Abstract: Objective To summarize the pharmacology and mechanisms of action of Ophiopogonin D (OPD) against high-altitude heart disease, and review the toxicological profile and current assessment of risks of its isomer, Ophiopogonin D′ (OPD′), in order to provide a reference for safe and rational application of ophiopogonin saponins. Methods Studies on the cardioprotective mechanisms of OPD, animal experiments on high-altitude myocardial injury, the cytotoxicity and hemolytic toxicity of OPD′, and the drug-drug interactions between OPD and OPD′ were reviewed. The findings from these studies were analyzed. Results OPD exerted cardioprotective effects through such mechanisms as the CYP2J3/EETs pathway and anti-inflammatory, anti-apoptotic and antioxidant actions. In an animal model of hypobaric hypoxia that simulated an altitude of 6000 m, OPD significantly reduced myocardial enzyme levels and biomarkers of injury, enhanced SOD activity, and attenuated myocardial histopathological damage. However, OPD′ evoked significant cytotoxicity and hemolytic toxicity, making the control of OPD′ contents in Ophiopogon japonicus-containing formulations critical to quality optimization. Acute toxicity studies found that OPD, when used before OPD′, could effectively reduce the acute toxicity of OPD′. Conclusion So far, progress has been made in research on the pharmacodynamics of OPD against high-altitude myocardial injury, but the toxicological profile of OPD′ and quality control of Ophiopogon japonicus-containing formulations remains to be investigated. Subsequent studies should elucidate the interactions between OPD and OPD′, and establish quality control standards that balance therapeutic efficacy with safety so as to facilitate the application of ophiopogonin saponins in high-altitude heart disease.

Key words: Ophiopogonin D, Ophiopogonin D′, High-Altitude Heart Disease, Cardioprotection, Toxicity, Quality Control