<p>The application of natural plant-based medicine has sparked a great interest in <i>Fagonia cretica</i>, a traditional herb with medicinal properties. However comprehensive evidence regarding anti-inflammatory mechanism remains limited. This study aimed to evaluate phytochemical, anti-inflammatory and toxicological profiles of <i>Fagonia cretica</i> ethanolic extract (EEFC). EEFC was prepared by Soxhlet extraction, and bioactive components were identified using GC-MS analysis. According to OECD guidelines, Swiss albino rats were orally administered at different doses in acute and subacute toxicity. GC-MS analysis revealed 30 phytocompounds with Octan-2-yl palmitate, Pyridine-3-carboxamide, and 2-Ethylhexyl stearate present abundantly. In acute and subacute toxicity, EEFC did not induce any toxicity or mortality, as well as no significant change in blood parameters. Bovine serum albumin assay (BSA), EEFC manifested significant concentration-dependent inhibition of protein denaturation at 50,100, 250, 500, and 1000&#xa0;µg/ml (IC<sub>50</sub>= 34.79&#xa0;µg/ml) as compared to the SC group (<i>p</i> &lt; 0.05) (IC<sub>50</sub>= 22.51&#xa0;µg/ml). In the COX-1 and COX-2 assays, EEFC has significant inhibitory activity as compared to the standard drug DS. In the carrageenan-induced paw edema model, 100&#xa0;mg/kg (5.71 ± 0.02), 200&#xa0;mg/kg (5.26 ± 0.03) and 400&#xa0;mg/kg (4.46 ± 0.01) reduced paw edema in a dose-dependent manner, showing a biphasic process. Furthermore, following Swiss ADME and toxicity analysis, molecular docking demonstrated strong binding affinities with COX-1 (6Y3C) and COX-2 (5KIR), with in the range − 7.7 and − 8.0, respectively. In conclusion, EEFC exhibited significant anti-inflammatory activity and demonstrated favorable preclinical safety profile.</p> Graphical abstract <p></p>

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Mechanistic insight into anti-inflammatory activity of Fagonia cretica via COX inhibition and multimodal pharmacological evaluation

  • Iqra Farzeen,
  • Zunaira Jaan,
  • Saima Muzammil,
  • Asma Ashraf

摘要

The application of natural plant-based medicine has sparked a great interest in Fagonia cretica, a traditional herb with medicinal properties. However comprehensive evidence regarding anti-inflammatory mechanism remains limited. This study aimed to evaluate phytochemical, anti-inflammatory and toxicological profiles of Fagonia cretica ethanolic extract (EEFC). EEFC was prepared by Soxhlet extraction, and bioactive components were identified using GC-MS analysis. According to OECD guidelines, Swiss albino rats were orally administered at different doses in acute and subacute toxicity. GC-MS analysis revealed 30 phytocompounds with Octan-2-yl palmitate, Pyridine-3-carboxamide, and 2-Ethylhexyl stearate present abundantly. In acute and subacute toxicity, EEFC did not induce any toxicity or mortality, as well as no significant change in blood parameters. Bovine serum albumin assay (BSA), EEFC manifested significant concentration-dependent inhibition of protein denaturation at 50,100, 250, 500, and 1000 µg/ml (IC50= 34.79 µg/ml) as compared to the SC group (p < 0.05) (IC50= 22.51 µg/ml). In the COX-1 and COX-2 assays, EEFC has significant inhibitory activity as compared to the standard drug DS. In the carrageenan-induced paw edema model, 100 mg/kg (5.71 ± 0.02), 200 mg/kg (5.26 ± 0.03) and 400 mg/kg (4.46 ± 0.01) reduced paw edema in a dose-dependent manner, showing a biphasic process. Furthermore, following Swiss ADME and toxicity analysis, molecular docking demonstrated strong binding affinities with COX-1 (6Y3C) and COX-2 (5KIR), with in the range − 7.7 and − 8.0, respectively. In conclusion, EEFC exhibited significant anti-inflammatory activity and demonstrated favorable preclinical safety profile.

Graphical abstract