Integration of Serum Medicinal Chemistry and Network Pharmacology to Investigate the Pharmacological Substances and Mechanisms of Gardenia jasminoides Ellis Root in Improving Cognitive Dysfunction in Nonalcoholic Fatty Liver Disease

Gardenia jasminoides Ellis root, a traditional Chinese medicine, exhibits various pharmacological activities, including hepatoprotective and anti-inflammatory. It is also effective in the treatment of nonalcoholic fatty liver disease. However, its pharmacological substances and mechanisms for alleviating cognitive dysfunction in nonalcoholic fatty liver disease remain unclear. This study explored the pharmacological substances and mechanisms of Gardenia jasminoides Ellis root in improving cognitive impairment in nonalcoholic fatty liver disease using serum medicinal chemistry, network pharmacology, molecular docking, and molecular dynamics simulation. Serum medicinal chemistry analysis was used to identify the blood components of Gardenia jasminoides Ellis root. Network pharmacology analysis further revealed interactions between its active ingredients and targets related to disease. Additionally, molecular docking experiments demonstrated that the active compounds genistein, glaucine, and 3-(benzyloxy)aniline interact with steroid hormone receptors, including HSP90AA1, AKT1, and EP300. At last, the molecular dynamics simulation of the HSP90AA1–genistein complex with high binding energy was carried out, and the binding of the complex was stable. The above results indicated that the core component genistein and HSP90AA1 protein complex in Gardenia jasminoides Ellis root may indirectly regulate nonalcoholic fatty liver cognitive impairment through the neuroactive ligand–receptor interaction, cAMP signaling pathway, and HIF-1 signaling pathway.