2′, 5′-Dihydroxyacetophenone alleviates cytokine storm by targeting Hdac1

Background and objectives

Cytokine storm is a severe immune response that is characterized by the release of large amounts of inflammatory mediators (e.g., cytokines). 2′,5′-Dihydroxyacetophenone (DHAP) is a small molecule with a variety of biological activities involving antioxidant, anti-inflammation and antitumor. The primary objective of the current investigation is to elucidate the underlying mechanism of DHAP in cytokine storm and perform a preliminary analysis of its potential applications.

Methods

The roles of DHAP in cytokine storm were investigated in vitro and in vivo. The molecular basis of DHAP was also studied by network pharmacological analysis and molecular docking.

Results

DHAP inhibited the production of inflammatory factors such as interleukin-1β, interleukin-6, and nitric oxide, alleviated the symptoms of the inflammatory response, and prolonged the survival of cytokine storm animal models. In vitro experiments showed that DHAP inhibited the proliferation of RAW264.7 cells in an inflammatory environment and suppressed the secretion of pro-inflammatory factors in RAW264.7 cells. Western blot results showed that DHAP increased the protein stability of Hdac1, decreased the acetylation level of P65, and inhibited the activation of the nuclear factor-kappa B signaling pathway.

Conclusions

In this study, we found that the plant-derived monomer DHAP may have the ability to inhibit inflammatory storms. HDAC1 is a histone deacetylase responsible for catalyzing the removal of acetyl groups from lysine residues on many protein substrates. HDAC1 has profound effects on the regulation of gene transcription and many processes associated with cell growth and cell death, including cell cycle progression, DNA repair and apoptosis. DHAP binds to the deacetylase Hdac1, increases the protein stability of Hdac1, reduces the acetylation level of P65, and inhibits the activation of the NF-κB signaling pathway. DHAP is a multifunctional bioactive molecule with a wide range of applications in alleviating inflammatory factor storms.

https://www.xiahepublishing.com/2472-0712/ERHM-2023-00062

The study was recently published in the Exploratory Research and Hypothesis in Medicine.

Exploratory Research and Hypothesis in Medicine (ERHM) publishes original exploratory research articles and state-of-the-art reviews that focus on novel findings and the most recent scientific advances that support new hypotheses in medicine. The journal accepts a wide range of topics, including innovative diagnostic and therapeutic modalities as well as insightful theories related to the practice of medicine. The exploratory research published in ERHM does not necessarily need to be comprehensive and conclusive, but the study design must be solid, the methodologies must be reliable, the results must be true, and the hypothesis must be rational and justifiable with evidence.

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