Cinnamon extracts, trans-cinnamaldehyde and trans-cinnamic acid inhibit HDAC 1 activity

Histone deacetylase (HDAC) enzymes play a key role in cell function and are implicated in several diseases such as inflammation, cancer, and neurodegeneration. Studies on natural products have revealed their potential and have led to increased research on natural HDAC inhibitors. Since the progression of these diseases is a prolonged process, dietary supplements and nutraceuticals consisting of plant extracts may be beneficial against HDAC related diseases. Beyond nutritional purposes, cinnamon (Cinnamomum cassia (L.) J. Presl), as a regularly consumed dietary additive due to its rich flavor, may present co-benefits during lifelong use. In this study, cinnamon extracts of differing polarities, trans-cinnamaldehyde and trans-cinnamic acid were evaluated for HDAC 1 inhibitory activity. The total phenol and flavonoid contents were quantified by spectrophotometry, while cinnamaldehyde and cinnamic acid analyses were performed using UPLC-DAD, ESI-MS/MS. Ethanol and dichloromethane extracts yielded the highest cinnamaldehyde and cinnamic acid contents of 389.17 mg per g extract and 11.85 mg per g extract, respectively. The essential oil (IC₅₀: 51.11 μg ml^-1) and 70% ethanol extract (IC₅₀: 107.90 μg ml^-1) showed the most potent HDAC 1 inhibitory activity. Individually, cinnamaldehyde and cinnamic acid were determined to have IC₅₀ values of 7.58 μg ml^-1 and 9.15 μg ml^-1, respectively. As the 70% ethanol extract was able to yield remarkably lower cinnamaldehyde and cinnamic acid amounts, the potential of other moderately polar phenolic compounds for HDAC 1 inhibitory activity was revealed. The essential oil and 70% ethanol extracts of Cinnamomum cassia bark can be further evaluated in future studies for use in products against HDAC 1 related diseases.