Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation:A case report

BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular arrhythmias.We describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and vasopressors.Nine hours after arrival,an electrocardiogram revealed a return to sinus rhythm.The patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,respectively.On hospital day 15,he was transferred to a psychiatric hospital.The other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the root.Serum on admission contained 1.50 ng/mL of aconitine.Beyond hospital day 2,neither were detected.Urine on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day 3.CONCLUSION The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

Recurrent ventricular arrhythmia due to aconite intoxication successfully treated with landiolol:A case report

BACKGROUND Ventricular arrhythmias,such as ventricular tachycardia and fibrillation,are the main causes of death in patients with aconite poisoning.CASE SUMMARY A 51-year-old man presented to our emergency department because he was vomiting after ingesting aconite root to attempt suicide.On arrival,the patient was hemodynamically unstable,and his electrocardiogram revealed polymorphic ventricular extrasystoles and non-sustained ventricular tachycardia.Amiodarone was immediately administered for ventricular arrhythmia.However,the patient remained unresponsive.We administered continuous intravenous landiolol as the ventricular arrhythmia worsened,gradually suppressing it.The patient returned to sinus rhythm 16 h after arriving at the hospital.Some aconitum alkaloids act on voltage-gated Na+-channels and induce ventricular or supraventricular tachyarrhythmias.Landiolol suppresses sympathetic nerve activity through its blocking effect,preventing arrhythmia.CONCLUSION Landiolol can be a therapeutic option for amiodarone-refractory ventricular arrhythmias caused by aconite intoxication.

Effects of ephedra asarum aconite decoction on Th1/Th2 balance in two animal models of allergic rhinitis

Objective:Ephedra asarum aconite decoction is used in the clinical treatment of allergic rhinitis.We investigated the effects of ephedra asarum aconite decoction on Th1/Th2 balance in two animal models of allergic rhinitis and in activated T cells in vitro.Methods:Animal models of simple and compound kidney yang deficiency types of allergic rhinitis were treated with ephedra asarum aconite decoction to observe the efficacy of this traditional Chinese medicine formula on allergic symptoms,serum cytokines,and tissue RNA levels.We also cultured and activated T cells from the mouse.After treatment with ephedra asarum aconite decoction,we tested the proliferation and differentiation of T cells.Results:Ephedra asarum aconite decoction relieved allergy symptoms in both types of animal models,and was more effective in the compound kidney yang deficiency model In addition to its anti-allergic efficacy,ephedra asarum aconite decoction significantly improved the health status of animals in the compound kidney yang deficiency groups,significantly made their bodyweight rising up,and significantly increased the T-bet mRNA/GATA-3 mRNA ratio.Moreover,ephedra asarum aconite decoction promoted the proliferation of activated T cells and inhibited the differentiation to Th2 cells in vitro.Conclusions:Ephedra asarum aconite decoction regulates the balance of Th1/Th2 to ameliorate allergic conditions.

Aconite Poisoning with Good Outcome, Case Study and Literature Review

Aconite poisoning has been reported in previously published literature and case reports. It may occur due to accidental consumption of aconite tubers or when it is used in medicinal preparations. In this case report we describe a case of aconite poisoning in a primary case of anxiety disorder, after use of herbal medicine. He gave history of consumption of herbal remedy with honey from folk medicine with unknown content. Our patient presented with symptoms of vomiting, diarrhea, numbness and dizziness that are common symptoms of aconite poisoning. The management was mainly supportive care depending on the symptoms. Our patient recovered after 30 hours, probably due to slow elimination of the metabolites overtime. Our case represents one case where poisoning was not due to wrong consumption but due to drug-drug interaction. It is important that physicians should take drug interactions into consideration while prescribing drugs and also educate patients regarding the same.

Energy pharmacology of aconite(Radix aconiti lateralis reparata)

Objective:To study the energy pharmacology of aconite(Radix aconiti lateralis reparata).Methods:Literature induction method was applied to study the energy properties,energy pharmacological connotation,and energy pharmacological effects of aconite(Radix aconiti lateralis reparata).Results:The warm and hot properties of aconite(Radix aconiti lateralis reparata)are exactly its energy properties.The energy pharmacology of aconite(Radix aconiti lateralis reparata)is based on its energy properties,which is different from the modern aconite(Radix aconiti lateralis reparata)pharmacology that is based on the chemical composition of aconite(Radix aconiti lateralis reparata).In addition,the energy pharmacology of aconite(Radix aconiti lateralis reparata)includes not only the traditional energy pharmacology but also the modern energy pharmacology of aconite(Radix aconiti lateralis reparata).The traditional energy pharmacology of aconite(Radix aconiti lateralis reparata)is mainly manifested as the energy effect of aconite(Radix aconiti lateralis reparata)at the whole-body level,warm yang and dissipate cold,whereas the modern energy pharmacology of aconite(Radix aconiti lateralis reparata)is manifested as the physiological and pathological energy effect of warm and thermal energy properties of aconite(Radix aconiti lateralis reparata)at the tissue,cellular,and molecular levels of the body,mainly strengthening the heart,protecting cardiac muscles,dilating blood vessels,and having anti-arrhythmia,anti-shock,anti-inflammatory,analgesic,and antineoplastic effects.The traditional energy pharmacology and modern energy pharmacology of aconite(Radix aconiti lateralis reparata)constitute the basic connotation of aconite(Radix aconiti lateralis reparata)energy pharmacology.For the aconite(Radix aconiti lateralis reparata)energy pharmacology,there is a substantial foundation,its chemical components such as alkaloids.In addition,the toxicity of aconite(Radix aconiti lateralis reparata)is a manifestation of its energy pharmacology.Conclusion:aconite(Radix aconiti lateralis reparata)has energy properties that have substantial foundation.The energy pharmacology of aconite(Radix aconiti lateralis reparata)is based on its high energy and hot properties and includes the traditional energy pharmacology and modern energy pharmacology of aconite(Radix aconiti lateralis reparata).

Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration

Objective:Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer;however,its exact molecular mechanisms in this process remain unclear.This study explores how aconite aqueous extract(AAE)inhibits hepatocellular carcinoma(HCC).Methods:An in vivo mouse model of subcutaneous liver cancer was established.After AAE treatment,immunohistochemistry(IHC)was used to determine the effect of AAE on natural killer(NK)cells.Subsequently,C57BL/6 mice were used to establish the subcutaneous tumor model,and a group of these mice were treated with anti-PK163 antibody to remove NK cells,which was verified by flow cytometry and IHC.The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8.The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay.The effect of AAE on the migration of NK cells was determined using a transwell assay.Finally,the molecular mechanism was investigated using the Western blotting method.Results:We demonstrated that the ability of AAE to induce overexpression of the cytokine C–C motif chemokine ligand 2(CCL2)in HCC cells is fundamental to the infiltration of NK cells into the tumor bed.Mechanistically,we found that the upregulation of CCL2 was achieved by the activation of c-Jun Nterminal kinase but not extracellular regulated protein kinase or p38.Conclusion:Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors,which could help to improve the efficacy of HCC treatments.

Establishment of one-step approach to detoxification of hypertoxic aconite based on the evaluation of alkaloids contents and quality

Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.

Traditional Chinese herbal medicine Astragalus Radix and its effects on intestinal absorption of aconite alkaloids in rats

Objective:Astragalus Radix(AR,Huangqi in Chinese) has been widely used as a qi(energy) restoring herb that is thought to act through reinvigorating the spleen and lung.Aconite is used to rebalance the body temperature during illness and played an irreplaceable role in disease control since ancient times,but it is limited by its strong neuro and cardiotoxicity.Since the Song Dynasty(1227),the two herbs have been commonly used as herbal pairs including in the famous Qifu Decotion,from the "Wei's Family Prescription".However,many ancient texts also record that they are not compatible using together,suggesting they can have negative outcomes when mixed.This study investigated whether Astragali Radix had either positive or negative effects on absorption of six different active alkaloids derived from aconite.Methods:Single intestinal perfusion model was used to study the effects of Astragali Radix on aconite alkaloids absorption.Response of ABC transporters and distribution of three tight junction proteins on the surface of intestinal enothelium were assessed by Reverse Transcription-Polymerase Chain Reaction(RT-PCR),Western blot and immunofluorescence microscopy,respectively.Results:The results showed that aconite alkaloids absorption could be inhibited,and different concentrations of Astragali Radix considerably increased the expression levels of the ABC transporters and tight junction proteins with Astragali Radix treatment.Conclusion:These results suggest that Astragali Radix can block absorption of aconite alkaloids through the upregulation expression of ATP-binding cassette transporters(ABC transporters) and tight junction proteins.It demonstrates that co-administration of Astragali Radix with other drugs might change the absorption profile of the second drug which is important to know in clinic therapy.

Understanding Poison:Study of a Word Du from the Perspective of Comparative History

This article investigates the word Du(毒)in premodern Chinese medicine and culture.It highlights the paradoxical meaning of the word that served as a foundation for the therapeutic use of poisons in traditional Chinese medicine.The article then situates the study in a comparative framework.By comparing the Chinese notion of Du with the Greek concept of pharmakon,it demonstrates significant similarities on the medical use of poisons in the two cultures.It further identifies a striking difference:While the European pharmacy started to separate poisons from medicines in the medieval era,poisons remained an integral part of healing repertoire throughout imperial China.The article ends with offering some cultural explanations for this divergence,and more broadly,a distinct worldview as revealed by the intimate relationship between poisons and medicines in traditional Chinese pharmacy.

Factorial study of moxibustion in treatment of diarrhea-predominant irritable bowel syndrome

AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome (D-IBS).

Clinical application of Aconitum carmichaelii Debx. (Fu Zi in Chinese) by traditional Chinese medicine physicians–A cross-sectional questionnaire survey in Beijing

Objective:To investigate clinical application of aconite root(Aconitum carmichaelii Debx.;hereinafter“aconite”)by traditional Chinese medicine(TCM)physicians in TCM hospitals in Beijing and explore the specific use of aconite and the effect of different doses on decoction time.Methods:This was a cross-sectional study using two-stage sampling.Questionnaires were administered among TCM physicians from TCM hospitals in Beijing between September 2020 and August 2021.The questionnaire mainly included general demographics,clinical backgrounds of TCM physicians,and clinical application of aconite.The data analyses were performed using SPSS 20.0.Results:A total of 387 questionnaires were collected,of which 385 were valid.Of the 385 participating TCM physicians,331(85.97%)used aconite in clinical practice.The top three medical diagnoses treated with aconite were heart failure,diarrhea without cause,and chronic gastritis.The TCM pattern treated most frequently with a high dose of aconite was spleen-kidney yang deficiency,and the TCM pattern treated most frequently with a low dose was spleen yang deficiency,while spleen-kidney yang deficiency was treated most frequently with a common dose of aconite.The top three common formulas were Sini decoction,Mahuang Xixin Fuzi decoction,and Zhenwu decoction.Hei Shun Pian was the most common herbal pieces of aconite.The highest frequency of the maximum dose of aconite was 15 g,that of the minimum dose was 3 g,and that of the common dose was 10 g.There was a certain correlation between decoction time and the dose of aconite.Most TCM physicians advised their patients to take medicine twice a day.Conclusion:In this study,we refined and quantified the use of aconite and enriched the exploration of the clinical application of aconite besides its provisions in the Pharmacopoeia of the People's Republic of China.

Mitochondrial ACOD1/IRG1 in infection and sterile inflammation

Immunometabolism is a dynamic process involving the interplay of metabolism and immune response in health and diseases.Increasing evidence suggests that impaired immunometabolism contributes to infectious and inflammatory diseases.In particular,the mitochondrial enzyme aconitate decarboxylase 1(ACOD1,best known as immunoresponsive gene 1[IRG1])is upregulated under various inflammatory conditions and serves as a pivotal regulator of immunometabolism involved in itaconate production,macrophage polarization,inflammasome activation,and oxidative stress.Consequently,the activation of the ACOD1 pathway is implicated in regulating the pathogenic process of sepsis and septic shock,which are part of a clinical syndrome of life-threatening organ failure caused by a dysregulated host response to pathogen infection.In this review,we discuss the latest research advances in ACOD1 expression and function,with particular attention to how the ACOD1-itaconate pathway affects infection and sterile inflammation diseases.These new insights may give us a deeper understanding of the role of immunometabolism in innate immunity.