Carpoxylon macrospermum leaf extract and its phenolic compounds: a multi-targeted therapeutic remedy for Alzheimer's disease

BACKGROUND: Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder with a significant impact, especially on elderly people. Although no current treatment is available for AD, several studies have been conducted to discover alternative remedies capable of managing its symptoms and slowing the progression. Accordingly, herein we analysed the phenolic composition and investigated the defatted aqueous methanol extract (DAE) of Carpoxylon macrospermum H.Wendl. & Drude (Family Arecaceae) leaves against key enzymes in addition to oxidative and inflammatory markers involved in AD progression. METHODS: NMR and mass spectrometry elucidated the phenolic compounds. Human carbonic anhydrase (hCA), human acetyl cholinesterase (AChE), and cyclo-oxygenase 2 (COX-2) inhibitor screening kits were used to assess the enzyme-inhibitory potential. Lipo-poly saccharide (LPS)-induced murine macrophage (RAW 264.7) in vitro model was used to test the anti-inflammatory effect. Molecular docking studies were conducted using AutoDock Vina. RESULTS: Chlorogenic acid (1), rutin (2), hesperidin (3), vanillic acid (4), and p-hydroxybenzoic acid (5) have been isolated. The DAE and compounds 2 and 4 significantly inhibited hCA enzyme with IC50 equivalent to 0.160 ± 0.008, 0.243 ± 0.012, and 0.290 ± 0.015 µg/mL, and AChE enzyme with an IC50 corresponding to 3.732 ± 0.13, 0.868 ± 0.03, and 0.597 ± 0.02 µg/mL, respectively. Additionally, they demonstrated potent anti-inflammatory activity by inhibiting the COX-2 enzyme with IC50 values of 4.602 ± 0.17, 2.806 ± 0.10, and 0.849 ± 0.03 µg/mL, respectively. The DAE, 2 and 4 reduced IL-2 to 3.49 ± 0.12—7.018 ± 0.24 pg/mL; IL-4 to 6.019 ± 0.21–12.07 ± 0.41 pg/mL, and TNF-α to 323.65 ± 11.10–501.88 ± 17.21 pg/mL, respectively. Western blotting revealed a decrease in iNOS protein expression. Rutin showed improved docking scores (-8.92 and -7.92 kcal/mol) with AChE and hCA, while 100 ns Molecular Dynamc Simulations (MDS) showed that rutin maintained stable interactions with the proteins throughout the simulations. CONCLUSION: C. macrospermum extract and its phenolics are promising candidates for AD management, though additional in vivo and clinical studies are needed.