Uncovering the molecular mechanisms of Fructus Choerospondiatis against coronary heart disease using network pharmacology analysis and experimental pharmacology.

Fructus Choerospondiatis (FC), a Mongolian medicine, was mainly used in Mongolian medical theory for the treatment of coronary heart disease (CHD). Nonetheless, the main components and mechanisms of action of FC in the treatment of coronary artery disease have not been studied clearly. AIM OF THE STUDY: The aim of this study is to identify the components of FC and analyze the pathways affected by the targets of these components to probe into the potential mechanisms of action of FC on coronary heart disease. MATERIALS AND METHODS: Identification of compounds in FC employing high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS) method, then further investigate the network pharmacology and molecular docking to obtain potential targets and elucidate the potential mechanism of action of FC in the therapy of CHD. Experimental validation was established to verify the mechanism of FC in vitro. RESULTS: 21 FC components were identified and 65 overlapping targets were gained. In addition, these ingredients regulated AMPK and PPAR signaling pathway by 65 target genes including IL6, AKT1 and PPARg, etc. Molecular docking displayed that the binding ability of the key target PPARg to FC components turned out to be better. Experimental validation proved that FC treatment decreased the expression of PPARg (p < 0.05) compare with model group, which may be involved in the PPAR signaling pathway. CONCLUSIONS: This study was the first to elucidate the mechanism of action of components of FC for the treatment of CHD using network pharmacology. It alleviated CHD by inhibiting the expression of PPARg to attenuate hypoxia/reoxygenation injury, and the results give a basis for elucidating the molecular mechanism of action of FC for the treatment of coronary heart disease.

Magnetic Ligand Fishing Using Immobilized Cyclooxygenase-2 for Identification and Screening of Anticoronary Heart Disease Ligands From Choerospondias axillaris.

Inhibition of cyclooxygenase-2 (COX-2) activity is an effective way for treatment of coronary heart disease. And as an important source of COX-2 inhibitors, bioactive compounds of Choerospondias axillaris and pharmacological mechanisms remained lacking in prospective researches. Therefore, for the purpose of accelerating the discovery of natural products targeting designed inhibitors, the COX-2 microreactor composed of functionalized microspheres and magnetic ligand fishing was developed and applied in Choerospondias axillaris, and the physicochemical properties of the COX-2 functionalized microspheres were characterized using Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Furthermore, the bioactive compounds singled out from ethanol decoction without prepurification were dissociated and identified by ultraperformance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive Orbitrap-MS/MS). Consequently, 21 bioactive compounds consisting of 6 organic acids, 8 flavonoids, and 7 others were separated and characterized from Choerospondias axillaris, which were reported to participate in the COX-2 inhibitory pathway to varying degrees. Therefore, this method could provide a prospective solution for the extraction and identification of active pharmaceutical ingredients and the rapid screening of some enzyme inhibitors in the complex mixtures.