Relationships between the Toxicities of Radix Aconiti Lateralis Preparata (Fuzi) and the Toxicokinetics of Its Main Diester-Diterpenoid Alkaloids

Abstract

The processed lateral root of Aconitum carmichaelii Deb (Aconiti Radix lateralis praeparata or Fuzi) is a potent traditional herbal medicine extensively used in treatment of cardiovascular diseases, rheumatism arthritis, and bronchitis in many Asian countries. Although Fuzi has promising therapeutic effects, its toxicities are frequently observed. Three main C19-diester-diterpenoid alkaloids (DDAs) are believed to be the principal toxins of the herb. Although toxicokinetic profiles of the toxic DDAs have already been examined in several studies, they have seldom been correlated with the toxicities of Fuzi. The current article aimed to investigate the relationship between the up-to-date toxicokinetic data of the toxic DDAs and the existing evidence of the toxic effects of Fuzi. Relationships between the cardiac toxicity and the plasma and heart concentration of DDAs in mice and rats were established. Based on our findings, clinical monitoring of the plasma concentrations of DDAs of Fuzi is recommended to prevent potential cardiac toxicities. Additionally, caution with respect to potential hepatic and renal toxicity induced by Fuzi should be exercised. In addition, further analyses focusing on the preclinical tissue distribution profile of DDAs and on the long-term toxicokinetic-toxicity correlation of DDAs are warranted for a better understanding of the toxic mechanisms and safer use of Fuzi.

Neuropharmacological effects of Aconiti Lateralis Radix Praeparata

“…There are many studies on the analgesic effect of mesaconitine. Their relationship of efficacy‐dosage and pharmacokinetic studies has been reported . However, the detailed analgesic mechanism of MA needs further clarification.…”

“…They are highly efficient, stable and durable . Moreover, metabolomics has been frequently used to examine Fuzi's toxicity and pharmacological mechanisms . This approach can be used to distinguish Aconitum carmichaelii and identify compounds that have development potential .…”

“…The Pharmacopoeia of China (2015) stipulates that the safe clinical dosage of Fuzi is 3000‐15000mg/day. Yang believes that better understanding of the toxic mechanisms of Fuzi, the preclinical tissue distribution profile of the C19‐diester‐diterpenoid alkaloids, and the toxicokinetic‐toxicity correlation of diester diterpene alkaloids are required . These advanced technologies and measures help to ensure that Fuzi is safe to use.…”

Neuropharmacological Effects of Mesaconitine: Evidence from Molecular and Cellular Basis of Neural Circuit

“…However, a comprehensive MA metabolism database still needs to be built for future pharmacological studies and clinical use [80]. In order to better understand the toxicity of MA, other advanced methods like an electrocardiogram, histopathology, serum biomarkers, and lipidomic profile changes need to be applied [79].…”

The toxicity and safety of traditional Chinese medicines: Please treat with rationality

“…Many common drugs in the Chinese materia medica are known to be toxic, causing damage to nervous, liver, renal, respiratory system, and reproductive system (Table 3) (6)(7)(8)(9)(10)(11)(12)(13)(14). The toxic components from TCM herbs include alkaloids, anthraquinones, aristolochic acids, cardiac glycosides and others (15).…”