In Silico Study Of Multi-target Effects Of Salviae Miltiorrhizae And Panax Notoginseng On Coronary Heart Disease

Salviae miltiornhizae (Labiatae sp. plant, Chinese name Danshen) and Panaxnotoginseng (Araliaceae plant, Chinese name Sanqi) are one of the representative herbcouples for treatment of coronary heart disease (CHD). Clinical studies have revealeda variety of desirable pharmacological effects of Salviae miltiornhizae and Panaxnotoginseng on CHD, such as increasing coronary flow rate, activating superoxidedismutase, dilating coronary vessels. However, the molecular details about howSalviae miltiornhizae and Panax notoginseng can be administrated on CHD are stillunclear. The research utilized molecular docking method to investigate theinteractions between main effective consitituents of Salviae miltiornhizae and Panaxnotoginseng and CHD targets.Based on relevant pharmacological activities,31compounds originated fromboth herbs were collected, including17from Salviae miltiornhizae and14fromPanax notoginseng, respectively. At the same time, a database comprised of63targetsrelated to CHD was constructed. Crystal structures of41targets were directlydownloaded from the RCSB protein data bank, other22protein structures weresimulated using homology modeling method due to their unavailable crystalstructures.Molecular docking method was employed to study the interaction between31compounds and63targets. Docking results showed that the31compounds displayeda total of946interactions with the CHD targets. All the compounds were predicted tohave at least one targets except caffeic acid, protocatechuic acid, protocatechuicaldehyde and dencichine. Of all the compounds,16had relatively strong interactionswith more than34targets. Furthermore,9compounds potentially binded to45targetsat least. Likewise, the CHD targets also displayed rich landscape of interactingcompounds.36targets were targeted by more than15compounds. Compounds withhigher degree would be key players in Salviae miltiornhizae and Panax notoginseng.The result showed that Salviae miltiornhizae and Panax notoginseng exertedtherapeutic actions based on the synergistic interactions of different componentsacting on multiple targets, reflecting the mechanism of TCM which is amulti-component and multi-target synergy. They could hit the mark of treating CHDby regulating lipid metabolism, controlling process of inflammation, protectingvascular endothelial cells, inhibiting platelet aggregation and blood cogulation andlowering blood pressure.In addition,17compounds showed strong binding abilities to corresponding targets with binding energies lower than-12kcal/mol. This indicated that they mightserve as promising starting points for the further discovery and optimisation of leadcompounds for certain targets.The methods and conclusions of the research provided a theoretical reference forfurther study on pharmacological mechanisms of Salviae miltiornhizae and Panaxnotoginseng from molecular level and shed light on the development of new leads forcertain targets related to cardiovascular disease.