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<p>This study evaluated <i>Tripleurospermum inodorum</i> extract for cytotoxic, anti-inflammatory, antioxidant, antimicrobial, and antibiofilm properties, alongside its phenolic profile, predicted pharmacological interactions and in vivo anti-inflammatory properties. The methanolic extract of <i>T. inodorum</i> was rich in apigenin derivatives, including apigenin-<i>O</i>-pentoside (5.234&#xa0;mg/g) and apigenin-<i>O</i>-acetyl hexoside (4.929&#xa0;mg/g), as identified using LC-DAD-ESI/MSⁿ. The extract demonstrated potent anti-inflammatory activity (IC₅₀ = 8.4&#xa0;µg/mL) by inhibiting nitric oxide production in a RAW 264.7 macrophage model, a key mechanism in controlling inflammatory responses. Its cytotoxicity against NCI-H460 lung carcinoma cells (GI₅₀ = 62.9&#xa0;µg/mL) suggests potential for targeting inflammation-driven carcinogenesis. Antioxidant activity, ranging from 204.4 (FRAP) to 442.2 (ABTS) mmol of gallic acid equivalents per 100&#xa0;mg dry weight, highlights its role in mitigating oxidative stress—a critical driver of chronic inflammation. The extract also displayed moderate antimicrobial activity (MIC: 3–12&#xa0;mg/mL) and strong antibiofilm potential (&gt; 70% inhibition in a crystal violet assay), which are essential for managing infection-associated inflammation. Network pharmacology revealed that dominant phenolic compound act as aldose reductase inhibitors, targeting inflammatory pathways linked to metabolic stress. In vivo assessment using a xylene-induced ear edema model revealed a dose-dependent, biphasic anti-inflammatory effect, with lower doses (125 and 250&#xa0;mg/kg) exhibiting greater efficacy compared to the highest dose (500&#xa0;mg/kg), suggesting a hormetic response that emphasizes the importance of optimal dosing. These findings indicate that the methanolic extract of <i>T. inodorum</i> possesses a broad spectrum of bioactivities relevant to inflammation control and supports its further development as a source of novel anti-inflammatory therapeutics.</p>

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Bioactive potential of Tripleurospermum inodorum with detailed insight into anti-inflammatory activity through in vitro, in vivo evaluations and network pharmacology

  • 期刊论文

  • 发表日期：

    2025年5月7日

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  • Marija Ivanov,
  • Aleksandra Popov Aleksandrov,
  • Jelena Božunović,
  • Maria Inês Dias,
  • Ricardo C. Calhelha,
  • Jelena Kulaš,
  • Lillian Barros,
  • Isabel C. F. R. Ferreira,
  • Dejan Stojković

摘要

This study evaluated Tripleurospermum inodorum extract for cytotoxic, anti-inflammatory, antioxidant, antimicrobial, and antibiofilm properties, alongside its phenolic profile, predicted pharmacological interactions and in vivo anti-inflammatory properties. The methanolic extract of T. inodorum was rich in apigenin derivatives, including apigenin-O-pentoside (5.234 mg/g) and apigenin-O-acetyl hexoside (4.929 mg/g), as identified using LC-DAD-ESI/MSⁿ. The extract demonstrated potent anti-inflammatory activity (IC₅₀ = 8.4 µg/mL) by inhibiting nitric oxide production in a RAW 264.7 macrophage model, a key mechanism in controlling inflammatory responses. Its cytotoxicity against NCI-H460 lung carcinoma cells (GI₅₀ = 62.9 µg/mL) suggests potential for targeting inflammation-driven carcinogenesis. Antioxidant activity, ranging from 204.4 (FRAP) to 442.2 (ABTS) mmol of gallic acid equivalents per 100 mg dry weight, highlights its role in mitigating oxidative stress—a critical driver of chronic inflammation. The extract also displayed moderate antimicrobial activity (MIC: 3–12 mg/mL) and strong antibiofilm potential (> 70% inhibition in a crystal violet assay), which are essential for managing infection-associated inflammation. Network pharmacology revealed that dominant phenolic compound act as aldose reductase inhibitors, targeting inflammatory pathways linked to metabolic stress. In vivo assessment using a xylene-induced ear edema model revealed a dose-dependent, biphasic anti-inflammatory effect, with lower doses (125 and 250 mg/kg) exhibiting greater efficacy compared to the highest dose (500 mg/kg), suggesting a hormetic response that emphasizes the importance of optimal dosing. These findings indicate that the methanolic extract of T. inodorum possesses a broad spectrum of bioactivities relevant to inflammation control and supports its further development as a source of novel anti-inflammatory therapeutics.