The Aromatherapeutic Effects of Herbal Compounds in Inhibiting Metal-Induced Structural Changes in Tau Protein...

The aggregation of tau protein into fibrillary structures within nerve cells is a hallmark of Alzheimer's disease (AD). There is growing evidence that metal ion accumulation in the brain may be associated with the onset and progression of this disease. Since tau protein undergoes structural changes upon binding metal ions including Zn²⁺, Cu²⁺, and Fe³⁺, this study aimed to explore compounds that can inhibit these metal-induced alterations. The following four herbal volatile compounds including α-Asarone (ASA), β-Caryophyllene (BCP), Cinnamaldehyde (Cin), and Phenylethyl alcohol (PEA), with known neuroprotective effects, were assessed for their ability to prevent tau fibrillation or aggregation in the presence of metal ions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and atomic force microscopy (AFM) analyses confirmed that metal ions promote tau fibrillation. The efficacy of the herbal volatile compounds varied in the presence of metal ions: ASA and BCP showed strong inhibitory effects, while Cin and PEA were less effective when metal ions were present. Tau samples treated with ASA and BCP in the presence of metal ions exhibited lower fluorescence intensity, reduced β-sheet content, increased 5,5'-dithio bis(2-nitrobenzoic) (DTNB) release, and the formation of less toxic species. In contrast, Cin, in the presence of any of the metal ions, led to the formation of neurotoxic species, while this was visible for PEA only in the presence of Fe³⁺ ions.