The literature was searched using the “combination of subject words + free words” search principle, and a parallel search of Chinese and English literature was conducted. We used the subject words to identify core research on the toxicology and pharmacology of aconite and the free words to expand related terms (e.g., “concocting to reduce toxicity” and “compounding to reduce toxicity”), while also considering both traditional medical records and current research advancements.

The databases, which included PubMed, Web of Science, CNKI, Wanfang Data, Chinese Pharmacopoeia 2025 Edition, and others, were divided into Chinese databases, English databases, and books.

Although the majority of the cited material was centered between 2017 and 2025, the reference publication dates ranged from 1990 to 2025. Early published literature was searched because the classical theory, the conventional concoction method, etc., are the main subjects of some early research, and have some reference value.

The following keywords were searched: “pharmacological effects,” “toxicological effects,” “compounding to reduce toxicity,” “concocting to minimize toxicity,” “aconite,” and some related terms like “Fuzi.”

In Chinese medicine theory, heart failure is attributed to “qi deficiency and yang deficiency,” and aconite, as a TCM that benefits yang, replenishes qi, and restores yang, is still widely used in modern clinical practice for cardiovascular diseases, such as heart failure, with a recommended clinical dosage of 1.5–3 g (Chan et al., 1994; Chan, 2009; Xing et al., 2023). The cardiotonic activity of aconite is mainly attributed to its chemical constituents, including alkaloids, such as demethyl coclaurine and aconitine; glycosides, such as cardiac glycosides; aconite glycosides, and the polysaccharide fraction (Xu et al., 2021; Wang Q. et al., 2023). The mechanism by which aconite exerts its cardiotonic effects can be summarized into the following aspects: (1) Disrupts ion concentrations within myocardial cells: Myocardial cells contain various ions and their corresponding enzymes, which affect cardiac contraction and relaxation. Water-soluble alkaloids increase intracellular Na⁺ concentrations by activating voltage-gated sodium channels, which, in turn, activate the Na⁺/Ca²⁺ exchanger retrograde transport mode and promote Ca²⁺ inward flow to enhance myocardial contractility, while inhibiting calcium-ion overload and apoptosis by regulating Na⁺/K⁺-ATPase activity. In vitro investigations showed that the water-soluble alkaloids of aconite at concentrations of 0.02 and 0.04 g/L could decrease the activity of Na⁺-K⁺-ATPase while increasing the activity of Ca²⁺-Mg²⁺-ATPase and Ca²⁺-ATPase on the cell membrane. The myocardial cells of the heart failure model in the treated groups (water-soluble alkaloids) showed noticeably improved cell viability and beating after 1.5 h. When aconitine, an aconite alkaloid, acts on potassium ion channels, it inhibits potassium ion efflux, prolongs the duration of the action potential, and enhances myocardial contractility (He et al., 2014; Xu et al., 2021; Zhou W. et al., 2021). (2) Acts on cardiac receptors: Aconite produces a positive inotropic action by exciting adrenergic receptors, including cardiac β1 and α receptors. The heart rate, cardiac output, and myocardial contractility of rats were all markedly elevated by a 30 g/kg dose of diluted aconite alcohol extract. Additionally, cardiac cell damage was decreased, and the TCM had a cardiotonic impact by inhibiting the overexpression of cytokines, such as nitric oxide (NO), tumor necrosis factor (TNF-α), and serum interleukin-6 (IL-6) (Zhao et al., 2012; Xing et al., 2022; Yang Y. et al., 2022). (3) Interferes with signaling pathways: The active ingredients in aconite can also regulate related proteins and signaling pathways, such as modulating apoptosis-associated proteins, protecting myocardial cells, and inhibiting cell apoptosis. Animal experimental results demonstrated that aconite decoction administered at doses of 5 g/kg, 2.5 g/kg, and 1.25 g/kg could significantly upregulate the PI3K/Akt signaling pathway (Wang et al., 2019; Liu et al., 2025).

The polysaccharide fraction of aconite also shows significant pharmacological activity in improving cardiac function, which can scavenge reactive oxygen species (ROS) and reduce mitochondrial damage, thus slowing cardiomyocyte apoptosis and minimizing cardiomyocyte damage. It also regulates the autonomic nervous system, enhances sympathetic nerve activity, and produces positive inotropic effects to further enhance myocardial contractility (Zhang J. et al., 2022).

Aconite has remarkable anti-inflammatory and immunomodulatory activity, which is mainly mediated by its diverse chemical components, especially the fat-soluble alkaloids. The anti-inflammatory mechanism of aconite (Aconitum tanguticum (Maxim.) Stapf, a related species of Aconitum carmichaelii Debx.) is primarily related to effects to inhibit pro-inflammatory signaling pathways and reduce cytokine release, such as alleviating inflammatory damage by blocking the nuclear factor (NF)-κB and MAPK signaling pathways and acting on macrophages (Ye et al., 2021; Ye et al., 2023). Among them, the mechanisms involving alkaloids primarily encompass the following aspects: (1) Benzoylaconine (BAC) exerts its effects by inhibiting the expression of Toll-like receptor 4 (TLR-4), reducing the phosphorylation of upstream TAK1, and subsequently blocking the activation of downstream NF-κB and MAPK pathways. For example, in cell experiments, RAW 264.7 macrophages activated by lipopolysaccharide (LPS) were treated with BAC at concentrations of 1 μM, 10 μM, and 100 μM. At all three concentrations, BAC inhibited the production of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) and inflammatory mediators (NO), while downregulating the expression of iNOS and COX-2, thereby exerting anti-inflammatory effects (Zhou C. et al., 2021). (2) In contrast, the water-soluble component demethyl coclaurine exerts its effects by inhibiting the NF-κB pathway and activating the Nrf2/HO-1 signaling axis. For example, when 0.5 μmol/L of demethyl Lindera aggregata alkaloid was applied to BV2 cells under inflammatory conditions (LPS activation) for 1 day, it significantly downregulated the expression of inflammatory markers, such as TNF-α, IL-6, NO, and prostaglandin E2 (Yang et al., 2020; Xu et al., 2021). (3) Aconite can also exert anti-inflammatory effects by downregulating costimulatory molecules, such as CD80, to inhibit dendritic cell maturation, while balancing Th1/Th2 differentiation and blocking the inflammatory cascade response. At a concentration of 2 mg/mL, formulations containing Aconitum carmichaelii significantly decreased the overexpression of IL-1β, IL-12, interferon (IFN)-γ, and IL-6 (Ji et al., 2017).

In addition to alkaloids, the polysaccharide fraction of aconite also plays a key role in immune regulation, with effects characterized by low toxicity and mild bioactivity. Its immune regulatory effects are manifested in multiple aspects: (1) Studies have shown that the polysaccharide fraction of aconite can enhance the organ coefficients of the spleen and thymus, promote the proliferation of splenic lymphocytes and abdominal macrophages, and increase the serum concentrations of NO and IFN-γ in mice. (2) The polysaccharides in Heshun tablets can antagonize cyclophosphamide-induced immunosuppression by activating immune effector cells, such as macrophages, and regulate immune homeostasis through both intrinsic and adaptive immunity. The polysaccharide fraction of aconite extract can also inhibit the differentiation of macrophages to pro-inflammatory phenotypes and alleviate excessive inflammatory responses (Hu Q. et al., 2023; Li et al., 2023). (3) Aconite polysaccharides can also improve immune function by regulating the composition of intestinal flora, elevating short-chain fatty acid levels and reversing decreases in the immune organ index and the abnormal expression of inflammatory factors in immunosuppressed mice (Ran T. et al., 2023).

In the basic theory of TCM, the pathogenesis of cancer can be summarized as “deficiency of yang qi, deficiency of the positive and the negative, and deficiency of the basic and the standard.” Aconite, as a representative herb for warming the yang and dispersing the cold, with its unique mechanism of “supporting the positive and consolidating the basic and warming the yang qi,” has demonstrated important value as an adjuvant treatment for tumors (He et al., 2024). Pharmacological studies have shown that the antitumor effects of aconite itself and its compound preparations are related to the alkaloidal components it contains and work well. Its anticancer mechanisms primarily include regulating signaling pathways, activating pro-apoptotic factors, modulating gene-protein pathways, and enhancing immune functions. These effects are achieved through the following four dimensions: (1) Diester alkaloids from aconite can inhibit tumor cell proliferation by regulating multiple signaling pathways and suppressing the expression of cell cycle-related proteins. For example, in melanoma, aconitine exerts antitumor effects by downregulating the MAPK/ERK1/2 and PI3K/AKT signaling pathways, thereby reducing the expression of the cell cycle-related protein proliferating cell nuclear antigen. Additionally, when liver cancer cells were treated with aconitine at concentrations below 20 μg/mL, alkaloids significantly inhibited the activation of the P38/ MAPK signaling pathway, thereby suppressing liver cancer cell proliferation (Du et al., 2013; Xiong et al., 2018; Gao Y. B. et al., 2022; Zhang W. et al., 2022). (2) The various alkaloids in aconite also exhibit varying degrees of regulatory effects on pro-apoptotic factors, manifested as inducing cancer cell apoptosis, reducing tumor volume, activating the mitochondrial-dependent apoptotic pathway, and exerting antitumor effects by enhancing autophagy. For example, aconitine at concentrations of 15–60 μM can significantly upregulate the pro-apoptotic factor Bax, inhibit the proliferation of pancreatic carcinoma cells, and induce apoptosis. In animal experiments, a dose of 100 mg/kg of aconitine significantly suppressed tumor growth and induced apoptosis (Ji et al., 2016; Zhang W. et al., 2022). (3) Network pharmacological studies have shown that the antitumor effects of aconite are also related to its regulation of the adenosine phosphorylase gene and related protein pathways (Lu et al., 2021). (4) Aconite water extract can also serve as an immune adjuvant by activating c-Jun N-terminal kinase to enhance the infiltration level of natural killer cells, thereby strengthening immune function and achieving antitumor effects (Yang et al., 2023).

In addition to alkaloids, phenolic compounds and the polysaccharide fraction in aconite also exhibit significant antitumor activity. Their mechanism of action involves upregulating the expression levels of pro-apoptotic proteins, such as Bax, regulating apoptotic pathways, mediating the process of apoptosis in tumor cells, inhibiting the abnormal proliferation of tumor cells, and blocking the key pathway of tumor angiogenesis (Zhang W. et al., 2022).

Pharmacological studies have confirmed that the alkaloids contained in aconite are of great value in treating mild-to-moderate pain, such as neuropathic pain, osteoarthralgia, and cancer pain, by modulating the nerve conduction pathway and inhibiting the release of inflammatory mediators (Luo et al., 2020; Li L. et al., 2022). In four classic mouse pain models, the hot plate model, the acetic acid-induced writhing phantom model, and the administration of aconitine at concentrations of 0.3 mg/kg and 0.9 mg/kg demonstrated significant antinociceptive activity, exhibiting marked therapeutic effects on acute thermal stimulation pain, visceral pain, and inflammatory pain (Deng et al., 2021). The mechanism of its analgesic effect can be summarized into the following aspects: (1) Overall analgesic mechanism: Diterpenoid alkaloids of aconite (Aconitum nagarum Stapf, a related species of Aconitum carmichaelii Debx.), as the central components of the analgesic mechanism, act mainly through a voltage-gated sodium channel blockade mechanism (Hu J. et al., 2023; Zhang W. et al., 2024). (2) Central analgesic mechanism: Aconite can activate spinal microglial cells and stimulate β-adrenergic receptors to exert analgesic effects. A microinjection (5–100 ng/rat) of Aconitum carmichaelii alkaloids into specific intracranial nuclei increased central norepinephrine levels within 30 min of administration, and accelerated norepinephrine turnover rates in the brainstem and spinal cord (Sun et al., 2020; Li S. L. et al., 2022). (3) Peripheral analgesic mechanism: Aconitine acts directly on dorsal root ganglion neurons in the non-central nervous system to reduce the generation and conduction of pain. The active component neoline extracted from the processed aconitum polysaccharide fraction was reported to significantly inhibit peripheral neural pain, such as cold sensation, pain sensation, and mechanical pain, in mice when subcutaneously injected at a concentration of 10 mg/kg for 4 days (Suzuki et al., 2016; Xu et al., 2021). In addition, analgesic effects are also achieved by activating the G protein/PI3K/PIP2 signaling pathway and shutting down TRPV1 channels (Xiao et al., 2019; Xu et al., 2021; Gao Y. B. et al., 2022).

In addition to the aforementioned pharmacological activities, aconite also exhibits various biological activities, such as antioxidant, hypoglycemic, and anti-arrhythmia effects. Research on the active components and their mechanisms of action provides experimental evidence for expanding clinical applications.

The cardiotoxicity of aconite (Aconitum leucostomum Worosch, a related species of Aconitum carmichaelii Debx.) possesses the most prominent toxicological characteristic, with the primary toxic components being diester C19-diterpenoid alkaloids. In vitro toxicity experiments in the rat H9c2 cardiomyocyte cell line showed a half-maximal inhibitory concentration (IC50) of aconitine of 562.06 μg/mL and significant dose-dependency. Other C19-type alkaloid components, such as delvestidine and anthranoyllycoctonine, exhibited markedly higher toxicity compared to aconitine (Nie et al., 2017). The mechanisms of cardiotoxicity induced by aconite can be roughly summarized as follows: (1) Electrophysiological mechanisms: Aconitine triggers persistent sodium inward flow by inhibiting the inactivation of cardiomyocyte voltage-gated sodium channels (Nav1.5), leading to the abnormal depolarization of cardiomyocyte membrane potentials (Coulson et al., 2017; Zhang X. C. et al., 2020). (2) Calcium homeostasis mechanism: The sustained opening of Na⁺ channels leads to the persistent opening of L-type calcium channels, thereby further triggering intracellular Ca²⁺ homeostasis imbalance manifested as tachyarrhythmia. Animal experiments demonstrated that 1 μmol/L Aconitum carmichaelii alkaloid promoted Ca²⁺ influx in rats, while 5 and 10 μmol/L induced ventricular arrhythmia in rat cardiomyocytes (Zhou et al., 2013; Jiang et al., 2021). (3) Molecular targets: Mechanistic studies have demonstrated that alkaloids from Aconitum carmichaelii disrupt myocardial calcium signaling and electrophysiological balance, ultimately inducing arrhythmia through pathways including interfering with sarcoplasmic reticulum ryanodine receptor (RyR2) function, upregulating RyR₂ expression, enhancing sarcoplasmic reticulum calcium release, and inhibiting L-type calcium channels (Fu et al., 2008; Chen R. C. et al., 2013). (4) Mitochondrial dysfunction: Mitochondrial dysfunction plays a significant role in the cardiotoxicity of Aconitum carmichaelii alkaloids. These alkaloids can induce mitochondrial oxidative stress and impair ATP synthesis, mediating cardiomyocyte apoptosis and lipid peroxidation. H9c2 cardiomyocytes treated with 25 g/L of aconite water extract for 1 day showed increased mitochondrial ROS levels, decreased mitochondrial membrane potential, and evident mitochondrial damage (Zhao et al., 2015; Jiang et al., 2021). (5) Clinical manifestations: In clinical practice, aconite poisoning often presents as multiple coexisting features caused by intersecting mechanisms. Symptoms can manifest in as little as 10 min and include palpitation, chest distress, tachycardia, and, in severe cases, the effects may even progress to heart failure (Lin et al., 2004; Sun et al., 2018; Hao et al., 2020).

Although the heart is the main target organ of aconite toxicity, its hepatotoxic effects have gradually attracted academic attention. Toxicokinetic analysis revealed that the active ingredient of aconite showed multi-organ distribution after absorption, in which the concentration of liver tissue distribution was significantly higher than that of other organs (Hao et al., 2020). Hepatotoxicity can be identified by the following: (1) Animal toxicology experiments: Male Wistar rats were continuously gavaged with the water extract of Hei shunpian (HSP, processed aconite root) for 20 days. Serum transaminase levels were significantly elevated in both the low- dose HSP group (20 g/kg) and the high-dose HSP group (40 g/kg), with an accumulation of lipid peroxidation products in liver tissues (Zhang K. et al., 2020). (2) Histopathological observation: Mesaconine can cause histopathological changes in rat liver tissue at specific dose thresholds. After a single oral mesaconine gavage dose of 10 mL/kg to Sprague-Dawley (SD) rats, followed by 4 h of fasting and continuous observation for 2 weeks, the liver of rats in each administration group exhibited fatty vacuoles or degeneration, along with hepatocyte necrosis (Chen et al., 2023). (3) Molecular mechanisms: The regulation of targets, such as RAC-alpha serine/ threonine-protein kinase 1 (AKT1), interleukin-2 (IL2), coagulation factor II (F2, also known as prothrombin), glutathione reductase (GSR), and epidermal growth factor receptor (EGFR), affects pathways including T-helper 17 cell (Th17 cell) differentiation, the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling pathway, and glutathione metabolism, inducing oxidative stress, metabolic disorders, cell apoptosis, immune responses, and the excessive release of inflammatory factors, ultimately leading to liver injury. HepG2 cells treated with aconitine demonstrated that the uptake of multiple diester- type alkaloids may rely on organic cation/proton antiport transporters, thereby achieving distribution in the liver (Cong et al., 2019; Zhang K. et al., 2020).

(1) Clinical and pathological characteristics: The acute toxicity of aconite is characterized by multi-organ dysfunction syndrome, with clinical symptoms including behavioral inhibition (idleness and prone stillness), gastrointestinal reactions (nausea), motor nerve disorders (limb paralysis), and central nervous system excitation-inhibition imbalance (paroxysmal muscle tonus and convulsions), with significant dose-dependent pathological changes. In an aconitine toxicity experiment in SD rats, the low-dose administration groups (1.00 and 2.15 mg/kg) exhibited toxic characteristic responses, such as lethargy and spasms, within 1 day, but returned to normal after 1 day. In contrast, the medium- and high-dose administration groups (4.64 and 10.0 mg/kg) showed toxic characteristics within 2 h and died successively within 4 h (Li et al., 2013; Chen et al., 2023). (2) Core toxicological mechanisms: Aconitine inhibits voltage-gated sodium channel inactivation, triggering the persistent sodium current-mediated depolarization of neuronal and myocardial cell membrane potentials, leading to fatal ventricular arrhythmia. This mechanism can also induce a series of toxic reactions, such as neuromuscular transmission blockade (reduced acetylcholine release). One patient ingested approximately 120 g of steamed aconite slices and developed palpitations and generalized numbness within 1 h, subsequently falling into a coma. Additionally, three patients died from severe systemic damage after consuming over 50 g of aconite (Yang X. et al., 2017; Chen et al., 2023). (3) Factors affecting toxicity: It is noteworthy that the toxicokinetic differences of Aconitum carmichaelii after administration may be closely related to cytochrome P450 enzyme polymorphism and processing parameters. Rat microsomes were selected for the in vitro analysis of aconitine metabolism measured by high-performance liquid chromatography (HPLC). The results indicated that CYP3A4 was responsible for the primary metabolism of aconitine. Moreover, rats of different sexes exhibited varying tolerance levels to the acute oral toxicity of aconitine (Ye et al., 2011; Chen et al., 2023). (4) Prevention strategies: Traditional water decoction and high-pressure moist heat processing techniques can effectively degrade the toxic components of diterpenoid alkaloids, significantly reducing the probability of acute poisoning. For example, the water extract of processed black aconite slices (a derivative of raw aconite) at doses of 0.8 g/kg, 1.6 g/kg, and 3.2 g/kg showed no effects on rat body weight compared to the raw aconite water extract group, while cardiovascular indicators, such as cardiac index exhibited a decrease (Chen P. et al., 2013; Li et al., 2024).

In addition to the aforementioned toxic reactions, the toxic effects of aconitine also involve multi-organ damage to the nervous system, digestive system, and other organs.

As the earliest surviving heirloom text that systematically records the concoction technology of aconite, Jin Gui Yu Han Jing laid the theoretical foundation for the control of toxic components in TCM. In TCM, the concoction process of aconite is of key significance in reducing its inherent toxicity and enhancing the safety of clinical use. The mechanism of aconite preparations to reduce toxicity has experienced a systematic historical evolution and technological innovation from traditional pretreatment processes to the classical method to modern innovative technology (Chen R. C. et al., 2013; Hu et al., 2025). The aconite pretreatment methods include peeling, breaking, and raw use. The peeling of Chinese medicine is aimed at purifying the drug and facilitating concoctions and clinical use of the drug. After aconite has been peeled to remove its root skin, its toxic components are significantly reduced, and alkaloids can be easily solubilized. “Breaking open” refers to increasing the heat area of the herbs through physical division and destroying toxic substances, such as biester alkaloids, after prolonged high-temperature decoction, thus realizing the purpose of reducing toxicity and increasing efficacy. Although raw aconite retains its inherent toxicity, it has the unique effect of quickly breaking yin and dispersing cold (Hou et al., 2024). The concoctions of aconite include fire, brine, steam, and boiling methods. The diversified concoctions of aconite provide multiple paths for its safe clinical application and the optimization of medicinal efficacy (Dong et al., 2020).

The Chinese Pharmacopoeia records five types of processed Radix Aconiti Lateralis Praeparata (processed forms of Aconitum carmichaelii Debx., commonly referred to as prepared aconite root), whose detoxification mechanisms are all directly related to the chemical degradation of diester-diterpenoid alkaloids (e.g., aconitine and hypaconitine) into monoester-diterpenoid alkaloids (e.g., benzoylaconine and benzoylhypaconine). The degradation pathways include the cleavage of the C-8 ester bond of diester-diterpenoid alkaloids under high-temperature steam to form monoester-diterpenoid alkaloids, whose toxicity is 1/200 to 1/500 that of diester diterpenoid alkaloids. As hydrolysis conditions intensify, the C-14 ester bond breaks, forming amino alcohol-type aconitine, whose toxicity is 1/2000 to 1/4000 that of diester-type aconitine (He, 2022): (1) Black shunpian: Mud aconite is washed and dipped in gall bladder water for a few days, boiled until it is heated through the heart, water-bleached and sliced, dipped and bleached to adjust the color, baked to half-dry after steaming, and then finally, dried in the sun or dried. After processing, the structure of biester-type alkaloids in aconite is destroyed and hydrolyzed into the low-toxicity mono- ester-type alkaloids. After processing by boiling for 8 min, water soaking and rinsing four times within 24 h, steaming for 3 h, and drying at 60 °C for 7.5 h, the hypaconitine and aconitine content in processed Aconitum carmichaelii slices fell below the detection limit. Additionally, the total content of diester-diterpenoid alkaloids significantly decreased after steaming, while the content of monoester-diterpenoid alkaloids notably increased, likely due to the conversion of diester-diterpenoid alkaloids during the steaming process (Ch, 2020; Gong et al., 2022). (2) Salt-processed aconite: Large and uniform aconite is washed, immersed in gall bladder water overnight and then soaked in salt and sun-dried daily until there is a large amount of salt cream on the surface and the texture becomes hard. This concocting process decreases the total alkaloid content in aconite to achieve the purpose of reducing the toxicity; however, the efficacy of aconite is also decreased after salt processing (Ch, 2020; Peng et al., 2022). (3) White sliced aconite: Uniform-sized mud aconites are soaked in brine for several days, boiled until thoroughly cooked, then peeled and longitudinally sliced. After water soaking, steaming, and sun-drying processes, HPLC testing showed that although the diester-type alkaloid content in the peeled aconite was reduced to approximately one-eighth the amount in raw aconite, it remained significantly higher than in other processed products. The white sliced aconite processing method involves removing the epidermis and high-temperature boiling, which decreases the diester-type alkaloid content and increases monoester-type alkaloid levels. Additionally, 5-hydroxymethylfurfural, a distinctive component not found in other processed forms, emerges, likely due to the high- temperature hydrolysis of Vitis vinifera sugars or fructose after epidermal removal (Zhu et al., 2011; Ch, 2020; Zhang C. et al., 2024). (4) Prepared aconite lateral root slices (with glycyrrhiza and black beans): Salt-processed aconite is soaked in clean water to remove salt, then boiled with Glycyrrhiza uralensis (common name: licorice root) and black beans until numbing sensations and bitterness disappear. Glycyrrhiza uralensis and the black beans are removed, then the aconite is sliced thinly and sun-dried. High-temperature steaming destroys the toxic components, while excipients help adsorb and promote the dissolution of toxic constituents. After processing with black beans and Glycyrrhiza uralensis, HPLC analysis shows increased monoester-diterpenoid alkaloid content and decreased diester-diterpenoid alkaloid levels (Guo et al., 2015; Ch, 2020; Yu et al., 2023). (5) Processed aconite lateral root slices: Black or white aconite lateral root slices are used as raw materials and sand-fried until puffed and slightly discolored. High-temperature processing reduces the diester-diterpenoid alkaloid content, thereby decreasing the leaching of toxic components. No diester-diterpenoid alkaloids (e.g., aconitine and neoaconitine) were detected in the processed slices. However, the monoester-diterpenoid alkaloid content decreased to 47.2, 58.1, and 67.1% of that in black aconite lateral root slices, respectively, with the total amount of the three monoester-diterpenoid alkaloids reduced to 54.9% of the raw product (Peng et al., 2019; Ch, 2020). The five detoxification mechanisms of processed aconite are summarized in Figure 2.

In recent years, significant research progress has been made on the detoxification mechanism of aconite by integrating traditional processing techniques and modern technologies. In contemporary aconite processing methods, the pressurized steaming technique effectively degrades diester-type alkaloids while preserving the cardiotonic activity of monoester-type alkaloids by applying high pressure at approximately 120 °C, achieving a detoxification rate exceeding 90%. When processed under moist heat and pressure at 120 °C for 1–1.5 h, the diester-type alkaloids in aconite fall below the detection limit, while the average detected content of monoester-type alkaloids was 1.567 mg/g (Tang et al., 2013). Microwave processing accelerates the decomposition of toxic components by regulating water molecule movement. Under the combined action of magnetic fields and microwaves, water molecules generate substantial heat, hydrolyzing diester-type alkaloids in raw aconite slices, thereby achieving efficient and rapid detoxification (He, 2022).

Junchen Zuoshi is the core theory of Chinese medicine prescriptions. In compound formulae, the king’s medicine dominates the therapeutic effect, and the adjuvants assist the king and minister’s efficacy through synergistic enhancement, toxicity control, slowing, and reporting mechanisms (Chen and Tan, 2020). As an important part of the diagnosis and treatment system of TCM, scientific compounding can effectively reduce the toxic side effects and produce synergistic effects. As a representative toxic herb, aconite holds significant value in classical formula research. Its detoxification mechanisms acting through compatibility include forming complexes by precipitating aconitine, interfering with aconitine metabolism, regulating ion channels, and modulating physiological microenvironments. This section will systematically review classic compatibility combinations of aconite (such as Glycyrrhiza uralensis-aconite), analyze their compatibility mechanisms, and summarize classical formulas containing aconite along with their clinical applications.