Compatibility of Fuzi and Ginseng Significantly Increase the Exposure of Aconitines

Abstract

The herb-pair ginseng-Fuzi (the root of Aconitum carmichaelii) is the material basis of Shenfu prescriptions and is popular in traditional Chinese medicine for the treatment of heart failure, and even shock with severe-stage of COVID-19. A narrow therapeutic window of Fuzi may cause significant regional loss of property and life in clinics. Therefore, systemic elucidation of active components is crucial to improve the safety dose window of Shenfu oral prescriptions. A high performance liquid chromatography-mass spectrometry method was developed for quantification of 10 aconitines in SD rat plasma within 9 min. The limit of detection and the limit of quantification were below 0.032 ng/ml and 0.095 ng/ml, respectively. Furthermore, a systemic comparison with their pharmacokinetic characteristics after oral administration of a safe dosage of 2 g/kg of Fuzi and ginseng-Fuzi decoction for 24 h was conducted. Eight representative diester, monoester, and non-ester aconitines and two new active components (i.e., songorine and indaconitine) were all adopted to elucidating the differences of the pharmacokinetic parameters in vivo. The compatibility of Fuzi and ginseng could significantly increase the in vivo exposure of active components. The terminal elimination half-life and the area under the concentration-time curve of mesaconitine, benzoylaconitine, benzoylmesaconitine, benzoylhypaconitine, and songorine were all increased significantly. The hypaconitine, benzoylmesaconitine, and songorine were regarded as the main active components in vivo, which gave an effective clue for the development of new Shenfu oral prescriptions.

Shenfu injection: a review of pharmacological effects on cardiovascular diseases

“…Ginsenosides can promote the metabolism of the toxic component aconitine, prolong the elimination half-life of active ingredients such as hypaconitine, benzoylmesaconine and songorine, and significantly increase the in vivo exposure of active ingredients. At the same time, some studies have found that ginseng can inhibit the ion disorders, toxicity in calcineurin-nuclear factor of activated T cells (CaN-NFAT3) pathway and inhibition of the cytochrome P450 2J3 (CYP2J3) expression caused by aconitine, and enhance the antioxidant effect of myocardial cells ( Liu et al, 2020 ; Yang et al, 2021 ; Chen Z. Y. et al, 2022 ; Bao et al, 2023 ). Therefore, the compatibility of aconite and ginseng has the effect of ‘reducing toxicity and increasing efficiency’.…”

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy

“…Fuzi, the lateral roots of Aconitum carmichaelii , is a representative medicine for invigorating Yang and saving lives. It has been widely used as a cardiotonic drug in the clinical applications of traditional Chinese medicine ( Liu et al, 2012 ; Yang et al, 2014 ; Chen et al, 2022 ). As a type of aconitine, mesaconine (MES) is an active compound isolated from Fuzi with a broad spectrum effect on biomedical pharmacology ( Jian et al, 2012 ).…”