Abstract
BackgroundAconiti 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.MethodsInitially, 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.ResultsNetwork 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 Ca2+–Mg2+–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.ConclusionsThis study provides scientific evidence for the clinical application of new products. It is of great benefit to innovate the industrial detoxification process of Aconitum.
Highlights
Aconiti Lateralis Radix Praeparata has been used as the first cardiac drug over a 1000 years in Asian countries
When these ones are hydrolyzed under heating conditions, the hydrolysates are converted into possible energy metabolism promoters, including benzoylaconitine, benzoylmesaconitine, and benzoylhypaconitine [10]
Network pharmacology analysis Network construction 124 predictive targets were obtained from BATMANTCM database
Summary
Aconiti Lateralis Radix Praeparata has been used as the first cardiac drug over a 1000 years in Asian countries. In previ‐ ous study, we designed a one-step detoxification product by fresh cutting and continuously dried, which preserved more water-soluble alkaloids while eliminating toxicity. Aconiti Lateralis Radix Praeparata (ALRP) is the daughter root of Aconitum carmichaelii Debx It is regarded as a magic drug for its severe cardiotoxicity and great cardiac effect. Other water-soluble alkaloids, such as higenamine and salsolinol [11, 12], are considered to be crucial substances in enhancing myocardial contractility by activating β receptors [13]. Both benzoyl alkaloids and water-soluble alkaloids have good water solubility and are easy to flow away
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