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.
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机译：强心苷的正性肌力作用在于它们对人心肌膜结合Na + / K + -ATPase的可逆抑制作用。在许多传统上用于促进血液循环的中药中发现类固醇样化合物，其核心结构类似于强心苷。其中一些被证明是Na + / K + -ATPase抑制剂，因此通过与强心苷相同的分子机制推定其治疗作用。另一方面，还提出了丹参的紫草酸镁B通过有效抑制Na + / K + -ATPase发挥心脏治疗作用。理论模型表明，各种药物有效成分与Na + / K + -ATPase结合口袋周围残基之间的氢键数量和疏水相互作用的强度对于这些活性成分的抑制效能至关重要。当人参和三七中的活性成分人参皂甙基本抑制Na + / K + -ATPase，这是因为糖部分仅附着于类固醇结构的C-3位置，相当于强心苷中的糖位置。但是，当糖部分与类固醇核的C-6或C-20位置相连时，它们的抑制作用就消失了。据推测，这些糖的附着导致人参皂甙进入Na + / K + -ATPase结合口袋的空间位阻。因此，在基于皮层脑切片的测定模型中已观察到强心苷，几种类固醇样化合物和紫草酸镁B对缺血性中风的神经保护作用，并且累积数据支持大脑中Na + / K + -ATPase的有效抑制剂可以成为治疗缺血性中风的潜在药物。
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