title: Inhibition of Na(+)/K(+) -ATPase by antcins, unique steroid-like compounds in Antrodia camphorate.
abstract: The inhibition of  Na(+)/K(+) -ATPase by versatile steroid-like compounds contributes to the putative therapeutic effects of many Chinese medicinal cardiac products via the same molecular mechanism triggered by cardiac glycosides. Five major steroid-like compounds, antcin A, B, C, H, and K were isolated from Niuchangchih (Antrodia camphorata), a unique Taiwan mushroom, and all inhibited  Na(+)/K(+) -ATPase. Antcin A exhibited significantly higher inhibitory potency than the other four antcins, though weaker than ginsenoside  Rh2 . In contrast, cortisone (an analogous steroid with anti-inflammatory effects stronger than antcin A) showed no detectable inhibitory potency. Molecular modeling has shown that antcins bind to  Na(+)/K(+) -ATPase with the steroidal skeleton structurally upside-down in comparison with ginsenoside  Rh2 . The inhibitory potency of antcin A is attributed to steroidal hydrophobic interaction within the binding pocket and the formation of three hydrogen bonds between its carboxyl group and two cationic residues around the cavity entrance of  Na(+)/K(+) -ATPase. The presence of an additional carbonyl or hydroxyl group at  C7  of the other four antcins leads to severe repulsion in the hydrophobic pocket, and thus significantly reduces inhibitory potency. It is proposed that antcin A is a bi-functional compound that exerts anti-inflammatory effects and that enhances blood circulation via two different molecular mechanisms.
authors.affiliation: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 40227,  Taiwan.
authors.forename: Tse-Yu
authors.initials: TY
authors.lastname: Chung
authors.forename: Feng-Yin
authors.initials: FY
authors.lastname: Li
authors.forename: Chi-I
authors.initials: CI
authors.lastname: Chang
authors.forename: Tzyy-Rong
authors.initials: TR
authors.lastname: Jinn
authors.forename: Jason T C
authors.initials: JT
authors.lastname: Tzen
mesh_terms: D000818:Animals; D055491:Antrodia / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000737:chemistry / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D008517:Phytotherapy; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D001688:Biological Products; D002317:Cardiovascular Agents; D013256:Steroids; C561899:antcin A; D000254:Sodium-Potassium-Exchanging ATPase