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<p>Alzheimer’s disease (AD) represents a multifactorial neurodegenerative disorder necessitating therapeutic interventions that simultaneously target cholinergic dysfunction and oxidative stress. This study evaluated the dual cholinesterase inhibitory and antioxidant properties of <i>Cousinia cylindracea Boiss</i>., as a potential multi-target therapeutic candidate. Flower and stem specimens were subjected to hydroalcoholic extraction followed by ethyl acetate fractionation. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were assessed using modified Ellman’s spectrophotometric method. Antioxidant capacity was evaluated via DPPH radical scavenging assay, while total phenolic content was quantified using Folin-Ciocalteu reagent. Statistical analyses included IC₅₀ determination and correlation assessment between phytochemical composition and bioactivities. The ethyl acetate flower fraction demonstrated superior cholinesterase inhibition (67.97 ± 8.82% AChE inhibition, 64.28 ± 5.71% BChE inhibition at 2.5&#xa0;mg/mL), showing qualitative inhibitory activity relative to galantamine under in vitro screening conditions. Conversely, the ethyl acetate stem fraction exhibited exceptional antioxidant activity (IC₅₀ = 0.03 ± 0.004&#xa0;mg/mL), significantly outperforming quercetin reference. Total phenolic content ranged from 112.9 ± 4.9 to 507.1 ± 12.7&#xa0;mg GAE/g across fractions. Notably, no direct correlation was observed between phenolic concentration and biological activities, suggesting structure-specific bioactivity rather than bulk phenolic effects. <i>Cousinia cylindracea</i> extracts demonstrate significant dual cholinesterase inhibitory and antioxidant activities, highlighting their potential as sources of bioactive compounds for further investigation. The distinct activity profiles between flower and stem extracts indicate tissue-specific accumulation of bioactive compounds with complementary neuroprotective mechanisms. These findings warrant further phytochemical characterization and preclinical evaluation to advance the development of novel plant-based therapeutics for neurodegenerative disorders.</p> Graphical Abstract <p></p>

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Multi-Target Therapeutic Properties of Cousinia cylindracea Boiss Against Alzheimer’s Disease: Cholinesterase Inhibition and Antioxidant Effects

  • 期刊论文

  • 发表日期：

    2026年5月16日

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  • Nadia Garmsiri,
  • Fatemeh Rasekh,
  • Farnia Garmsiri,
  • Reza HajiHosseini,
  • Saber SamadiAfshar

摘要

Alzheimer’s disease (AD) represents a multifactorial neurodegenerative disorder necessitating therapeutic interventions that simultaneously target cholinergic dysfunction and oxidative stress. This study evaluated the dual cholinesterase inhibitory and antioxidant properties of Cousinia cylindracea Boiss., as a potential multi-target therapeutic candidate. Flower and stem specimens were subjected to hydroalcoholic extraction followed by ethyl acetate fractionation. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were assessed using modified Ellman’s spectrophotometric method. Antioxidant capacity was evaluated via DPPH radical scavenging assay, while total phenolic content was quantified using Folin-Ciocalteu reagent. Statistical analyses included IC₅₀ determination and correlation assessment between phytochemical composition and bioactivities. The ethyl acetate flower fraction demonstrated superior cholinesterase inhibition (67.97 ± 8.82% AChE inhibition, 64.28 ± 5.71% BChE inhibition at 2.5 mg/mL), showing qualitative inhibitory activity relative to galantamine under in vitro screening conditions. Conversely, the ethyl acetate stem fraction exhibited exceptional antioxidant activity (IC₅₀ = 0.03 ± 0.004 mg/mL), significantly outperforming quercetin reference. Total phenolic content ranged from 112.9 ± 4.9 to 507.1 ± 12.7 mg GAE/g across fractions. Notably, no direct correlation was observed between phenolic concentration and biological activities, suggesting structure-specific bioactivity rather than bulk phenolic effects. Cousinia cylindracea extracts demonstrate significant dual cholinesterase inhibitory and antioxidant activities, highlighting their potential as sources of bioactive compounds for further investigation. The distinct activity profiles between flower and stem extracts indicate tissue-specific accumulation of bioactive compounds with complementary neuroprotective mechanisms. These findings warrant further phytochemical characterization and preclinical evaluation to advance the development of novel plant-based therapeutics for neurodegenerative disorders.

Graphical Abstract