Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan.
Am J Chin Med. 2012;40(5):953-65. doi: 10.1142/S0192415X1250070X.
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.
多功能甾体样化合物对 Na(+)/K(+) -ATP 酶的抑制作用，通过与强心苷触发的相同分子机制，为许多中药心脏产品的潜在治疗效果做出贡献。从牛樟芝（樟芝）中分离出五种主要的甾体样化合物，即安特辛 A、B、C、H 和 K，均抑制 Na(+)/K(+) -ATP 酶。安特辛 A 的抑制活性比其他四种安特辛强，尽管比人参皂苷 Rh2 弱。相比之下，皮质酮（一种与安特辛 A 相比具有更强抗炎作用的类似甾体）没有检测到抑制活性。分子建模表明，与 Rh2 相比，安特辛以甾体骨架结构倒置的方式与 Na(+)/K(+) -ATP 酶结合。安特辛 A 的抑制活性归因于结合口袋内甾体疏水性相互作用和其羧基与 Na(+)/K(+) -ATP 酶腔入口周围两个阳离子残基之间形成的三个氢键。其他四种安特辛 C7 上的额外羰基或羟基会导致疏水性口袋中严重的排斥，从而显著降低抑制活性。据推测，安特辛 A 是一种双功能化合物，通过两种不同的分子机制发挥抗炎作用并增强血液循环。
