Identification of antagonistic fungi and their antifungal activities against aconite root rot pathogens.

Root rot is one of the main diseases affecting Aconitum carmichaelii Debx. during cultivation, seriously limiting yields of this herb. Currently, there is no effective control measure for aconite root rot. The antifungal activities of antagonistic strains against aconite root rot pathogens (Fusarium proliferatum, Fusarium solani, and Fusarium oxysporum) were investigated in this study. Three antagonistic strains, JKT7, JKT28 and JKT39, were screened and identified as Trichoderma asperellum, Trichoderma hamatum and Trichoderma virens, respectively. Dual culture tests showed that the inhibition rates of the three Trichoderma strains on the pathogens were all approximately 70%. The volatile metabolites had inhibitory effects on the mycelial growth of pathogens, while the nonvolatile metabolites in the culture filtrates did not show significant inhibitory effects. The volatile components analyzed by GC‒MS were mainly ketones, esters, and alcohols. These results indicate that these strains of Trichoderma and their secondary metabolites have antimicrobial activities against the pathogens of aconite root rot. This study could provide a scientific basis for the biocontrol of aconite root rot.

Aconicumines A-D, an advanced class of norditerpenoid alkaloids with an unprecedented N,O-diacetal motif from Aconitum taipeicum Hand.-Mazz., exhibit anti-inflammatory properties in vitro.

Aconicumines A-D, an advanced class of norditerpenoid alkaloids, and seven known alkaloids, were isolated from Aconitum taipaicum Hand.-Mazz. (Ranunculaceae). The structures of the previously undescribed compounds, including their absolute configurations, were fully elucidated based on spectroscopic and single-crystal X-ray diffraction data analysis. Aconicumines A-D exhibit interesting cage-like structure, characterised by an unprecedented N,O-diacetal moiety (C6-O-C19-N-C17-O-C7) that has not been previously observed in diterpenoid alkaloids. Possible biosynthetic pathways for aconicumines A-D were proposed. Aconitine, hypaconitine, and aconicumine A showed significant inhibition of nitric oxide production in RAW 264.7 macrophages induced by lipopolysaccharide with IC50 values ranging from 4.1 to 19.7 µM compared to positive control (dexamethasone, IC50 = 12.5 µM). Furthermore, the primary structure-activity relationships for aconicumines A-D were also represented.

Spatial distribution and comparative analysis of Aconitum alkaloids in Fuzi using DESI-MSI and UHPLC-QTOF-MS.

Aconitum L. poisoning is a major type of poisoning caused by herbal medicines in many countries. However, despite its toxicity, Aconitum L. is still used because of its therapeutic value. Fuzi, the lateral root of Aconitum L., is one of the most important pharmacological parts. It is necessary for rational medication to figure out the types and contents of toxic Aconitum alkaloids (AAs) in Fuzi and its processed products. The present study aims to investigate the spatial distribution of toxic AAs in Fuzi and the quantification of AAs in various processing products through mass spectrometry methods. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to directly image the sections of raw Fuzi. The results showed a high content of diester alkaloids (DAs) and a relatively uniform distribution in the sections, while the content of monoester alkaloids (MAs) was low and uneven in the sections, distributed in the cortex, epidermis, vascular column, and other parts of the tissues. The content of non-ester alkaloids (NAs) was relatively minimum, and most of the NAs were distributed in the vascular column and the tightly connected cortex of the tissue. To further investigate the difference between raw and processed Fuzi, 60 known compounds were identified using UHPLC-QTOF-MS. The total contents of alkaloids in 7 processed Fuzi were lower than that in Shengfupian (SFP). Paofupian (PFP), Paotianxiong (PTX), Paofupian (PFP*), Danfupian (DFP), and Shufupian (SFP*) were the least similar. Zhengfupian (ZFP) and Chaofupian (CFP) had significantly reduced toxicity and increased efficacy compared with other processed products because the contents of active alkaloids in other processed products were also reduced. Understanding the distribution of metabolites and the composition changes after processing can guide users and herbal manufacturers to carefully choose the relatively safe and better therapeutic species of Fuzi. The information gathered from this study can contribute towards the improved and effective management of therapeutically important, nonetheless toxic, drugs such as Aconitum L.

Aconitum carmichaelii Debx. Attenuates Heart Failure through Inhibiting Inflammation and Abnormal Vascular Remodeling.

Heart failure (HF) is the most common complication following myocardial infarction, closely associated with ventricular remodeling. Aconitum carmichaelii Debx., a traditional Chinese herb, possesses therapeutic effects on HF and related cardiac diseases. However, its effects and mechanisms on HF-associated cardiac diseases are still unclear. In the present study, a water extraction of toasted Aconitum carmichaelii Debx. (WETA) was verified using UPLC-Q/TOF-MS. The heart function of HF rats was assessed by echocardiography and strain analysis, and myocardial injury was measured by serum levels of CK-MB, cTnT, and cTnI. The pathological changes of cardiac tissues were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and Masson's trichrome staining. Additionally, the levels of inflammation-related genes and proteins and components related to vascular remodeling were detected by RT-qPCR, Western blot, and immunofluorescence. WETA significantly inhibited the changes in echocardiographic parameters and the increase in heart weight, cardiac infarction size, the myonecrosis, edema, and infiltration of inflammatory cells, collagen deposition in heart tissues, and also mitigated the elevated serum levels of CK-MB, cTnT, and cTnI in ISO-induced rats. Additionally, WETA suppressed the expressions of inflammatory genes, including IL-1ß, IL-6, and TNF-α and vascular injury-related genes, such as VCAM1, ICAM1, ANP, BNP, and MHC in heart tissues of ISO-induced HF rats, which were further confirmed by Western blotting and immunofluorescence. In summary, the myocardial protective effect of WETA was conferred through inhibiting inflammatory responses and abnormal vascular remodeling in ISO-treated rats.

Complete chloroplast genome sequences of the medicinal plant Aconitum transsectum (Ranunculaceae): comparative analysis and phylogenetic relationships.

BACKGROUND: Aconitum transsectum Diels. (Ranunculaceae) is an important medicinal plant that is widely used in traditional Chinese medicine, but its morphological traits make it difficult to recognize from other Aconitum species. No research has sequenced the chloroplast genome of A.transsectum, despite the fact that phylogenetic analysis based on chloroplast genome sequences provides essential evidence for plant classification. RESULTS: In this study, the chloroplast (cp) genome of A. transsectum was sequenced, assembled, and annotated. A. transsectum cp genome is a 155,872 bp tetrameric structure including a large single copy (LSC, 87,671 bp) and a small single copy (SSC, 18,891 bp) section, as well as a pair of inverted repeat sequences (IRa and IRb, 25,894 bp each). 131 genes are encoded by the complete cp genome, comprising 86 protein-coding genes, 37 tRNAs, and 8 rRNAs. The most favored codon in the A. transsectum cp genome is AUG, and 46 repeats and 241 SSRs were also identified. The A. transsectum cp genome is similar in size, gene composition, and IR expansion and contraction to the cp genomes of seven Ranunculaceae species. Phylogenetic analysis of cp genomes of 28 plants from the Ranunculaceae family shows that A. transsectum is most closely related to A. vilmorinianum, A. episcopale, and A. forrestii of Subgen. Aconitum. CONCLUSIONS: Overall, this study provides complete cp genome resources for A. transsectum that will be beneficial for identifying potential.

Comprehensive quality evaluation of Aconiti Lateralis Radix Praeparata based on pseudotargeted metabolomics and simultaneous determination of fifteen components, and development of new processed products of black slices with less toxicity.

Aconiti Lateralis Radix Praeparata is one of the most famous traditional Chinese medicines possessing a variety of pharmacological activities on top of the toxicities. Due to the heterogeneity and non-standardization of the processing procedures, the subtypes and contents of the differential compounds between different processed products still remained indistinct, causing great risk in their proper use. In order to achieve the comparison and quality evaluation of different processed products of Aconiti Lateralis Radix Praeparata and develop new processed products with less toxicity, a quantification and pseudotargeted metabolomics method was developed based on the dynamic MRM mode of triple quadrupole (QqQ) mass spectrometry, and multivariate statistical analysis methods were applied to compare different processed products. Method validation results indicated good specificity, linearity, repeatability, precision, stability and recovery of the established quantification method and good linearity, precision and stability of the pseudotargeted metabolomics method. Differential compounds of different processed products were screened out and further confirmed by the quantification results. At last, the processing procedures were optimized to obtain new processed products of "Heishunpian" (black slices) with less toxicity, in which the contents of the toxic diester-type diterpenoid alkaloids were reduced from 106.98 µg/g to 0.85-12.96 µg/g. This study provided a valuable reference for the establishment of comprehensive quality evaluation methods of herbal medicines and a scientific basis for the optimization of processing procedures of Aconiti Lateralis Radix Praeparata.

[Comparison of alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata based on UHPLC-Q-Exactive Orbitrap MS/MS].

UHPLC-Q-Exactive Orbitrap MS/MS was used to systematically analyze and compare the alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata. After the samples were pretreated in the solid-phase extraction cartridges, 0.1% ammonium hydroxide(A)-acetonitrile(B) was used for gradient elution. The LC-MS method for characterization of alkaloids in the three herbal medicines was established in ESI positive ion mode to collect high resolution MS data of reference substances and samples. On the basis of the information of reference substance cracking behavior, retention time, accurate molecular mass, and related literature, a total of 155 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Prae-parata. Specifically, 130, 127, and 92 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata, respectively. Monoester alkaloids and amino-alcohol alkaloids were dominant in the three herbal medicines, and the alkaloids in Aconiti Kusnezoffii Radix and Aconiti Radix were similar. This paper can provide a reference for elucidating the pharmacological effects and clinical application differences of the three herbal medicines produced from plants of Aconitum.

[Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty: a randomized controlled trial].

OBJECTIVE: To investigate the clinical effect of aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty and the influence on hypercoagulation. METHODS: Seventy-three patients of knee osteoarthritis with lower extremity venous thrombosis after total knee arthroplasty (KOA) were randomly divided into an observation group (37 cases, 2 cases dropped off) and a control group (36 cases, 1 case dropped off). The patients in the control group took orally rivaroxaban tablets, 10 mg a time, once a day. On the basis of the treatment as the control group, the aconite-isolated moxibustion was applied to Yongquan (KI 1) for the patients of the observation group, once daily and 3 moxa cones were used in each treatment. The duration of treatment was 14 days in both groups. Before treatment and 14 days into treatment, the ultrasonic B test was adopted to determine the conditions of lower extremity venous thrombosis in the two groups. Before treatment, 7 and 14 days into treatment, the coagulation indexes (platelet [PLT], prothrombin time [PT], activated partial prothrombin time [APTT], fibrinogen [Fib] and D-dimer[D-D]), the blood flow velocity of the deep femoral vein and the circumference of the affected side were compared between the two groups separately, and the clinical effect was evaluated. RESULTS: Fourteen days into treatment, the venous thrombosis of the lower extremity was relieved in both groups (P<0.05), and that of the observation group was better than the control group (P<0.05). Seven days into treatment, the blood flow velocity of the deep femoral vein was increased compared with that before treatment in the observation group (P<0.05), and the blood flow rate in the observation group was higher than that in the control group (P<0.05). Fourteen days into treatment, PT, APTT and the blood flow velocity of the deep femoral vein were increased in the two groups compared with those before treatment (P<0.05); and PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all reduced in the two groups (P<0.05). Compared with the control group 14 days into treatment, the blood flow velocity of the deep femoral vein was higher (P<0.05), PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all lower in the observation group (P<0.05). The total effective rate was 97.1% (34/35) in the observation group, higher than 85.7% (30/35) in the control group (P<0.05). CONCLUSION: Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban can effectively treat lower extremity venous thrombosis after total knee arthroplasty, relieve hypercoagulation, accelerate the blood flow velocity and alleviate swelling of the lower extremity in the patients with knee osteoarthritis.

Chemical constituents, pharmacological effects, toxicology, processing and compatibility of Fuzi (lateral root of Aconitum carmichaelii Debx): A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The lateral root of Aconitum carmichaelii Debx is known as Fuzi in Chinese. It is traditionally valued and used for dispelling cold, relieving pain effects, restoring 'Yang,' and treating shock despite its high toxicity. This review aims to provide comprehensive information on the chemical composition, pharmacological research, preparation, and compatibility of Fuzi to help reduce its toxicity and increase its efficiency, based on the scientific literature. In addition, this review will establish a new foundation for further studies on Fuzi. MATERIALS AND METHODS: A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases. RESULTS: Fuzi extracts contain diester-type alkaloids, monoester-type alkaloids, other types of alkaloids, and non-alkaloids types, and have various pharmacological activities, such as strong heart effect, effect on blood vessels, and antidepressant, anti-diabetes, anti-inflammatory, pain-relieving, antitumor, immunomodulatory, and other therapeutic effects. However, these extracts can also lead to various toxicities such as cardiotoxicity, neurotoxicity, reproductive toxicity, hepatotoxicity, and embryonic toxicity. In vivo and in vitro experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Fuzi. CONCLUSION: The therapeutic potential of Fuzi has been demonstrated in conditions, such as heart failure, various pains, inflammation, and tumors, which is attributed to the diester-type alkaloids, monoester-type alkaloids, other types of alkaloids, and non-alkaloid types. In contrast, they are also toxic components. Proper processing and suitable compatibility can effectively reduce toxicity and increase the efficiency of Fuzi. Thus more pharmacological and toxicological mechanisms on main active compounds are necessary to be explored.

A mid-infrared spectroscopy-random forest system for the origin tracing of Chinese geographical indication Aconiti Lateralis Radix Praeparata.

Reliable origin certification methods are essential for the protection of high-value genuine medicinal material with designated origins and geographical indication (GI) products. Aconiti Lateralis Radix Praeparata (Fuzi), one well-known traditional Chinese medicine and geographical indication products have remarkable efficacy and wide clinical application, with high demand in domestic and international markets. The efficacy and price of Fuzi from different origins vary, and it is difficult for the general public to accurately identify them through traditional experience. The mass spectrometry detection technology based on the plant metabolomics is tedious and lengthy in test sample preparation, complicated in operation, long in detection time, and low in reproducibility. As a sophisticated, green, fast, and low-loss detection technique, infrared spectroscopy is integrated by machine learning to bring new ways for quality regulation and control of traditional Chinese medicines. An analytical method based on mid-infrared spectroscopy combined with a random forest algorithm was developed to verify the geographical origin of authentic herbs and/or GI products. The method successfully predicted and classified three varieties of Chinese GI Fuzi and four varieties of non-GI Fuzi. In this study, an environment-friendly traceability strategy with fast analysis, low sample loss and high precision was used to provide a new strategy for identifying the origin of Fuzi.

Comparative Pharmacokinetic Investigation on Multiple Active Aminoalcohol-Diterpenoid Alkaloids after Single Oral Administrations of Monomers and Aqueous Extract of Fuzi (Aconiti Lateralis Radix Praeparata) by UFLC-MS/MS.

To further study the aminoalcohol-diterpenoid alkaloids (ADAs) in Fuzi (Aconiti Lateralis Radix Praeparata), a simple and sensitive UFLC-MS/MS method was established and validated for the determination of five ADAs, aconine, mesaconine, hypaconine, deoxyaconine and fuziline, in rat plasma to compare the pharmacokinetic characteristics of pure ADAs and Fuzi decoction. After precipitating protein with methanol, plasma samples were isolated at 0.5 mL/min flow rate on Waters Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm). The mobile phase was composed of 0.1% formic acid-water and methanol with gradient elution. Mass spectrometric inspection was conducted on a 5500 UFLC-MS/MS system with an electrospray ionization source in patterns of positive ion and multiple reaction-monitoring (MRM). All calibration curves were proved to have acceptable linearity (r2 > 0.99) in linear ranges. Intra-day and inter-day precision and the accuracy met the requirements. The matrix effects of all analytes were between 85% and 115% of three concentration levels. This method has been under verification for comparative pharmacokinetic research after oral administration between aqueous extract of Fuzi and single pure ADAs. The results demonstrated that there are evident pharmacokinetic discrepancies between them, and administration in the extract form instead of pure form may contribute to higher absorption.

Inhibition of SLC7A11-GPX4 signal pathway is involved in aconitine-induced ferroptosis in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum species, with a long history of traditional application, were applied to treat rheumatism, arthritis, stroke, and pain in Chinese medical practice. However, misuse of Aconitum species may induce central nervous toxic effects, such as numbness, vomiting, and even coma. Aconitine has been proved to be the main toxic component of Aconitum plants. Neurotoxicity is the main toxic effect of aconitine, while the underlying mechanism of aconitine remains unclear. AIM OF THE STUDY: The purpose of the study is to explore the effects and molecular mechanism of ferroptosis caused by aconitine in vivo and in vitro. MATERIALS AND METHODS: Six-dpf zebrafish larvae and SH-SY5Y cells were treated with different concentrations of aconitine for 24 h. Inhibitors treatment, e.g. pretreatment with Necrostain-1 (Nec-1) and Z-VZD-FMK for 12 h, or with Ferrostain-1 (Fer-1) for 4 h, were involved in the identification of aconitine-induced ferroptosis. Transient transfection experiment was conducted to explore the effects of SLC7A11 in the process of aconitine-induced ferroptosis. The effects of aconitine on morphological changes, lipid peroxidation, ferrous ion, and ferroptosis were detected by transmission electron microscope, flow cytometry, confocal microscopy, enzyme-linked immunosorbent assay and western blotting. RESULTS: In SH-SY5Y cells, morphological changes including shrunken mitochondria, increased mitochondrial membranes density and ruptured mitochondrial membranes were captured in aconitine-treated group. The cell viability and GSH content dose-dependently declined, levels of lipid reactive oxygen species (ROS), malondialdehyde (MDA), and ferrous ion significantly increased after aconitine exposure for 24 h. Ferroptosis inhibitor Fer-1 pretreatment effectively increased cell viability, GSH content, and decreased levels of MDA and lipid peroxidation, suggesting that aconitine induced ferroptosis. In addition, the protein expression of SLC7A11 and GPX4 were improved after Fer-1 preincubation, which indicated that aconitine triggered ferroptosis via the inhibition of SLC7A11 and the inactivation of GPX4. Ferroptotic characteristics, including GSH depletion and lipid peroxidation accumulation, were alleviated via overexpression of SLC7A11 to increase protein expression of GPX4. In zebrafish experiment, GSH depletion, lipid peroxidation accumulation, iron overload, and the decreased protein expression of SLC7A11 and GPX4 were also induced in zebrafish larvae after aconitine exposure. Taken together, aconitine triggered ferroptotic cell death via inhibiting SLC7A11/GPX4 signal pathway in vivo and in vitro. CONCLUSION: All results indicated that aconitine triggered ferroptosis of SH-SY5Y cells and zebrafish larvae nerve cells, which involved the inhibition of SLC7A11/GPX4 signal pathway mediated by lipid peroxidation damage and iron overload.

Compositions analysis and insecticidal activity of Aconitum polycarpum Chang ex W.T.Wang petroleum ether fractions and essential oils.

ETHNOPHARMACOLOGICAL RELEVANCE: The Aconitum genus plants as a natural pesticide for insecticide and rodent control has been recorded in Chinese folk. However, the insecticide effect, mechanism, and active composition of Aconitum polycarpum Chang ex W.T.Wang have not been studied further. AIM OF THE STUDY: This study was designed to analyze the chemical composition, evaluate contact toxicity of petroleum ether extracts (PEEs) and essential oils (EOs) of A. polycarpum, and further explore their possible insecticidal mechanism. MATERIALS AND METHODS: The roots of A. polycarpum were extracted with 90% methanol, and then extracted with petroleum ether to obtain PEEs; the EOs was extracted by distillation. The chemical compositions of PEEs and EOs were analyzed by GC-MS. Contact toxicity was evaluated by the immersion method. Exploring insecticidal mechanisms through in vitro enzyme inhibitory activity. RESULTS: 12 compounds were identified from PEEs by GC-MS, mainly including aliphatic (94.8%), the main compositions were Octadecadienol (ODO) (aliphatic, 53.2%) and L-Ascorbyl dipalmitate (LADP) (aliphatic, 36.1%). 24 compounds were identified in EOs. About 44.6% of the identified components were terpenoids and their derivatives, and the rest were mainly aliphatic (34.7%) and phenols (3.0%). The main chemical components were L (-)-Borneol (LB) (terpenoid, 28.3%), LADP (aliphatic, 19.1%), and Isoborneol (terpenoid, 9.1%). The contact toxicity indicated that the PEEs showed great contact toxicity against Spodoptera exigua (LC50 = 126.2 mg/L). Meanwhile, LADP (LC50 = 128.1 mg/L) and ODO (LC50 = 121.3 mg/L) was similar to that of Cyhalothrin (LC50 = 124.2 mg/L) in contact toxicity. In addition, we found that LADP and ODO exhibited excellent inhibitory activity against CarE (IC50 = 58.0, 56.1 mg/L, respectively) by measuring in vitro enzyme inhibitory activity, which was superior than Cyhalothrin (IC50 = 68.1 mg/L). CONCLUSIONS: The chemical compositions and contact toxicity of EOs and PEEs of A. polycarpum were analyzed and evaluated, and their insecticidal mechanisms were preliminarily discussed for the first time. It proved PEEs of A. polycarpum and its main components (LADP and ODO) exhibited excellent contact toxicity against S. exigua, and CarE was identified as a potential target for contact toxicity. This study indicated that the insecticidal activity of petroleum ether extracts from A. polycarpum is quite promising, and provides a practical and scientific basis for the development and application of botanical pesticides.

Diverse alkaloids from the aerial parts of Aconitum carmichaelii and antiproliferative activity of costemline via inhibiting SIRT1/ROCK1/P-STAT3 pathways.

Six undescribed alkaloids together with 15 known alkaloids were isolated from the aerial parts of Aconitum carmichaelii. Their structures were elucidated extensively by NMR and HRESIMS spectroscopy. The absolute configurations of N-formyllaurotetanine, and the known compounds glaucine-ß-N-oxide and glaucine-α-N-oxide were established by electronic circular dichroism (ECD) spectra. Notably, it was the discovery of rare indole alkaloids from the genus Aconitum, and biosynthetic pathway of compounds 1 and 6 was deduced. Evaluation of the antiproliferative activity of these alkaloids demonstrated that costemline exhibited significant anti-proliferation effects against HCT116, SKOV3, and A549 cells with IC50 values of 5.6, 14.2, and 6.8 µM, respectively. Costemline could also inhibit the cell invasion activity of HCT116 cells. Mechanistic studies in HCT116 cells suggested that the antiproliferative activity of costemline was attributable to SIRT1/ROCK1/P-STAT3 pathways regulation. This study revealed the potential for developing and utilizing the aerial parts of Aconitum carmichaelii.

Detoxification mechanisms of ginseng to aconite: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconite (Fuzi, FZ), the processed root tuber of Aconitum carmichaelii Debx., is utilized as a classic medicine to treat diseases of the cardiovascular system and immune system. Resulting from the narrow margin of safety between a therapeutic dose and a toxic dose, FZ often causes cardiotoxicity including hypotension, palpitation, and bradycardia. Contributing to the detoxification effects of the other famous herbal medicine ginseng (Renshen, RS), which is the dried root and rhizome of Panax ginseng C. A. Meyer, people broadly combine FZ and RS as compatibility more than 1800 years to attenuate the toxicity of FZ. However, the systematic detoxification mechanisms of RS to FZ have not been fully revealed. AIM OF THE REVIEW: Aiming to provide a comprehensive interpretation of the attenuation processes of FZ via RS, this review summarizes the up-to-date information about regulatory mechanisms of RS to FZ to shed the light on the essence of detoxification. MATERIALS AND METHODS: Literature was searched in electronic databases, including PubMed, Web of Science ScienceDirect, Google Scholar, CNKI and WanFang Data. Relevant studies on detoxification mechanisms were included while irrelevant and duplicate studies were excluded. According to the study design, subject, intervention regime, outcome, first author and year of publication of included data, detoxification mechanisms of RS to FZ were summarized and visualized. RESULTS: A total of 144 studies were identified through databases from their inception up to Oct. 2022. Included information indicated that diester-diterpenoid alkaloids (DDAs) were the main toxic substances of FZ. The main mechanisms that RS attenuates the toxicity of FZ were transforming toxic compounds of FZ, affecting the absorption and metabolism of FZ as well as the FZ-induced cell toxicity alleviation. CONCLUSION: FZ, as a famous traditional Chinese medicine, has good prospects for utilization. The narrow margin of safety between a therapeutic dose and a toxic dose of FZ limits its clinical effect and safety while RS is always combined with FZ to alleviate its toxicity. However, mechanisms responsible for the detoxification process have not been well identified. Therefore, detoxification mechanisms of RS to FZ are reviewed to ensure the safety and effectiveness of FZ.

Root endophytic bacterial community composition of Aconitum carmichaelii debx. from three main producing areas in China.

Aconitum carmichaelii Debx. is famous for the bioactive aconitum alkaloids as traditional Chinese medicine. Endophytic bacteria play vital roles in plant growth, health, and the production of secondary metabolites such as alkaloids. In this study, we employed 16 S rRNA amplicon high-throughput sequencing to determine the root endophytic bacterial community of A. carmichaelii Debx. collected from three main producing areas including the geo-authentic area in China, high performance liquid chromatography to measure the contents of six bioactive alkaloids and correlation analysis to explore the relationship among environmental factors, alkaloids contents, and endophytic bacterial community. The results indicated that the root core microbiota of A. carmichaelii Debx. was dominated by Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Root endophytic bacterial community in the geo-authentic area was distinct from the other two regions. Soil nitrogen contents, organic matter, and temperature were the main factors contributing to the endophytic bacterial community structure. Significant correlation was found between alkaloids contents and some bacterial genera. Particularly, the abundance of Lactobacillus was positively correlated with the contents of benzoyl-mesaconitine and benzoyl-aconine. This study provided the first insight into the root endophytic bacterial community composition of A. carmichaelii Debx., and can direct further isolation of functional bacterial strains.

Insecticidal potential of extracts, fractions, and molecules of Aconitum heterophyllum Wall ex. Royle against aphid Aphis craccivora Koch (Hemiptera: Aphididae).

BACKGROUND: Aphis craccivora is the major sap-sucking pest of leguminous crops and vector of plant viruses that cause damage to plants and reduce yield. Indiscriminate and nonjudicious use of synthetic insecticides led to resistance development and harmful to environment. Therefore, it is important to discover plant-based lead(s) which can replace synthetic insecticides. In the current study the residual toxicity of extracts, fractions, and isolated compounds of Aconitum heterophyllum were evaluated against A. craccivora to identify lead(s) for further development of botanical formulation. RESULTS: In residual contact assay, ethanolic (LC50  = 2837.17 mg L-1 ) and aqueous methanolic extracts (LC50  = 2971.59 mg L-1 ) were effective against A. craccivora. Among fractions, the n-butanol fraction of the aqueous methanolic extract (LC50  = 986.96 mg L-1 ) was found to be most effective, followed by the ethyl acetate fraction of the ethanolic extract (LC50  = 1037.52 mg L-1 ) and the n-hexane fraction of both extracts (LC50  = 1113.85 to 1233.11 mg L-1 ). Among pure molecules, aconitic acid was found to be the most effective (68% mortality; LC50  = 1313.19 mg L-1 ) and was on a par with azadirachtin 0.15% EC (66% mortality; LC50  = 1921.10 mg L-1 ). Furthermore, from the effect of ethanoic extract on detoxification enzyme inhibition in A. craccivora we concluded that the target site of action of this extract in A. craccivora might be glutathione S-transferase. CONCLUSIONS: The parent extract/fractions of A. heterophylum showed promising activity against A. craccivora. Among phytoconstituents of the active extract and fractions, aconitic acid was found to be on a par with azadirachtin 0.15% EC. © 2022 Society of Chemical Industry.

[Medication rule of traditional Chinese medicine for heart failure after myocardial infarction: based on data mining].

This study aims to explore the medication rule of traditional Chinese medicine(TCM) for heart failure after myocardial infarction via data mining. To be specific, articles on the treatment of the disease with Chinese medicine were retrieved from CNKI, Wanfang, VIP, and SinoMed and related information was collected. A database was created with Microsoft Excel 2019, and SPSS Clementine 12.0 and IBM SPSS Statistics 23.0 were applied for association rules analysis, cluster analysis, and factor analysis. Finally, a total of 81 TCM prescriptions were screened out, involving 91 medicinals with cumulative use frequency of 740. The main syndromes were Qi deficiency and blood stasis, Yang Qi deficiency and blood stasis together with retained morbid fluid, deficiency of both Qi and Yin and blood stasis. The medicinals with high-frequency were Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Poria, and Aconiti Lateralis Radix Praeparata. The effects of the medicinals were tonifying deficiency, activating blood and resolving stasis, and promoting urination and draining dampness. The association rules analysis yielded "Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma" "Astragali Radix-Aconiti Lateralis Radix Praeparata-Salviae Miltiorrhizae Radix et Rhizoma" "Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix" combinations. Cluster analysis yielded 6 basic formulas for heart failure after myocardial infarction. Factor analysis extracted a total of 8 common factors. Heart failure after myocardial infarction is characterized by the syndrome of deficiency in nature and excess in superficiality. The core pathogenesis is "deficiency" "stasis" "retained morbid fluid", particularly "deficiency". This disease is closely related to the heart, lung, and spleen. The basic treatment principle is replenishing Qi and activating blood, and warming Yang, excreting water, and nourishing yin should also be emphasized. The common basic prescriptions, such as Siwu Decoction, Shengmai Powder, Xuefu Zhuyu Decoction, Linggui Zhugan Decoction, and Shenfu Decoction, have been discovered. This study provided data for clinical medication and drug development for heart failure after myocardial infarction.

Integrating Metabolomics and Transcriptomics to Unveil Atisine Biosynthesis in Aconitum gymnandrum Maxim.

Diterpene alkaloids (DAs) are characteristic compounds in Aconitum, which are classified into four skeletal types: C18, C19, C20, and bisditerpenoid alkaloids. C20-DAs are thought to be the precursor of the other types. Their biosynthetic pathway, however, is largely unclear. Herein, we combine metabolomics and transcriptomics to unveil the methyl jasmonate (MJ) inducible biosynthesis of DAs in the sterile seedling of A. gymnandrum, the only species in the Subgenus Gymnaconitum (Stapf) Rapaics. Target metabolomics based on root and aerial portions identified 51 C19-DAs and 15 C20-DAs, with 40 inducible compounds. The highest content of C20-DA atisine was selected for further network analysis. PacBio Isoform sequencing integrated with RNA sequencing not only provided the full-length transcriptome but also their response to induction, revealing 1994 genes that exhibited up-regulated expression. Further, 38 genes involved in terpenoid biosynthesis were identified, including 7 diterpene synthases. In addition to the expected function of the four diterpene synthases, AgCPS5 was identified to be a new ent-8,13-CPP synthase in Aconitum and could also combine with AgKSL1 to form the C20-DAs precursor ent-atiserene. Combined with multiple network analyses, six CYP450 and seven 2-ODD genes predicted to be involved in the biosynthesis of atisine were also identified. This study not only sheds light on diterpene synthase evolution in Aconitum but also provides a rich dataset of full-length transcriptomes, systemic metabolomes, and gene expression profiles, setting the groundwork for further investigation of the C20-DAs biosynthesis pathway.

Poisonous Piperidine Plants and the Biodiversity of Norditerpenoid Alkaloids for Leads in Drug Discovery: Experimental Aspects.

There are famous examples of simple (e.g., hemlock, Conium maculatum L.) and complex (e.g., opium poppy, Papaver somniferum L., Papaveraceae) piperidine-alkaloid-containing plants. Many of these are highly poisonous, whilst pepper is well-known gastronomically, and several substituted piperidine alkaloids are therapeutically beneficial as a function of dose and mode of action. This review covers the taxonomy of the genera Aconitum, Delphinium, and the controversial Consolida. As part of studying the biodiversity of norditerpenoid alkaloids (NDAS), the majority of which possess an N-ethyl group, we also quantified the fragment occurrence count in the SciFinder database for NDA skeletons. The wide range of NDA biodiversity is also captured in a review of over 100 recently reported isolated alkaloids. Ring A substitution at position 1 is important to determine the NDA skeleton conformation. In this overview of naturally occurring highly oxygenated NDAs from traditional Aconitum and Delphinium plants, consideration is given to functional effect and to real functional evidence. Their high potential biological activity makes them useful candidate molecules for further investigation as lead compounds in the development of selective drugs.