Metabolomics of Clinical Poisoning by Aconitum Alkaloids Using Derivatization LC-MS

Zhang, Yida; Yang, Jing; Wu, Haiying; Wu, Jian‐Lin; Li, Na

doi:10.3389/fphar.2019.00275

Cited by 8 publications

(5 citation statements)

References 29 publications

(36 reference statements)

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“…Traditional Chinese Medicine (TCM) has become popular all over the world [1,2] . Although TCM of natural origin is considered a safe and effective treatment, its use is not always dependable [3] . Promoting pharmacology and toxicology studies of TCM has attracted growing attention from researchers globally and is critical to guaranteeing safe medication within harmless ranges of dosages in clinical settings.…”

Section: Introductionmentioning

confidence: 99%

Aconitum carmichaelii triggers neurotoxicity and Parkinson‐like symptoms through initiation of ROS‐mitochondrial apoptosis and the Nox5/DJ‐1 signaling pathway

Pang

Song

Miao

et al. 2023

BMEMat

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Background Aconitum carmichaelii, the mother root of Aconitum, has a long‐applied history for treating many diseases in China. Increased use of it has prompted significant concerns regarding its extensive cardiotoxicity and neurotoxicity. The molecular mechanisms underlying A. carmichaelii‐induced neurotoxicity are poorly understood. Methods We took advantage of the zebrafish model to investigate the neurotoxic mechanism of A. carmichaelii. In addition to the behavior and neuronal activity testing, gene expression of neuronal oxidative stress, and apoptosis levels were also analyzed. Results In contrast to the excitatory effect of low‐dose A. carmichaelii decoction, hypoactivity of locomotor behavior, and neural activity, especially telencephalon, were detected in the 20 mg/mL group. High doses of A. carmichaelii induced excessive ROS by downregulating DJ‐1 and activating Nox5, and further triggered cell apoptosis through the bax/bcl2a‐caspase‐9 pathway in zebrafish larva. Mitochondrial protection‐related genes PinK1 and Parkin were upregulated to protect against mitochondrial dysfunction during cellular stress. The ROS scavenger‐NAC significantly alleviated neurotoxicity in the 20 mg/mL group. Conclusion The study reveals the potential mechanism of A. carmichaelii‐induced neurotoxicity and provides new insights into a significant risk marker of A. carmichaelii poisoning.

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Section: Introductionmentioning

confidence: 99%

Aconitum carmichaelii triggers neurotoxicity and Parkinson‐like symptoms through initiation of ROS‐mitochondrial apoptosis and the Nox5/DJ‐1 signaling pathway

Pang

Song

Miao

et al. 2023

BMEMat

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“…In the extraction and preparation process, prolonging high-temperature decoction time can promote the degradation of diester alkaloids into monoester alkaloids, reducing the toxicity and improving the efficacy of the drug ( Zhang et al, 2016 ). When patients experience toxic reactions induced by FZ, the blood concentrations of AC, MA, and HA can reach 0.031, 0.086, and 0.125 ng/mL ( Zhang et al, 2019 ), respectively, which are 0.6, 1.72, and 2.5 times the LLOQ of AC, MA, and HA obtained in this study, whereas the blood concentrations of the three diester alkaloids in this study were all lower than the LLOQ. Furthermore, the blood concentration of the monoester alkaloid, BMA, in FZ poisoning patients, reached 4.665 ng/mL, which is 11.4 times the C max of BMA in this study.…”

Section: Discussionmentioning

confidence: 99%

“…However, our study found that the phenylalanine level was significantly reduced in the 50 and 75 g treatment groups, which may characterize the safety of FQGBG in healthy individuals. AC poisoning also upregulates various amino and fatty acids ( Zhang et al, 2019 ). The abnormal peroxidation of polyunsaturated fatty acids such as arachidonic acid and its metabolites can damage the myocardial mitochondria, leading to cardiac arrhythmia ( Cai et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial

Cao,

Liu,

Sun

et al. 2024

Front. Pharmacol.

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Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation.Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method.Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed.Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism.Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

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“…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).…”

Section: How To Reduce the Toxicity Of Tcms?mentioning

confidence: 99%

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

Cai

Qiu²,

et al. 2019

BST

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For a long time, many people have believed that traditional Chinese medicines (TCMs) are safe because they derive from natural products. However, this belief has been greatly challenged in recent years especially after some reports on aristolochic acid involved in the genesis of cancer. According to the Chinese pharmacopoeia, many TCMs are known to be toxic, causing damage to the nervous, liver, renal, respiratory, and reproductive system. How to reduce the toxicity of TCMs and how to avoid abuse of TCMs in daily practice is the question? Here, we will give a brief summary and some tips on these issues. First, the accurate differentiation of a specific syndrome is the foundation of an effective and individualized treatment strategy, as well as the key to applying TCMs. Second, through standard processing, proper compatibility, rational decoction, and appropriate dose for TCMs, the harm of TCMs can be effectively avoided. Third, it should be remembered that Chinese herbs cannot be taken continuously as dietary supplements. Finally, Chinese patent medicines should be used with caution. In addition, the dosage of TCMs should not exceed the limit prescribed by the current China Pharmacopoeia, which will ensure the balance of efficacy and toxicity. Taken together, it is necessary to treat the toxicity and safety of TCMs with rationality. The more toxicity we can find, the more safety patients will have.

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Metabolomics of Clinical Poisoning by Aconitum Alkaloids Using Derivatization LC-MS

Cited by 8 publications

References 29 publications

Aconitum carmichaelii triggers neurotoxicity and Parkinson‐like symptoms through initiation of ROS‐mitochondrial apoptosis and the Nox5/DJ‐1 signaling pathway

Aconitum carmichaelii triggers neurotoxicity and Parkinson‐like symptoms through initiation of ROS‐mitochondrial apoptosis and the Nox5/DJ‐1 signaling pathway

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial

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

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