Processed lateral root of Aconitum carmichaelii Debx.: A review of cardiotonic effects and cardiotoxicity on molecular mechanisms

Abstract

Fuzi, the lateral root of A. carmichaelii Debx., is a typical traditional herbal medicine with both poisonousness and effectiveness, and often used in the treatment of heart failure and other heart diseases. In this review, we searched domestic and foreign literature to sort out the molecular mechanisms of cardiotonic and cardiotoxicity of Fuzi, also including its components. The major bioactive components of Fuzi for cardiotonic are total alkaloids, polysaccharide and the water-soluble alkaloids, with specific mechanisms manifested in the inhibition of myocardial fibrosis, apoptosis and autophagy, and improvement of mitochondrial energy metabolism, which involves RAAS system, PI3K/AKT, JAK/STAT, AMPK/mTOR signaling pathway, etc. Diester-diterpenoid alkaloids in Fuzi can produce cardiotoxic effects by over-activating Na+ and Ca2+ ion channels, over-activating NLRP3/ASC/caspase-3 inflammatory pathway and mitochondria mediated apoptosis pathway. And three clinically used preparations containing Fuzi are also used as representatives to summarize their cardiac-strengthening molecular mechanisms. To sum up, Fuzi has shown valuable cardiotonic effects due to extensive basic and clinical studies, but its cardiotonic mechanisms have not been systematically sorted out. Therefore, it is a need for deeper investigation in the mechanisms of water-soluble alkaloids with low content but obvious therapeutic effect, as well as polysaccharide.

Cardiovascular protection of YiyiFuzi powder and the potential mechanisms through modulating mitochondria-endoplasmic reticulum interactions

“…Fuzi can be used in the treatment of CVD especially in HF, due to its valuable cardiotonic effect which helps improve heart function and enhance the contractility of the heart muscle ( Zhao et al, 2012 ; Zhang J. et al, 2022 ). In addition, Fuzi has been studied for its potential anti-MI effects, including mitigating mitochondrial dysfunction caused by MI and restoring energy metabolism in the heart ( Wu H. et al, 2019 ).…”

“…These biological processes protect myocardial tissue. Furthermore, water-soluble alkaloids in Fuzi also modulate mitochondria-mediated pathways to promote mitochondrial energy metabolism ( Zhang J. et al, 2022 ).…”

“…Both mitochondrial energy metabolism and apoptosis can be influenced by ER function which Fuzi has been shown to improve ( Wu H. et al, 2019 ; Zhang J. et al, 2022 ). FZL was found to protect against isoproterenol (ISO)-induced myocardial injury in vivo by suppressing ER stress via downregulating the PERK/eukaryotic initiation factor 2 alpha (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) pathway ( Fan et al, 2020 ).…”

Synthesis, Pharmacological Evaluation, and Molecular Modeling of Lappaconitine–1,5-Benzodiazepine Hybrids

“…Regarding the mechanism of action, lappaconitine 1 , its major metabolite N -deacetyllappaconitine 2 , and some other alkaloids of Aconitum sp. were found to act as sodium channel blockers [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. It was shown that voltage-dependent Na + channel blockers possesses antinociceptive activity and neuronal activity [ 12 , 15 , 18 ].…”

Exploring Potential Targets and Pathways of Toxicity Attenuation Through Serum Pharmacochemistry and Network Pharmacology in the Processing of Aconiti Lateralis Radix Praeparata

“…side effects of FZ seriously affect its clinical use (Huang et al, 2018;Yang et al, 2018;Zhang et al, 2022). Processing is an important method to reduce the toxicity of toxic Chinese medicines, and FZ is generally processed before being used in medicines (Xin et al, 2024;Zhang et al, 2021).…”