ETHNOPHARMACOLOGICAL RELEVANCE:Ovarian function decline (OFD) represents a principal contributor to infertility among women of reproductive age, yet no definitive therapy has been established. It has been suggested that ferroptosis exists in OFD. A traditional Chinese medicine formula called Xin Jia Congrong Tusizi Decoction (XJCTD) has shown potential in improving OFD. However, the mechanism remains unclear. AIM OF THE STUDY:This study aims to elucidate the protective effect of XJCTD on ovarian function in OFD and to clarify its underlying molecular mechanisms. MATERIALS AND METHODS:Triptolide (TP)-induced rat and COV434 cell models were established to evaluate XJCTD efficacy. The role of the p53-Nrf2 axis was interrogated using p53 overexpression plasmids, Nrf2 siRNA, and inhibitors Pifithrin-α. Ovarian pathological changes were assessed using H&E staining. The major compounds of XJCTD were identified by UPLC-Q-TOF-MSE analysis and network pharmacology analysis. Direct interactions between core compounds and p53 were validated using molecular docking, surface plasmon resonance (SPR); and the interaction between XJCTD and TP53 was confirmed by cellular thermal shift assay (CETSA). Expression of p53 and Nrf2 was analyzed by Western blot (WB) or immunofluorescence, and their physical interaction validated by co-immunoprecipitation. We evaluated the impact of XJCTD on ferroptosis-related markers in both ovarian tissues and COV434 cells, including Fe2+, MDA, ROS and GSH. Ferroptosis-related proteins were further examined by WB and immunohistochemistry. RESULTS:XJCTD significantly attenuated TP-induced ovarian injury and ferroptosis by suppressing Fe2+, lipid peroxidation, and ROS accumulation while restoring GSH levels. Furthermore, XJCTD facilitated p53 ubiquitination and degradation, consequently alleviating Nrf2 suppression to activate the SLC7A11/GPX4 pathway. Rescue experiments demonstrated that p53 overexpression or Nrf2 silencing reversed these protective benefits. SPR analysis confirmed direct binding between p53 and core XJCTD bioactive components, including Epimedin A, Isoquercitrin, and Isoacteoside. CONCLUSIONS:XJCTD functions as a suppressor of ferroptosis to protect ovarian function. The underlying mechanism involves the targeted degradation of p53, which alleviates the inhibition of Nrf2 nuclear accumulation and enhances the SLC7A11/GPX4 antioxidant defense system.

Introduction Chinese herbal medicine (CHM) has long been extensively applied in China for the management of adenomyosis, particularly as an adjunct to conventional therapies. This study aimed to assess the efficacy and safety of combining CHM with a levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis. Methods A comprehensive literature search was performed across seven electronic databases from their inception to December 2024. Randomized controlled trials (RCTs) comparing CHM combined with LNG-IUS against LNG-IUS monotherapy were eligible for inclusion. Two reviewers independently screened the records and assessed the methodological certainty. Meta-analysis was employed to quantitively synthesize the effect estimates. To ensure the robustness of the results, subgroup analysis, sensitivity analysis, and publication bias assessment were performed. This study was registered on PROSPERO (CRD42020145842; Date: April 28, 2020) and OSF (DOI: 10.17605/OSF.IO/A2GHY, Date: April 26, 2020). Results Twenty RCTs involving 2,114 women were included. The methodological certainty of most included trials were low or very low. Meta-analysis demonstrated that the adjuvant use of CHM therapy might be superior in decreasing visual analogue scale (VAS) scores (MD -1.44, 95% CI -1.89 to -0.99, P<0.00001, low-certainty evidence) and the pictorial blood assessment chart (PBAC) (MD -13.00, 95% CI -18.98 to -7.01, P<0.0001, very low-certainty evidence). In terms of the secondary outcomes, the results indicated that CHM adjuvant therapy significantly reduced the endometrial thickness (MD -2.03, 95% CI -2.52 to -1.53, P < 0.00001, very low-certainty evidence), the serum CA125 level (MD -7.58, 95% CI -10.11 to -5.05, P < 0.00001, low-certainty evidence), and the uterine volume (MD -10.23, 95% CI -15.06 to -5.04, P < 0.0001, low-certainty evidence). Furthermore, the combination group exhibited a lower incidence of adverse events than the LNG-IUS monotherapy group (RR 0.53, 95% CI 0.45 to 0.63, P<0.00001, low-certainty evidence). Conclusion CHM combined with LNG-IUS may enhance additional therapeutic outcomes and reduce adverse events in patients with adenomyosis. However, given the methodological limitations and considerable heterogeneity across the included trials, these findings should be interpreted with caution.

To analyze the efficacy of high-intensity focused ultrasound (HIFU) for adenomyosis and postoperative recurrence and its influencing factors. Clinical and follow-up data of 308 patients with adenomyosis who were treated with HIFU in Haifu Center, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from September 2017 to January 2022 were retrospectively analyzed. The recurrence of adenomyosis and the efficacy of HIFU at 6 months after surgery were followed up. To explore factors influencing postoperative prognosis and recurrence, the following variables were analyzed: patients’ age, course of disease, gravidity and parity, size of the uterus, duration of HIFU, duration of irradiation, treatment intensity, dysmenorrhea score, time of follow-up, combined treatment of traditional Chinese medicine (TCM), western medicine adjuvant treatment, lesion location and type, and menorrhagia. Among the 308 patients, 238 (77

ETHNOPHARMACOLOGICAL RELEVANCE:The lateral root of Aconitum carmichaelii Debeaux. (also known as Fuzi in Chinese) is a toxic Chinese medicine but widely used in clinical practice with remarkable effects. It is specifically used to treat cardiovascular diseases, rheumatoid arthritis, and other diseases, in Korea, Japan, and India.AIM OF THIS REVIEW:This study aimed to summarize and discuss the effects of drug processing on toxicity, chemical composition, and pharmacology of the lateral root of Aconitum carmichaelii Debeaux. This review could provide feasible insights for further studies.MATERIALS AND METHODS:Relevant information on phytochemistry, pharmacology, and toxicology of Fuzi was collected through published materials and electronic databases, including the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar, and CNKI.RESULTS:More than 100 chemical compounds, including alkaloids, flavonoids, and polysaccharides were revealed. Modern pharmacological studies show that these chemical components have good effects on anti-inflammatory, anti-tumor, anti-aging, treatment of cardiovascular diseases, and improving immunity. Di-ester alkaloids are the main source of Fuzi toxicity. Increasing studies have shown that Fuzi can induce multiple organ damage, especially cardiotoxicity and neurotoxicity. At present, most of the Fuzi used in clinical practice are processed. The processing affects the chemical structure, pharmacology, and toxicology of Fuzi. Moreover, different processing methods have different effects on Fuzi.CONCLUSIONS:This review analyzed the effects of Fuzi processing methods on its toxicity and efficiency. The lateral roots of aconite are the known medicinal part of Fuzi; however, the aerial parts of aconite are understudied and require further research to expand its medicinal potential. Processing and compatibility are the primary means to reduce Fuzi toxicity. Nevertheless, establishing a reasonable unified safe dose range requires further discussion.

Aims: Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast in liver fibrosis remains unknown. In this study, we examined whether the pharmacological inhibition of CysLTR1 could protect mice against hepatic fibrosis. Materials and methods: Carbon tetrachloride (CCl4) and methionine-choline deficient (MCD) diet models were used in this study. The expression of CysLTR1 in liver were detected by RT-qPCR and Western blot analysis. Liver hydroxyproline levels, fibrotic genes expression, serum biochemical indexes and inflammatory factors were used to evaluate the effect of montelukast on liver fibrosis, injury, and inflammation. In vitro, we used the RT-qPCR and Western blot analysis to assess CysLTR1 in mouse primary hepatic stellate cell (HSC) and human LX-2 cell line. The role of montelukast on HSC activation and the underlying mechaisms were determined using RT-qPCR analysis, Western blot and immunostaining assays. Key findings: Chronic stimulation from CCl4 and MCD diet upregulated the mRNA and protein levels of CysLTR1 in the liver. Pharmacological inhibition of CysLTR1 by montelukast ameliorated liver inflammation and fibrosis in both models. Mechanistically, montelukast suppressed HSC activation by targeting the TGF ss/Smad pathway in vitro. The hepatoprotective effect of montelukast was also associated with reduced liver injury and inflammation. Significance: Montelukast suppressed CCl4- and MCD-induced chronic hepatic inflammation and liver fibrosis. CysLTR1 might be a therapeutic target for treating liver fibrosis.

Chinese olive is a popular fruit with a long history of cultivation and consumption. As a fruit with edible, nutritional, and even medicinal value, the Chinese olive has attracted increased interest from both nutrition researchers and health-conscious consumers. Chinese olive is a rich nutrient source, including essential and non-essential amino acids, various fatty acids, organic acids, vitamins, microelements, and high-quality dietary fibers. It is also an important natural source of phytochemicals such as phenolic acids, flavonoids, phenylpropanoids, and other bioactive compounds. The nutritional and phytochemical compounds obtained from the Chinese olive exhibit unique and potent biological activities, explaining its various benefits to human health, including anti-Helicobacter pylori, anti-influenza, anti-diabetes, anti-inflammatory, anti-tumor effects, among others. This review focuses on recent studies on Chinese olives and aims to summarize the major advances in their nutritional value, phytochemical composition, health benefits, and practical applications. It provides a reference for further research on Chinese olives and their properties and the development of novel functional products.

Abstract The aim of this study was to explore plant-derived peptides as carrier material with the function of anti-hot-melt stickiness of traditional Chinese herbal extracts during spray drying. Crataegi fructus extract (CFE) with a severe hot-melt stickiness problem was used as a model drug, and soy peptides (SPT) were screened as the most effective and suitable carrier material among seven plant-derived proteins and peptides which include soy protein isolate, walnut protein and five kinds of peptides (corn peptides, wheat peptides, walnut peptides, rice peptides and SPT). The addition of 15% SPT also exhibited a strong anti-stickiness effect in other four hot-melt sticky herbal extracts from Chinese herbs (Lycii fructus, Corni fructus, Chaenomelis fructus and Mume fructus) since the obtained powder increased from completely sticking to the wall to more than 50% powder yield. The dynamic surface tensions (DST) of CFE decreased consistently with the increase of SPT from 5% to 20%, and DST1000ms had consistent reduction with the addition of SPT from zero to 20%. Meanwhile, the adhesive force of the single droplet at 28 min decreased below 18.5 N. The softening point of the spray-dried powder of CFE added 15% SPT increased by about 40 °C, and the addition of 15% SPT improved the stability which might be similar with the addition of 50% MD based on scanning electron microscope analysis but more efficiently. These findings confirmed that SPT plant-derived could serve as effective and stable carrier material with good anti-stickiness ability during spray drying.

Objective: The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products. Methods: The diterpenoid alkaloid 3-acetylaconitine was heated at 180 & DEG;C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products. Results: Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity. Conclusion: Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314. & COPY; 2023 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. All rights reserved.

Lozenge is one of the traditional dosage forms of Chinese medicine. It has been recorded in traditional Chinese medical classics of all dynasties since the Eastern Han Dynasty and has been developing and evolving continuously. The unique pharmaceutical methods and application scope are the driving force of its emergence, existence, and development. Up to now, lozenge has been included in the Chinese Pharmacopoeia as an independent dosage form. Lozenge has been endowed with new meaning by modern Chinese medicine pharmaceutics, which is worth tracing origin and exploring value. The present study reviewed the origin and development of lozenge, compared lozenge with other similar dosage forms, analyzed the characteristics of modern and ancient dosage forms of lozenge, and discussed the development prospect and potential of lozenge in combination with the demand development of modern Chinese medicine preparation, so as to provide references for expanding the modern application of lozenge.

The transformation pathways of diterpenoid alkaloids have been clarified in the boiling and steaming process. Aconitine, a famous diterpenoid alkaloid, is successively transformed into benzoylaconine and aconine during the processes of boiling and steaming, but the transformation pathway remains to be determined in the sand frying process. The present study aims at investigating the transformation pathways of aconitine in the process of sand frying, as well as assessing the cardiotoxicity and antiarrhythmic activity of aconitine and its converted products. The parameters of temperature and time for the structural transformation of aconitine were confirmed by HPLC. The converted products were further separated and identified by column chromatography, NMR, and HR-ESI-MS. Furthermore, by observing the lead II electrocardiogram (ECG) changes in rats under an equivalent dose, the cardiotoxicity of aconitine and its converted products were compared. Ultimately, the antiarrhythmic effect of the converted products was investigated by employing the model of aconitine-induced arrhythmia. Consequently, the structure of aconitine was converted when processed at 120°C–200°C for 1–40 min. Two diterpenoid alkaloids, a pair of epimers, namely, pyroaconitine and 16-epi-pyroaconitine, were further isolated from processed aconitine. 0.03 mg/kg aconitine induced arrhythmias in normal rats, while the converted products did not exhibit arrhythmias under an equal dose. In the antiarrhythmic assay, 16-epi-pyroaconitine could dose-dependently delay the onset time of VPB, reduce the incidence of VT, and increase the arrhythmia inhibition rate, demonstrating comparatively strong antiarrhythmic activity. Conclusively, compared with the prototype compound aconitine, the converted products exhibited lower cardiotoxicity. Further investigations on the cardiotoxicity indicated that pyroaconitine with β configuration had a stronger cardiotoxicity than 16-epi-pyroaconitine with α configuration. Furthermore, 16-epi-pyroaconitine could antagonize the arrhythmogenic effect caused by the prototype compound aconitine; the antiarrhythmic effect of 16-epi-pyroaconitine was stronger than lidocaine and propafenone, which had the potential to be developed as antiarrhythmic drugs.

The transformation pathways of diterpenoid alkaloids have been clarified clearly in the boiling and steaming process, but remain to be determined in the sand frying process. The aims of the study were to investigate the transformation pathways of indaconitine in the sand frying process, as well as examine the cardiotoxicity and anti-arrhythmic activity of indaconitine and its transformed products. The transformed product was separated by column chromatography, and the structure was identified by 1 H NMR, 13 C NMR, and HR-ESI-MS. The cardiotoxicity of indaconitine and its transformed products was clarified by observing the electrocardiogram (ECG) changes at the same dose. Furthermore, the anti-arrhythmic activity of the transformed products was investigated using an aconitine-induced rat arrhythmia model. Consequently, Δ 15(16) -16-demethoxyindaconitine, a new diterpenoid alkaloid, was isolated from processed indaconitine. Intravenous injection of 0.06 mg/kg indaconitine induced arrhythmias in SD rats, while Δ 15(16) -16-demethoxyindaconitine did not exhibit arrhythmias at the same dose. In the anti-arrhythmic assay, mithaconitine, obtained in the previous research, together with Δ 15(16) -16-demethoxyindaconitine, could dose-dependently delay the onset time of ventricular premature beat (VPB) and reduce the incidence of ventricular tachycardia (VT), combined with the increasing arrhythmia inhibition rate, exhibiting strong anti-arrhythmic activities. These results indicated that two or more pathways exist in the sand frying process, and the transformed products exhibited lower cardiotoxicity and strong anti-arrhythmic activities, which had the possibility of being developed into anti-arrhythmic drugs.

Objective. To explore the mechanism of Dahuang Fuzi decoction in the treatment of incomplete intestinal obstruction (IIO) based on network pharmacology and molecular docking. Methods. The chemical components of Rhubarb, Aconite, and Asarum were searched by the Traditional Chinese Medicine Systems Pharmacology database, where the possible active components were screened by oral bioavailability and drug likeness as filtering indicators. The relevant targets in the Swiss Target Prediction database were obtained according to the structure of the chemical components confirmed by the PubChem database. Disease targets of IIO were collected using GeneCards and OMIM databases. We obtained the cross-target using VENNY to capture the common targets. PPI analysis was performed on the intersection genes combined with Cytoscape 3.7.2. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out by David database. The core targets and active ingredients were molecularly docked through AutoDock Vina software to predict the detailed molecular mechanism of Dahuang Fuzi decoction for treating IIO. Results. There are 45 active components in Dahuang Fuzi decoction, with 709 corresponding targets, 538 IIO targets, and 97 common targets, among which kaempferol, deltoin, and eupatin are the main active ingredients. 10 core targets were obtained by protein-protein interaction network analysis. Through GO enrichment analysis, it was found that Dahuang Fuzi decoction may be involved in biological processes such as signal transduction, anti-apoptosis, promotion of gene expression, regulation of cell proliferation, and differentiation. Besides, KEGG pathway analysis revealed that it mainly relates to PI3K-AKT signal pathway and HIF-1 signal pathway, etc. Molecular docking results showed that the active ingredients of Dahuang Fuzi decoction possess a good binding activity with the core targets. Conclusion. Dahuang Fuzi decoction may act on target genes such as TNF, IL6, AKT1, VEGFA, SRC, EGFR, and STAT3 through active ingredients such as kaempferol, deltoin, and eupatin to regulate signaling pathways such as PI3K-AKT and HIF-1 and reduce the expression of various inflammatory factors such as TNF-α, IL-6, iNOS, and COX-2 to play a role in the treatment of IIO.

Sequela of pelvic inflammatory disease (SPID) is a common and frequently occurring disease clinically. Traditional Chinese medicine (TCM) provided unique advantages in the treatment of SPID. In this study, we aimed to investigate the protective mechanism of Shipi Shugan Decoction (SSD), a Chinese herbal formula, on SPID using a SPID rat model. Mixed bacterial infection and mechanical injury were used for modeling. The chemical composition of SSD was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA) and western blot techniques. We found that SSD dose-dependently inhibited the content of IL-18, IL-1β, TNF-α, and IL-6 in serum samples of SPID rats. The results from the hematoxylin and eosin (H&E) stain showed that SSD improved pathological injury of the uterus and fallopian tubes induced by a pathogen. In addition, SSD dose-dependently inhibited mitochondrial dysfunction and oxidative stress of SPID rats. The expression of SIRT1 was promoted, and NLRP3 inflammasome was deactivated by SSD gavage compared with the SPID group. Specifically, SIRT1 inhibitor EX-527 cotreatment significantly reversed the improvement effect of SSD on pelvic inflammatory disease in rats. Taken together, the results of this study suggest that Shipi Shugan Decoction may be an effective TCM for the treatment of SPID.

Background: In recent years, the incidence and mortality rates of non-small cell lung cancer (NSCLC) have increased significantly. Shan Ci Gu is commonly used as an anticancer drug in traditional Chinese medicine; however, its specific mechanism against NSCLC has not yet been elucidated. Here, the mechanism was clarified through network pharmacology and molecular docking.Methods: The Traditional Chinese Medicine Systems Pharmacology database was searched for the active ingredients of Shan Ci Gu, and the relevant targets in the Swiss Target Prediction database were obtained according to the structure of the active ingredients. GeneCards were searched for NSCLC-related disease targets. We obtained the cross-target using VENNY to obtain the core targets. The core targets were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins database, and Cytoscape software was used to operate a mesh chart. R software was used to analyze the Gene Ontology biological processes (BPs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The core targets and active compounds were molecularly docked through Auto-Dock Vina software to predict the detailed molecular mechanism of Shan Ci Gu for NSCLC treatment. We did a simple survival analysis with hub gene to assess the prognosis of NSCLC patients.Results: Three compounds were screened to obtain 143 target genes and 1,226 targets related to NSCLC, of which 56 genes were related to NSCLC treatment. Shan Ci Gu treatment for NSCLC involved many BPs and acted on main targets including epidermal growth factor receptor (EGFR), ESR1, and SRC through signaling pathways including the endocrine resistance, EGFR tyrosine kinase inhibitor resistance, and ErbB signaling pathways. Shan Ci Gu might be beneficial for treating NSCLC by inhibiting cell proliferation and migration. Molecular docking revealed that the active compounds β-sitosterol, stigmasterol, and 2-methoxy-9,10-dihydrophenanthrene-4,5-diol had good affinity with the core target genes (EGFR, SRC, and ESR1). Core targets included EGFR, SRC, ESR1, ERBB2, MTOR, MCL1, matrix metalloproteinase 2 (MMP2), MMP9, KDR, and JAK2. Key KEGG pathways included endocrine resistance, EGFR tyrosine kinase inhibitor resistance, ErbB signaling, PI3K-Akt signaling, and Rap1 signaling pathways. These core targets and pathways have an inhibitory effect on the proliferation of NSCLC cells.Conclusion: Shan Ci Gu can treat NSCLC through a multi-target, multi-pathway molecular mechanism and effectively improve NSCLC prognosis. This study could serve as a reference for further mechanistic research on wider application of Shan Ci Gu for NSCLC treatment.

To ensure safety and efficacy, most Aconitum herbs should be processed before clinical application. The processing methods include boiling, steaming, and sand frying. Among these methods, the transformation pathways of diterpenoid alkaloids in the process of sand frying are more complicated. Therefore, crassicauline A, a natural product with two ester bonds, was chosen as the experimental object. Consequently, a known alkaloid, together with three new alkaloids, was derived from crassicauline A. Meanwhile, the cardiotoxicity of converted products was reduced compared with their parent compound. Interestingly, some diterpenoid alkaloids have similar structures but opposite effects, such as arrhythmia and antiarrhythmic. Considering the converted products are structural analogues of crassicauline A, herein, the antiarrhythmic activity of the transformed products was further investigated. In a rat aconitine-induced arrhythmia assay, the three transformed products, which could dose-dependently delay the ventricular premature beat (VPB) incubation period, reduce the incidence of ventricular tachycardia (VT), combined with the increasing arrhythmia inhibition rate, exhibited prominent antiarrhythmic activities. Our experiments speculated that there might be at least two transformation pathways of crassicauline A during sand frying. The structure-activity data established in this paper constructs the critical pharmacophore of diterpenoid alkaloids as antiarrhythmic agents, which could be helpful in searching for the potential drugs that are equal or more active and with lower toxicity, than currently clinical used antiarrhythmic drugs.

目的 研究印乌碱在砂炒(油浴模拟)过程中的结构转化途径并比较印乌碱及其转化产物的毒性.方法 采用HPLC法筛选出印乌碱发生结构转化的温度和时间参数;通过柱色谱法和NMR、MS等波谱法,分离、鉴定出印乌碱的砂炒转化产物;采用心脏毒性实验比较原型成分印乌碱及其转化产物的毒性.结果 通过比较不同炮制温度、时间样品的HPLC色谱图,筛选出印乌碱在160～180℃,加热10～30min时发生结构转化;分离、鉴定出砂炒产物mithaconitine;Ⅱ导联心电图(electrocardiogram,ECG)表明,0.06 mg/kg印乌碱可引起正常大鼠出现室性早搏(ventricular premature beat,VPB)、室性心动过速(ventricular tachyrhythmia,VT)等心律失常现象;mithaconitine在该剂量下未引起大鼠典型的心律失常ECG.结论 砂炒过程中,印乌碱的C-8位脱去乙酰基,转化为14-benzoylpseudaconine;接着,14-benzoylpseudaconine的C-8位、C-15位发生脱水反应转化为mithaconitine,达到砂炒减毒的目的.

Aconitum vilmorinianum Komarov is a local medicinal plant used in many well-known clinical preparations to treat rheumatism and pains in Yunnan Province, China. Phytochemical examination of the roots of A. vilmorinianum led to the isolation of three novel imine-type norditerpenoid alkaloids named vilmorrianines E–G (1–3), and a new natural alkaloid N-desethyl-N-formyl-8-O-methyltalatisamine (4), together with 14 known alkaloids. Their structures were elucidated on the basis of spectroscopic evidence. Vilmorrianine E is the first known norditerpenoid alkaloid containing both an imine group and a three-membered ring formed by C8, C9, and C10.