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Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy. [ABSTRACT FROM AUTHOR]

Cerebral ischemic stroke (CIS) is a kind of acute cerebrovascular disease with fast onset, low-cure rate, and high case-fatality rate. The application of Aconitum coreanum on CIS was recorded in many ancient books in China with it mechanism and effective components unclear. This study aimed to analyze the potential mechanism and effetvie components of A. coreanum on treating CIS. Neurological function score, cerebral infarction rate, and inflammatory indicators were applied to evaluate the efficacy of A. coreanum on gerbils with CIS. The prototype compounds in A. coreanum which were absorbed into blood was analyzed and identified by Ultra high performance liquid chromatography-Q exactive focus-Mass spectrometer (UPLC-QE-MS). And bioinformatics analysis was used to predict their potential targets or pathways of action. Western blotting and immunofluorescence were adopted to validate the targets or pathway with high relation. After treatment with A. coreanum, the neurological function status of gerbils with CIS was significantly improved, the ischemic area of the brain and the levels of inflammatory indicators significantly reduced. 22 prototype compounds in A. coreanum absorbed into blood were identified mainly including C-20 and C-19 diterpenoid alkaloids. Gene ontology (GO) function enrichment analysis illustrated that A. coreanum acted on protein phosphorylation, receptor complexes, protein kinase activity, and inflammatory response to impove CIS. The kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis results revealed that PI3K/Akt signaling pathway was a key pathway. Western blotting and immunofluorescence validated that A. coreanum acted on PI3K/Akt signaling pathway. In conclusion, A. coreanum improved the inflammantory condition in CIS by acting on PI3K/Akt signaling pathway and the effective components were the diterpenoid alkaloids in it.

Aconitum coreanum (H. Lév.) Rapaics listed in the Korean Red List is a medicinal herb. We presented complete chloroplast genome, which is 157,024 bp long and has four subregions: 87,637 bp of large single-copy and 16,901 bp of small single-copy regions, which are separated by two 26,243 bp inverted repeat regions including 132 genes (86 protein-coding genes, 8 rRNAs, and 37 tRNAs). The overall GC content of the chloroplast is 38.0%. Phylogenetic trees show that A. coreanum occupied a basal position at subgenus Aconitum clade and two A. coreanum isolated from midwestern and eastern regions of Korea are clustered together.

Объектом исследования явился Aconitum coreanum, являющийся единственным на Дальнем Востоке представителем секции Anthora. Ареал вида охватывает северо-восток Китая, полуостров Корея, российский Дальний Восток (Приморский край). Целью исследования явилось выявление анатомических диагностических признаков A. coreanum. Анатомический метод исследования структуры черешка листа, стебля, семени и семенной кожуры перспективен для идентификации видов и более крупных таксономических групп в семействе Ranunculaceae. Для работы использовали растения, собранные в фазе цветения. Черешки листьев, часть стебля и семена фиксировали в 70%-м этаноле. Поперечные срезы черешков стеблевых листьев срединной формации, а также стеблей и семян исследовали с помощью светового микроскопа. В результате исследования выявлены специфические признаки А. coreanum: радиальный V – образный на поперечном срезе черешок листа с 8–11 коллатеральными проводящими пучками разного размера; городчатые выросты наружной стенки эпидермальных клеток черешка; эпидермальные клетки стебля со значительно утолщенной наружной стенкой; стебель слаборебристый, полый внутри; cемена A. сoreanum на поперечном срезе с тремя хорошо выраженными крыловидными ребрами. Таким образом, диагностическими признаками вида являются: форма черешка на поперечном срезе, количество проводящих коллатеральных пучков, особенности строения внешних стенок эпидермальных клеток черешка, строение стебля и форма семени на поперечном срезе.

Cerebral ischemic stroke (CIS) is a kind of acute cerebrovascular disease with fast onset, low-cure rate, and high case-fatality rate. The application of Aconitum coreanum on CIS was recorded in many ancient books in China with it mechanism and effective components unclear. This study aimed to analyze the potential mechanism and effetvie components of A. coreanum on treating CIS. Neurological function score, cerebral infarction rate, and inflammatory indicators were applied to evaluate the efficacy of A. coreanum on gerbils with CIS. The prototype compounds in A. coreanum which were absorbed into blood was analyzed and identified by Ultra high performance liquid chromatography-Q exactive focus-Mass spectrometer (UPLC-QE-MS). And bioinformatics analysis was used to predict their potential targets or pathways of action. Western blotting and immunofluorescence were adopted to validate the targets or pathway with high relation. After treatment with A. coreanum , the neurological function status of gerbils with CIS was significantly improved, the ischemic area of the brain and the levels of inflammatory indicators significantly reduced. 22 prototype compounds in A. coreanum absorbed into blood were identified mainly including C-20 and C-19 diterpenoid alkaloids. Gene ontology (GO) function enrichment analysis illustrated that A. coreanum acted on protein phosphorylation, receptor complexes, protein kinase activity, and inflammatory response to impove CIS. The kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis results revealed that PI3K/Akt signaling pathway was a key pathway. Western blotting and immunofluorescence validated that A. coreanum acted on PI3K/Akt signaling pathway. In conclusion, A. coreanum improved the inflammantory condition in CIS by acting on PI3K/Akt signaling pathway and the effective components were the diterpenoid alkaloids in it., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Aconitum coreanum (H. Lév.) Rapaics listed in the Korean Red List is a medicinal herb. We presented complete chloroplast genome, which is 157,024 bp long and has four subregions: 87,637 bp of large single-copy and 16,901 bp of small single-copy regions, which are separated by two 26,243 bp inverted repeat regions including 132 genes (86 protein-coding genes, 8 rRNAs, and 37 tRNAs). The overall GC content of the chloroplast is 38.0%. Phylogenetic trees show that A. coreanum occupied a basal position at subgenus Aconitum clade and two A. coreanum isolated from midwestern and eastern regions of Korea are clustered together. [ABSTRACT FROM AUTHOR]

The aim of this paper was to seek an efficient method to preparative separation of alkaloid compounds from Aconitum coreanum (Guanbaifu), a well-known traditional Chinese medicinal plant for heart disease. Seven alkaloid compounds were successfully purified by pH-zone-refining counter-current chromatography with two-phase solvent system of petroleum ether–ethyl acetate–methanol–water (5:5:1:9, v/v/v/v), 10 mM triethylamine in upper phase and 10 mM hydrochloric acid in lower phase. From 3.5 g of crude extract, 356 mg of Guanfu base I, 578 mg of Guanfu base A, 74 mg of atisine, 94 mg of Guanfu base F, 423 mg of Guanfu base G, 67 mg of Guanfu base R and 154 mg of Guanfu base P were obtained with the purity of 96.40%, 97.2%, 97.5%, 98.1%, 98.9%, 98.3% and 98.4%. Their chemical structures were identified by TOF-MS and 1H-NMR. This study indicated that pH-zone-refining counter-current chromatography was an efficient method for separating the kind of alkaloids with low absorbance values.

Polysaccharides extracted from medicinal plants possess multiple functions. However, the inhibitory capacity of polysaccharides on the metastasis of breast cancer remains unclear. In the present study, we investigated the inhibitory activity of Aconitum coreanum polysaccharide (ACP1) and its sulphated derivative ACP1-s on migratory behaviour of human breast cancer cells MDA-MB-435s and evaluated the underlying molecular mechanism. The data from Transwell assay indicated that ACP1 and ACP1-s caused a significant inhibition of MDA-MB-435s cell migration in vitro . ACP1 and ACP1-s significantly impaired MDA-MB-435s cell migratory behaviour, and the accumulated distance and average velocity of ACP1- and ACP1-s-treated cells were reduced markedly. We also found ACP1 and ACP1-s treatment could affect dynamic remodeling of actin cytoskeleton, and suppress phosphorylation and activation of signalling molecules, attributing to anti-metastatic role of ACP1 and ACP1-s. These findings reveal a novel therapeutic potential of A. coreanum polysaccharide and its sulphated derivative for breast cancer metastasis. [ABSTRACT FROM AUTHOR]

In this study, we observed that a Aconitum coreanum polysaccharide (CACP) exhibited an effective inhibitory effect on H22 cell growth in vitro and in vivo via the induction of apoptosis. Further, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting assays revealed that the expression of pituitary tumor transforming gene 1 (PTTG1), one proto-oncogene, was evidently suppressed in both transcript and protein levels in H22 cell model or mice after CACP treatment. Particularly, CACP (40 μg/ml) treatment or transfection with PTTG1 small interfering RNA (siRNA) could greatly reduce the phosphorylation of Akt (p-Akt) but increase phospho-p38 mitogen-activated protein kinase (p-p38 MARK) protein levels in H22 cells as compared with vehicle-treated cells. Likewise, following treatment of H22-tumor-bearing mice with CACP (100 mg/kg), doxorubicin (DOX, 3 mg/kg), and their combination, tumor tissues showed an attenuated p-Akt protein expression, but a striking p-p38 MARK level when compared with those in model mice. Taken together, we demonstrated here the inhibitory effect of CACP on the growth of H22 cells in vitro and in vivo, which may be through, at least partly, repression of PTTG1 and then followed by the inactivation of P13/Akt and activation of p38 MARK signaling pathways. These findings offered a novel approach for the treatment of hepatocellular carcinoma (HCC) in the future. [ABSTRACT FROM AUTHOR]

Abstract: Two new diterpenoid alkaloids, Guan-Fu base J (GFJ, 1) and Guan-Fu base N (GFN, 2) along with nineteen known alkaloids (3–21) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics, which is the raw material of a new approval anti-arrhythmia drug “Acehytisine Hydrochloride”. The structures of isolated compounds were established by means of 1D, 2D NMR spectroscopic and chemical methods. All isolates obtained in the present study were evaluated for their inhibitory effects on blocking the ventricular specific sodium current using a whole-cell patch voltage-clamp technique. Among these 21 compounds, Guan-Fu base S (GFS, 3) showed the strongest inhibitory effect with an IC50 value of 3.48μM, and only hetisine-type C20 diterpenoid alkaloids showed promising IC50 values for further development. [Copyright &y& Elsevier]

A high yield method to extract alkaloids from Aconitum coreanum using pulsed electric field (PEF) was developed, and the optimized extraction method compared to the other four extraction methods, consisting of cold maceration extraction, percolation extraction, heat reflux extraction (HRE), and ultrasonic-assisted extraction (UE). The experimental factors of the extraction methods such as electric field intensity, pulse frequency and solid-to-solvent ratio were evaluated. The content of Guanfu base A (GFA) was quantified by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The results indicated that the highest yield of GFA was 3.94 mg g by PEF with conditions of 20 kV cm electric field intensity, 8 pulse, 1:12 solid-to-solvent ratio, and 90 % ethanol-water solution. Meanwhile, the extraction time of PEF was <1 min, which is much less than the HRE of 10 h and even the newly used technique UE of 40 min. Moreover, the results of PEF extraction method showed obvious advantages, with the highest efficiency (120 L h), the shortest extraction time (0.5-1 min), and the lowest energy costs, which could be applied in the industrial production of alkaloids from A. coreanum. Therefore, the application of the PEF extraction method is a promising and constructive method for extraction of GFA. [ABSTRACT FROM AUTHOR]

Abstract: In this study, a polysaccharide (ACP-a1), with a molecular weight of 3.2×105 Da, was successfully purified and identified from the roots of Aconitum coreanum (Lèvl.) Rapaics. Gas chromatography (GC) analysis indicated that ACP-a1 was mainly composed of β-d-mannose and β-d-glucose in a molar ratio of 1.2:3.5. The effects of ACP-a1 on the tumor growth and immune function were assessed in hepatoma H22 bearing mice. Results showed that ACP-a1 significantly inhibited the growth of hepatoma H22 transplanted in mice and prolonged the survival time of H22 tumor-bearing mice. Besides, the body weight, peripheral white blood cells (WBC), thymus index and spleen index of H22 tumor-bearing were also improved after ACP-a1 treatment. Furthermore, ACP-a1 could promote the secretion of serum cytokines in H22 tumor-bearing mice, such as IL-2, TNF-α and IFN-γ. Taken together, our results indicate that ACP-a1 inhibits tumor growth in vivo at least partly via improving immune responses of host organism, and seems to be safe and effective as a novel agent with immunomodulatory activity for the use of anti-tumor therapy. [Copyright &y& Elsevier]

Abstract: Three new hetisine-type diterpenoid alkaloids, Guan-fu base V (GFV, 1), Guan-fu base W (GFW, 2) and Guan-fu base X (GFX, 3) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics. Their structures were established by direct interpretation of their spectral data, mainly high resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D and 2D NMR (1H–1H COSY, ROESY, HSQC and HMBC). GFX is the third N-oxygenated hetisine-type diterpenoid alkaloid isolated from A. coreanum. [Copyright &y& Elsevier]

Abstract: Crude polysaccharides (CACP) were extracted from the stems of Aconitum coreanum by water extraction and ethanol precipitation. In the present investigation, the chemical properties and antitumor activities of CACP were valuated. The results showed the oral administration of CACP could specifically inhibit the growth of H22 tumor cells by in vitro and in vivo model, and exhibited a significant lower cytotoxicity to nontumorous cell lines. Moreover, CACP treatment greatly prolonged the survival period in H22 ascites tumor-bearing mice. After CACP treated, most of H22 cells were arrested in G0/G1 phage determined by flow cytometry. These results suggested CACP exhibited significant antitumor activity, and it possessed a great potential for developing a novel antitumor drug. [Copyright &y& Elsevier]

Abstract: Preparative high-speed counter-current chromatography (HSCCC) coupled with evaporative light scattering detection (ELSD) was used to isolate and separate bioactive constituents from the roots of Aconitum coreanum. Two new diterpenoid alkaloid isomers were successfully separated for the first time by HSCCC with an optimized two-phase solvent system composed of ethyl acetate–n-butanol–methanol–2% acetic acid (3.5:1.5:2:4.5, v/v/v/v), 25.4mg of GFT (1) and 18.3mg of GFU (2) were isolated form 1g crude extract in one step HSCCC experiment. The purities of the two new compounds were all over 95% as analyzed by HPLC and their structures were identified by ESI–MS, 1H NMR, 13C NMR, and 2D NMR analysis. [Copyright &y& Elsevier]

Abstract: Preparative high-speed counter-current chromatography (HSCCC) coupled with evaporative light scattering detection (ELSD) was employed for the isolation and purification of alkaloids from the roots of Aconitum coreanum (Lèvl.) Rapaics. The two-phase solvent system used in HSCCC was n-hexane-ethyl acetate–methanol–0.2M HCl (1:3.5:2:4.5, v/v/v/v). Six alkaloids were obtained and yielded 10.4mg of Guanfu base P, 9.2mg of Guanfu base G, 9.5mg of Guanfu base F, 8.9mg of atisine, 11.9mg of Guanfu base A and 25.7mg of Guanfu base I from 2g of crude extracts. The purity of these compounds was 96.9%, 95.7%, 91.5%, 98.9%, 95.8% and 95.5%, respectively, as determined by high-performance liquid chromatography (HPLC). Their chemical structures were identified by MS, 1H NMR and 13C NMR. [Copyright &y& Elsevier]

The biological activity of 11 alkaloids isolated from Aconitum coreanum was studied. The compounds exhibit myorelaxant activity. Isoatisine and coryphine, which contain oxazolidine rings, are the most active. N-Oxides of 2-isobutyryl-14-hydroxyhetisine and 2-isobutyryl-13-acetyl-14-hydroxyhetisine are least active. [ABSTRACT FROM AUTHOR]

Four new hetisine-type C 20 -diterpenoid alkaloids, named as coreanines A-D (1-4), were isolated from the roots of Aconitum coreanum, together with thirteen known alkaloids (5-17). Their structures were elucidated by extensive spectroscopic methods including IR, HR-ESI-MS and NMR techniques. All the isolated compounds were screened for the acetylcholinesterase (AChE) inhibitory effects, and none of them showed considerable inhibitory activity., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Aconitum coreanum (H. Lév.) Rapaics listed in the Korean Red List is a medicinal herb. We presented complete chloroplast genome, which is 157,024 bp long and has four subregions: 87,637 bp of large single-copy and 16,901 bp of small single-copy regions, which are separated by two 26,243 bp inverted repeat regions including 132 genes (86 protein-coding genes, 8 rRNAs, and 37 tRNAs). The overall GC content of the chloroplast is 38.0%. Phylogenetic trees show that A. coreanum occupied a basal position at subgenus Aconitum clade and two A. coreanum isolated from midwestern and eastern regions of Korea are clustered together., Competing Interests: The authors declare that they have no competing interests., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: This study sought to investigate the effects of Guanfu total base on Bcl-2 and Bax expression and the correlation of Bcl-2 and Bax expression with atrial fibrillation., Methods: Twenty-four male Sprague-Dawley rats were randomly divided into control, model, and treatment groups (n = 8 each). A combined intravenous injection of CaCl 2 (10 mg/mL) and acetylcholine (Ach; 66 μg/mL) was administered to the model and treatment groups for 7 consecutive days to induce atrial fibrillation. After 3 days, the treatment group was administered orally with Aconitum coreanum. Controls received saline for 7 consecutive days. Atrial fibrillation duration was monitored by using an electrocardiogram. Immunohistochemical analysis was used to measure the expression and distribution of Bcl-2 and Bax in the atrial myocardial tissues, RT-PCR was used to measure the Bcl-2 and Bax mRNA expression, and western blot was used to measure Bcl-2 and Bax expression in the atrial myocardial tissue., Results: The model group showed prolonged atrial fibrillation, but this was absent in the control and treatment groups, indicating that treatment with A. coreanum effectively reduced atrial fibrillation duration. Immunohistochemical analysis showed that Bcl-2 expression in the atrial muscle tissue was significantly lower, but Bax expression was significantly higher in the model group compared to that in the control group. After treatment, Bcl-2 expression increased and Bax expression decreased (P < 0.01) in the treatment group compared to those in the model group. RT-PCR and western blot presented the same trends., Conclusion: Bcl-2 and Bax expression was correlated with atrial fibrillation. Guanfu total base was effective in treating atrial fibrillation, upregulating Bcl-2 expression, and downregulating Bax expression., (Copyright © 2018 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

In this study, we observed that a Aconitum coreanum polysaccharide (CACP) exhibited an effective inhibitory effect on H22 cell growth in vitro and in vivo via the induction of apoptosis. Further, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting assays revealed that the expression of pituitary tumor transforming gene 1 (PTTG1), one proto-oncogene, was evidently suppressed in both transcript and protein levels in H22 cell model or mice after CACP treatment. Particularly, CACP (40 μg/ml) treatment or transfection with PTTG1 small interfering RNA (siRNA) could greatly reduce the phosphorylation of Akt (p-Akt) but increase phospho-p38 mitogen-activated protein kinase (p-p38 MARK) protein levels in H22 cells as compared with vehicle-treated cells. Likewise, following treatment of H22-tumor-bearing mice with CACP (100 mg/kg), doxorubicin (DOX, 3 mg/kg), and their combination, tumor tissues showed an attenuated p-Akt protein expression, but a striking p-p38 MARK level when compared with those in model mice. Taken together, we demonstrated here the inhibitory effect of CACP on the growth of H22 cells in vitro and in vivo, which may be through, at least partly, repression of PTTG1 and then followed by the inactivation of P13/Akt and activation of p38 MARK signaling pathways. These findings offered a novel approach for the treatment of hepatocellular carcinoma (HCC) in the future.