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<p><i>Clematis flamumla</i> (Ranunculaceae) is traditionally used in Algeria for the treatment of inflammatory disorders. Despite its ethnomedicinal relevance and preliminary in vitro evidence of biological activity, its pharmacological properties have not been previously investigated in animal models. Therefore, the aim of the present study was to explore, for the first time, the anti-inflammatory, analgesic and antipyretic potentials of two <i>C. flammula</i> leaf extracts, ethanolic (EECF) and aqueous (Aq-ECF). The antioxidant activity of the extracts was evaluated by in vitro methods (DPPH radical scavenging activity, β-carotene radical bleaching assay and FRAP test). The carrageenan paw edema model, hot plate, writhing tests were employed to assess anti-inflammatory, central and peripheral analgesic activities, respectively. The antipyretic potential was evaluated by the Brewer’s yeast assay. UPLC-DAD-QTOF<b>-</b>MS analysis was undertaken for the structural characterization of bioactive polyphenols. Phytochemical analyses revealed higher levels of flavonol glycosides and proanthocyanidins in the Aq-ECF which were associated with higher ferric reducing power (363.98 ± 20.57&#xa0;mg AAE/g extract) and DPPH scavenging capacity (IC<sub>50</sub> = 45.55 ± 1.05&#xa0;μg/mL) and a greater inhibition of protein denaturation (IC<sub>50</sub> = 47.52 ± 1.18&#xa0;μg/mL). Conversely, the EECF extract inhibited significantly β-carotene bleaching (IC<sub>50</sub> = 116.63 ± 0.21&#xa0;μg/mL). Consistent with these findings, the Aq-ECF extract elicited a dose-dependent reduction of edema reaching a peak 5&#xa0;h after carrageenan injection. At the same dose, a maximal dose–response reduction of abdominal writhings and hyperpyrexia was observed. On the other hand, the EECF extract demonstrated a more pronounced central analgesic effect, as evidenced by a significant increase in the latency period. UPLC-DAD-QTOF-MS led to the identification of eight quercetin and kaempferol glycosides in the parent ethanolic extract. The results indicate that the leaves of <i>C. flammula</i> are a valuable source of antioxidant molecules with anti-inflammatory, analgesic and antipyretic properties, supporting the traditional use of the plant in the management of inflammatory conditions.</p> Graphical Abstract <p></p>

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Unraveling the Anti-inflammatory, Analgesic, and Antipyretic Activities of Clematis flammula Leaf Extracts as a Source of Flavonol Glycosides Identified by UPLC-DAD-QTOF-MS

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Salima Sebaihi-Harzoun,
  • Dina Atmani-Kilani,
  • Nassima Cheraft-Bahloul,
  • Djebbar Atmani,
  • Naima Saidene,
  • Marie Begoћa Ruiz-Larrea,
  • José Ignacio Ruiz Sanz

摘要

Clematis flamumla (Ranunculaceae) is traditionally used in Algeria for the treatment of inflammatory disorders. Despite its ethnomedicinal relevance and preliminary in vitro evidence of biological activity, its pharmacological properties have not been previously investigated in animal models. Therefore, the aim of the present study was to explore, for the first time, the anti-inflammatory, analgesic and antipyretic potentials of two C. flammula leaf extracts, ethanolic (EECF) and aqueous (Aq-ECF). The antioxidant activity of the extracts was evaluated by in vitro methods (DPPH radical scavenging activity, β-carotene radical bleaching assay and FRAP test). The carrageenan paw edema model, hot plate, writhing tests were employed to assess anti-inflammatory, central and peripheral analgesic activities, respectively. The antipyretic potential was evaluated by the Brewer’s yeast assay. UPLC-DAD-QTOF-MS analysis was undertaken for the structural characterization of bioactive polyphenols. Phytochemical analyses revealed higher levels of flavonol glycosides and proanthocyanidins in the Aq-ECF which were associated with higher ferric reducing power (363.98 ± 20.57 mg AAE/g extract) and DPPH scavenging capacity (IC50 = 45.55 ± 1.05 μg/mL) and a greater inhibition of protein denaturation (IC50 = 47.52 ± 1.18 μg/mL). Conversely, the EECF extract inhibited significantly β-carotene bleaching (IC50 = 116.63 ± 0.21 μg/mL). Consistent with these findings, the Aq-ECF extract elicited a dose-dependent reduction of edema reaching a peak 5 h after carrageenan injection. At the same dose, a maximal dose–response reduction of abdominal writhings and hyperpyrexia was observed. On the other hand, the EECF extract demonstrated a more pronounced central analgesic effect, as evidenced by a significant increase in the latency period. UPLC-DAD-QTOF-MS led to the identification of eight quercetin and kaempferol glycosides in the parent ethanolic extract. The results indicate that the leaves of C. flammula are a valuable source of antioxidant molecules with anti-inflammatory, analgesic and antipyretic properties, supporting the traditional use of the plant in the management of inflammatory conditions.

Graphical Abstract