exploratory test, and the open field test (OFT). The anticonvulsant effect of SSE (1-100 mg/kg) was evaluated in mice administered with different convulsant agents: strychnine, pentylenetetrazol (PTZ), isoniazid (INH) or yohimbine. RESULTS: The main compound found in SSE was D-pinitol (42.2%). SSE (100 mg/kg) increased the urinary volume (2.67-fold), as well as the excretion of Na (5.60-fold) and K (7.2-fold). The co-administration of SSE with L-NAME or indomethacin reverted the diuretic activity shown by SSE alone. SSE lacked sedative effects and did not affect motor coordination in mice. SSE (100 mg/kg) showed higher and similar antidepressant-like effect, compared to 20 mg/kg fluoxetine, in the FST and TST, respectively. The co-administration of SSE with yohimbine reverted the antidepressant-like activity shown by SSE alone. SSE (100 mg/kg) showed anxiolytic-like activity in the four models of anxiety, with similar activity with 1.5 mg/kg clonazepam. The seizure-protective effect of SSE was ED50 = 73.9 ±â€¯8.4 mg/kg (INH) and 40.4 ±â€¯5.2 mg/kg (yohimbine). CONCLUSION: The diuretic effects of SSE involve the possible contribution of prostaglandins and nitric oxide. SSE showed moderate anxiolytic and anticonvulsant effects, whereas the participation of α2-adrenoceptors is probably associated in the antidepressant-like effects of SSE.