Evidence for the anti-NAFLD effectiveness of chlorogenic acid as a HAT inhibitor using in vivo experiments supported by virtual molecular docking

• Published in: Phytomedicine Plus : International journal of phytotherapy and phytopharmacology 2021-11, Vol.1 (4), p.100055, Article 100055
• Main Authors: Xu, Jing, Gao, Liangqin, Liang, Huiqing, Zhang, Shaoliang, Lai, Penghua, Chen, Shaodong
• Format: Article
• Language: English
• Subjects: Chlorogenic acid; Histone acetyltransferase inhibition; Molecular docking; Nonalcoholic fatty liver disease
• ISSN: 2667-0313; 2667-0313
• DOI: 10.1016/j.phyplu.2021.100055

•The p300 histone acetyltransferase enzyme was used as a ligand for virtual molecular docking to screen anti-non-alcoholic fatty liver disease phytomedicine.•Chlorogenic acid were screened as a novel histone acetyltransferase inhibitor due to its favorable molecular weight, drug similarity and low binding energy.•In vivo studies showed that CA could inhibit lipid accumulation and alleviate liver injury.•It is feasible to screen histone acetyltransferase inhibitors for the treatment of nonalcoholic fatty liver disease by targeting p300 histone acetyltransferase. Targeted histone acetyltransferase (HAT) may screen out phytomedicine for the treatment of nonalcoholic fatty liver disease (NAFLD) Study Design: In this study, the transcriptional co-activator p300, a type of HAT, was used as a ligand for virtual molecular docking to screen small molecular compounds with HAT-inhibitory effects from algae. Subsequently, in vivo experiments were conducted to verify the therapeutic effects of selected phytomedicine on NAFLD. A small database containing 382 bioactive compounds from seaweed sources was established through literature mining. Molecular weight (MW) and drug-likeness index were used for preliminary screening. the transcriptional co-activator p300, a type of HAT, was used as a ligand for virtual molecular docking to screen small molecular compounds with HAT-inhibitory effects. Potential phytomedicine were tried by subjecting them to binding at the active site of P300 one after the other, and the one with the lowest binding energy was identified as a novel HAT inhibitor, which was subsequently validated in vivo for its role in NAFLD. Thirty clean grades male Wistar rats were randomly divided into the control group, the model group and the phytomedicine group, with 10 rats in each group. The control group was given a standard chow diet and water, while the model group and the phytomedicine group received a high fat diet for 4 weeks to induce obesity. Subsequently, the phytomedicine group was administrated with 1 ml/100 g phytomedicine for another 4 weeks, while the model group was fed with the same amount of drinking water. At the end of experiment, body weight, liver triglyceride (TG) levels, low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) were measured. HE staining results were analyzed to evaluate liver injury. Chlorogenic acid (CA) was identified as a potential a