Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Phytochemical characterization and multi-target protective effects of Lycopodium serratum var. longipetiolatum against dysmenorrhea.
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Chiang Yi-Fen, Chung Cheng-Pei, Huang Ko-Chieh, Li Yi-PeI, Hung Wei-Lun, Hamdy Nadia M, Hsia Shih-Min
Аннотация
BACKGROUND: Primary dysmenorrhea is associated with aberrant uterine contractility, inflammatory activation, and oxidative stress, resulting in nociceptive hypersensitivity and impaired quality of life. Lycopodium serratum Thunb. var. longipetiolatum Spring. (LS), a fern endemic to Taiwan, has been traditionally used to alleviate menstrual disorders; however, its mechanistic basis remains undefined.
PURPOSE: This study aimed to investigate the chemical constituents, uterine relaxant, and antinociceptive effects of LS extracts, and to elucidate their molecular mechanisms in dysmenorrhea.
METHODS: Ethanolic extracts of LS and their solvent-partitioned fractions, ethyl acetate (LSE-EA), n-butanol (LSE-BuOH), and aqueous (LSE-H₂O) were characterized by LC-MS/MS for phenolic constituents. The relaxant and antinociceptive effects were assessed in ex vivo uterine contraction assays induced by prostaglandin F₂α (PGF₂α), oxytocin, acetylcholine, and carbachol, and in acetic acid- and oxytocin-induced pain models in ICR mice. Western blot, biochemical, and histopathological analyses were performed to delineate molecular and oxidative pathways.
RESULTS: LSE-EA exhibited the strongest inhibition of uterine contraction and pain responses. LC-MS/MS identified ferulic acid, caffeic acid, and chlorogenic acid as major metabolites. Mechanistically, LSE-EA downregulated oxytocin receptor (OTR) and myosin light chain kinase (MLCK), suppressed TLR-4/NF-κB/COX-2 and ERK activation, reduced uterine IL-6 expression, and attenuated oxidative stress, as evidenced by decreased malondialdehyde levels and restoration of redox balance.
CONCLUSION: Lycopodium serratum extract confers protection against dysmenorrhea through concurrent suppression of Ca²⁺-dependent uterine contraction, inflammatory signaling, and oxidative stress. These findings identify LSE-EA as a novel bioactive fraction with therapeutic potential in redox-mediated uterine dysfunction.
PURPOSE: This study aimed to investigate the chemical constituents, uterine relaxant, and antinociceptive effects of LS extracts, and to elucidate their molecular mechanisms in dysmenorrhea.
METHODS: Ethanolic extracts of LS and their solvent-partitioned fractions, ethyl acetate (LSE-EA), n-butanol (LSE-BuOH), and aqueous (LSE-H₂O) were characterized by LC-MS/MS for phenolic constituents. The relaxant and antinociceptive effects were assessed in ex vivo uterine contraction assays induced by prostaglandin F₂α (PGF₂α), oxytocin, acetylcholine, and carbachol, and in acetic acid- and oxytocin-induced pain models in ICR mice. Western blot, biochemical, and histopathological analyses were performed to delineate molecular and oxidative pathways.
RESULTS: LSE-EA exhibited the strongest inhibition of uterine contraction and pain responses. LC-MS/MS identified ferulic acid, caffeic acid, and chlorogenic acid as major metabolites. Mechanistically, LSE-EA downregulated oxytocin receptor (OTR) and myosin light chain kinase (MLCK), suppressed TLR-4/NF-κB/COX-2 and ERK activation, reduced uterine IL-6 expression, and attenuated oxidative stress, as evidenced by decreased malondialdehyde levels and restoration of redox balance.
CONCLUSION: Lycopodium serratum extract confers protection against dysmenorrhea through concurrent suppression of Ca²⁺-dependent uterine contraction, inflammatory signaling, and oxidative stress. These findings identify LSE-EA as a novel bioactive fraction with therapeutic potential in redox-mediated uterine dysfunction.