Aconitum japonicum, native to the mountainous regions of Japan, is a toxic perennial plant widely recognized for its therapeutic potential. Despite its pharmacological importance, the complete biosynthetic pathway of diterpene alkaloids, bioactive compounds with significant pharmaceutical implications and derived from Aconitum species, remains elusive. In this study, leveraging high-throughput metabolome and transcriptome analyses, we conducted a comprehensive investigation using four tissues of A. japonicum, including leaf, mother root, daughter root, and rootlet. By integrating these multi-omics datasets, we achieved a holistic insight into the gene expression patterns and metabolite profiles intricately linked with diterpene alkaloid biosynthesis. Our findings unveil potential regulatory networks and pinpoint key candidate genes pivotal in diterpene alkaloid synthesis. Through comparative analyses across tissues, we delineate tissue-specific variations in gene expression and metabolite accumulation, shedding light on the spatial regulation of these biosynthetic pathways within the plant. Furthermore, this study contributes to a deeper understanding of the molecular mechanisms dictating the production of diterpene alkaloids in A. japonicum. Besides advancing our knowledge of plant secondary metabolism in A. japonicum, this study also provides a high-quality multi-omics resource for future studies aimed at functionally characterizing the target genes involved in different metabolic processes.

The world of plant diversity is endlessly fascinating and essential for life on Earth. Since the inception of early civilization, humans have utilized plants for several purposes, particularly for their medicinal value. While some plants are known for their toxicity, they also contain beneficial phytochemicals that are important for both plants and humans, indicating their dual nature. This study aims to explore and synthesize the existing knowledge on various poisonous plant species found worldwide. It primarily focuses on the therapeutic potential of specific types of phytochemicals responsible for treating multiple diseases. This review includes a list of 70 poisonous plants with medicinal properties for treating various ailments, as well as some of their traditional uses. A few of these plants are emphasized, which have been tremendously explored and studied, hold significant potential to contribute to modern drug discovery. Furthermore, it addresses the possible prospects and challenges of using poisonous plants and their phytochemicals as therapeutic agents. Although the therapeutic potential of poisonous plants is substantial, many toxins remain unexplored. This review accentuates the need for rigorous scientific investigations, prior to clinical trials to validate their traditional uses, which would reveal the pharmacological interventions that will eventually advance human health and well-being.

Rheumatoid arthritis (RA), a highly disabling autoimmune disease, is characterized by joint damage and synovial hyperplasia. This paper was designed to explore the effect and mechanisms of Aconitum diphtheria on the proliferation and apoptosis of RA fibroblast-like synoviocytes (RA-FLS). First, RA-FLS was treated with different doses of A. diphtheria extracts. Then, an inverted biological microscope was adopted to observe the RA-FLS morphology. Subsequently, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining, Cell Counting Kit-8 and western blot were utilized to analyze the apoptosis, proliferation, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway-related proteins in RA-FLS, respectively. The experimental results disclosed that, after treatment of RA-FLS with A. diphtheria extracts, the cells became round and the intercellular space was increased. Besides, the RA-FLS proliferation was effectively inhibited by A. diphtheria extracts, while the apoptosis was promoted. Additionally, A. diphtheria extracts could effectively downregulate the expression levels of p-NF-κB (p50), NF-κB (p50), p-NF-κB (p65), and NF-κB (p65). Collectively, A. diphtheria can effectively inhibit RA-FLS proliferation and promote apoptosis in a dose-dependent manner. Similarly, A. diphtheria is able to downregulate p-NF-κB and NF-κB protein expression, but there is no dose-response relationship.

Alkaloids are naturally occurring compounds with complex structures found in natural plants. To further improve the understanding of plant alkaloids, this review focuses on the classification, toxicity and mechanisms of action, providing insight into the occurrence of alkaloid-poisoning events and guiding the safe use of alkaloids in food, supplements and clinical applications. Based on their chemical structure, alkaloids can be divided into organic amines, diterpenoids, pyridines, isoquinolines, indoles, pyrrolidines, steroids, imidazoles and purines. The mechanisms of toxicity of alkaloids, including neurotoxicity, hepatoxicity, nephrotoxicity, cardiotoxicity and cytotoxicity, have also been reviewed. Some cases of alkaloid poisoning have been introduced when used as food or clinically, including accidental food poisoning, excessive consumption, and poisoning caused by the improper use of alkaloids in a clinical setting, and the importance of safety evaluation was illustrated. This review summarizes the toxicity and mechanism of action of alkaloids and provides evidence for the need for the safe use of alkaloids in food, supplements and clinical applications.

Aconitine poisoning is highly prone to causing malignant arrhythmias. The elimination of aconitine from the body takes a considerable amount of time, and during this period, patients are at a significant risk of death due to malignant arrhythmias associated with aconitine poisoning.

A 30-year-old male patient was admitted due to accidental ingestion of aconitine-containing drugs. Upon arrival at the emergency department, the patient intermittently experienced malignant arrhythmias including ventricular tachycardia, ventricular fibrillation, ventricular premature beats, and cardiac arrest. Emergency interventions such as cardiopulmonary resuscitation and defibrillation were promptly administered. Additionally, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy was initiated. Successful resuscitation was achieved before ECMO placement, but upon initiation of ECMO, the patient experienced recurrent malignant arrhythmias. ECMO was utilized to maintain hemodynamics and respiration, while continuous blood purification therapy for toxin clearance, mechanical ventilation, and hypothermic brain protection therapy were concurrently administered. On the third day of VA-ECMO support, the patient's respiratory and hemodynamic status stabilized, with only frequent ventricular premature beats observed on electrocardiographic monitoring, and echocardiography indicated recovery of cardiac contractile function. On the fourth day, a significant reduction in toxin levels was observed, along with stable hemodynamic and respiratory functions. Following a successful pump-controlled retrograde trial occlusion test, ECMO assistance was terminated. The patient gradually improved postoperatively and achieved recovery. He was discharged 11 days later.

VA-ECMO can serve as a bridging resuscitation technique for patients with reversible malignant arrhythmias.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and, in its advanced stages, has a 5-year survival rate of only 3% to 5%. Despite novel mechanisms and treatments being uncovered over the past few years, effective strategies for HCC are currently limited. Previous studies have proven that aconite can suppress tumor growth and progression and prevent the recurrence and metastasis of multiple cancers, but the underlying molecular mechanisms are largely unknown. In this study, different doses of aconite were applied to mice bearing subcutaneous HCC tumors. It was found that aconite had a therapeutic effect on H22 tumor-bearing mice in a dose-dependent manner by reducing tumor volumes and prolonging survival times, which could be attributed to the immunoregulatory effect of aconite. Furthermore, results showed that high-dose administration of aconite could enhance adaptive immunity and natural killer (NK) cell-mediated immunity by regulating the secretion of interferon-γ, upregulating T cells and NK cells, and modulating the expression of the NK cytotoxicity biomarker CD107a and the inhibitory receptor TIGIT. This study revealed a novel mechanism through which aconite exerts antitumor effects, not merely through apoptosis induction pathways, providing more sound evidence that aconite has the potential to be developed into an effective anti-HCC agent.

Aconiti Radix (Chuanwu [CW]), is widely used for the treatment of the chronic and intractable diseases due to its remarkable curative effect. CW has been combined with honey for thousands of years to reduce toxicity and enhance efficacy. This study first clarified compatibility mechanism of CW co-used with honey using a comparative pharmacokinetic idea. We developed and validated a simple, sensitive, specific, and accurate UHPLC-MS/MS method to simultaneously determine five Aconitum alkaloids in rat plasma after oral administration of CW decoction and CW-honey concentrated solution. Pharmacokinetic parameters were significantly different between the two groups (P<0.01 and P<0.05). Compared with CW group, C_max and AUC_0→t were decreased in CW-honey group for three diester-diterpenoid alkaloids (hypaconitine, mesaconitine and aconitine); T_max and T_1/2 were prolonged. However, C_max and AUC_0→t were increased in CW-honey group for two monoester-diterpenoid alkaloids (benzoylaconine and benzoylmesaconine); T_max was shortened; T_1/2 was prolonged. These findings suggest that honey affected the pharmacokinetic behaviors of five Aconitum alkaloids. We speculate that the detoxification and synergism of honey might result from reducing the toxicity of diester-diterpenoid alkaloids and promoting the biological activity of monoester-diterpenoid alkaloids in vivo. This study provides a theoretical basis for the clinical use of CW combined with honey.

Background: Sepsis has high mortality and is responsible for significant healthcare costs. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for sepsis. Therefore, this study assessed and ranked the effectiveness of CHIs to provide more sights for the selection of sepsis treatment. Method: Eight databases were searched from their inception up to September 1, 2021. The methodological quality of included study was evaluated by the Revised Cochrane risk-of-bias tool for randomized trials. Then Bayesian network meta-analysis was performed by OpenBUGS 3.2.3 and STATA 14.0 software. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Publication bias was reflected by a funnel plot. Results: A total of 50 eligible randomized controlled trials involving 3,394 participants were identified for this analysis. Five CHIs including Shenfu injection, Shenmai injection, Shengmai injection, Shenqifuzheng injection, and Huangqi injection were included. The results of the NMA and sensitivity analysis showed that Shenqifuzheng (MD = -4.48, 95% CI = -5.59 to -3.24), Shenmai (MD = -3.38, 95% CI = -4.38 to -2.39), Shenfu (MD = -2.38, 95% CI = -3.03 to -1.70) and Shengmai (MD = -1.90, 95% CI = -3.47 to -0.31) combined with Western medicine (WM) had a superior effect in improving the APACHE II score. Based on SUCRA values, Shenqifuzheng injection (95.65%) ranked highest in the APACHE II score, followed by Shenmai (74%), Shenfu (47.1%), Shengmai (35.3%) and Huangqi injection (33.2%). Among the secondary outcomes, Shenmai injection was the most favorable intervention in reducing PCT and CRP levels, and Shenqifuzheng injection was the second favorable intervention in reducing CRP level. Shenfu injection combined with WM was more effective than the other treatments in decreasing the serum IL-6 and TNF-α levels and lowering the 28-days mortality. Regarding the improvement of immune function, Shenqifuzheng injections had obvious advantages. Conclusion: In conclusion, Shenqifuzheng injection was the optimum treatment regimen to improve APACHE II score, reduce CRP level, and regulate immune function. Shenfu injection was superior in reducing the expression of inflammatory factors and decreasing 28-days mortality. Nevertheless, more multicenter, diverse, and direct comparisons randomized controlled trials are needed to further confirm the results. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=254531, identifier CRD42021254531.

Heart failure (HF) is one of the main public health problems at present. Although some breakthroughs have been made in the treatment of HF, the mortality rate remains very high. However, we should also pay attention to improving the quality of life of patients with HF. Traditional Chinese medicine (TCM) has a long history of being used to treat HF. To demonstrate the clinical effects and mechanisms of TCM, we searched published clinical trial studies and basic studies. The search results showed that adjuvant therapy with TCM might benefit patients with HF, and its mechanism may be related to microvascular circulation, myocardial energy metabolism, oxidative stress, and inflammation.

Higenamine is a β2 agonist of plant origin. The compound has been included in WADA's prohibited list since 2017. Higenamine may be detected in different plants and many food supplements of natural origin.

Our literature search was conducted through PubMed, Science Direct, Google Scholar, and Web of Science studies investigating the presence of higenamine in plants that are used in traditional folk medicine or included in food supplements. Our study aimed to assess the risk of adverse analytical findings caused by higenamine-containing plants.

Based on our literature search, Nelumbo nucifera, Tinospora crispa, Nandina domestica, Gnetum parvifolium, Asarum siebodii,Asarum heterotropoides, Aconitum carmichaelii, and Aristolochia brasiliensis are higenamine-containing plants. Based on data from Eastern folk medicine, these plants can provide numerous health benefits. Professional athletes likely ingest these plants without knowing that they contain higenamine; these herbs are used in treatments for different conditions and various foods/food supplements in addition to folk medicine.

Athletes and their teams must be aware of the issues associated with the use of plant-based products. They should avoid consuming higenamine-containing plants during and outside of competition periods.