Cardiac function evaluation for a novel one-step detoxification product of Aconiti Lateralis Radix Praeparata

新型附子一步解毒产品心脏功能评价

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作者:Ya-Nan He #, Ding-Kun Zhang #, Jun-Zhi Lin, Xue Han, Ya-Ming Zhang, Hai-Zhu Zhang, Jin Pei, Ming Yang, Jia-Bo Wang

Background

Aconiti Lateralis Radix Praeparata has been used as the first cardiac drug over a 1000 years in Asian countries. Although most detoxification products are confirmed to be safe, the effect is not potent as desired. In previous study, we designed a one-step detoxification product by fresh cutting and continuously dried, which preserved more water-soluble alkaloids while eliminating toxicity. It is thus necessary to find more in vivo evidence to support its industrial development.

Conclusions

This study provides scientific evidence for the clinical application of new products. It is of great benefit to innovate the industrial detoxification process of Aconitum.

Methods

Initially, network pharmacology was applied to analyze the related pathways of candidate components acting on heart failure diseases. Then, two heart failure models that were induced by propafenone hydrochloride and nimodipine (v/v, 1:1) and were given doxorubicin were carried out to test the cardiac activity. Moreover, the effect on mitochondrial energy metabolism was further assessed.

Results

Network pharmacology results indicated that Aconiti Lateralis Radix Praeparata treated heart failure through cAMP signaling pathway, calcium signaling pathway, adrenergic signaling in cardiomyocytes and so on. These pathways were highly correlated with myocardial contractility and mitochondrial energy metabolism. Trials on heart failure rats demonstrated that the novel processed-product could produce a stronger positive inotropic action and increase more Na +-K +-ATPase and Ca 2+-Mg 2+-ATPase than Heishunpian. Pathological results also revealed the novel one could better restore the morphology of cardiomyocytes and reduce vacuolar lesions. It also could inspire more energy with a lower concentration. Conclusions: This study provides scientific evidence for the clinical application of new products. It is of great benefit to innovate the industrial detoxification process of Aconitum.

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