Active ingredients in Chinese medicines promoting blood circulation as Na+/K+ -ATPase inhibitors.

Abstract

The positive inotropic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na(+)/K(+)-ATPase in human myocardium. Steroid-like compounds containing a core structure similar to cardiac glycosides are found in many Chinese medicines conventionally used for promoting blood circulation. Some of them are demonstrated to be Na(+)/K(+)-ATPase inhibitors and thus putatively responsible for their therapeutic effects via the same molecular mechanism as cardiac glycosides. On the other hand, magnesium lithospermate B of danshen is also proposed to exert its cardiac therapeutic effect by effectively inhibiting Na(+)/K(+)-ATPase. Theoretical modeling suggests that the number of hydrogen bonds and the strength of hydrophobic interaction between the effective ingredients of various medicines and residues around the binding pocket of Na(+)/K(+)-ATPase are crucial for the inhibitory potency of these active ingredients. Ginsenosides, the active ingredients in ginseng and sanqi, substantially inhibit Na(+)/K(+)-ATPase when sugar moieties are attached only to the C-3 position of their steroid-like structure, equivalent to the sugar position in cardiac glycosides. Their inhibitory potency is abolished, however, when sugar moieties are linked to C-6 or C-20 position of the steroid nucleus; presumably, these sugar attachments lead to steric hindrance for the entrance of ginsenosides into the binding pocket of Na(+)/K(+)-ATPase. Neuroprotective effects of cardiac glycosides, several steroid-like compounds, and magnesium lithospermate B against ischemic stroke have been accordingly observed in a cortical brain slice-based assay model, and cumulative data support that effective inhibitors of Na(+)/K(+)-ATPase in the brain could be potential drugs for the treatment of ischemic stroke.

• Authors: Ronald J Y Chen, Tzyy-rong Jinn, Yi-ching Chen, Tse-yu Chung, Wei-hung Yang, Jason T C Tzen
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 32 Issue 2 Pg. 141-51 (Feb 2011) ISSN: 1745-7254 [Electronic] United States
• PMID: 21293466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cardiac Glycosides
• Drugs, Chinese Herbal
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Blood Circulation (drug effects)
• Cardiac Glycosides (pharmacology)
• Drugs, Chinese Herbal (chemistry, pharmacology)
• Humans
• Hydrogen Bonding
• Hydrophobic and Hydrophilic Interactions
• Models, Theoretical
• Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors)