Roots Of Aconitum Carmichaelii Research Articles

Research on quality marker based on the processing from Aconiti lateralis radix praeparata to Heishunpian.

Aconiti lateralis radix praeparata (ALRP), the sub root of Aconitum carmichaelii Debx., is a traditional Chinese medicine with good pharmacological effects. Heishunpian (HSP), prepared through the process of brine immersing, boiling, rinsing, dyeing, and steaming ALRP is one of the most widely used forms of decoction pieces in clinical practice. This study aims to investigate the mechanisms of component changes and transformations during the processing from ALRP to HSP, and to screen for their quality markers through UHPLC-QTOF-MS analysis. Samples from ALRP to HSP during processing were prepared and analyzed by UHPLC-QTOF-MS. By comparing the differences between before and after each processing step, the purpose of processing and the transformation of components during processing were studied. In addition, multiple batches of ALRP and HSP were determined, and potential quality markers were screened. Through the analysis of ALRP and five key processing samples, 55 components were identified. Immersing in brine, rinsing, and dyeing were the main factors of component loss, and boiling caused a slight loss of components. Some components were enhanced during the steaming process. Combining the screened differences components between multiple ALRP and HSP, 10 components were considered as potential quality biomarkers. This study found that the adjacent hydroxyl groups of the ester group may have a positive impact on the hydrolysis of the ester group, and 10 quality markers were preliminarily screened. It provides a reference for quality control and clinical application of ALRP and HSP.

Polysaccharides from Aconitum carmichaelii leaves: Structure, immunomodulatory and anti-inflammatory activities

Roots of Aconitum carmichaelii are used in Asian countries due to its content of bioactive alkaloids. In the production of root preparations, tons of leaves are usually discarded, leading to a huge waste of herbal material. The aim of this study is to investigate the polysaccharides in these unutilized leaves. A neutral polysaccharide (AL-N) appeared to be a mixture of heteromannans, and two purified acidic polysaccharides (AL-I-I and AL-I-II) were shown to be pectins containing a homogalacturonan backbone substituted with terminal β-Xylp-units. AL-I-I consisted of a type-I rhamnogalacturonan core, with arabinan and type-II arabinogalactan domains while AL-I-II was less branched. AL-N and AL-I-I were able to modulate the complement system, while AL-I-II was inactive. Interestingly, AL-N, AL-I-I and AL-I-II were shown to exert anti-inflammatory effects on porcine enterocyte IPEC-J2 cells. AL-I-I and AL-I-II were able to down-regulate the expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain 1 (NOD1).

Compatibility of Fuzi and Ginseng Significantly Increase the Exposure of Aconitines.

The herb-pair ginseng-Fuzi (the root of Aconitum carmichaelii) is the material basis of Shenfu prescriptions and is popular in traditional Chinese medicine for the treatment of heart failure, and even shock with severe-stage of COVID-19. A narrow therapeutic window of Fuzi may cause significant regional loss of property and life in clinics. Therefore, systemic elucidation of active components is crucial to improve the safety dose window of Shenfu oral prescriptions. A high performance liquid chromatography-mass spectrometry method was developed for quantification of 10 aconitines in SD rat plasma within 9 min. The limit of detection and the limit of quantification were below 0.032 ng/ml and 0.095 ng/ml, respectively. Furthermore, a systemic comparison with their pharmacokinetic characteristics after oral administration of a safe dosage of 2 g/kg of Fuzi and ginseng-Fuzi decoction for 24 h was conducted. Eight representative diester, monoester, and non-ester aconitines and two new active components (i.e., songorine and indaconitine) were all adopted to elucidating the differences of the pharmacokinetic parameters in vivo. The compatibility of Fuzi and ginseng could significantly increase the in vivo exposure of active components. The terminal elimination half-life and the area under the concentration-time curve of mesaconitine, benzoylaconitine, benzoylmesaconitine, benzoylhypaconitine, and songorine were all increased significantly. The hypaconitine, benzoylmesaconitine, and songorine were regarded as the main active components in vivo, which gave an effective clue for the development of new Shenfu oral prescriptions.

Assessment of reproductive toxicity and genotoxicity of Aconiti Lateralis Radix Praeparata and its processed products in male mice

Ethnopharmacological relevanceAconiti Lateralis Radix Praeparata (Chinese name: Fuzi), the root of Aconitum carmichaelii Debx., is a representative medicine for restoring yang and rescuing patient from collapse. However, less studies had been reported on the reproductive toxicity and genotoxicity of Fuzi. According to the principle of reducing toxicity and preserving efficiency, only processed products of Fuzi are commonly applied in clinic, including Baifupian, Heishunpian and Danfupian. However, whether processing could alleviate the reproductive toxicity and genotoxicity of Fuzi had not been revealed. Aim of the studyTo assess the effect and possible mechanism of Fuzi and its processed products on reproductive toxicity and genotoxicity in male mice. Materials and methodsAqueous extracts of Fuzi and its processed products (Baifupian, Heishunpian and Danfupian, 5.85 g/kg) were administrated by gavage once daily for fourteen consecutive days. The reproductive toxicity was evaluated by testis weight, testis ratio, testis histopathology, sperm count, sperm viability rate and sperm deformity rate. The genotoxicity was evaluated by comet assay and micronucleus test in sperm, peripheral blood cell and bone marrow cell. Possible mechanisms of attenuating toxicity by processing were analyzed by detecting the level of testosterone, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and catalase (CAT). ResultsFuzi significantly caused different degrees of reproductive toxicity and genotoxicity, specifically reducing the weight and testicular coefficient of testis, causing obvious pathological changes in testicular tissue, reducing sperm count and sperm viability rate, increasing sperm deformity rate and DNA damage in sperm/peripheral blood cells/bone marrow cells. Moreover, Fuzi decreased the level of testosterone, SOD, GSH and CAT, while increased the level of MDA in serum. Notably, the reproductive toxicity and genotoxicity induced by the processed products, especially Heishunpian and Danfupian, were significantly lowered compared to Fuzi. Processing could increase the level of testosterone, SOD, GSH, CAT and decrease the level of MDA compared to Fuzi. ConclusionFuzi and its processed products had reproductive toxicity and genotoxicity, but the toxicity of processed products was significantly weakened compared to Fuzi. The protective mechanism of processing to reduce the toxicity of Fuzi might be related to increasing the level of testosterone and decreasing oxidative stress.

Mechanism of action of a diterpene alkaloid hypaconitine on cytotoxicity and inhibitory effect of BAPTA-AM in HCN-2 neuronal cells.

Hypaconitine, a neuromuscular blocker, is a diterpene alkaloid found in the root of Aconitum carmichaelii. Although hypaconitine was shown to affect various physiological responses in neurological models, the effect of hypaconitine on cell viability and the mechanism of its action of Ca2+ handling is elusive in cortical neurons. This study examined whether hypaconitine altered viability and Ca2+ signalling in HCN-2 neuronal cell lines. Cell viability was measured by the cell proliferation reagent (WST-1). Cytosolic Ca2+ concentrations [Ca2+ ]i was measured by the Ca2+ -sensitive fluorescent dye fura-2. In HCN-2 cells, hypaconitine (10-50μmol/L) induced cytotoxicity and [Ca2+ ]i rises in a concentration-dependent manner. Removal of extracellular Ca2+ partially reduced the hypaconitine's effect on [Ca2+ ]i rises. Furthermore, chelation of cytosolic Ca2+ with BAPTA-AM reduced hypaconitine's cytotoxicity. In Ca2+ -containing medium, hypaconitine-induced Ca2+ entry was inhibited by modulators (2-APB and SKF96365) of store-operated Ca2+ channels and a protein kinase C (PKC) inhibitor (GF109203X). Hypaconitine induced Mn2+ influx indirectly suggesting that hypaconitine evoked Ca2+ entry. In Ca2+ -free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished hypaconitine-induced [Ca2+ ]i rises. Conversely, treatment with hypaconitine inhibited thapsigargin-induced [Ca2+ ]i rises. However, inhibition of phospholipase C (PLC) with U73122 did not inhibit hypaconitine-induced [Ca2+ ]i rises. Together, hypaconitine caused cytotoxicity that was linked to preceding [Ca2+ ]i rises by Ca2+ influx via store-operated Ca2+ entry involved PKC regulation and evoking PLC-independent Ca2+ release from the endoplasmic reticulum. Because BAPTA-AM loading only partially reversed hypaconitine-induced cell death, it suggests that hypaconitine induced a second Ca2+ -independent cytotoxicity in HCN-2 cells.

Comparison with Pharmacokinetic Characteristics of Aconitines after Compatibility with Fuzi and Ginseng

The herb-pair Gingseng-Fuzi (the root of Aconitum carmichaelii ) is named as Shenfu prescriptions and is popular in traditional Chinese medicine for treatment of heart failure, and even shock with severe-stage COVID-19. However, a narrow therapeutic window of Fuzi may cause significant regional loss of property and life in clinics. Therefore, systemic elucidation of compatibility mechanism using in vivo comparative exposure is particularly crucial to improve the safety dose window of Shenfu prescriptions. A high performance liquid chromatography-mass spectrometry method was developed for quantification of 11 aconitines in SD rat plasma within 9 min, and a systemic comparison with their pharmacokinetic characteristics after oral administration of a safe dosage of 2 g/Kg of Fuzi and Ginseng-Fuzi decoction for 24 h was conducted. Nine representative diester, monoester, and non-ester aconitines and two new active components ( e . g . songorine and indaconitine) were all adopted to elucidation of the differences of the contents in decoction and the pharmacokinetic parameters in vivo , including the terminal elimination half-life (T1/2), area under the concentration-time curve, mean residence time, time to achieve maximum concentration (Cmax), and maximum plasma concentration. It was found that the compatibility with Fuzi and gingseng could significantly increase their bioavailability of active components. Moreover, the in vivo exposure and the T1/2 of diester aconitines (aconitine and mesaconitine) and the monoester aconitines (benzoylaconitine, benzoylmesaconitine, and benzoylhypaconitine) were all increased significantly, indicating the efficacy was increased simultaneously. Songorine shown the largest Cmax with a potential decardiotoxicity ability. This study provided a solid pharmacokinetic parameters for development of safe and effective new Shenfu oral prescriptions.

Antiviral Activity and Molecular Docking of Active Constituents from the Root of Aconitum carmichaelii

Antiviral Activity and Molecular Docking of Active Constituents from the Root of Aconitum carmichaelii

Four New Diterpenoid Alkaloids from the Roots of Aconitum carmichaelii

Aconitum carmichaelii Debeaux is a widely used traditional Chinese medicine and an important source of clinical drugs, of which the parent and lateral roots are known as 'Chuanwu' and 'Fuzi', respectively. Four new C19 -diterpenoid alkaloids, carmichasines A - D (1 - 4), were isolated from the roots of Aconitum carmichaelii, together with twelve known compounds (5 - 16). Their structures were elucidated via spectroscopic analyses, including HR-ESI-MS, IR, and NMR. Carmichasine A (1) is the first natural C19 -diterpenoid alkaloid possessing a cyano group. Most of the diterpenoid alkaloids isolated were C19 -category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The cytotoxicity of the new compounds was also investigated against several human cancer cell lines, including MCF-7, HCT116, A549, and 786-0, and none of them showed considerable cytotoxic activity.

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2′-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-β-D-allopyranosyl-ferulate (3), and methyl-4-β-D-gulopyranosyl-cinnamate (4), along with six known compounds (5–10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94 μM, respectively.

Anti-cancer and anti-inflammatory new vakognavine-type alkaloid from the roots of Aconitum carmichaelii

Vakognavine-type alkaloids are a rare kind of diterpenoid alkaloid isolated from Delphinium and Aconitum species. During our research on the chemical constituents of the roots of Aconitum carmichaelii, a new vakognavine-type alkaloid (1) along with a known vakognavine-type alkaloid, trifoliolasine E (2), and two known hetisine-type alkaloids (3 and 4) were obtained. The structures were elucidated by a combination of high resolution ESI-MS, 1D and 2D NMR spectra. Compound 1 showed strong inhibitory effects on HT-29, SGC-7901, and HepG2 cell lines with IC50 values of 0.948, 0.983, and 3.645μM, respectively, while trifoliolasine E (2) exhibited moderate activities. Compound 1 was also found to dose-dependently inhibit the activity of cyclooxygenase-2 (COX-2) with an IC50 value of 29.75μM. To the best of our knowledge, this is the first report on the bioactivity of vakognavine-type diterpenoid alkaloids.

Simultaneous determination of 14 organic acids in Shenfu injection by hydrophilic interaction chromatography-tandem mass spectrometry

Organic acids are widely distributed in plants and related products, and participate in a wide range of metabolic pathways (e.g. tricarboxylic acid cycle), showing diverse pharmacological activities. As a widely used Chinese patent medicine, its adverse reactions are often reported. Therefore, we should further clarify the chemical components of Shenfu injection, and prepare strict quality standards to ensure the safety and effectiveness of its clinical use. Shenfu injection is prepared from red ginseng (steamed roots of Panax ginseng) and black prepared lateral roots of Aconitum carmichaelii (Heishunpian) by using modern extraction process, and organic acids are regarded as one of its main components. In current study, a hydrophilic interaction chromatography (HILIC) coupled with mass spectrometric method (HILIC-LC-MS) was developed and validated for the simultaneous determination of 14 organic acids, including cinnamic acid, ferulic acid, 4-hydroxylbenzoic acid, L-(+)-lactic acid, adipic acid, fumaric acid, caffeic acid, succinic acid, maleic acid, malonic acid, D-malic acid, (-)-shikimic acid, D-tartaric acid, and quinic acid in Shenfu injection. Satisfactory retention and separation were achieved for all organic acids on HILIC chromatographic column. Except cinnamic acid (231 μg•L⁻¹), lactic acid (113 μg•L⁻¹) and malonic acid (32.5 μg•L⁻¹), the limit of quantitation for the remaining 11 compounds were less than 10 μg•L⁻¹. D-Malic acid, malonic acid, quinic acid, L-(+)-lactic acid, and cinnamic acid were observed to have higher contents in Shenfu injection (>1.89 mg•L⁻¹), whereas caffeic acid and adipic acid were undetectable in all batches. Above all, the developed method is suitable for the simultaneous determination of organic acids in Shenfu and some other traditional Chinese medicine injections.

Traditional formula, modern application: chinese medicine formula sini tang improves early ventricular remodeling and cardiac function after myocardial infarction in rats.

Sini Tang (SNT) is a traditional Chinese herbal formula consisting of four different herbs: the root of Aconitum carmichaelii, the bark of Cinnamomum cassia, the rhizome of Zingiber officinale, and the root of Glycyrrhiza uralensis. This study aims to evaluate the improvement of early ventricular remodeling and cardiac function in myocardial infarction (MI) rats by SNT. A MI model was established by ligation of the left anterior descending coronary artery. Following treatment for 4 weeks, ultrasonic echocardiography was performed. Myocardial histopathological changes were observed using haematoxylin and eosin staining. Collagens (type I and type III), transforming growth factor-β1 (TGF-β1), and Toll-like receptors (TLR-2 and TLR-4) were measured in plasma, serum, and myocardial tissue. SNT treatment decreased the infarct size, the left ventricular cavity area/heart cavity area ratio, and the left ventricle dimension at end systole and increased the left ventricular ejection fraction. SNT reduced the levels of TLR-2 and TLR-4 in myocardial tissue significantly and decreased the collagens content in serum and in myocardial tissue. SNT could partially reduce the level of TGF-β1 in serum and in myocardial tissue. Our data suggest that the Chinese medicine formula SNT has the potential to improve early ventricular remodeling and cardiac function after MI.

Correction to Diterpenoid Alkaloids from the Lateral Root of Aconitum carmichaelii

Correction to Diterpenoid Alkaloids from the Lateral Root of <i>Aconitum carmichaelii</i>

Difference evaluation of three kinds of root of Aconitum carmichaelii in Sichuan based on UPLC analysis of six alkaloids and chemometrics

An ultra performance liquid chromatography (UPLC) method was established and validated to simultaneously determine the contents of six aconitum alkaloids in mother, daughter and fibrous roots of 19 batches of Aconitum carmichaelii from Sichuan province. The separation of the six alkaloids was achieved on a ACQUITY UPLC BEH C18 (2.1 mm x 100 mm, 1.7 microm) column at 40 degrees C with a mobile phase consisting of acetonitrile in 30 mmol x L(-1) ammonium acetate buffer solution (adjusted to pH 10.0 with aqueous ammonia) in gradient mode. The data and plots showed that the six aconitum alkaloids have different distributions. Four aconitum alkaloids were almost same in mother and daughter root except benzoylmesaconine and mesaconitine, while the fibrous root differed from the other two roots. The comparisons of significant differences of six aconitum alkaloids between the mother and daughter roots definitely demonstrated that benzoylmesaconine and mesaconitine were the representative components. The 38 detecting samples were classified as two clusters by hierarchical clustering analysis (HCA) and principle component analysis (PCA), the results indicated that the mother root was different from the daughter root on chemical material basis. The study might contribute to the reasonable clinical application of A. carmichaelii.

Constituents from Commonly used Traditional Chinese Medicines

The isolation and structure elucidation of chemical constituents from traditional Chinese medicines (TCMs) are still important and attractive, especially for finding lead compounds with a potential use of new drug development. TCMs are used for treatment of diseases from ancient times up to today (thousands of years), and are clinically effective. However, studies have only been carried out for about 20 years, and the active components are seldom identified. Because the chemical components of TCMs and pharmacological responses of a drug are very complex, it is extremely difficult to identify an active compound from a TCM to represent its clinical efficacy. This situation is actually like mechanisms of many diseases, which are not known yet. As a part of a program to assess the chemical and biological diversity of traditional Chinese medicines, we focused on minor components, particularly on those from water extracts of TCMs based on their traditional use of decoctions. Our efforts have led to the characterization of a great numbers of previously unknown constituents, such as homosecoiridoids (1–5) from the flower buds of Lonicera japonica [1], indole alkaloids (6–9) from the root of Isatis indigotica [2,3], and conformational isomers of aconitane diterpenoids (10–15) from the lateral root of Aconitum carmichaelii [4]. In this presentation recent works on these commonly used TCMs will be outlined. Acknowledgements: Financial support from the National Natural Sciences Foundation of China (No. 30825044) is acknowledged.

Talatisamine, a C19-diterpenoid alkaloid from Chinese traditional herbal `Chuanwu'

The title compound [systematic name: (1S,4S,5R,7S,8S,9R,10R,11S,13S,14S,16S,17R)-N-methyl-8,14-dihy­droxy-1,16-tri­meth­oxy-4-(meth­oxy­methyl­ene)aconitane], C24H39NO5, was isolated from the roots of Aconitum carmichaelii Debx., which is known as ‘Chuanwu’ in Chinese traditional herbal medicine. The mol­ecule has an aconitane carbon skeleton with four six-membered rings and two five-membered rings, including a six-membered N-containing heterocyclic ring. Both five-membered rings adopt envelope conformations. The four six-membered adopt chair conformations. Two intra­molecular O—H⋯O hydrogen bonds occur.