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Zhao Z, Fang Z. Extracorporeal membrane oxygenation combined with hemoperfusion to assist in the rescue of aconitine poisoning: A case report. Perfusion 2025; 40:1062-1067. [PMID: 39196956 DOI: 10.1177/02676591241280163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2024]
Abstract
Extracorporeal membrane oxygenation (ECMO) has been widely used as a clinical bridge for cardiopulmonary failure. We recently used combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and haemoperfusion to successfully treat a patient with acute aconitine poisoning. The patient was admitted to the Emergency Intensive Care Unit (EICU) in a state of coma and shock. Her received comprehensive treatment, including haemoperfusion and anti-shock therapy. 40 minutes after admission, the patient experienced sudden respiratory and cardiac arrest. After conventional defibrillation and cardiopulmonary resuscitation proved ineffective, veno-arterial ECMO was immediately initiated. One hour after initiation of VA-ECMO, the patient's heart rhythm stabilised to sinus rhythm. After 33 h of supportive care, the patient was awake, haemodynamically stable and the VA-ECMO was successfully removed. The patient made full recovery 7 days after admission.
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Affiliation(s)
- Zhiwen Zhao
- Department of Emergency Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Zhicheng Fang
- Department of Emergency Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China
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2
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Ya-Zhu W, Xiao-Ting W, Shu-Qing T, Tian-Zhu J, Hui G. Discussion on the effects of Chinese medicine processing on the changes of medicinal properties based on the changes of chemical constituents and pharmacodynamic perspective. JOURNAL OF ETHNOPHARMACOLOGY 2025; 346:119687. [PMID: 40127830 DOI: 10.1016/j.jep.2025.119687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 03/14/2025] [Accepted: 03/21/2025] [Indexed: 03/26/2025]
Abstract
ETHNOPHARMACOLOGY RELEVANCE The theory of medicinal properties in Traditional Chinese Medicine (TCM) has a long history and serves as the foundation and core of TCM's theoretical system. It plays an irreplaceable role in guiding clinical medication and enhancing therapeutic efficacy. TCM processing is a traditional technology for processing and treating Chinese medicinal materials, which is a major characteristic of clinical TCM practice. Through processing, the chemical components and pharmacological effects of Chinese medicinal materials will change, manifested as changes in several aspects of their medicinal properties. These changes lead to corresponding alterations in their therapeutic functions and clinical applications, enabling them to meet diverse clinical needs for treating various diseases and conditions. AIMS OF THE STUDY This study begins with an exploration of ancient books on the relationship between TCM processing and medicinal properties. It aims to provide a modern scientific basis for clarifying how processing affects TCM's medicinal properties, while offering a systematic interpretation of traditional theories through the lens of chemical composition and pharmacological changes. MATERIALS AND METHODS We collected and analyzed relevant articles from different scientific databases regarding TCM processing and medicinal properties theory. By concentrating on well-studied TCM varieties as representatives, the effects of processing on the changes of medicinal properties of TCM were explained by examples from the perspective of chemical composition and pharmacodynamic changes. RESULTS The findings of this study indicate that analyzing the impact of TCM processing on its medicinal properties not only enhances the application of TCM but also serves as a crucial reference for the development of new pharmaceuticals. In addition, the study reveals the complexity of the changes in the characteristics of TCM, which brings new challenges and opportunities for further research. Especially in the perspective of modern pharmacology, in-depth study of the relationship between the processing of TCM and its efficacy will provide a scientific basis for the standardization and normalization of TCM. CONCLUSION This study enriches the theoretical framework of TCM processing and establishes an empirical foundation for optimizing its clinical use. We hope that these findings will stimulate further research, so as to promote the modernization of TCM, which will lay a more solid foundation for the scientific research and clinical application of TCM.
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Affiliation(s)
- Wang Ya-Zhu
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Liaoning, Dalian, 116600, China; Traditional Chinese Medicine Processing Technology Inheritance Base (Liaoning) of the National Administration of Traditional Chinese Medicine, Dalian, 116600, China; Liaoning Provincial Traditional Chinese Medicine Processing Technology Innovation Center, Dalian, 116600, China
| | - Wang Xiao-Ting
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Liaoning, Dalian, 116600, China; Traditional Chinese Medicine Processing Technology Inheritance Base (Liaoning) of the National Administration of Traditional Chinese Medicine, Dalian, 116600, China; Liaoning Provincial Traditional Chinese Medicine Processing Technology Innovation Center, Dalian, 116600, China
| | - Tian Shu-Qing
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Liaoning, Dalian, 116600, China; Traditional Chinese Medicine Processing Technology Inheritance Base (Liaoning) of the National Administration of Traditional Chinese Medicine, Dalian, 116600, China; Liaoning Provincial Traditional Chinese Medicine Processing Technology Innovation Center, Dalian, 116600, China
| | - Jia Tian-Zhu
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Liaoning, Dalian, 116600, China; Traditional Chinese Medicine Processing Technology Inheritance Base (Liaoning) of the National Administration of Traditional Chinese Medicine, Dalian, 116600, China; Liaoning Provincial Traditional Chinese Medicine Processing Technology Innovation Center, Dalian, 116600, China
| | - Gao Hui
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Liaoning, Dalian, 116600, China; Traditional Chinese Medicine Processing Technology Inheritance Base (Liaoning) of the National Administration of Traditional Chinese Medicine, Dalian, 116600, China; Liaoning Provincial Traditional Chinese Medicine Processing Technology Innovation Center, Dalian, 116600, China.
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3
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Ma J, Qiang Y, Li L, Wang Y, Zhao M, Cui F, Hu F, Li Y. Characterization changes of volatile organic compounds in Aconitum sinomontanum Nakai (Gao Wu Tou) with different proportions of yellow wine steamed by GC-IMS, E-nose. J Chromatogr A 2025; 1742:465654. [PMID: 39798481 DOI: 10.1016/j.chroma.2025.465654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 12/21/2024] [Accepted: 01/02/2025] [Indexed: 01/15/2025]
Abstract
Gas chromatography-ion mobility spectrometry (GC-IMS) combined with multiple analytical methods and E-nose were used to study the differences in volatile organic compounds (VOCs) in 0 %, 10 %, 15 %, 20 %, 25 % yellow wine steamed A. sinomontanum and its raw products. The results indicated that the VOCs in different proportions of yellow wine steamed A. sinomontanum and its raw products were mainly composed of aldehydes, ketones, alcohols, ethers, esters, acids, and heterocycles. Among them, the contents of the aldehydes, ketones, heterocycles, alcohols and esters are remarkably higher than those of other compounds. The results based on multiple analysis methods such as PCA and fingerprint analysis showed that there were certain differences between steaming A. sinomontanum with different proportions of yellow wine and the raw products. Among them, yellow wine has a 15 % proportion and the highest content of VOCs, and perhaps the best proportion of yellow wine for steaming A. sinomontanum. Simultaneously, it is speculated that the unique odor of steamed A. sinomontanum may be related to the aldehydes and esters it contains, such as benzalde-hyde, 2-Methylbutanol acetate. In addition, the E-nose results of this study could be helpful for flavor identification and distinction of raw and processed products from A. sinomontanum.
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Affiliation(s)
- Jiarong Ma
- Gansu University of Chinese Medicine, Lanzhou 730000, China
| | - Yujing Qiang
- Gansu University of Chinese Medicine, Lanzhou 730000, China
| | - Li Li
- Gansu University of Chinese Medicine, Lanzhou 730000, China
| | - Yuhui Wang
- Gansu University of Chinese Medicine, Lanzhou 730000, China
| | - Min Zhao
- Gansu University of Chinese Medicine, Lanzhou 730000, China
| | - Fang Cui
- Gansu University of Chinese Medicine, Lanzhou 730000, China
| | - Fangdi Hu
- Lanzhou University, Lanzhou 730000, China
| | - Yun Li
- Gansu University of Chinese Medicine, Lanzhou 730000, China.
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4
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Meng Y, Cai XL, Cong S, Sun J, Hu YW, Luo L. Effect of Aconitum diphtheria on the Proliferation, Apoptosis, and Inflammatory Response of Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Cell Biochem Funct 2024; 42:e70026. [PMID: 39682028 DOI: 10.1002/cbf.70026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 11/12/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024]
Abstract
Rheumatoid arthritis (RA), a highly disabling autoimmune disease, is characterized by joint damage and synovial hyperplasia. This paper was designed to explore the effect and mechanisms of Aconitum diphtheria on the proliferation and apoptosis of RA fibroblast-like synoviocytes (RA-FLS). First, RA-FLS was treated with different doses of A. diphtheria extracts. Then, an inverted biological microscope was adopted to observe the RA-FLS morphology. Subsequently, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining, Cell Counting Kit-8 and western blot were utilized to analyze the apoptosis, proliferation, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway-related proteins in RA-FLS, respectively. The experimental results disclosed that, after treatment of RA-FLS with A. diphtheria extracts, the cells became round and the intercellular space was increased. Besides, the RA-FLS proliferation was effectively inhibited by A. diphtheria extracts, while the apoptosis was promoted. Additionally, A. diphtheria extracts could effectively downregulate the expression levels of p-NF-κB (p50), NF-κB (p50), p-NF-κB (p65), and NF-κB (p65). Collectively, A. diphtheria can effectively inhibit RA-FLS proliferation and promote apoptosis in a dose-dependent manner. Similarly, A. diphtheria is able to downregulate p-NF-κB and NF-κB protein expression, but there is no dose-response relationship.
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Affiliation(s)
- Yan Meng
- Department of Rheumatology and Immunology, The First Affiliated Hospital at Xinjiang Medical University, Urumqi, People's Republic of China
| | - Xuan-Lin Cai
- Graduate School, Xinjiang Medical University, Urumqi, People's Republic of China
| | - Shan Cong
- Department of Rheumatology and Immunology, The First Affiliated Hospital at Xinjiang Medical University, Urumqi, People's Republic of China
| | - Jiao Sun
- Department of Rheumatology and Immunology, The First Affiliated Hospital at Xinjiang Medical University, Urumqi, People's Republic of China
| | - Yong-Wei Hu
- Department of Rheumatology and Immunology, The First Affiliated Hospital at Xinjiang Medical University, Urumqi, People's Republic of China
| | - Li Luo
- Department of Rheumatology and Immunology, The First Affiliated Hospital at Xinjiang Medical University, Urumqi, People's Republic of China
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Moon CS, Kang HM, Nam Y, Lim J, Kim J, Lee TH, Lee J, Chang MS, Lee JY. Structural Modification and Characteristics of Lappaconitine Alkaloid for the Discovery of Bioactive Components by Hypervalent Iodine Reagent. Org Lett 2024; 26:6535-6539. [PMID: 39087787 DOI: 10.1021/acs.orglett.4c01927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
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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Affiliation(s)
- Chang Sang Moon
- Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Heung Mo Kang
- Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Yunchan Nam
- Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
| | - Jiwoong Lim
- Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States
- Center for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States
| | - Jiewan Kim
- Qgenetics, Seoul Bio Cooperation Center 504, 23 Kyunghee dae-ro, Dongdaemun-gu Seoul 02447, Republic of Korea
| | - Tae-Hee Lee
- Qgenetics, Seoul Bio Cooperation Center 504, 23 Kyunghee dae-ro, Dongdaemun-gu Seoul 02447, Republic of Korea
| | - Junho Lee
- Qgenetics, Seoul Bio Cooperation Center 504, 23 Kyunghee dae-ro, Dongdaemun-gu Seoul 02447, Republic of Korea
| | - Mun Seog Chang
- Qgenetics, Seoul Bio Cooperation Center 504, 23 Kyunghee dae-ro, Dongdaemun-gu Seoul 02447, Republic of Korea
- Department of Prescriptionology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Jae Yeol Lee
- Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea
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Guo J, Jiang X, Lian J, Li H, Zhang F, Xie J, Deng J, Hou X, Du Z, Hao E. Evaluation of the effect of GSK-3β on liver cancer based on the PI3K/AKT pathway. Front Cell Dev Biol 2024; 12:1431423. [PMID: 39156976 PMCID: PMC11327086 DOI: 10.3389/fcell.2024.1431423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 07/22/2024] [Indexed: 08/20/2024] Open
Abstract
The PI3K/AKT/GSK-3β signaling pathway plays a pivotal role in numerous physiological and pathological processes, including cell proliferation, apoptosis, differentiation, and metabolic regulation. Aberrant activation of the PI3K/AKT pathway is intricately linked to development of tumor. GSK-3β, belonging to the serine/threonine protein kinase family, is crucial in the pathogenesis of liver cancer. As a key rate-limiting enzyme in the glucose metabolism pathway, GSK-3β significantly impacts the growth, proliferation, metastasis, and apoptosis of liver cancer cells. It is also implicated in chemotherapy resistance. Elevated expression of GSK-3β diminishes the sensitivity of liver cancer cells to chemotherapeutic agents, thereby playing a substantial role in the development of drug resistance. Consequently, targeting of GSK-3β, particularly within the PI3K/AKT signaling pathway, is regarded as a promising therapeutic strategy for liver cancer. The precise identification and subsequent modulation of this pathway represent a substantial potential for innovative clinical interventions in the management of liver cancer.
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Affiliation(s)
- Jiageng Guo
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
| | - Xinya Jiang
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Jing Lian
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
| | - Huaying Li
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
| | - Fan Zhang
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
| | - Jinling Xie
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
| | - Jiagang Deng
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
| | - Xiaotao Hou
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
| | - Zhengcai Du
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
| | - Erwei Hao
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Collaborative Innovation Center of Study on Functional Ingredients of Agricultural Residues, Guangxi University of Chinese Medicine, Nanning, China
- Guangxi Key Laboratory of TCM Formulas Theory and Transformation for Damp Diseases, Guangxi University of Chinese Medicine, Nanning, China
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Zhang W, Mi S, He X, Cui J, Zhi K, Zhang J. Advancements in Non-Addictive Analgesic Diterpenoid Alkaloid Lappaconitine: A Review. Int J Mol Sci 2024; 25:8255. [PMID: 39125825 PMCID: PMC11311510 DOI: 10.3390/ijms25158255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 07/13/2024] [Accepted: 07/23/2024] [Indexed: 08/12/2024] Open
Abstract
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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Affiliation(s)
- Wen Zhang
- College of Life Science, Northwest Normal University, Lanzhou 730070, China; (S.M.); (X.H.); (J.C.); (K.Z.)
- Institute of New Rural Development, Northwest Normal University, Lanzhou 730070, China
| | - Shujuan Mi
- College of Life Science, Northwest Normal University, Lanzhou 730070, China; (S.M.); (X.H.); (J.C.); (K.Z.)
| | - Xinxin He
- College of Life Science, Northwest Normal University, Lanzhou 730070, China; (S.M.); (X.H.); (J.C.); (K.Z.)
| | - Jiajia Cui
- College of Life Science, Northwest Normal University, Lanzhou 730070, China; (S.M.); (X.H.); (J.C.); (K.Z.)
- Institute of New Rural Development, Northwest Normal University, Lanzhou 730070, China
| | - Kangkang Zhi
- College of Life Science, Northwest Normal University, Lanzhou 730070, China; (S.M.); (X.H.); (J.C.); (K.Z.)
- Institute of New Rural Development, Northwest Normal University, Lanzhou 730070, China
| | - Ji Zhang
- College of Life Science, Northwest Normal University, Lanzhou 730070, China; (S.M.); (X.H.); (J.C.); (K.Z.)
- Institute of New Rural Development, Northwest Normal University, Lanzhou 730070, China
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8
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Bian YY, Hou J, Khakurel S. Treatment of a patient with aconitine poisoning using veno-arterial membrane oxygenation: A case report. World J Clin Cases 2024; 12:4842-4852. [PMID: 39070832 PMCID: PMC11235513 DOI: 10.12998/wjcc.v12.i21.4842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 05/23/2024] [Accepted: 06/12/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Aconitine poisoning is highly prone to causing malignant arrhythmias. The elimination of aconitine from the body takes a considerable amount of time, and during this period, patients are at a significant risk of death due to malignant arrhythmias associated with aconitine poisoning. CASE SUMMARY A 30-year-old male patient was admitted due to accidental ingestion of aconitine-containing drugs. Upon arrival at the emergency department, the patient intermittently experienced malignant arrhythmias including ventricular tachycardia, ventricular fibrillation, ventricular premature beats, and cardiac arrest. Emergency interventions such as cardiopulmonary resuscitation and defibrillation were promptly administered. Additionally, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy was initiated. Successful resuscitation was achieved before ECMO placement, but upon initiation of ECMO, the patient experienced recurrent malignant arrhythmias. ECMO was utilized to maintain hemodynamics and respiration, while continuous blood purification therapy for toxin clearance, mechanical ventilation, and hypothermic brain protection therapy were concurrently administered. On the third day of VA-ECMO support, the patient's respiratory and hemodynamic status stabilized, with only frequent ventricular premature beats observed on electrocardiographic monitoring, and echocardiography indicated recovery of cardiac contractile function. On the fourth day, a significant reduction in toxin levels was observed, along with stable hemodynamic and respiratory functions. Following a successful pump-controlled retrograde trial occlusion test, ECMO assistance was terminated. The patient gradually improved postoperatively and achieved recovery. He was discharged 11 days later. CONCLUSION VA-ECMO can serve as a bridging resuscitation technique for patients with reversible malignant arrhythmias.
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Affiliation(s)
- Yu-Yao Bian
- Department of Emergency Medicine, Hebei Petro China Central Hospital, Langfang 065000, Hebei Province, China
| | - Jin Hou
- Department of Internal Medicine, Langfang Health Vocational College, Langfang 065000, Hebei Province, China
| | - Sudha Khakurel
- Dallas Campus, UT Health Houston School of Public Health, Dallas, TX 75201, United States
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9
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Xing Z, Yang C, Feng Y, He J, Peng C, Li D. Understanding aconite's anti-fibrotic effects in cardiac fibrosis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 122:155112. [PMID: 37924690 DOI: 10.1016/j.phymed.2023.155112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 09/14/2023] [Accepted: 09/19/2023] [Indexed: 11/06/2023]
Abstract
BACKGROUND The prevalence of cardiac fibrosis, intricately linked to various cardiovascular diseases, continues to rise. Aconite, a traditional Chinese herb renowned for its cardiovascular benefits, holds promise in treating heart ailments. However, the mechanisms underlying its anti-fibrotic effects, particularly in cardiac fibrosis, remain elusive. HYPOTHESIS/PURPOSE This study aims to shed light on aconite's potential as an anti-fibrotic agent and elucidate its mechanisms in a rat model of isoproterenol (ISO)-induced cardiac fibrosis. METHODS By inducing cardiac fibrosis through ISO injection, the study investigates the role of decoction of white aconite (DWA) in mitigating fibrotic processes. Techniques including metabolomics, RT-qPCR, western blot, and immunofluorescence were employed to unveil the molecular changes induced by DWA. RESULTS DWA exhibited a remarkable reduction in echocardiographic parameters, cardiac weight increase, myocardial infarction extent, inflammatory cell infiltration, collagen deposition in heart tissue, and serum CK-MB, cTnT, cTnI levels post ISO injection. Metabolomic analysis unveiled DWA's modulation of 27 metabolites, especially in galactose metabolism, addressing metabolic disturbances in cardiac fibrosis. Additionally, DWA suppressed mRNA expression of fibrosis markers (Collagen I, CTGF, TGF-β), inhibited protein levels of MMP-9, α-SMA, and Galectin-3, while elevating TIMP1 expression. CONCLUSION DWA demonstrated potent anti-fibrotic effects by curbing collagen deposition and alleviating metabolic disruptions in cardiac fibrosis via the galactose metabolism pathway, possibly mediated by the Gal-3/TGF-β/Smad signaling pathway.
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Affiliation(s)
- Ziwei Xing
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu, China
| | - Chao Yang
- National Engineering Research Center for Marine Aquaculture, Institute of Innovation & Application, Zhejiang Ocean University, Zhoushan, China
| | - Yaqian Feng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu, China
| | - Junyao He
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu, China.
| | - Dan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu, China.
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10
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Cheremnykh KP, Bryzgalov AO, Baev DS, Borisov SA, Sotnikova YS, Savelyev VA, Tolstikova TG, Sagdullaev SS, Shults EE. Synthesis, Pharmacological Evaluation, and Molecular Modeling of Lappaconitine-1,5-Benzodiazepine Hybrids. Molecules 2023; 28:4234. [PMID: 37241973 PMCID: PMC10223824 DOI: 10.3390/molecules28104234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 05/19/2023] [Accepted: 05/20/2023] [Indexed: 05/28/2023] Open
Abstract
Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, have long interested scientists due to their medicinal uses and infamous toxicity which has limited the clinical application of the native compound. Alkaloid lappaconitine extracted from various Aconitum and Delphinium species has displayed extensive bioactivities and active ongoing research to reduce its adverse effects. A convenient route to construct hybrid molecules containing diterpenoid alkaloid lappaconitine and 3H-1,5-benzodiazepine fragments was proposed. The key stage involved the formation of 5'-alkynone-lappaconitines in situ by acyl Sonogashira coupling of 5'-ethynyllappaconitine, followed by cyclocondensation with o-phenylenediamine. New hybrid compounds showed low toxicity and outstanding analgesic activity in experimental pain models, which depended on the nature of the substituent in the benzodiazepine nucleus. An analogous dependence was also shown for the antiarrhythmic activity in the epinephrine arrhythmia test in vivo. Studies on the isolated atrium have shown that the mechanism of action of the new compounds is included the blockade of beta-adrenergic receptors and potassium channels. Molecular docking analysis was conducted to determine the binding potential of target molecules with the voltage-gated sodium channel NaV1.5. All obtained results provide a basis for future rational modifications of lappaconitine, reducing side effects, while retaining its therapeutic effects.
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Affiliation(s)
- Kirill P. Cheremnykh
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; (K.P.C.); (A.O.B.); (D.S.B.); (S.A.B.); (Y.S.S.); (V.A.S.); (T.G.T.)
| | - Arkadiy O. Bryzgalov
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; (K.P.C.); (A.O.B.); (D.S.B.); (S.A.B.); (Y.S.S.); (V.A.S.); (T.G.T.)
| | - Dmitry S. Baev
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; (K.P.C.); (A.O.B.); (D.S.B.); (S.A.B.); (Y.S.S.); (V.A.S.); (T.G.T.)
| | - Sergey A. Borisov
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; (K.P.C.); (A.O.B.); (D.S.B.); (S.A.B.); (Y.S.S.); (V.A.S.); (T.G.T.)
| | - Yulia S. Sotnikova
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; (K.P.C.); (A.O.B.); (D.S.B.); (S.A.B.); (Y.S.S.); (V.A.S.); (T.G.T.)
| | - Victor A. Savelyev
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; (K.P.C.); (A.O.B.); (D.S.B.); (S.A.B.); (Y.S.S.); (V.A.S.); (T.G.T.)
| | - Tatyana G. Tolstikova
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; (K.P.C.); (A.O.B.); (D.S.B.); (S.A.B.); (Y.S.S.); (V.A.S.); (T.G.T.)
| | - Shamansur S. Sagdullaev
- S.Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Mirzo Ulugbek Str. 77, Tashkent 100170, Uzbekistan;
| | - Elvira E. Shults
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; (K.P.C.); (A.O.B.); (D.S.B.); (S.A.B.); (Y.S.S.); (V.A.S.); (T.G.T.)
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Xu K, Song Z, Liu J, Yang L, Sun G, Lei L, Huang S, Gao F, Chen L, Zhou X. Compositions analysis and insecticidal activity of Aconitum polycarpum Chang ex W.T.Wang petroleum ether fractions and essential oils. JOURNAL OF ETHNOPHARMACOLOGY 2023; 303:115989. [PMID: 36509259 DOI: 10.1016/j.jep.2022.115989] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 11/23/2022] [Accepted: 11/24/2022] [Indexed: 06/17/2023]
Abstract
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.
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Affiliation(s)
- Ke Xu
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Ziyu Song
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Junqi Liu
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Liu Yang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Guoqing Sun
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Lijie Lei
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Shuai Huang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Feng Gao
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Lin Chen
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China.
| | - Xianli Zhou
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China; Affiliated Hospital of Southwest Jiaotong University & the Third People Hospital of Chengdu, Chengdu 610031, Sichuan, PR China.
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Calderon-Rivera A, Loya-Lopez S, Gomez K, Khanna R. Plant and fungi derived analgesic natural products targeting voltage-gated sodium and calcium channels. Channels (Austin) 2022; 16:198-215. [PMID: 36017978 PMCID: PMC9423853 DOI: 10.1080/19336950.2022.2103234] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Voltage-gated sodium and calcium channels (VGSCs and VGCCs) play an important role in the modulation of physiologically relevant processes in excitable cells that range from action potential generation to neurotransmission. Once their expression and/or function is altered in disease, specific pharmacological approaches become necessary to mitigate the negative consequences of such dysregulation. Several classes of small molecules have been developed with demonstrated effectiveness on VGSCs and VGCCs; however, off-target effects have also been described, limiting their use and spurring efforts to find more specific and safer molecules to target these channels. There are a great number of plants and herbal preparations that have been empirically used for the treatment of diseases in which VGSCs and VGCCs are involved. Some of these natural products have progressed to clinical trials, while others are under investigation for their action mechanisms on signaling pathways, including channels. In this review, we synthesize information from ~30 compounds derived from natural sources like plants and fungi and delineate their effects on VGSCs and VGCCs in human disease, particularly pain. [Figure: see text].
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Affiliation(s)
- Aida Calderon-Rivera
- Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY, USA,NYU Pain Research Center, New York University, New York, NY, USA
| | - Santiago Loya-Lopez
- Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY, USA,NYU Pain Research Center, New York University, New York, NY, USA
| | - Kimberly Gomez
- Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY, USA,NYU Pain Research Center, New York University, New York, NY, USA
| | - Rajesh Khanna
- Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY, USA,NYU Pain Research Center, New York University, New York, NY, USA,CONTACT Rajesh Khanna
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