RESUMEN
Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) is widely used in the clinical treatment of tumors. This study aims to explore the active fractions and underlying mechanisms of Fuzi in the treatment of non-small cell lung cancer (NSCLC). Fuzi alkaloids (FZA) is prepared and found to inhibit the growth of NSCLC both in vitro and in vivo significantly. A total of 53 alkaloids are identified in FZA by UPLC-Q-TOF-MS. Proteomics experiment show that 238 differentially expressed proteins regulated by FZA are involved in amino acid anabolism, pyrimidine metabolism and PI3K/Akt-mTOR signaling pathway. Metabolomics analyses identify 32 significant differential metabolites which are mainly involved in amino acid metabolism, TCA cycle and other pathways. Multi-omics research combined with molecular biological assays suggest that FZA might regulate glycolysis through PI3K/Akt-mTOR pathway to treat NSCLC. The study lays a foundation for the anti-cancer investigation of Fuzi and provides a possible scientific basis for its clinical application.
Asunto(s)
Aconitum , Alcaloides , Carcinoma de Pulmón de Células no Pequeñas , Glucólisis , Neoplasias Pulmonares , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Humanos , Alcaloides/farmacología , Glucólisis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Aconitum/química , Ratones , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Línea Celular Tumoral , Ratones Desnudos , Antineoplásicos Fitogénicos/farmacología , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Lappaconitine, a diterpene alkaloid isolated from Aconitum sinomontanum Nakai, exhibits a wide range of biological activities, making it a promising candidate for the development of novel derivatives with therapeutic potential. In our research, we executed a two-step transformation via oxidative cleavage of lappaconitine's vicinal diol using the hypervalent iodine reagent PhI(OAc)2, followed by strong alkaline hydrolysis. This approach yielded four new unanticipated compounds, whose structures were identified by spectroscopic methods and/or X-ray crystallography. Thus, we proposed plausible reaction mechanisms for their formations and particularly investigated the remarkable diastereoselectivity for the formation of single stereoisomer 8 observed during the alkaline hydrolysis step. Among them, compound 8 (code name: QG3030) demonstrated both enhanced osteogenic differentiation of human mesenchymal stem cells and significant osteogenic effect in an ovariectomized rat model with no acute oral toxicity.
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Aconitina , Yodo , Aconitina/análogos & derivados , Aconitina/química , Aconitina/farmacología , Humanos , Animales , Estructura Molecular , Ratas , Yodo/química , Alcaloides/química , Alcaloides/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Aconitum/química , Cristalografía por Rayos X , Osteogénesis/efectos de los fármacos , Estereoisomerismo , Diferenciación Celular/efectos de los fármacosRESUMEN
The perennial herb Aconitum sinomontanum Nakai (Ranunculaceae) has been utilized as a traditional oriental medicine in China for numerous years. The principal pharmacological constituent of A. sinomontanum, lappaconitine (LA), exhibits analgesic, anti-inflammatory, anti-tumor, anti-arrhythmic, and anti-epileptic activities. Due to its potent efficacy and non-addictive nature, LA is widely utilized in the management of cancer pain and postoperative analgesia. This review encompasses the research advancements pertaining to LA including extraction methods, separation techniques, pharmacological properties, chemical modifications, and clinical applications. Additionally, it offers insights into the potential applications and current challenges associated with LA to facilitate future research endeavors.
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Aconitina , Aconitum , Analgésicos , Aconitina/análogos & derivados , Aconitina/farmacología , Aconitina/uso terapéutico , Humanos , Analgésicos/uso terapéutico , Analgésicos/farmacología , Animales , Aconitum/química , Diterpenos/uso terapéutico , Diterpenos/farmacología , Diterpenos/químicaRESUMEN
In this work, electromembrane extraction (EME) was used for the first time to separate aconitine (AC), mesaconitine (Mes-AC) and hypaconitine (Hyp-AC) from biological samples and Chinese herbal medicines. Efficient EME of polar and high molecular weight aconitine alkaloids from different sample matrices was achieved with the solvent of 1-ethyl-2-nitrobenzene (ENB). Under the optimal EME conditions, EME provided recoveries for all targets in the range of 72%-74 %, 85%-103 % and 92%-94 % for whole blood, urine and aqueous samples. The proposed EME systems combined with LC-MS/MS and HPLC-UV were evaluated using different sample matrices, and the methods displayed satisfactory analytical characteristic including negligible matrix effect. The LOD and LOQ of AC, Mes-AC, and Hyp-AC by EME-LC-MS/MS were in the range of 0.002-0.068 ng/mL and 0.005-0.228 ng/mL respectively. The LOD and LOQ of AC, Mes-AC, and Hyp-AC by EME-HPLC-UV were in the range of 0.06-0.26 µg/mL and 0.20-0.86 µg/mL, respectively. The coefficient of determination, R2-value was ≥0.9926 for all cases, and the accuracy in the linear ranges was in the range of 91%-111 %. Finally, the method was successfully applied for the qualitative and quantitative analysis of AC and Mes-AC in the whole blood and herbal medicine dreg samples from an actual forensic case, and poisoning by aconitum alkaloids was identified as the cause of death. Therefore, we believe that EME could be a powerful tool to identify poisoning, and EME has great potential for efficient separation of polar and high molecular weight substances. These are of great importance in the fields of but not limited to forensic science, Traditional Chinese Medicine and clinics.
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Aconitum , Humanos , Aconitum/química , Aconitum/envenenamiento , Alcaloides/análisis , Alcaloides/orina , Alcaloides/sangre , Membranas Artificiales , Espectrometría de Masas en Tándem/métodos , Técnicas Electroquímicas , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión , Aconitina/análogos & derivados , Aconitina/análisis , Aconitina/sangre , Fraccionamiento Químico/métodos , Límite de DetecciónRESUMEN
Seven previously undescribed compounds, including one amino acid hybrid sesquiterpene areolatol A (1), two unusual natural sesquiterpenoid skeleton areolatones A-B (2-3) and four benzo[j]fluoranthene areolaranes A-D (4-7) were characterized from Annulohypoxylon areolatum. The structures of the compounds were determined by extensive spectroscopic analysis, X-ray diffraction analysis, and ECD and NMR computational. Notably, areolatol A (1) was the first reported sesquiterpene featuring a 5/7/3-ring system and hybridized with two molecular amino acids. In addition, areolaranes A-D (4-7) were identified as possible chemophenetic markers.
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Aconitum , Aconitum/química , Endófitos/química , Endófitos/metabolismo , Estructura Molecular , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Conformación Molecular , Modelos MolecularesRESUMEN
Traditional herbs have a history of clinical use in anti-fatigue. However, several adverse effects of herbs have been identified. Pityriasis rosea-like eruption (PR-LE) is a rare cutaneous complication of herbs. To the best of our knowledge, there have been few reports of PR-LE following herbs. Here, we described a case of PR-LE that developed 6 days after taking anti-fatigue herbs. After the 17 days of stopping Aconitum carmichaelii Debx and Panax Ginseng, it notably faded. So, when anti-fatigue herbs being authorized for fatigue use, monitoring for potential adverse effects is necessary.
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Aconitum , Panax , Pitiriasis Rosada , Humanos , Pitiriasis Rosada/tratamiento farmacológico , Fatiga/tratamiento farmacológico , Femenino , Masculino , Adulto , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Erupciones por Medicamentos/tratamiento farmacológico , Erupciones por Medicamentos/etiologíaRESUMEN
RATIONAL: Aconiti Lateralis Radix Praeparata (AC) is a traditional Chinese medicine with a long history of use. However, the current research on the material basis of AC and its processed products is still not comprehensive, especially the changes in lipo-diterpenoid alkaloids (LDAs) that can be hydrolyzed into diester-diterpenoid alkaloids in AC before and after processing. This study aimed to provide material basis guidance for the clinical use of AC and its processed products by comprehensively analyzing the changes in substances between AC and its processed products. METHODS: An ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) approach was optimized to chemical profiling. The MS data were processed using molecular networking combined with the in-house library database to fast characterize the compounds. Multivariate statistical methods were adopted to determine the dissimilarities of components in AC and its processed products. RESULTS: A total of 310 compounds were tentatively identified from AC, including 109 potential new alkaloids, of which 98 were potential novel LPAs. A metabolomics approach was applied to find the characteristic marker components. As a result, 52 potential chemical markers were selected to distinguish the AC samples of different extraction methods and 42 potential chemical markers for differentiating between AC and its processed products were selected. CONCLUSION: The results indicate that UHPLC/Q-TOF-MS/MS and Global Natural Products Social Molecular Networking coupled with multivariate analysis strategies was a powerful tool to rapidly identify and screen the chemical markers of alkaloids between the AC samples and its processed products. These results also indicate that the toxicity of water extracts of AC and its processed products were decreased. This research not only guides the clinical safe use of AC and its processed products, but also extends the application of the molecular networking strategy in traditional herbal medicine.
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Aconitum , Alcaloides , Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Alcaloides/análisis , Alcaloides/química , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Aconitum/química , Análisis Multivariante , HumanosRESUMEN
We have developed a rapid genus identification method for poisonous plants. The real-time PCR using the TaqMan® probe method was employed for detection, with the amplified targets being the "trnL (UAA)-intron" or "trnL-trnF intergenic spacer" regions of chloroplast DNA. The targeted plants were selected six genera (Aconitum, Colchicum, Veratrum, Brugmansia, Scopolia and Narcissus), which have been implicated in many instances of food poisoning in Japan. A tissue lysis solution was used for DNA extraction, which can be completed within approximate 30 min. A master mix corresponding to the tissue lysis solution was used for real-time PCR reagents. As a result, we were able to complete the entire process from DNA extraction to genus identification in 4 to 5 hr. The detection sensitivity was estimated at approximately 1 pg of DNA for all six plant genera. Remarkably, an amplification plot was discerned even with the crude cell lysates of all samples. It was also possible to obtain amplification curves for three plant samples that had been subjected to simulated cooking (boiling). This study suggests that the developed method can rapidly identify six genera of poisonous plants.
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Plantas Tóxicas , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Plantas Tóxicas/clasificación , Plantas Tóxicas/genética , ADN de Cloroplastos/genética , ADN de Cloroplastos/análisis , ADN de Plantas/genética , ADN de Plantas/análisis , Veratrum/genética , Veratrum/química , Veratrum/clasificación , Aconitum/genética , Aconitum/clasificación , Aconitum/química , Sensibilidad y Especificidad , Factores de Tiempo , Enfermedades Transmitidas por los Alimentos/prevención & controlRESUMEN
Activated hepatic stellate cells differentiate into myofibroblasts, which synthesize and secrete extracellular matrix (ECM) leading to liver fibrosis. It was previously demonstrated that bulleyaconitine A (BLA), an alkaloid from Aconitum bulleyanum, inhibits proliferation and promotes apoptosis of human hepatic Lieming Xu-2 (LX-2) cells. In this study, we analyzed the effect of BLA on the production of ECM and related proteins by LX-2 cells activated with acetaldehyde (AA). The cells were randomized into the control group, AA group (cells activated with 400 µM AA), and BLA+AA group (cells cultured in the presence of 400 µM AA and 18.75 µg/ml BLA). In the BLA+AA group, the contents of collagens I and III and the expression of α-smooth muscle actin and transforming growth factor-ß1 (TGF-ß1) were statistically significantly higher than in the control, but lower than in the AA group. Expression of MMP-1 in the BLA+AA group was also significantly higher than in the AA group, but lower than in the control. Expression of TIMP-1 in the BLA+AA group was significantly higher than in the control, but lower than in the AA group. Thus, BLA suppressed activation and proliferation of LX-2 cells by inhibiting TGF-ß1 signaling pathway and decreasing the content of collagens I and III by reducing the MMP-1/TIMP-1 ratio.
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Acetaldehído , Aconitina , Actinas , Colágeno Tipo I , Matriz Extracelular , Células Estrelladas Hepáticas , Inhibidor Tisular de Metaloproteinasa-1 , Factor de Crecimiento Transformador beta1 , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Humanos , Acetaldehído/farmacología , Acetaldehído/análogos & derivados , Aconitina/farmacología , Aconitina/análogos & derivados , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Actinas/metabolismo , Actinas/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 1 de la Matriz/genética , Línea Celular , Colágeno Tipo III/metabolismo , Colágeno Tipo III/genética , Proliferación Celular/efectos de los fármacos , Aconitum/química , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patologíaRESUMEN
Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2Dâ NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19â mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests.
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Aconitum , Alcaloides , Diterpenos , Aconitum/química , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Tetranychidae/efectos de los fármacos , Estructura Molecular , Conformación Molecular , Cristalografía por Rayos X , Insecticidas/química , Insecticidas/aislamiento & purificación , Insecticidas/farmacología , Modelos MolecularesRESUMEN
Ischemic stroke (IS) remains one of the most serious threats to human life. Early blood-brain barrier damage (BBB) is the cause of parenchymal cell damage. Repair of the structure and function of the BBB is beneficial for the treatment of IS. The traditional prescription ginseng aconitum decoction (GAD) has a long history in the treatment of cardiovascular and cerebrovascular diseases, however, the effect of GAD on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, in vitro models of BBB were established with brain endothelial cells (bEnd.3). We found that GAD reduced the leakage of the fluorescent probe FITC-dextran (P < 0.01) and increased the expression of tight junction proteins (Claudin-5, ZO-1) (P < 0.05) in the BBB model in vitro. Furthermore, to investigate the BBB protective effects of GAD in vivo. A total of 25 male C57/BL6 mice (20 - 22 g) were randomly divided into 5 groups (n = 5 per group): (1) Sham group (saline), (2) MCAO group (saline), (3) MCAO + CG group (Chinese ginseng 8 mg/kg/day), (4) MCAO + AC group (aconite 8 mg/kg/day), (5) MCAO + GAD group (GAD 8 mg/kg/day).We constructed IS model in mice and found that GAD treatment reduced IgG leakage (P < 0.05), up-regulated the expression of tight junction proteins Claudin-5, Occludin, and ZO-1 (P < 0.05). Further mechanism study showed that fatty acid oxidation (FAO) of vascular endothelial cells is involved in the protection of the BBB after IS, and GAD regulates FAO (P < 0.05) to protect BBB. In addition, we found the effect of GAD was stronger than that of Chinese ginseng (CG) (P < 0.05) and aconite (AC) (P < 0.01) alone. We concluded that GAD ameliorated the BBB dysfunction by regulating FAO involving vascular endothelial cells after IS. At the same time, the prescription is more effective than single traditional Chinese medicine.
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Barrera Hematoencefálica , Medicamentos Herbarios Chinos , Ratones Endogámicos C57BL , Fármacos Neuroprotectores , Daño por Reperfusión , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Masculino , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Medicamentos Herbarios Chinos/farmacología , Fármacos Neuroprotectores/farmacología , Ratones , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Aconitum , Proteína de la Zonula Occludens-1/metabolismo , Claudina-5/metabolismo , Modelos Animales de Enfermedad , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , PanaxRESUMEN
OBJECTIVES: To explore the postmortem diffusion rule of Aconitum alkaloids and their metabolites in poisoned rabbits, and to provide a reference for identifying the antemortem poisoning or postmortem poisoning of Aconitum alkaloids. METHODS: Twenty-four rabbits were sacrificed by tracheal clamps. After 1 hour, the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration. Then, they were placed supine and stored at 25 â. The biological samples from 3 randomly selected rabbits were collected including heart blood, peripheral blood, urine, heart, liver, spleen, lung and kidney tissues at 0 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h and 96 h after intragastric administration, respectively. Aconitum alkaloids and their metabolites in the biological samples were analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: At 4 h after intragastric administration, Aconitum alkaloids and their metabolites could be detected in heart blood, peripheral blood and major organs, and the contents of them changed dynamically with the preservation time. The contents of Aconitum alkaloids and their metabolites were higher in the spleen, liver and lung, especially in the spleen which was closer to the stomach. The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration. In contrast, the contents of Aconitum alkaloids and their metabolites in kidney were all lower. Aconitum alkaloids and their metabolites were not detected in urine. CONCLUSIONS: Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits, diffusing from high-content organs (stomach) to other major organs and tissues as well as the heart blood. The main mechanism is the dispersion along the concentration gradient, while urine is not affected by postmortem diffusion, which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.
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Aconitum , Alcaloides , Hígado , Espectrometría de Masas en Tándem , Animales , Conejos , Aconitum/química , Alcaloides/metabolismo , Alcaloides/orina , Alcaloides/análisis , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Hígado/metabolismo , Riñón/metabolismo , Pulmón/metabolismo , Aconitina/análogos & derivados , Aconitina/farmacocinética , Aconitina/orina , Aconitina/metabolismo , Aconitina/análisis , Raíces de Plantas/química , Distribución Tisular , Bazo/metabolismo , Cambios Post Mortem , Toxicología Forense/métodos , Miocardio/metabolismo , Factores de Tiempo , MasculinoRESUMEN
BACKGROUND: Radix Aconiti Lateralis (Fuzi), a mono-herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining "in vitro and in vivo component mining-virtual multi-target screening-active component prediction-literature verification" to screen potential nephrotoxic substances rapidly. METHOD: The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi's in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi's components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened. RESULTS: Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi. CONCLUSIONS: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi.
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Aconitum , Medicamentos Herbarios Chinos , Riñón , Espectrometría de Masas , Aconitum/química , Riñón/efectos de los fármacos , Animales , Medicamentos Herbarios Chinos/toxicidad , Medicamentos Herbarios Chinos/química , Espectrometría de Masas/métodos , Cromatografía Líquida de Alta Presión/métodos , Aconitina/análogos & derivados , Aconitina/toxicidad , Mapas de Interacción de Proteínas/efectos de los fármacos , Simulación del Acoplamiento Molecular , DiterpenosRESUMEN
The authors present a narrative that details the cause and process of a woman's transformation from beauty to ugliness in a Japanese tale. In " Tokaido Yotsuya Kaidan ," the metamorphosis from a beauty to an ugly woman is analyzed. After taking medication to recover from childbirth, Oiwa's face became disfigured and grotesque. Oiwa: It seems to be good for my blood, but when I drink it, it causes fraying and breakdown, causing sudden pain. I feel a numbing dullness. When she looked at herself in the mirror, she was shocked. Oiwa: What's wrong with my face? I hate this, it's such a disgusting thing. Neighbor: It was a lie that the medicine you drank was a helpful medicine that protects the appearance of people's faces. Your face is that of a wicked woman (). Oiwa: Is it really me? Why does she have the face of an evil woman? Her hair falls out in a gruesome combing scene, driving her mad. The poison Oiwa took was aconite, which grows wild in Japan. Both aconite tincture and raw aconite roots contain high concentrations of Aconitum alkaloids, which can penetrate the stratum corneum following the diffusion gradient. As her hair fell out during a horrific combing session, she abandoned her maternal role and sought revenge, having lost what she considered a symbol of her femininity. In treating female patients with facial disfigurement, it is important to be mindful of their psychological state, akin to that of Oiwa, who became disfigured through no fault of her own.
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Aconitum , Belleza , Adulto , Femenino , Humanos , Aconitum/efectos adversos , Pueblos del Este de Asia , JapónRESUMEN
The adoption of green chemistry protocols in nanoparticle (NP) synthesis has exhibited substantial potential and is presently a central focus in research for generating versatile NPs applicable across a broad spectrum of applications. In this scientific contribution, we, for the first time, examined the ability of Aconitum Laeve (A. Laeve) crude extract to synthesize silver and gold nanoparticles (AgNPs@AL; AuNP@AL) and explored their potential applications in biological activities and the catalytic degradation of environmental pollutants. The synthesized NPs exhibited a distinctive surface plasmon resonance pattern, a spherical morphology with approximate sizes of 5-10 nm (TEM imaging), a crystalline architecture (XRD analysis), and potential functional groups identified by FTIR spectroscopy. The antibacterial activity was demonstrated by inhibition zones that measured 16 and 14 mm for the AgNPs@AL and AuNP@AL at a concentration of 80 µg/mL against Staphylococcus aureus and 14 and 12 mm against Escherichia coli, respectively. The antioxidant potential of the synthesized NPs was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO), and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. Our findings suggest that the AuNP@AL effectively countered the tested radicals considerably, displaying IC50 values of 115.9, 103.54, and 180.85 µg/mL against DPPH, PTIO, and ABTS, respectively. In contrast, the AgNPs@AL showed IC50 values of 144.9, 116.36, and 95.39 µg/mL against the respective radicals. In addition, both the NPs presented significant effectiveness in the photocatalytic degradation of methylene blue and rhodamine B. The overall observations indicate that A. Laeve possesses a robust capability to synthesize spherical nanoparticles, exhibiting excellent dispersion and showcasing potential applications in both biological activities and environmental remediation.
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Aconitum , Antibacterianos , Antioxidantes , Oro , Nanopartículas del Metal , Extractos Vegetales , Plata , Nanopartículas del Metal/química , Plata/química , Oro/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Aconitum/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Catálisis , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Tecnología Química Verde , Escherichia coli/efectos de los fármacosRESUMEN
A total of twenty-two diterpenoid alkaloids, including ten unprecedented ones, namely refractines C-L, were isolated from the roots of Aconitum refractum (Finet et Gagnep.) Hand.-Mazz. Refractine C was the first example of a natural diterpenoid alkaloid wherein C-19 is linked to N position by an oxaziridine ring. Refractine L was a rare glycosidic diterpenoid alkaloid with fructofuranoside. Most of the isolated compounds obtained from a previous study were screened for their anti-inflammatory and myocardial protective activities. The autophagy-inducing effects of some of these compounds on RAW 264.7 cells were evaluated by assessing the expression of microtubule-associated protein 1 light chain 3 (LC3-II/LC3-I). Results revealed that some compounds exerted varying levels of inhibitory effects on the proliferative activity of RAW 264.7 cells.
Asunto(s)
Aconitum , Alcaloides , Autofagia , Diterpenos , Aconitum/química , Ratones , Animales , Autofagia/efectos de los fármacos , Células RAW 264.7 , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Alcaloides/química , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Raíces de Plantas/químicaRESUMEN
Acute kidney injury (AKI) is characterized by a sudden decline in renal function. Traditional Chinese medicine has employed Fuzi for kidney diseases; however, concerns about neurotoxicity and cardiotoxicity have constrained its clinical use. This study explored mesaconine, derived from processed Fuzi, as a promising low-toxicity alternative for AKI treatment. In this study, we assessed the protective effects of mesaconine in gentamicin (GM)-induced NRK-52E cells and AKI rat models in vitro and in vivo, respectively. Mesaconine promotes the proliferation of damaged NRK-52E cells and down-regulates intracellular transforming growth factor ß1 (TGF-ß1) and kidney injury molecule 1 (KIM-1) to promote renal cell repair. Concurrently, mesaconine restored mitochondrial morphology and permeability transition pores, reversed the decrease in mitochondrial membrane potential, mitigated mitochondrial dysfunction, decreased ATP production, inhibited inflammatory factor release, and reduced early apoptosis rates. In vivo, GM-induced AKI rat models exhibited elevated AKI biomarkers, in which mesaconine was effectively reduced, indicating improved renal function. Mesaconine enhanced superoxide dismutase activity, reduced malondialdehyde content, alleviated inflammatory infiltrate, mitigated tubular and glomerular lesions, and downregulated NF-κB (nuclear factor-κb) p65 expression, leading to decreased tumor necrosis factor-α (TNF-α) and IL-1ß (interleukin-1ß) levels in GM-induced AKI animals. Furthermore, mesaconine inhibited the expression of renal pro-apoptotic proteins (Bax, cytochrome c, cleaved-caspase 9, and cleaved-caspase 3) and induced the release of the anti-apoptotic protein bcl-2, further suppressing apoptosis. This study highlighted the therapeutic potential of mesaconine in GM-induced AKI. Its multifaceted mechanisms, including the restoration of mitochondrial dysfunction, anti-inflammatory and antioxidant effects, and apoptosis mitigation, make mesaconine a promising candidate for further exploration in AKI management.
Asunto(s)
Aconitum , Lesión Renal Aguda , Apoptosis , Riñón , Mitocondrias , Ratas Sprague-Dawley , Animales , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Apoptosis/efectos de los fármacos , Aconitum/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Masculino , Ratas , Línea Celular , Riñón/efectos de los fármacos , Riñón/patología , Gentamicinas/toxicidad , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Aconitina/análogos & derivados , Aconitina/farmacología , Aconitina/uso terapéutico , Modelos Animales de Enfermedad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , DiterpenosRESUMEN
Isopentenyl diphosphate isomerase (IDI), a key enzyme in the biosynthetic pathway of diterpenoid alkaloids (DAs), plays an essential regulatory role in the synthesis and accumulation of DAs. In this study, the coding sequence (CDS) of AcIDI1 was isolated from the mother roots of Aconitum carmichaelii Debx. (GeneBank accession number OR915879). Bioinformatics analysis showed that the CDS of AcIDI1 was 894 bp, encoding a protein with 297 amino acids and the putative protein localized in the chloroplast. AcIDI1 exhibited significant homology with sequences encoding IDI in other species, and was most closely related to Aconitum vilmorinianum. Furthermore, the fusion protein has been successfully expressed in Escherichia coli (E. coli), providing a basis for future functional studies of AcIDI1. The expression pattern of AcIDI1 was analyzed by real-time quantitative PCR (qPCR), which demonstrates that AcIDI1 is a tissue-specific gene in the roots of A. carmichaelii and exhibits high expression in both daughter and mother roots. By comparing the expression levels of AcIDI1 in three tissues of the roots of A. carmichaelii at different growth stages, we propose that the mother roots (MRs) are the centers of resources allocation. The roots of A. carmichaelii continuously absorb the energy from external environment, while resources transfer behavior from MRs to both daughter roots (DRs) and axillary buds (ABs) occurs as the plant grows. This study establishes a foundation for applying the IDI gene to regulate the biosynthesis and accumulation of DAs in A. carmichaelii.
Asunto(s)
Aconitum , Alcaloides , Diterpenos , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Raíces de Plantas , Aconitum/genética , Aconitum/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Diterpenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Alcaloides/metabolismo , Alcaloides/biosíntesis , Filogenia , Escherichia coli/genética , Escherichia coli/metabolismoRESUMEN
The study aims to investigate the effects and potential mechanism of raw and processed Aconitum pendulum Busch on rheumatoid arthritis(RA) and analyze their toxicity attenuating and efficacy retaining effects. The bovine type â ¡ collagen-induced arthritis(CIA) rat model was established. The weight, cardiac index, immune organ index, and arthritis index of the rats were recorded and calculated after administration. ELISA was used to measure the expressions of creatine kinase(CK), cardiac troponin T(cTnT), and multiple factors. The pathological morphological changes in heart tissue and ankle joint tissue were observed by hematoxylin-eosin staining. Connexin 43(Cx43) expression in the hearts of CIA rats was detected via immunohistochemical method. The levels of endogenous metabolites in the serum of CIA rats were detected by UPLC-Q-TOF-MS. Potential biomarkers were screened, and related metabolic pathways were analyzed. The results showed that raw A. pendulum could induce local myocardial fiber degeneration and necrosis, increase the cardiac index, decrease the average positive area of Cx43 expression significantly, and increase the expressions of CK and cTnT in cardiac tissue of rats. Meanwhile, raw A. pendulum could decrease the immune organ index, interleukin-6(IL-6), and other inflammatory cytokine contents in the serum and improve the damaged synovium and joint surface of CIA rats, with toxicity and efficacy coexisting. The Zanba stir-fired A. pendulum could reduce the index of arthritis, immune organ index, and content of IL-6 and inflammatory cytokines in serum and improve damaged synovium and joint surface of CIA rats with no obvious cardiac toxicity, showing significant toxicity attenuating and efficacy retaining effects. A total of 19 potential biomarkers of raw A. pendulum and Zanba stir-fired A. pendulum against RA were screened by serum metabolomics, including glycerophospholipid metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and steroid hormone synthesis. In conclusion, Xizang medicine A. pendulum is preventive and curative for RA. Raw A. pendulum has certain cardiotoxicity, and Zanba stir-fired A. pendulum has significant toxicity attenuating and efficacy retaining effects. The anti-RA mechanism may be related to the regulation of glycerophospholipid and amino acid metabolism.
Asunto(s)
Aconitum , Artritis Reumatoide , Medicamentos Herbarios Chinos , Metabolómica , Animales , Aconitum/química , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Ratas , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Femenino , Humanos , Ratas Sprague-Dawley , Conexina 43/metabolismo , Conexina 43/genética , Bovinos , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Creatina Quinasa/sangreRESUMEN
Zhenwu Decoction (ZWD), a classic formula from Zhang Zhongjing's "Treatise on Typhoid Fever" in the Han Dynasty, consists of five traditional Chinese medicines: Aconiti Lateralis Radix Praeparata (ALRP), Paeoniae Radix Alba, Poria Cocos, Ginger, and Rhizoma Atractylodis Macrocephalae. To evaluate the chemical constituent consistency of ZWD before and after compatibility, an ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry was established to comprehensively study the constituents of ZWD. By normalizing the peak area, the pairwise compatibility of ALRP and the other four medicinal herbs, as well as the compatibility of the entire formula were studied, respectively. Multivariate statistical analysis was used to identify the differences. The processed data were analyzed by principal component analysis and supervised orthogonal partial least squared discriminant analysis, and an S-plot was generated to compare the differences in the chemical composition of the two types of decoction samples. The results showed that during the decoction process of ZWD, a total of seven components were recognized as differential compounds before and after compatibility of ZWD, namely 6-gingerol, zingerone, benzoylhypaconine, hypaconitine, benzoylaconine, paeoniflorin and fuziline. The results of this study provide basic data reference for understanding the law of ZWD compatibility and are valuable for the compatibility study of other herbal medicines.