Antinociceptive effects of Laelia anceps Lindl. and Cyrtopodium macrobulbon (Lex.) G.A. Romero %26 Carnevali, and comparative evaluation of their metabolomic profiles
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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. © 2022 Elsevier B.V.
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Antinociceptive; Cyrtopodium macrobulbon; Laelia anceps; Nitric oxide 2 arylbenzofuran; 3 prenylated flavone; 4' o methylated; 7 o methylisoflavones; acetic acid; anthraquinone derivative; antinociceptive agent; benzofuran derivative; benzopyran derivative; bibenzyl derivative; chalcone derivative; cinnamic acid derivative; coumaric acid; Cyrtopodium macrobulbon extract; flavanone derivative; flavonoid; furosemide; glycoside; guaiacol; hydroxybenzoic acid derivative; isoflavone derivative; Laelia anceps extract; n(g) nitroarginine methyl ester; naproxen; neoflavene; plant extract; pyranoflavonoid; pyranoisoflavonoid; salicylic acid derivative; shikimic acid derivative; stilbene; tannin derivative; tramadol; unclassified drug; analgesic agent; plant extract; acute toxicity; animal experiment; antinociception; Article; bioethics; cell viability; comparative study; controlled study; Cyrtopodium macrobulbon; diuretic activity; HaCat cell line; Laelia anceps; liquid chromatography; male; mass spectrometry; metabolomics; mouse; nonhuman; Olive tail moment; chemistry; Orchidaceae; pain; pain measurement; Analgesics; Orchidaceae; Pain; Pain Measurement; Plant Extracts
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