Preventive effects of coixol, an active compound of adlay seed, in NGF-differentiated PC12 cells against beta-amyloid25-35-induced neurotoxicity.

Background: The health benefits of coixol, an active compound of adlay seed, have attracted certain attention. Adlay seed is often adopted in traditional Chinese medicine for the treatment of various inflammatory disorders. Thus, it is hypothesized that coixol could protect neuronal cells.

Objectives: The preventive effects of coixol against Abeta_25-35-induced damage in nerve growth factor-differentiated PC12 cells were explored.

Methods: Differentiated PC12 cells were treated with coixol at 0.125 μM, 0.25 μM, 0.5 μM, 1 μM, and 2 μM for 48 h. Then, cells were further exposed to Abeta_25-35 at 20 μM for 24 h.

Results: Coixol treatments at 0.25-2 μM exhibited antiapoptotic effect via increasing Bcl-2 mRNA expression, mitochondrial membrane potential, and Na⁺-K⁺ ATPase activity as well as decreasing Bax mRNA expression, caspase-3 activity, and intracellular Ca²⁺ release. In addition, coixol treatments at 0.25-2 μM alleviated oxidative and inflammatory responses via lowering reactive oxygen species level, increasing glutathione content, promoting the activity of glutathione peroxidase, glutathione reductase, and catalase, decreasing the generation of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and prostaglandin E₂. Furthermore, coixol treatments at 0.25-2 μM diminished intracellular Ca²⁺ release, and restricted nuclear factor kappa B-binding activity and phosphorylation of p65 and p38. Coixol treatments at 0.5-2 μM increased protein generation of nuclear factor E2-related factor 2, and limited protein production of inducible nitric oxide synthase and receptor of advanced glycation end product.

Conclusion: Our novel findings suggested that coixol was a compelling agent against beta-amyloid peptide-induced neurotoxicity.