Abstract
Salvia miltiorrhiza
(SM)–Dalbergia odorifera (DO) is a commonly used circulating blood and transforming stasis drug pair for the treatment of cardiovascular and cerebrovascular diseases, but systematic studies on the optimal ratio for the treatment of cerebrovascular diseases have not been reported. In this study, we determined the optimal ratio of SM–DO for the treatment of ischemic stroke (IS) through the mixture design.
Five different ratios of SM and DO were applied to middle cerebral artery occlusion (MCAO) mice using an enhanced simplex center-of-mass mixture design by Minitab 17 software. The experimental ratios of SM and DO as independent variables and dependent variables including modified neurological severity scores, corner test, sticker removal test, cylinder test, 2,3,5-triphenyltetrazolium chloride staining, lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) levels, and the optimal ratio of the two herbs was obtained by fitting regression equations through mixture design and multi-objective synchronization optimization. The therapeutic effects of the optimal ratio of SM–DO on MCAO mice were verified and evaluated by the indicators of neurological function, brain swelling, cerebral infarction volume, brain histopathological morphology, and the levels of LDH and NSE. The optimal ratio of SM:DO = 0.61:0.39 was obtained by multi-objective synchronization optimization. The results of pharmacodynamic validation showed that the optimal ratio of SM–DO significantly improved the neurological function scores of MCAO mice, the motor functions of the left forelimb, the sensory functions of the left paw, the motor functions of the right steering, the cerebral infarct volume, and the release of LDH and NSE and exerted the therapeutic effect on IS. The optimal ratio of SM (0.61) and DO (0.39) was found to be effective in the treatment of IS mice based on mixture design.
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