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Ye XW, Zhang HX, Li Q, Li CS, Zhao CJ, Xia LJ, Ren HM, Wang XX, Yang C, Wang YJ, Jiang SL, Xu XF, Li XR. Scientometric analysis and historical review of diabetic encephalopathy research: Trends and hotspots (2004-2023). World J Diabetes 2025; 16:91200. [DOI: 10.4239/wjd.v16.i5.91200] [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: 01/03/2024] [Revised: 12/18/2024] [Accepted: 02/20/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Diabetic encephalopathy (DE) is a common and serious complication of diabetes that can cause death in many patients and significantly affects the lives of individuals and society. Multiple studies investigating the pathogenesis of DE have been reported. However, few studies have focused on scientometric analysis of DE.
AIM To analyze literature on DE using scientometrics to provide a comprehensive picture of research directions and progress in this field.
METHODS We reviewed studies on DE or cognitive impairment published between 2004 and 2023. The latter were used to identify the most frequent keywords in the keyword analysis and explore the hotspots and trends of DE.
RESULTS Scientometric analysis revealed 1308 research papers on DE, a number that increased annually over the past 20 years, and that the primary topics explored were domain distribution, knowledge structure, evolution, and emergence of research topics related to DE. The inducing factors, comorbidities, pathogenesis, treatment, and animal models of DE help clarify its occurrence, development, and treatment. An increasing number of studies on DE may be a result of the recent increase in patients with diabetes, unhealthy lifestyles, and unhealthy eating habits, which have aggravated the incidence of this disease.
CONCLUSION We identified the main inducing factors and comorbidities of DE, though other complex factors undoubtedly increase social and economic burdens. These findings provide vital references for future studies.
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Affiliation(s)
- Xian-Wen Ye
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Hai-Xia Zhang
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Qian Li
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Chun-Shuai Li
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Chong-Jun Zhao
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Liang-Jing Xia
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Hong-Min Ren
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Xu-Xing Wang
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Chao Yang
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Yu-Jie Wang
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Shui-Lan Jiang
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Xin-Fang Xu
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Xiang-Ri Li
- Traditional Chinese Medicine Processing Technology Inheritance Base of the National Administration of Traditional Chinese Medicine/Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
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Mehrnoosh F, Rezaei D, Pakmehr SA, Nataj PG, Sattar M, Shadi M, Ali-Khiavi P, Zare F, Hjazi A, Al-Aouadi RFA, Sapayev V, Zargari F, Alkhathami AG, Ahmadzadeh R, Khedmatgozar M, Hamzehzadeh S. The role of Panax ginseng in neurodegenerative disorders: mechanisms, benefits, and future directions. Metab Brain Dis 2025; 40:183. [PMID: 40232582 DOI: 10.1007/s11011-025-01610-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 04/07/2025] [Indexed: 04/16/2025]
Abstract
Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), and Huntington's disease (HD) represent a growing global health challenge, especially with aging populations. Characterized by progressive neuronal loss, these diseases lead to cognitive, motor, and behavioral impairments, significantly impacting patients' quality of life. Current therapies largely address symptoms without halting disease progression, underscoring the need for innovative, disease-modifying treatments. Ginseng, a traditional herbal medicine with well-known adaptogenic and neuroprotective properties, has gained attention as a potential therapeutic agent for neurodegeneration. Rich in bioactive compounds called ginsenosides, ginseng exhibits antioxidant, anti-inflammatory, and anti-apoptotic effects, making it a promising candidate for addressing the complex pathology of neurodegenerative diseases. Recent studies demonstrate that ginsenosides modulate disease-related processes such as oxidative stress, protein aggregation, mitochondrial dysfunction, and inflammation. In AD models, ginsenosides have been shown to reduce amyloid-beta accumulation and tau hyperphosphorylation, while in PD, they help protect dopaminergic neurons and mitigate motor symptoms. Ginseng's effects in ALS, MS, and HD models include improving motor function, extending neuronal survival, and reducing cellular toxicity. This review provides a comprehensive overview of the neuroprotective mechanisms of ginseng, emphasizing its therapeutic potential across various neurodegenerative diseases and discussing future research directions for its integration into clinical practice.
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Affiliation(s)
- Faranak Mehrnoosh
- Department of Food Science and Technology, Faculty of Agriculture and Natural Resources, Urmia University, Urmia, Iran
| | | | | | | | - Mustafa Sattar
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Melina Shadi
- Department of Environmental Toxicology, University of California, Davis, CA, USA
| | - Payam Ali-Khiavi
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farshad Zare
- Student Research Committee, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
| | | | - Valisher Sapayev
- General Professional Science Department, Mamun University, Khiva, Uzbekistan
| | - Faranak Zargari
- Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran
| | - Ali G Alkhathami
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha, 9088, Saudi Arabia
| | - Roya Ahmadzadeh
- Medicine Faculty, Zahedan University of Medical Sciences, Zahedan, Iran.
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Kaur N, Aran KR. Uncovering the intricacies of IGF-1 in Alzheimer's disease: new insights from regulation to therapeutic targeting. Inflammopharmacology 2025; 33:1311-1330. [PMID: 39883327 DOI: 10.1007/s10787-025-01641-0] [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: 12/29/2024] [Accepted: 01/12/2025] [Indexed: 01/31/2025]
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques and tau tangles, leading to cognitive decline and dementia. Insulin-like Growth Factor-1 (IGF-1) is similar in structure to insulin and is crucial for cell growth, differentiation, and regulating oxidative stress, synaptic plasticity, and mitochondrial function. IGF-1 exerts its physiological effects by binding to the IGF-1 receptor (IGF-1R) and activating PI3K/Akt pathway. In addition to the physiological activities in the brain, numerous studies point to a potential protective role of the IGF-1 pathway in the pathogenesis of neurodegenerative diseases, such as AD. Interestingly, patients with AD often exhibit altered insulin and IGF-1 levels, along with an inadequate insulin response. Dysregulation of IGF-1 signaling contributes to hyperphosphorylation of tau, NFT accumulation, increased β- and γ-secretase activity, elevated Aβ production, and impaired Aβ clearance, highlighting the need to explore the role of this signaling for potential therapeutic targets of AD. This review explores the role of IGF signaling in AD pathology, highlighting IGF-1 as a promising therapeutic target due to its significant involvement in disease mechanisms. Modulating IGF-1 activity could help mitigate neurodegeneration and preserve cognitive function in AD. A comprehensive understanding of the mechanisms underlying IGF-1 dysregulation is crucial for developing targeted therapeutic strategies to address the complex and multifaceted nature of AD.
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Affiliation(s)
- Navpreet Kaur
- Department of Pharmacy Practice, ISF College of Pharmacy, Moga, Punjab, India
| | - Khadga Raj Aran
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
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Miao J, Zhang Y, Su C, Zheng Q, Guo J. Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies. Mol Neurobiol 2025; 62:3195-3225. [PMID: 39240280 PMCID: PMC11790777 DOI: 10.1007/s12035-024-04457-1] [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: 04/24/2024] [Accepted: 08/27/2024] [Indexed: 09/07/2024]
Abstract
Alzheimer's disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for central nervous system (CNS) development, metabolism, repair, cognition, and emotion regulation, includes IGF-1, IGF-2, IGF-1R, IGF-2R, insulin receptor (IR), and six insulin-like growth factor binding proteins (IGFBPs). Research has identified abnormalities in IGF signaling in individuals with AD and AD models. Dysregulated expression of IGFs, receptors, IGFBPs, and disruptions in downstream phosphoinositide 3-kinase-protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways collectively increase AD susceptibility. Studies suggest modulating the IGF pathway may ameliorate AD pathology and cognitive decline. This review explores the CNS pathophysiology of IGF signaling in AD progression and assesses the potential of targeting the IGF system as a novel therapeutic strategy. Further research is essential to elucidate how aberrant IGF signaling contributes to AD development, understand underlying molecular mechanisms, and evaluate the safety and efficacy of IGF-based treatments.
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Affiliation(s)
- Jie Miao
- Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
| | - Yanli Zhang
- Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
- Department of Neurology, Sixth Hospital of Shanxi Medical University (General Hospital of Tisco), Taiyuan, 030001, Shanxi, China
| | - Chen Su
- Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
| | - Qiandan Zheng
- Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
| | - Junhong Guo
- Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
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Niu H, Zhang M, Zhang K, Aishan S, Li H, Wu W. In-Depth Investigation on Potential Mechanism of Forest-Grown Ginseng Alleviating Alzheimer's Disease via UHPLC-MS-Based Metabolomics. Metabolites 2025; 15:93. [PMID: 39997718 PMCID: PMC11857256 DOI: 10.3390/metabo15020093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 01/24/2025] [Accepted: 01/30/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Alzheimer's disease is a central nervous system degenerative disease closely related to age with a complex pathogenesis. As a natural medicinal plant, forest-grown ginseng (GSF) contains abundant ginsenosides and offers significant neuroprotective effects. METHODS In this study, we comprehensively investigated the effect of GSF on the cell viability of PC12 cells in an AD model alongside metabolic changes in the serum and brains of mice, combined with an efficacy evaluation of PC12 cells in vitro and UHPLC-MS-based metabolomics in vivo. The goal of this study is to clarify the potential mechanism of GSF in treating AD. RESULTS The PC12 cell results showed that GSF can promote the proliferation of PC12 cells, reduce the content of IL-8, increase the activity of SOD, and alleviate the inflammation and oxidative stress induced by Aβ25~35. The immunohistochemical results for the mouse brain tissue also showed that GSF could reduce the inflammatory response of mouse brain tissue by reducing the overexpression of IBa1. AD was alleviated by reducing Aβ protein deposition in the mouse brain tissue. An untargeted metabolomics analysis was performed using UHPLC-Q-Exactive MS and principal component analysis (PCA) to identify the differentially expressed metabolites in the serum and brain tissue of AD mice after treatment. Twenty and seventeen different metabolites were identified in the serum and brain tissue, respectively. The pathway enrichment analysis of differential metabolites showed that GSF could treat AD by up-regulating succinic acid semialdehyde, carbamoyl phosphate, Sphingosine 1-phosphate, L-cystathionine, 2-ketobutyric acid, Vanillylmandelic acid, and D-Ribose to regulate sphingomyelin metabolism, the synthesis and metabolism of neurotransmitters and precursors, and energy metabolism. CONCLUSIONS GSF can reduce neuroinflammation and alleviate Alzheimer's disease by regulating the metabolic disorders of amino acids, sphingolipids, unsaturated fatty acids, and arachidonic acid in mice serum and brain tissue metabolites. These results suggest a link between metabolite imbalance and AD, and reveal the basis for the mechanism of ginsenosides in AD treatment.
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Affiliation(s)
| | | | | | | | | | - Wei Wu
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China
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Ma M, Jing G, Tian Y, Yin R, Zhang M. Ferroptosis in Cognitive Impairment Associated with Diabetes and Alzheimer's Disease: Mechanistic Insights and New Therapeutic Opportunities. Mol Neurobiol 2025; 62:2435-2449. [PMID: 39112768 PMCID: PMC11772472 DOI: 10.1007/s12035-024-04417-9] [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: 04/27/2024] [Accepted: 07/30/2024] [Indexed: 01/28/2025]
Abstract
Cognitive impairment associated with diabetes and Alzheimer's disease has become a major health issue affecting older individuals, with morbidity rates growing acutely each year. Ferroptosis is a novel form of cell death that is triggered by iron-dependent lipid peroxidation. A growing body of evidence suggests a strong correlation between the progression of cognitive impairment and diabetes, Alzheimer's disease, and ferroptosis. The pharmacological modulation of ferroptosis could be a promising therapeutic intervention for cognitive impairment associated with diabetes and Alzheimer's disease. In this review, we summarize evidence on ferroptosis in the context of cognitive impairment associated with diabetes and Alzheimer's disease and provide detailed insights into the function and potential action pathways of ferroptosis. Furthermore, we discuss the therapeutic importance of natural ferroptosis products in improving the cognitive impairment associated with diabetes and Alzheimer's disease and provide new insights for clinical treatment.
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Affiliation(s)
- Mei Ma
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Guangchan Jing
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yue Tian
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Ruiying Yin
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Mengren Zhang
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
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Liang J, Zhu Y, Liu S, Kuang B, Tian Z, Zhang L, Yang S, Lin M, Chen N, Liu X, Ai Q, Yang Y. Progress of Exosomal MicroRNAs and Traditional Chinese Medicine Monomers in Neurodegenerative Diseases. Phytother Res 2024; 38:5323-5349. [PMID: 39225243 DOI: 10.1002/ptr.8322] [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: 01/01/2024] [Revised: 07/14/2024] [Accepted: 08/10/2024] [Indexed: 09/04/2024]
Abstract
Exosomes, extracellular vesicles secreted by various cells, actively participate in intercellular communication by facilitating the exchange of crucial molecular information such as DNA, RNA, and lipids. Within this intricate network, microRNAs, endogenous non-coding small RNAs, emerge as pivotal regulators of post-transcriptional gene expression, significantly influencing the development of neurodegenerative diseases. The historical prominence of traditional Chinese medicine (TCM) in clinical practice in China underscores its enduring significance. Notably, TCM monomers, serving as active constituents within herbal medicine, assume a critical role in the treatment of neurodegenerative diseases, particularly in mitigating oxidative stress, inhibiting apoptosis, and reducing inflammation. This comprehensive review aims to delineate the specific involvement of exosomal microRNAs in various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. Furthermore, the exploration extends to the application of TCM monomers, elucidating their efficacy as therapeutic agents in these conditions. Additionally, the review examines the utilization of exosomes as drug delivery carriers in the context of neurodegenerative diseases, providing a nuanced understanding of the potential synergies between TCM and modern therapeutic approaches. This synthesis of knowledge aims to contribute to the advancement of our comprehension of the intricate molecular mechanisms underlying neurodegeneration and the potential therapeutic avenues offered by TCcom interventions.
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Affiliation(s)
- Jinping Liang
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Yuchen Zhu
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Shasha Liu
- Department of Pharmacy, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, China
| | - Boyu Kuang
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Zhifeng Tian
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Ling Zhang
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Songwei Yang
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Meiyu Lin
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Naihong Chen
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuan Liu
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Qidi Ai
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Yantao Yang
- Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
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Zhao D, Li Z, Liu X, Zhang Z, Ma H, Wang P, Zhang Z, Song J, Hu K. Fe 3O 4@MXene@PEI aerogel immobilized acetylcholinesterase for inhibitor screening from herbal plants. J Chromatogr B Analyt Technol Biomed Life Sci 2024; 1247:124345. [PMID: 39490207 DOI: 10.1016/j.jchromb.2024.124345] [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: 09/08/2024] [Revised: 10/08/2024] [Accepted: 10/16/2024] [Indexed: 11/05/2024]
Abstract
Screening of acetylcholinesterase (AChE) inhibitors is a common strategy in drug discovery for treating Alzheimer's disease. Herein, AChE was immobilized onto magnetic polyethyleneimine-based MXene aerogels through both electrostatic interactions and covalent bonds, enabling its application in AChE activity assays and inhibitor screening of herbal plants. The composite was analyzed using a range of techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and Zeta potential analysis, to gain insight into its chemical and physical properties. The proposed Fe3O4@MXene@PEI-AChE composite exhibited enhanced temperature and pH stability, as evaluated by Ellman's method, along with good reusability. The Michaelis Menten constant (Km) of the immobilized AChE was calculated to be 0.68 mmol/L. Additionally, an inhibition kinetic study was conducted to verify the feasibility of utilizing the immobilized enzyme to screen for inhibitors, with huperzine A employed as a model inhibitor. The proposed strategy was employed to compare the AChE inhibitory activity of 18 commonly used herbal medicines for treating AD, revealing both the aqueous and alcoholic extracts of Coptis chinensis as exhibiting the highest AChE inhibitory activity. Finally, the screening of AChE inhibitors in Coptis chinensis extracts were conducted by combining the proposed strategy with UPLC-Q-Orbitrap high resolution mass spectrometry. This study presents a feasible strategy for monitoring AChE activity and holds considerable potential for further exploration of AChE-inhibiting active ingredients in herbal medicines.
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Affiliation(s)
- Di Zhao
- Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Zhonghua Li
- Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Xiaobing Liu
- Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Zhiyu Zhang
- Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Huifen Ma
- Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Pan Wang
- Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Zhenqiang Zhang
- Henan University of Chinese Medicine, Zhengzhou 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan Province, China.
| | - Junying Song
- Henan University of Chinese Medicine, Zhengzhou 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan Province, China
| | - Kai Hu
- Henan University of Chinese Medicine, Zhengzhou 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan Province, China.
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Piva A, Benvegnù G, Negri S, Commisso M, Ceccato S, Avesani L, Guzzo F, Chiamulera C. Whole Plant Extracts for Neurocognitive Disorders: A Narrative Review of Neuropsychological and Preclinical Studies. Nutrients 2024; 16:3156. [PMID: 39339756 PMCID: PMC11434991 DOI: 10.3390/nu16183156] [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: 08/14/2024] [Revised: 09/09/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
The incidence of neurodegenerative disorders like Alzheimer's or Parkinson's Disease, characterized by a progressive cognitive decline, is rising worldwide. Despite the considerable efforts to unveil the neuropsychological bases of these diseases, there is still an unmet medical need for effective therapies against cognitive deficits. In recent years, increasing laboratory evidence indicates the potential of phytotherapy as an integrative aid to improve cognitive functions. In this review, we describe the data of plant whole extracts or single compounds' efficacy on validated preclinical models and neuropsychological tests, aiming to correlate brain mechanisms underlying rodent behavioral responses to human findings. After a search of the literature, the overview was limited to the following plants: Dioscorea batatas, Ginkgo biloba, Melissa officinalis, Nigella sativa, Olea europaea, Panax ginseng, Punica granatum, and Vitis vinifera. Results showed significant improvements in different cognitive functions, such as learning and memory or visuospatial abilities, in both humans and rodents. However, despite promising laboratory evidence, clinical translation has been dampened by a limited pharmacological characterization of the single bioactive components of the herbal products. Depicting the contribution of the single phytochemicals to the phytocomplex's pharmacological efficacy could enable the comprehension of their potential synergistic activity, leading to phytotherapy inclusion in the existing therapeutic package against cognitive decline.
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Affiliation(s)
- Alessandro Piva
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (A.P.); (G.B.); (C.C.)
- NBFC, National Biodiversity Future Center, 90133 Palermo, Italy; (S.N.); (M.C.); (L.A.); (F.G.)
| | - Giulia Benvegnù
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (A.P.); (G.B.); (C.C.)
| | - Stefano Negri
- NBFC, National Biodiversity Future Center, 90133 Palermo, Italy; (S.N.); (M.C.); (L.A.); (F.G.)
- Department of Biotechnology, University of Verona, 37134 Verona, Italy
| | - Mauro Commisso
- NBFC, National Biodiversity Future Center, 90133 Palermo, Italy; (S.N.); (M.C.); (L.A.); (F.G.)
- Department of Biotechnology, University of Verona, 37134 Verona, Italy
| | - Sofia Ceccato
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (A.P.); (G.B.); (C.C.)
| | - Linda Avesani
- NBFC, National Biodiversity Future Center, 90133 Palermo, Italy; (S.N.); (M.C.); (L.A.); (F.G.)
- Department of Biotechnology, University of Verona, 37134 Verona, Italy
| | - Flavia Guzzo
- NBFC, National Biodiversity Future Center, 90133 Palermo, Italy; (S.N.); (M.C.); (L.A.); (F.G.)
- Department of Biotechnology, University of Verona, 37134 Verona, Italy
| | - Cristiano Chiamulera
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (A.P.); (G.B.); (C.C.)
- NBFC, National Biodiversity Future Center, 90133 Palermo, Italy; (S.N.); (M.C.); (L.A.); (F.G.)
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Kwon D, Kim Y, Cho SH. Antidepressant Effects of Ginsenoside Rc on L-Alpha-Aminoadipic Acid-Induced Astrocytic Ablation and Neuroinflammation in Mice. Int J Mol Sci 2024; 25:9673. [PMID: 39273621 PMCID: PMC11396248 DOI: 10.3390/ijms25179673] [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: 07/09/2024] [Revised: 08/29/2024] [Accepted: 09/05/2024] [Indexed: 09/15/2024] Open
Abstract
Depression is a prevalent and debilitating mental disorder that affects millions worldwide. Current treatments, such as antidepressants targeting the serotonergic system, have limitations, including delayed onset of action and high rates of treatment resistance, necessitating novel therapeutic strategies. Ginsenoside Rc (G-Rc) has shown potential anti-inflammatory and neuroprotective effects, but its antidepressant properties remain unexplored. This study investigated the antidepressant effects of G-Rc in an L-alpha-aminoadipic acid (L-AAA)-induced mouse model of depression, which mimics the astrocytic pathology and neuroinflammation observed in major depressive disorder. Mice were administered G-Rc, vehicle, or imipramine orally after L-AAA injection into the prefrontal cortex. G-Rc significantly reduced the immobility time in forced swimming and tail suspension tests compared to vehicle treatment, with more pronounced effects than imipramine. It also attenuated the expression of pro-inflammatory cytokines (TNF-α, IL-6, TGF-β, lipocalin-2) and alleviated astrocytic degeneration, as indicated by increased GFAP and decreased IBA-1 levels. Additionally, G-Rc modulated apoptosis-related proteins, decreasing caspase-3 and increasing Bcl-2 levels compared to the L-AAA-treated group. These findings suggest that G-Rc exerts antidepressant effects by regulating neuroinflammation, astrocyte-microglia crosstalk, and apoptotic pathways in the prefrontal cortex, highlighting its potential as a novel therapeutic agent for depression.
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Affiliation(s)
- Dohyung Kwon
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Yunna Kim
- College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Neuropsychiatry of Korean Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul 02447, Republic of Korea
- Research Group of Neuroscience, East-West Medical Research Institute, WHO Collaborating Center, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Seung-Hun Cho
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
- College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Neuropsychiatry of Korean Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul 02447, Republic of Korea
- Research Group of Neuroscience, East-West Medical Research Institute, WHO Collaborating Center, Kyung Hee University, Seoul 02447, Republic of Korea
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11
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Liu S, Wang M, Xiao H, Ye J, Cao L, Li W, Sun G. Advancements in research on the effects of panax notoginseng saponin constituents in ameliorating learning and memory disorders. Heliyon 2024; 10:e28581. [PMID: 38586351 PMCID: PMC10998096 DOI: 10.1016/j.heliyon.2024.e28581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 03/20/2024] [Accepted: 03/20/2024] [Indexed: 04/09/2024] Open
Abstract
Learning and memory disorder is a cluster of symptoms caused by neuronal aging and other diseases of the central nervous system (CNS). Panax notoginseng saponins (PNS) are a series of saponins derived from the natural active ingredients of traditional Chinese medicine (TCM) that have neuroprotective effects on the central nervous system. In this paper, we review the ameliorative effects and mechanisms of Panax notoginseng saponin-like components on learning and memory disorders to provide valuable references and insights for the development of new drugs for the treatment of learning and memory disorders. Our summary results suggest that Panax ginseng saponins have significant effects on improving learning and memory disorders, and these effects and potential mechanisms are mediated by their anti-inflammatory, anti-apoptotic, antioxidant, β-amyloid lowering, mitochondrial homeostasis in vivo, neuronal structure and function improving, neurogenesis promoting, neurotransmitter release regulating, and probiotic homeostasis in vivo activities. These findings suggest the potential of Panax notoginseng saponin-like constituents as drug candidates for improving learning and memory disorders.
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Affiliation(s)
- Shusen Liu
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Min Wang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Haiyan Xiao
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Jingxue Ye
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Li Cao
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Wenlan Li
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Guibo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
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Mao Y, Yuan W, Gai J, Zhang Y, Wu S, Xu EY, Wang L, Zhang X, Guan J, Mao S. Enhanced brain distribution of Ginsenoside F1 via intranasal administration in combination with absorption enhancers. Int J Pharm 2024; 654:123930. [PMID: 38387820 DOI: 10.1016/j.ijpharm.2024.123930] [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: 12/23/2023] [Revised: 01/31/2024] [Accepted: 02/19/2024] [Indexed: 02/24/2024]
Abstract
Ginsenoside F1 (GF1) is a potential drug candidate for the treatment of Alzheimer's disease. Nevertheless, its low oral bioavailability and poor solubility limit clinical application. By utilizing either a direct or indirect approach, intranasal administration is a non-invasive drug delivery method that can deliver drugs to the brain rapidly. But large molecule drug delivered to the brain through intranasal administration may be insufficient to reach required concentration for therapeutic effect. In this study, using GF1 as a model drug, the feasibility of intranasal administration in combination with absorption enhancers to increase brain distribution of GF1 was explored. First of all, the appropriate absorption enhancers were screened by in situ nasal perfusion study. GF1-HP-β-CD inclusion complex was prepared and characterized. Thereafter, in vivo absorption of GF1 after intranasal or intravenous administration of its inclusion complex with/without absorption enhancers was investigated, and safety of the formulations was evaluated. The results showed that 2% Solutol HS 15 was a superior absorption enhancer. HP-β-CD inclusion complex improved GF1 solubility by 150 fold. Following intranasal delivery, the absolute bioavailability of inclusion complex was 46%, with drug brain targeting index (DTI) 247% and nose-to-brain direct transport percentage (DTP) 58%. Upon further addition of 2% Solutol HS 15, the absolute bioavailability was increased to 75%, with DTI 315% and DTP 66%. Both nasal cilia movement and biochemical substances (total protein and lactate dehydrogenase) leaching studies demonstrated 2% Solutol HS 15 was safe to the nasal mucosa. In conclusion, intranasal administration combining with safe absorption enhancers is an effective strategy to enhance drug distribution in the brain, showing promise for treating disorders related to the central nervous system.
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Affiliation(s)
- Ying Mao
- School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Weihua Yuan
- School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Jiayi Gai
- School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Yixuan Zhang
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China
| | | | - En-Yu Xu
- Department of Forensic Toxicological Analysis, School of Forensic Medicine, China Medical University, Shenyang 110122, China.
| | - Luyao Wang
- School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xin Zhang
- School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, China
| | - Jian Guan
- School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, China
| | - Shirui Mao
- School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, China.
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Elsaman T, Muddathir AM, Mohieldin EAM, Batubara I, Rahminiwati M, Yamauchi K, Mohamed MA, Asoka SF, Büsselberg D, Habtemariam S, Sharifi-Rad J. Ginsenoside Rg5 as an anticancer drug: a comprehensive review on mechanisms, structure-activity relationship, and prospects for clinical advancement. Pharmacol Rep 2024; 76:287-306. [PMID: 38526651 DOI: 10.1007/s43440-024-00586-5] [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: 09/14/2023] [Revised: 03/02/2024] [Accepted: 03/04/2024] [Indexed: 03/27/2024]
Abstract
Cancer remains one of the leading causes of death in the world. Despite the considerable success of conventional treatment strategies, the incidence and mortality rates are still high, making developing new effective anticancer therapies an urgent priority. Ginsenoside Rg5 (Rg5) is a minor ginsenoside constituent obtained exclusively from ginseng species and is known for its broad spectrum of pharmacological activities. This article aimed to comprehensively review the anticancer properties of Rg5, focusing on action mechanisms, structure-activity relationship (SAR), and pharmacokinetics attributes. The in vitro and in vivo activities of Rg5 have been proven against several cancer types, such as breast, liver, lung, bone, and gastrointestinal (GI) cancers. The modulation of multiple signaling pathways critical for cancer growth and survival mediates these activities. Nevertheless, human clinical studies of Rg5 have not been addressed before, and there is still considerable ambiguity regarding its pharmacokinetics properties. In addition, a significant shortage in the structure-activity relationship (SAR) of Rg5 has been identified. Therefore, future efforts should focus on further optimization by performing extensive SAR studies to uncover the structural features essential for the potent anticancer activity of Rg5. Thus, this review highlights the value of Rg5 as a potential anticancer drug candidate and identifies the research areas requiring more investigation.
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Affiliation(s)
- Tilal Elsaman
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf, Saudi Arabia
| | - Ali Mahmoud Muddathir
- Department of Horticulture, Faculty of Agriculture, University of Khartoum, Shambat, 13314, Khartoum North, Sudan
| | | | - Irmanida Batubara
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University (Bogor Agricultural University), Bogor, Indonesia
- Tropical Biopharmaca Research Center, IPB University (Bogor Agricultural University), Bogor, Indonesia
| | - Min Rahminiwati
- Division of Pharmacology, School of Veterinary Medicine and Biomedical Science, IPB University, Jln Agathis Dramaga, Bogor, West Java, 16680, Indonesia
- Tropical Biopharmaca Research Center, IPB University, Jl. Taman Kencana No. 3, Bogor, West Java, 16128, Indonesia
| | - Kosei Yamauchi
- Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan
| | - Magdi Awadalla Mohamed
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf, Saudi Arabia
| | - Shadila Fira Asoka
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University (Bogor Agricultural University), Bogor, Indonesia
- Tropical Biopharmaca Research Center, IPB University (Bogor Agricultural University), Bogor, Indonesia
| | - Dietrich Büsselberg
- Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, P.O. Box 24144, Doha, Qatar
| | - Solomon Habtemariam
- Pharmacognosy Research and Herbal Analysis Services UK, Central Avenue , Chatham, Kent, ME4 4TB, UK
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He S, Shi J, Chai H, Ma L, Pei H, Zhang P, Shi D, Li H. Mechanisms with network pharmacology approach of Ginsenosides in Alzheimer's disease. Heliyon 2024; 10:e26642. [PMID: 38434355 PMCID: PMC10906400 DOI: 10.1016/j.heliyon.2024.e26642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 01/23/2024] [Accepted: 02/16/2024] [Indexed: 03/05/2024] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, cognitive disorder, language dysfunction, and mental disability. The main neuropathological changes in AD mainly include amyloid plaque deposition, neurofibrillary tangles, synapse loss, and neuron reduction. However, the current anti-AD drugs do not demonstrate a favorable effect in altering the pathological course of AD. Moreover, long-term use of these drugs is usually accompanied with various side effects. Ginsenosides are the major active constituents of ginseng and have protective effects on AD through various mechanisms in both in vivo and in vitro studies. In this review, we focused on discussing the therapeutic potential effects and the mechanisms of pharmacological activities of ginsenosides in AD, to provide new insight for further research and clinical application of ginsenosides in the future. Recent studies on the pharmacological effects and mechanisms of ginsenosides were retrieved from Chinese National Knowledge Infrastructure, National Science and Technology Library, Wanfang Data, Elsevier, ScienceDirect, PubMed, SpringerLink, and the Web of Science database up to April 2023 using relevant keywords. Network pharmacology and bioinformatics analysis were used to predict the therapeutic effects and mechanisms of ginsenosides against AD. Ginsenosides presented a wide range of therapeutic and biological activities, including alleviating Aβ deposition, decreasing tau hyperphosphorylation, regulating the cholinergic system, resisting oxidative stress, modulating Ca2+ homeostasis, as well as anti-inflammation and anti-apoptosis in neurons, respectively. For further developing the therapeutic potential as well as clinical applications, the network pharmacology approach was combined with a summary of published studies.
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Affiliation(s)
- Shan He
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Junhe Shi
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hua Chai
- Hepingli Hospital, Beijing, China
| | - Lina Ma
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hui Pei
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ping Zhang
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Dazhuo Shi
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hao Li
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Zhao F, Zhang K, Chen H, Zhang T, Zhao J, Lv Q, Yu Q, Ruan M, Cui R, Li B. Therapeutic potential and possible mechanisms of ginseng for depression associated with COVID-19. Inflammopharmacology 2024; 32:229-247. [PMID: 38012459 PMCID: PMC10907431 DOI: 10.1007/s10787-023-01380-0] [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: 08/19/2023] [Accepted: 10/17/2023] [Indexed: 11/29/2023]
Abstract
Recently, a global outbreak of COVID-19 has rapidly spread to various national regions. As the number of COVID-19 patients has increased, some of those infected with SARS-CoV-2 have developed a variety of psychiatric symptoms, including depression, cognitive impairment, and fatigue. A distinct storm of inflammatory factors that contribute to the initial disease but also a persistent post-acute phase syndrome has been reported in patients with COVID-19. Neuropsychological symptoms including depression, cognitive impairment, and fatigue are closely related to circulating and local (brain) inflammatory factors. Natural products are currently being examined for their ability to treat numerous complications caused by COVID-19. Among them, ginseng has anti-inflammatory, immune system stimulating, neuroendocrine modulating, and other effects, which may help improve psychiatric symptoms. This review summarizes the basic mechanisms of COVID-19 pneumonia, psychiatric symptoms following coronavirus infections, effects of ginseng on depression, restlessness, and other psychiatric symptoms associated with post-COVID syn-dromes, as well as possible mechanisms underlying these effects.
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Affiliation(s)
- Fangyi Zhao
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Kai Zhang
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Hongyu Chen
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Tianqi Zhang
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Jiayu Zhao
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Qianyu Lv
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Qin Yu
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Mengyu Ruan
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Ranji Cui
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China
| | - Bingjin Li
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, People's Republic of China.
- Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, People's Republic of China.
- Jilin Provincial Key Laboratory on Target of Traditional Chinese Medicine with Anti-Depressive Effect, Changchun, People's Republic of China.
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Lee MY, Kim M. Effects of Red ginseng on neuroinflammation in neurodegenerative diseases. J Ginseng Res 2024; 48:20-30. [PMID: 38223824 PMCID: PMC10785270 DOI: 10.1016/j.jgr.2023.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 07/17/2023] [Accepted: 08/25/2023] [Indexed: 01/16/2024] Open
Abstract
Red ginseng (RG) is widely used as a herbal medicine. As the human lifespan has increased, numerous diseases have developed, and RG has also been used to treat various diseases. Neurodegenerative diseases are major problems that modern people face through their lives. Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are featured by progressive nerve system damage. Recently, neuroinflammation has emerged as a degenerative factor and is an immune response in which cytokines with nerve cells that constitute the nervous system. RG, a natural herbal medicine with fewer side effects than chemically synthesized drugs, is currently in the spotlight. Therefore, we reviewed studies reporting the roles of RG in treating neuroinflammation and neurodegenerative diseases and found that RG might help alleviate neurodegenerative diseases by regulating neuroinflammation.
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Affiliation(s)
- Min Yeong Lee
- Department of Chemistry & Life Science, Sahmyook University, Hwarangro 815, Nowongu, Seoul, Republic of Korea
| | - Mikyung Kim
- Department of Chemistry & Life Science, Sahmyook University, Hwarangro 815, Nowongu, Seoul, Republic of Korea
- Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, Hwarangro 815, Nowongu, Seoul, Republic of Korea
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17
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Wang Y, Chen K, Qiao ZX, Bao XR. Chronic Kidney Disease Induces Cognitive Impairment in the Early Stage. Curr Med Sci 2023; 43:988-997. [PMID: 37755634 DOI: 10.1007/s11596-023-2783-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 08/07/2023] [Indexed: 09/28/2023]
Abstract
OBJECTIVE Previous research indicates a link between cognitive impairment and chronic kidney disease (CKD), but the underlying factors are not fully understood. This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early- and late-stage CKD models in Sprague-Dawley rats. METHODS The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery. Histopathologic examinations were conducted to examine renal and hippocampal damage. Real-time PCR, Western blotting analysis, and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor (BDNF), choline acetyltransferase (ChAT), and synaptophysin (SYP). RESULTS Compared with the control rats, the rats with early-stage CKD exhibited mild renal damage, while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage. The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats, with further deterioration observed in the rats with late-stage CKD. Additionally, we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD, which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD. CONCLUSION These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly. In addition, the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.
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Affiliation(s)
- Yu Wang
- Department of Nephrology, Jinshan Hospital, Fudan University, Shanghai, 201508, China
| | - Kai Chen
- Department of Nephrology, Jinshan Hospital, Fudan University, Shanghai, 201508, China
| | - Zi-Xuan Qiao
- Department of Nephrology, Jinshan Hospital, Fudan University, Shanghai, 201508, China
| | - Xiao-Rong Bao
- Department of Nephrology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
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Shan M, Bai Y, Fang X, Lan X, Zhang Y, Cao Y, Zhu D, Luo H. American Ginseng for the Treatment of Alzheimer's Disease: A Review. Molecules 2023; 28:5716. [PMID: 37570686 PMCID: PMC10420665 DOI: 10.3390/molecules28155716] [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: 06/25/2023] [Revised: 07/19/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
Alzheimer's disease (AD) is a prevalent degenerative condition that is increasingly affecting populations globally. American ginseng (AG) has anti-AD bioactivity, and ginsenosides, as the main active components of AG, have shown strong anti-AD effects in both in vitro and in vivo studies. It has been reported that ginsenosides can inhibit amyloid β-protein (Aβ) production and deposition, tau phosphorylation, apoptosis and cytotoxicity, as well as possess anti-oxidant and anti-inflammatory properties, thus suppressing the progression of AD. In this review, we aim to provide a comprehensive overview of the pathogenesis of AD, the potential anti-AD effects of ginsenosides found in AG, and the underlying molecular mechanisms associated with these effects. Additionally, we will discuss the potential use of AG in the treatment of AD, and how ginsenosides in AG may exert more potent anti-AD effects in vivo may be a direction for further research.
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Affiliation(s)
- Mengyao Shan
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (M.S.); (Y.B.); (X.F.); (X.L.); (Y.Z.); (Y.C.)
- Department of Pharmaceutical Chemistry and Traditional Chinese Medicine Chemistry, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Yunfan Bai
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (M.S.); (Y.B.); (X.F.); (X.L.); (Y.Z.); (Y.C.)
- Department of Pharmaceutical Chemistry and Traditional Chinese Medicine Chemistry, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Xiaoxue Fang
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (M.S.); (Y.B.); (X.F.); (X.L.); (Y.Z.); (Y.C.)
- Department of Pharmaceutical Chemistry and Traditional Chinese Medicine Chemistry, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Xintian Lan
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (M.S.); (Y.B.); (X.F.); (X.L.); (Y.Z.); (Y.C.)
- Department of Pharmaceutical Chemistry and Traditional Chinese Medicine Chemistry, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Yegang Zhang
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (M.S.); (Y.B.); (X.F.); (X.L.); (Y.Z.); (Y.C.)
- Department of Pharmaceutical Chemistry and Traditional Chinese Medicine Chemistry, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Yiming Cao
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (M.S.); (Y.B.); (X.F.); (X.L.); (Y.Z.); (Y.C.)
- Department of Pharmaceutical Chemistry and Traditional Chinese Medicine Chemistry, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Difu Zhu
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (M.S.); (Y.B.); (X.F.); (X.L.); (Y.Z.); (Y.C.)
- Department of Biopharmaceutical and Health Food, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Haoming Luo
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (M.S.); (Y.B.); (X.F.); (X.L.); (Y.Z.); (Y.C.)
- Department of Pharmaceutical Chemistry and Traditional Chinese Medicine Chemistry, Changchun University of Chinese Medicine, Changchun 130117, China
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Li N, Duan YH, Chen L, Zhang K. Iron metabolism: An emerging therapeutic target underlying the anti-Alzheimer's disease effect of ginseng. J Trace Elem Med Biol 2023; 79:127252. [PMID: 37418790 DOI: 10.1016/j.jtemb.2023.127252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 06/05/2023] [Accepted: 06/22/2023] [Indexed: 07/09/2023]
Abstract
Finding neuroprotective drugs with fewer side effects and more efficacy has become a major problem as the global prevalence of Alzheimer's disease (AD) rises. Natural drugs have risen to prominence as potential medication candidates. Ginseng has a long history of use in China, and it has a wide range of pharmacological actions that can help with neurological issues. Iron loaded in the brain has been linked to AD pathogenesis. We reviewed the regulation of iron metabolism and its studies in AD and explored how ginseng might regulate iron metabolism and prevent or treat AD. Researchers utilized network pharmacology analysis to identify key factive components of ginseng that protect against AD by regulating ferroptosis. Ginseng and its active ingredients may benefit AD by regulating iron metabolism and targeting ferroptosis genes to inhibit the ferroptosis process. The results present new ideas for ginseng pharmacological studies and initiatives for further research into AD-related drugs. To provide comprehensive information on the neuroprotective use of ginseng to modulate iron metabolism, reveal its potential to treat AD, and provide insights for future research opportunities.
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Affiliation(s)
- Nan Li
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, China
| | - Yu-Han Duan
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, China
| | - Lei Chen
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, China
| | - Kun Zhang
- Department of Medical Research Center, The Second Hospital of Jilin University, Changchun, China.
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Lv JM, Zhang LM, Wang JX, Shao JJ, Guo XG, Wang LY, Kang LQ, Zheng WC, Xin Y, Song RX, Guo W, Zhang DX. Abdominal surgery plus sevoflurane exposure induces abnormal emotional changes and cognitive dysfunction in aged rats. Behav Brain Res 2023; 442:114328. [PMID: 36740076 DOI: 10.1016/j.bbr.2023.114328] [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: 10/11/2022] [Revised: 01/26/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023]
Abstract
BACKGROUND Cognitive impairment, which includes perioperative psychological distress and cognitive dysfunction, can be determined by preoperative and post-operative neuropsychological tests. Several mechanisms have been proposed regarding the two-way communication between the immune system and the brain after surgery. We aimed to understand the mechanisms underlying perioperative neurocognitive disorders (PND) in elderly rats using an experimental abdominal surgery model. METHODS 24-month-old SD rats were exposed to the abdominal surgery model (AEL) under 3% anesthesia. On day 15 and day 30 post-surgery, fractional anisotropy (FA) using diffusion kurtosis imaging (DKI) was measured. From day 25 to day 30 post-surgery, behavioral tests, including open field test (OFT), Morris water maze (MWM), novel object recognition (NOR), force swimming test (FST), and elevated plus maze (EPM), were performed. Then, the rats were euthanized to perform pathological analysis and western blot measurement. RESULTS The rats exposed to AEL surgical treatment demonstrated significantly decreased time crossing the platform in the MWM, decreased recognition index in the NOR, reduced time in the open arm in the EPM, increased immobility time in the FST, and increased number of crossings in the OFT. Aged rats, after AEL exposure, further demonstrated decreased FA in the mPFC, nucleus accumbens (NAc), and hippocampus, together with reduced MAP2 intensity, attenuation of GAD65, VGlut2, CHAT, and phosphorylated P38MAPK expression, and increased reactive astrocytes and microglia. CONCLUSIONS In this study, the aged rats exposed to abdominal surgery demonstrated both emotional changes and cognitive dysfunction, which may be associated with neuronal degeneration and reduced phosphorylated P38MAPK.
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Affiliation(s)
- Jin-Meng Lv
- Department of Anesthesia and Trauma Research, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China.
| | - Li-Min Zhang
- Department of Anesthesiology, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China.
| | - Jie-Xia Wang
- Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China.
| | - Jing-Jing Shao
- Department of Anesthesiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
| | - Xin-Gui Guo
- Department of Medical Iconography, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China.
| | - Lu-Ying Wang
- Department of Anesthesia and Trauma Research, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China.
| | - Li-Qing Kang
- Department of Medical Iconography, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China.
| | - Wei-Chao Zheng
- Department of Anesthesiology, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China.
| | - Yue Xin
- Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China.
| | - Rong-Xin Song
- Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China.
| | - Wei Guo
- Department of Orthopedics, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China.
| | - Dong-Xue Zhang
- Department of Gerontology, Cangzhou Central Hospital, Cangzhou, China.
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Wang Z, Zhang Z, Liu J, Guo M, Li H. Panax Ginseng in the treatment of Alzheimer's disease and vascular dementia. J Ginseng Res 2023. [DOI: 10.1016/j.jgr.2023.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023] Open
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The Effective Components, Core Targets, and Key Pathways of Ginseng against Alzheimer's Disease. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2023; 2023:9935942. [PMID: 36726526 PMCID: PMC9886485 DOI: 10.1155/2023/9935942] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 08/02/2022] [Accepted: 08/04/2022] [Indexed: 01/24/2023]
Abstract
Background Panax ginseng C. A. Mey (ginseng) is a traditional Chinese medicinal herb used for the treatment of nervous system disorders, such as Alzheimer's disease (AD). However, the pharmacological mechanisms of ginseng involved in AD have not been systematically investigated. Here, a network pharmacology approach was adopted to explore the effective components, core targets, and key pathways of ginseng against AD. Methods TCMSP database was used to screen the active ingredients of ginseng. Prediction of the targets of ginseng and AD-related genes was performed using online public databases. "Compound-Target," "Compound-Target-Disease," "Protein-Protein Interaction (PPI)," "Compound-Target-Pathway," and "Compound-Target-GO-Pathway" networks were constructed with Cytoscape 3.7.2 software. Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed by using the DAVID database. Results A total of 22 bioactive compounds were identified from ginseng, and 481 targets of ginseng and 763 AD-related targets were obtained from public databases. The PPI network screened out 19 hub genes of ginseng against AD. According to GO function enrichment, ginseng influenced cell proliferation, death, the nitric oxide biosynthetic process, hypoxia response, and synaptic transmission. Neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling, cAMP signaling, FoxO signaling, Ras signaling, and PI3K-AKT signaling were among the most key regulatory pathways. The compound-target-GO-route network found EGFR, MAPK1, MAPK14, AKT1, CASP3, and PRKACA as key genes, with PI3K-AKT signaling being the most important pathway for ginseng's anti-AD activity. Conclusion Ginseng exerts neuroprotective effects in AD patients through multicomponent, multitarget, and multipathway modes, providing novel insight into the pharmacological and experimental research on ginseng against AD.
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Role of amyloid beta (25-35) neurotoxicity in the ferroptosis and necroptosis as modalities of regulated cell death in Alzheimer's disease. Neurotoxicology 2023; 94:71-86. [PMID: 36347329 DOI: 10.1016/j.neuro.2022.11.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 10/26/2022] [Accepted: 11/03/2022] [Indexed: 11/06/2022]
Abstract
Neuronal cell death as a prominent pathological feature contributes to cognitive decline and memory loss in Alzheimer's disease. We investigated the role of two forms of cell death pathways, ferroptosis and necroptosis, and their interactions following entorhinal cortex (EC) amyloidopathy. The Aβ25-35 was bilaterally injected into the rat's EC, and Morris Water Maze was applied to determine spatial performance one week after Aβ injection. For evaluation of ferroptosis and necroptosis involvement in Aβ induced pathology, ferroptosis inhibitor, Ferrostatin (Fer-1), and necroptosis inhibitor, Necrostatin (Nec-1), were injected into the EC during training days of behavioral test. Our behavioral and histological assessment showed spatial learning and memory impairment, along with neuropathology changes such as cell survival and intracellular Aβ deposits in response to EC amyloidopathy, which were ameliorated by treatment with Fer-1 or Nec-1. The expression of ferroptosis key factors GPX4 and SLC7A11 were decreased and the level of TfR was increased following Aβ toxicity. Also, Necroptosis pathway related factors RIP1, RIP3, and MLKL were modulated by Aβ neurotoxicity. However, application of Fer-1 or Nec-1 could inhibit the hippocampal ferroptosis and necroptosis pathways due to EC amyloidopathy. Our data also demonstrated that Aβ-induced necroptosis suppressed by Fer-1, although Nec-1 had no effect on ferroptosis, indicating that ferroptosis pathway is upstream of necroptosis process in the Aβ neurotoxicity. Moreover, Aβ induced hippocampal mGLUR5 overexpression and reduced level of STIM1/2 recovered by Fer-1 or Nec-1. According to our findings ferroptosis and necroptosis pathways are involved in Aβ neurotoxicity through modulation of mGLUR5 and STIM1/2 signaling.
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Tan W, Qi L, Hu X, Tan Z. Research progress in traditional Chinese medicine in the treatment of Alzheimer's disease and related dementias. Front Pharmacol 2022; 13:921794. [PMID: 36506569 PMCID: PMC9729772 DOI: 10.3389/fphar.2022.921794] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 11/09/2022] [Indexed: 11/25/2022] Open
Abstract
Alzheimer's disease (AD) is the world's leading cause of dementia and has become a huge economic burden on nations and families. However, the exact etiology of AD is still unknown, and there are no efficient medicines or methods to prevent the deterioration of cognition. Traditional Chinese medicine (TCM) has made important contributions in the battle against AD based on the characteristics of multiple targets of TCM. This study reviewed the treatment strategies and new discoveries of traditional Chinese medicine in current research, which may be beneficial to new drug researchers.
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Affiliation(s)
- Wanying Tan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lingjun Qi
- Sichuan Academy of Traditional Chinese Medicine, Chengdu, China
| | - Xiaoyu Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhenghuai Tan
- Sichuan Academy of Traditional Chinese Medicine, Chengdu, China
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Omer AB, Dalhat MH, Khan MK, Afzal O, Altamimi ASA, Alzarea SI, Almalki WH, Kazmi I. Butin Mitigates Memory Impairment in Streptozotocin-Induced Diabetic Rats by Inhibiting Oxidative Stress and Inflammatory Responses. Metabolites 2022; 12:1050. [PMID: 36355133 PMCID: PMC9694489 DOI: 10.3390/metabo12111050] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 10/17/2022] [Accepted: 10/27/2022] [Indexed: 11/10/2023] Open
Abstract
It has been reported from the previous literature that butin restores mitochondrial dysfunction by modulation of oxidative stress and glutamate-induced neurotoxicity in mouse hippocampus HT22 cells. Butin also possesses an anti-Huntington's effect in rats. Considering the current background, this study was designed to evaluate the neuroprotective effect of butin against memory loss caused by streptozotocin (STZ). STZ (40 mg/kg) was intraperitoneally injected into rats. Three days later, diabetic rats were identified and included in the study. A total of 30 rats (12 nondiabetic and 18 diabetics) were grouped as Group A (control-non-diabetic rats) and Group B (STZ diabetic control) were treated with 1 mL of sodium CMC (0.5% w/v). Group C (STZ+ butin 25) were treated with butin 25 mg/kg. Group D (STZ+ butin 50) and Group E (butin per se) were administered with butin 50 mg/kg. Each therapy was administered orally once each day for 15-day. The Morris water maze and the Y-maze behavioural tests were run throughout the experimental programme. Animals were put to death on day 15 and their brains were removed for biochemical assays (CAT, SOD, GSH, MDA, nitrite, acetylcholinesterase (AchE), IL-1, and mitochondrial enzyme complexes). Rats with neurobehavioral impairments brought on by STZ have less spontaneous movement, learning capacity, and memory. Additionally, STZ decreased endogenous antioxidants and increased pro-inflammatory cytokines, nitrite, MDA, and AchE. Neurobehavioral deficits and metabolic markers were dramatically improved by butin.
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Affiliation(s)
- Asma B. Omer
- Department of Basic Health Sciences, Foundation Year for the Health Colleges, Princess Nourah bint Abdul Rahman University, Riyadh 11671, Saudi Arabia
| | - Mahmood Hassan Dalhat
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Mohammad Kaleem Khan
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Pharmacology, Dadasaheb Balpande College of Pharmacy, Nagpur 440037, India
| | - Obaid Afzal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Abdulmalik S. A. Altamimi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Sami I. Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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Medicinal Herbs and Their Derived Ingredients Protect against Cognitive Decline in In Vivo Models of Alzheimer’s Disease. Int J Mol Sci 2022; 23:ijms231911311. [PMID: 36232612 PMCID: PMC9569503 DOI: 10.3390/ijms231911311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 11/24/2022] Open
Abstract
Alzheimer’s disease (AD) has pathological hallmarks including amyloid beta (Aβ) plaque formation. Currently approved single-target drugs cannot effectively ameliorate AD. Medicinal herbs and their derived ingredients (MHDIs) have multitarget and multichannel properties, engendering exceptional AD treatment outcomes. This review delineates how in in vivo models MHDIs suppress Aβ deposition by downregulating β- and γ-secretase activities; inhibit oxidative stress by enhancing the antioxidant activities and reducing lipid peroxidation; prevent tau hyperphosphorylation by upregulating protein phosphatase 2A expression and downregulating glycogen synthase kinase-3β expression; reduce inflammatory mediators partly by upregulating brain-derived neurotrophic factor/extracellular signal-regulated protein kinase 1/2-mediated signaling and downregulating p38 mitogen-activated protein kinase (p38 MAPK)/c-Jun N-terminal kinase (JNK)-mediated signaling; attenuate synaptic dysfunction by increasing presynaptic protein, postsynaptic protein, and acetylcholine levels and preventing acetylcholinesterase activity; and protect against neuronal apoptosis mainly by upregulating Akt/cyclic AMP response element-binding protein/B-cell lymphoma 2 (Bcl-2)-mediated anti-apoptotic signaling and downregulating p38 MAPK/JNK/Bcl-2-associated x protein (Bax)/caspase-3-, Bax/apoptosis-inducing factor-, C/EBP homologous protein/glucose-regulated protein 78-, and autophagy-mediated apoptotic signaling. Therefore, MHDIs listed in this review protect against Aβ-induced cognitive decline by inhibiting Aβ accumulation, oxidative stress, tau hyperphosphorylation, inflammation, synaptic damage, and neuronal apoptosis in the cortex and hippocampus during the early and late AD phases.
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Feng H, Xue M, Deng H, Cheng S, Hu Y, Zhou C. Ginsenoside and Its Therapeutic Potential for Cognitive Impairment. Biomolecules 2022; 12:1310. [PMID: 36139149 PMCID: PMC9496100 DOI: 10.3390/biom12091310] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 09/12/2022] [Accepted: 09/13/2022] [Indexed: 11/16/2022] Open
Abstract
Cognitive impairment (CI) is one of the major clinical features of many neurodegenerative diseases. It can be aging-related or even appear in non-central nerve system (CNS) diseases. CI has a wide spectrum that ranges from the cognitive complaint with normal screening tests to mild CI and, at its end, dementia. Ginsenosides, agents extracted from a key Chinese herbal medicine (ginseng), show great promise as a new therapeutic option for treating CI. This review covered both clinical trials and preclinical studies to summarize the possible mechanisms of how ginsenosides affect CI in different diseases. It shows that ginsenosides can modulate signaling pathways associated with oxidative stress, apoptosis, inflammation, synaptic plasticity, and neurogenesis. The involved signaling pathways mainly include the PI3K/Akt, CREB/BDNF, Keap1/Nrf2 signaling, and NF-κB/NLRP3 inflammasome pathways. We hope to provide a theoretical basis for the treatment of CI for related diseases by ginsenosides.
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Affiliation(s)
- Hui Feng
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210024, China
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210024, China
| | - Mei Xue
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210024, China
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210024, China
| | - Hao Deng
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300073, China
| | - Shiqi Cheng
- Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330008, China
| | - Yue Hu
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210024, China
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210024, China
| | - Chunxiang Zhou
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210024, China
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210024, China
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Ginseng ® Alleviates Malathion-Induced Hepatorenal Injury through Modulation of the Biochemical, Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Markers in Male Rats. LIFE (BASEL, SWITZERLAND) 2022; 12:life12050771. [PMID: 35629437 PMCID: PMC9144712 DOI: 10.3390/life12050771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 11/17/2022]
Abstract
This study aims to see if Ginseng® can reduce the hepatorenal damage caused by malathion. Four groups of forty male Wistar albino rats were alienated. Group 1 was a control group that got orally supplied corn oil (vehicle). Group 2 was intoxicated by malathion dissolved in corn oil orally at 135 mg/kg/day. Group 3 orally received both malathion + Panax Ginseng® (300 mg/kg/day). Group 4 was orally given Panax Ginseng® at a 300 mg/kg/day dose. Treatments were administered daily and continued for up to 30 consecutive days. Malathion's toxic effect on both hepatic and renal tissues was revealed by a considerable loss in body weight and biochemically by a marked increase in liver enzymes, LDH, ACP, cholesterol, and functional renal markers with a marked decrease in serum TP, albumin, and TG levels with decreased AchE and Paraoxonase activity. Additionally, malondialdehydes, nitric oxide (nitrite), 8-hydroxy-2-deoxyguanosine, and TNFα with a significant drop in the antioxidant activities were reported in the malathion group. Malathion upregulated the inflammatory cytokines and apoptotic genes, while Nrf2, Bcl2, and HO-1 were downregulated. Ginseng® and malathion co-treatment reduced malathion's harmful effects by restoring metabolic indicators, enhancing antioxidant pursuit, lowering the inflammatory reaction, and alleviating pathological alterations. So, Ginseng® may have protective effects against hepatic and renal malathion-induced toxicity on biochemical, antioxidant, molecular, and cell levels.
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Shi K, Chen L, Chen L, Tan A, Xie G, Long Q, Ning F, Lan Z, Wang P. Epimedii Folium and Curculiginis Rhizoma ameliorate lipopolysaccharides-induced cognitive impairment by regulating the TREM2 signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2022; 284:114766. [PMID: 34688798 DOI: 10.1016/j.jep.2021.114766] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 09/05/2021] [Accepted: 10/19/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Neuroinflammation induced by microglia is closely related to a variety of neurodegenerative diseases including Alzheimer's disease (AD). Previous study has found that aqueous extract of Epimedii Folium and Curculiginis Rhizoma (EX) had anti-inflammatory effect on AD by activating the NLRP3 inflammasome and inhibiting NF-κB/MAPK pathway. However, whether the anti-neuroinflammatory effect of EX is related to microglia or not remains unclear. AIM OF THE STUDY The present study aimed to investigate the protective effect of EX on cognitive impairment induced by LPS and explore the underlying mechanism of EX. MATERIALS AND METHODS High performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was performed to qualify the major components of EX, EX in the serum and cerebrospinal fluid. To evaluate the anti-inflammatory effects of EX in vivo, the mice were orally administrated with EX (2.34, 4.68 g kg-1•d-1) for 28 days before cotreatment with LPS (1 mg kg-1•d-1, i.p.). The leaning and memory abilities of mice were examined by Morris water maze test. The expression of inflammatory related proteins and the activation of microglia were detected by ELISA, immunofluorescence, real-time PCR and Western blotting. RESULTS HPLC-MS analysis confirmed and quantified 9 components in EX, 5 components in the serum and 4 components in the cerebrospinal fluid. In a LPS-induced neuroinflammatory mouse model, EX was found to exert anti-inflammatory activity by reducing the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), regulating the expression of different phenotypes of microglia, and increasing the expression of proteins related with TREM2 in the hippocampus tissue. Moreover, LPS-induced microglia activation was markedly attenuated in the hippocampus. CONCLUSIONS These findings demonstrate that EX exerts anti-neuroinflammatory effects via reducing the production of inflammatory mediators, regulating the conversion of microglia and activating the proteins related with TREM2. EX might become a novel herb pairs to treat neuroinflammatory diseases.
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Affiliation(s)
- Kun Shi
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, PR China
| | - Lvyi Chen
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, PR China
| | - Linlin Chen
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, PR China
| | - Aihua Tan
- School of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, PR China
| | - Guangjing Xie
- School of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, PR China
| | - Qinghua Long
- School of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, PR China
| | - Funan Ning
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, PR China
| | - Zhou Lan
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, PR China.
| | - Ping Wang
- School of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, PR China.
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The Study of Steaming Durations and Temperatures on the Chemical Characterization, Neuroprotective, and Antioxidant Activities of Panax notoginseng. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3698518. [PMID: 35035502 PMCID: PMC8758266 DOI: 10.1155/2022/3698518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 11/02/2021] [Accepted: 12/02/2021] [Indexed: 11/17/2022]
Abstract
Panax notoginseng (PN) is one of the most valuable traditional Chinese medicines and has extensive pharmacological effects. Recent studies demonstrated that PN exhibited pharmacological effect related to Alzheimer's disease (AD). However, whether steaming process can boost its anti-AD activity is still unexplored. To fill this gap, effects of steaming durations and temperatures on the chemical characterization, neuroprotective and antioxidant activities of PN were systematically investigated in this study. HPLC fingerprint coupled with quantitative analysis demonstrated striking conversion of original saponins to less polar ones with the increase in the steaming time and temperature. In the viewpoint of anti-AD activity on neuroprotective and antioxidant effects, several steamed PN samples (110°C-6/8/10 h, 120°C ‐4/6 h samples) displayed a significant increase both in cell viability and oxygen radical absorption capacity (ORAC) values compared with the no steamed one (P < 0.01 or P < 0.005). Steaming temperature had the greater impact on the change of chemical composition and anti-AD activity of PN. Moreover, the spectrum-effect relationship analysis revealed that the transformed saponins were partially responsible for the increased neuroprotective and antioxidant effects of steamed PN. Therefore, steamed PN could be used as a potential crude drug for prevention and treatment of AD.
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Zarneshan SN, Fakhri S, Khan H. Targeting Akt/CREB/BDNF signaling pathway by ginsenosides in neurodegenerative diseases: A mechanistic approach. Pharmacol Res 2022; 177:106099. [DOI: 10.1016/j.phrs.2022.106099] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/14/2022] [Accepted: 01/23/2022] [Indexed: 12/15/2022]
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Arafa ESA, Refaey MS, Abd El-Ghafar OAM, Hassanein EHM, Sayed AM. The promising therapeutic potentials of ginsenosides mediated through p38 MAPK signaling inhibition. Heliyon 2021; 7:e08354. [PMID: 34825082 PMCID: PMC8605069 DOI: 10.1016/j.heliyon.2021.e08354] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/06/2021] [Accepted: 11/05/2021] [Indexed: 12/21/2022] Open
Abstract
The p38 mitogen-activated protein kinases (p38 MAPK) is a 38kD polypeptide recognized as the target for many potential anti-inflammatory agents. Accumulating evidence indicates that p38 MAPK could perform many roles in human disease pathophysiology. Therefore, great therapeutic benefits can be attained from p38 MAPK inhibitors. Ginseng is an exceptionally valued medicinal plant of the family Araliaceae (Panax genus). Recently, several studies targeted the therapeutic effects of purified individual ginsenoside, the most significant active ingredient of ginseng, and studied its particular molecular mechanism(s) of action rather than whole-plant extracts. Interestingly, several ginsenosides: ginsenosides compound K, F1, Rb1, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, Rg5, Rh1, Rh2, Ro, notoginsenoside R1, and protopanaxadiol have shown to possess great therapeutic potentials mediated by their ability to downregulate p38 MAPK signaling in different cell lines and experimental animal models. Our review compiles the research findings of various ginsenosides as potent anti-inflammatory agents, highlighting the crucial role of p38 MAPK suppression in their pharmacological actions. In addition, in silico studies were conducted to explore the probable binding of these ginsenosides to p38 MAPK. The results obtained proposed p38 MAPK involvement in the beneficial pharmacological activities of ginsenosides in different ailments.
p38 MAPK plays many roles in human disease pathophysiology. Therefore, great therapeutic benefits can be attained from p38 MAPK inhibitors. Several ginsenosides showed to possess great therapeutic potentials mediated by its ability to downregulate p38 MAPK signaling. in silico studies were conducted to explore the binding of these ginsenosides to p38 MAPK and evidenced the promising their inhibitory effect.
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Affiliation(s)
- El-Shaimaa A Arafa
- Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates.,Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates.,Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Mohamed S Refaey
- Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufiya, 32958, Egypt
| | - Omnia A M Abd El-Ghafar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt
| | - Emad H M Hassanein
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
| | - Ahmed M Sayed
- Biochemistry Laboratory, Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
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Kim M, Mok H, Yeo WS, Ahn JH, Choi YK. Role of ginseng in the neurovascular unit of neuroinflammatory diseases focused on the blood-brain barrier. J Ginseng Res 2021; 45:599-609. [PMID: 34803430 PMCID: PMC8587512 DOI: 10.1016/j.jgr.2021.02.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 12/28/2020] [Accepted: 02/17/2021] [Indexed: 12/18/2022] Open
Abstract
Ginseng has long been considered as an herbal medicine. Recent data suggest that ginseng has anti-inflammatory properties and can improve learning- and memory-related function in the central nervous system (CNS) following the development of CNS neuroinflammatory diseases such as Alzheimer's disease, cerebral ischemia, and other neurological disorders. In this review, we discuss the role of ginseng in the neurovascular unit, which is composed of endothelial cells surrounded by astrocytes, pericytes, microglia, neural stem cells, oligodendrocytes, and neurons, especially their blood-brain barrier maintenance, anti-inflammatory effects and regenerative functions. In addition, cell-cell communication enhanced by ginseng may be attributed to regeneration via induction of neurogenesis and angiogenesis in CNS diseases. Thus, ginseng may have therapeutic potential to exert cognitive improvement in neuroinflammatory diseases such as stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, and Alzheimer's disease.
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Affiliation(s)
- Minsu Kim
- Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea
| | - Hyejung Mok
- Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea
| | - Woon-Seok Yeo
- Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea
| | - Joong-Hoon Ahn
- Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea
| | - Yoon Kyung Choi
- Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea
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Liang YY, Zhang LD, Luo X, Wu LL, Chen ZW, Wei GH, Zhang KQ, Du ZA, Li RZ, So KF, Li A. All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease. Neural Regen Res 2021; 17:1210-1227. [PMID: 34782555 PMCID: PMC8643060 DOI: 10.4103/1673-5374.325012] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Age-related neurodegenerative disorders such as Alzheimer’s disease (AD) have become a critical public health issue due to the significantly extended human lifespan, leading to considerable economic and social burdens. Traditional therapies for AD such as medicine and surgery remain ineffective, impractical, and expensive. Many studies have shown that a variety of bioactive substances released by physical exercise (called “exerkines”) help to maintain and improve the normal functions of the brain in terms of cognition, emotion, and psychomotor coordination. Increasing evidence suggests that exerkines may exert beneficial effects in AD as well. This review summarizes the neuroprotective effects of exerkines in AD, focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise. The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages, genders, and health conditions.
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Affiliation(s)
- Yi-Yao Liang
- Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University; Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou, Guangdong Province, China
| | - Li-Dan Zhang
- Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University; Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou, Guangdong Province, China
| | - Xi Luo
- Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University; Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou, Guangdong Province, China
| | - Li-Li Wu
- Department of Medical Ultrasonics, Third Affiliated Hospital of Sun Yat-sen University; Guangdong Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Zhao-Wei Chen
- Department of Clinical Medicine, School of Medicine, Jinan University, Guangzhou, Guangdong Province, China
| | - Guang-Hao Wei
- Department of Clinical Medicine, School of Medicine, Jinan University, Guangzhou, Guangdong Province, China
| | - Kai-Qing Zhang
- Department of Clinical Medicine, School of Medicine, Jinan University, Guangzhou, Guangdong Province, China
| | - Ze-An Du
- Department of Clinical Medicine, International School, Jinan University, Guangzhou, Guangdong Province, China
| | - Ren-Zhi Li
- International Department of the Affiliated High School of South China Normal University, Guangzhou, Guangdong Province, China
| | - Kwok-Fai So
- Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University; Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
| | - Ang Li
- Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University; Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province, China
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Panossian A, Abdelfatah S, Efferth T. Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations. Pharmaceuticals (Basel) 2021; 14:ph14100999. [PMID: 34681222 PMCID: PMC8537973 DOI: 10.3390/ph14100999] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 09/27/2021] [Indexed: 01/01/2023] Open
Abstract
Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than those detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major “rare” ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10−4 to 10−18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10−6 M to 10−18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10−4 M. Network pharmacology analyses of genes’ expression profiles using ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.
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Affiliation(s)
| | - Sara Abdelfatah
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, 55131 Mainz, Germany;
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, 55131 Mainz, Germany;
- Correspondence: (A.P.); (T.E.)
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Liu MY, Liu F, Gao YL, Yin JN, Yan WQ, Liu JG, Li HJ. Pharmacological activities of ginsenoside Rg5 (Review). Exp Ther Med 2021; 22:840. [PMID: 34149886 PMCID: PMC8210315 DOI: 10.3892/etm.2021.10272] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 05/07/2021] [Indexed: 12/11/2022] Open
Abstract
Ginseng, a perennial plant belonging to genus Panax, has been widely used in traditional herbal medicine in East Asia and North America. Ginsenosides are the most important pharmacological component of ginseng. Variabilities in attached positions, inner and outer residues and types of sugar moieties may be associated with the specific pharmacological activities of each ginsenoside. Ginsenoside Rg5 (Rg5) is a minor ginsenoside synthesized during ginseng steaming treatment that exhibits superior pharmaceutical activity compared with major ginsenosides. With high safety and various biological functions, Rg5 may act as a potential therapeutic candidate for diverse diseases. To date, there have been no systematic studies on the activity of Rg5. Therefore, in this review, all available literature was reviewed and discussed to facilitate further research on Rg5.
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Affiliation(s)
- Ming-Yang Liu
- Department of Immunity, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
- Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Fei Liu
- Department of Obstetrics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Yan-Li Gao
- Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Jia-Ning Yin
- Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Wei-Qun Yan
- Department of Tissue Engineering, School of Pharmaceutical Sciences in Jilin University, Changchun, Jilin 130021, P.R. China
| | - Jian-Guo Liu
- Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Hai-Jun Li
- Department of Immunity, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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Pien-Tze-Huang, a Chinese patent formula, attenuates NLRP3 inflammasome-related neuroinflammation by enhancing autophagy via the AMPK/mTOR/ULK1 signaling pathway. Biomed Pharmacother 2021; 141:111814. [PMID: 34146853 DOI: 10.1016/j.biopha.2021.111814] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/29/2021] [Accepted: 06/07/2021] [Indexed: 01/14/2023] Open
Abstract
NLRP3 inflammasome is a key mediator in ischemic stroke-induced neuroinflammation and subsequent brain injury. Our previous study demonstrated the potent activity of Pien-Tze-Huang (PTH), a well-known Chinese patent formula, in reducing mitochondria-mediated neuronal apoptosis in cerebral ischemia/reperfusion impaired rats. This study aims to elucidate the mechanistic action of PTH related to neuroinflammation in LPS-induced BV2 microglial cells and cerebral ischemia/reperfusion impaired rats. BV2 cells were stimulated with LPS for 12 h and treated with PTH with various concentrations. Modulation by PTH of relevant genes (IL-6, IL-1β, IL-18, TNF-α, COX-2 and iNOS mRNA) and proteins (NLRP3 inflammasome, autophagy and AMPK/mTOR/ULK signaling) was analyzed by real-time PCR and western blot, respectively. Similar analyses were conducted in middle cerebral artery occlusion rat model including neurological deficit, infarct volume, microglial activation, and key genes and proteins in modulating autophagy and NLRP3. Our results showed that PTH significantly inhibited the production of key proinflammatory mediators and protein expressions of NLRP3 and caspase-1 p20 in LPS induced BV2 cells. It also enhanced the autophagy response by modulating the key autophagy proteins via AMPK/mTOR/ULK related pathway. The reduced inflammatory responses and NLRP3 expressions by PTH were partially blocked by the autophagy inhibitor (3-MA) and AMPK blocker (compound C). In rats, PTH significantly reduced infarct size, suppressed microglial activation, and improved neuron deficit. It also promoted autophagy and reduced NLRP3 activity. Our study demonstrated that PTH inhibited NLRP3 inflammasome-mediated neuroinflammation, which was associated with enhanced autophagy via AMPK/mTOR/ULK1 pathway in vitro and in vivo.
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Kim CJ, Ryu HY, Lee S, Lee HJ, Chun YS, Kim JK, Yu CY, Ghimire BK, Lee JG. Neuroprotective Effect and Antioxidant Potency of Fermented Cultured Wild Ginseng Root Extracts of Panax ginseng C.A. Meyer in Mice. Molecules 2021; 26:3001. [PMID: 34070099 PMCID: PMC8158381 DOI: 10.3390/molecules26103001] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/13/2021] [Accepted: 05/14/2021] [Indexed: 12/22/2022] Open
Abstract
Wild ginseng has better pharmacological effects than cultivated ginseng. However, its industrialization is limited by the inability to grow wild ginseng on a large scale. Herein, we demonstrate how to optimize ginseng production through cultivation, and how to enhance the concentrations of specific ginsenosides through fermentation. In the study, we also evaluated the ability of fermented cultured wild ginseng root extract (HLJG0701-β) to inhibit acetylcholinesterase (AChE), as well as its neuroprotective effects and antioxidant activity. In invitro tests, HLJG0701-β inhibited AChE activity and exerted neuroprotective and antioxidant effects (showing increased catalyst activity but decreased reactive oxygen species concentration). In invivo tests, after HLJG0701-β was orally administered at doses of 0, 125, 250, and 500 mg/kg in an animal model of memory impairment, behavioral evaluation (Morris water maze test and Y-maze task test) was performed. The levels of AChE, acetylcholine (ACh), blood catalase (CAT), and malondialdehyde (MDA) in brain tissues were measured. The results showed that HLJG0701-β produced the best results at a dose of 250 mg/kg or more. The neuroprotective mechanism of HLJG0701-β was determined to involve the inhibition of AChE activity and a decrease in oxidative stress. In summary, both invitro and invivo tests confirmed that HJG0701-β administration can lead to memory improvement.
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Affiliation(s)
- Chul-Joong Kim
- Research Institute of Biotechnology, HwajinBioCosmetics CO., LTD, Chuncheon 24232, Korea;
| | - Hyeon-Yeol Ryu
- Korea Conformity Laboratories, Yeonsu, Incheon 21999, Korea; (H.-Y.R.); (S.L.)
| | - Somin Lee
- Korea Conformity Laboratories, Yeonsu, Incheon 21999, Korea; (H.-Y.R.); (S.L.)
| | - Han-Joo Lee
- Aribio H&B CO.LTD, Yongin 16914, Korea; (H.-J.L.); (Y.-S.C.); (J.-K.K.)
| | - Yoon-Soek Chun
- Aribio H&B CO.LTD, Yongin 16914, Korea; (H.-J.L.); (Y.-S.C.); (J.-K.K.)
| | - Jong-Kyu Kim
- Aribio H&B CO.LTD, Yongin 16914, Korea; (H.-J.L.); (Y.-S.C.); (J.-K.K.)
| | - Chang-Yeon Yu
- Department of Bio-Resource Sciences, Kangwon National University, Chuncheon 21341, Korea;
| | - Bimal Kumar Ghimire
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Gwangjin, Seoul 05029, Korea;
| | - Jae-Geun Lee
- Research Institute of Biotechnology, HwajinBioCosmetics CO., LTD, Chuncheon 24232, Korea;
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Alzobaidi N, Quasimi H, Emad NA, Alhalmi A, Naqvi M. Bioactive Compounds and Traditional Herbal Medicine: Promising Approaches for the Treatment of Dementia. Degener Neurol Neuromuscul Dis 2021; 11:1-14. [PMID: 33880073 PMCID: PMC8051957 DOI: 10.2147/dnnd.s299589] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 03/23/2021] [Indexed: 12/13/2022] Open
Abstract
Dementia is a term that encompasses a group of clinical symptoms affecting memory, thinking and social abilities, characterized by progressive impairment of memory performance and cognitive functions. There are several factors involved in the pathogenesis and progression of dementia, such as old age, brain ischemia, toxin exposure, and oxidative stress. There are extensive similarities between dementia and Alzheimer's disease (AD) either in clinical manifestations or experimental animal models. AD is the most dominant form of dementia, characterized by the accumulation of beta-amyloid protein and cholinergic neurotransmission deficits in the brain. Currently available medications for the treatment of dementia, such as choline esterase inhibitors, N-methyl-D-aspartate (NMDA) antagonists (memantine), have short-term efficacy and only relieve symptoms rather than targeting the main underlying pathogenesis. Several animal studies and clinical trials are being conducted to provide a rational approach to these medicinal plants in the prevention or treatment of memory deficits. This review highlights the potential effects of medicinal plants and their derived lead molecules, and explains the related mechanisms and effects reviewed from published literature as major thrust aspects and hopeful strategies in the prevention or treatment of dementia.
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Affiliation(s)
- Nafaa Alzobaidi
- Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India
| | - Huma Quasimi
- Department of Physiology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India
| | - Nasr A Emad
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Abdulsalam Alhalmi
- Department of Pharmaceutics, College of Pharmacy, Aden University, Aden, Yemen
| | - Maaz Naqvi
- Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India
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Ghafouri-Fard S, Abak A, Mohaqiq M, Shoorei H, Taheri M. The Interplay Between Non-coding RNAs and Insulin-Like Growth Factor Signaling in the Pathogenesis of Neoplasia. Front Cell Dev Biol 2021; 9:634512. [PMID: 33768092 PMCID: PMC7985092 DOI: 10.3389/fcell.2021.634512] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 02/02/2021] [Indexed: 12/11/2022] Open
Abstract
The insulin-like growth factors (IGFs) are polypeptides with similar sequences with insulin. These factors regulate cell growth, development, maturation, and aging via different processes including the interplay with MAPK, Akt, and PI3K. IGF signaling participates in the pathogenesis of neoplasia, insulin resistance, diabetes mellitus, polycystic ovarian syndrome, cerebral ischemic injury, fatty liver disease, and several other conditions. Recent investigations have demonstrated the interplay between non-coding RNAs and IGF signaling. This interplay has fundamental roles in the development of the mentioned disorders. We designed the current study to search the available data about the role of IGF-associated non-coding RNAs in the evolution of neoplasia and other conditions. As novel therapeutic strategies have been designed for modification of IGF signaling, identification of the impact of non-coding RNAs in this pathway is necessary for the prediction of response to these modalities.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefe Abak
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdi Mohaqiq
- School of Advancement, Centennial College, Ashtonbee Campus, Toronto, ON, Canada
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, United States
| | - Hamed Shoorei
- Department of Anatomical Sciences, Faculty of Medicine, Biranjd University of Medical Sciences, Birjand, Iran
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Liu H, Lu X, Hu Y, Fan X. Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy. Pharmacol Res 2020; 161:105263. [PMID: 33127555 DOI: 10.1016/j.phrs.2020.105263] [Citation(s) in RCA: 173] [Impact Index Per Article: 34.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/15/2020] [Accepted: 10/18/2020] [Indexed: 02/06/2023]
Abstract
Panax ginseng (Meyer) and Panax notoginseng (Burkill), belonging to the family Araliaceae, are used worldwide as medicinal and functional herbs. Numerous publications over the past decades have revealed that both P. notoginseng and P. ginseng contain important bioactive ingredients such as ginsenosides and exert multiple pharmacological effects on nervous system and immune diseases. However, based on traditional Chinese medicine (TCM) theory, their applications clearly differ as ginseng reinforces vital energy and notoginseng promotes blood circulation. In this article, we review the similarities and differences between ginseng and notoginseng in terms of their chemical composition and pharmacological effects. Their chemical comparisons indicate that ginseng contains more polysaccharides and amino acids, while notoginseng has more saponins, volatile oil, and polyacetylenes. Regarding pharmacological effects, ginseng exhibits better protective effects on cardiovascular disease, nerve disease, cancer, and diabetes mellitus, whereas notoginseng displays a superior protective effect on cerebrovascular disease. The evidence presented in this review facilitates further research and clinical applications of these two herbs, and exploration of the relationship between the chemical components and disease efficacy may be the critical next step.
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Affiliation(s)
- Hanbing Liu
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xiaoyan Lu
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yang Hu
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xiaohui Fan
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
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☆Protective effects of ginseng on memory and learning and prevention of hippocampal oxidative damage in streptozotocin-induced Alzheimer's in a rat model. ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.npbr.2020.08.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Network Pharmacology Analysis and Molecular Characterization of the Herbal Medicine Formulation Qi-Fu-Yin for the Inhibition of the Neuroinflammatory Biomarker iNOS in Microglial BV-2 Cells: Implication for the Treatment of Alzheimer's Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:5780703. [PMID: 32952851 PMCID: PMC7481926 DOI: 10.1155/2020/5780703] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/12/2020] [Indexed: 12/23/2022]
Abstract
Aberrant microglial activation drives neuroinflammation and neurodegeneration in Alzheimer's disease (AD). The present study is aimed at investigating whether the herbal formula Qi-Fu-Yin (QFY) could inhibit the inflammatory activation of cultured BV-2 microglia. A network pharmacology approach was employed to predict the active compounds of QFY, protein targets, and affected pathways. The representative pathways and molecular functions of the targets were analyzed by Gene Ontology (GO) and pathway enrichment. A total of 145 active compounds were selected from seven herbal ingredients of QFY. Targets (e.g., MAPT, APP, ACHE, iNOS, and COX-2) were predicted for the selected active compounds based on the relevance to AD and inflammation. As a validation, fractions were sequentially prepared by aqueous extraction, ethanolic precipitation, and HPLC separation, and assayed for downregulating two key proinflammatory biomarkers iNOS and COX-2 in lipopolysaccharide- (LPS-) challenged BV-2 cells by the Western blotting technique. Moreover, the compounds of QFY in 90% ethanol downregulated iNOS in BV-2 cells but showed no activity against COX-2 induction. Among the herbal ingredients of QFY, Angelicae Sinensis Radix and Ginseng Radix et Rhizoma contributed to the selective inhibition of iNOS induction. Furthermore, chemical analysis identified ginsenosides, especially Rg3, as antineuroinflammatory compounds. The herbal formula QFY may ameliorate neuroinflammation via downregulating iNOS in microglia.
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Shakerin Z, Esfandiari E, Razavi S, Alaei H, Ghanadian M, Dashti G. Effects of Cyperus rotundus Extract on Spatial Memory Impairment and Neuronal Differentiation in Rat Model of Alzheimer's Disease. Adv Biomed Res 2020; 9:17. [PMID: 32775310 PMCID: PMC7282694 DOI: 10.4103/abr.abr_173_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 09/04/2019] [Accepted: 02/26/2020] [Indexed: 11/04/2022] Open
Abstract
Background Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the older population and characterized by progressive memory and cognitive impairment. Cyperus rotundus, a traditional medicinal herb, has analgesic, sedative, and anti-inflammatory effects and also used to increase memory in Islamic traditional medicine. This study was designed to consider the effects of C. rotundus extract on memory impairment and neurogenesis in the Beta-Amyloid rats' model. Materials and Methods Forty-two male Wistar rats were randomly divided into six groups (n = 7) for the evaluation of baseline training performance in the Morris water maze test. Then, amyloid-beta (Aβ1-42) was injected in animal hippocampal CA1 bilaterally in four groups. The first probe trial was performed 21 days after Aβ injection. Then, 250, 500, and 750 mg/kg of C. rotundus extract were administered to three Aβ-injected groups for 1 month; after that, the second probe trial was performed, and rats were sacrificed after 28 days of the second probe trial. The neurogenesis was detected in the hippocampus, by immunohistochemical staining. Results This study showed that spatial memory increased in the behavioral test in AD treated group with C. rotundus extract, compared with the AD group (P = 0.02). Immunohistochemical staining revealed that neuronal differentiation has been occurred in the hippocampus in the AD-treated group with C. rotundus extract compared with the AD group (P = 0.01). Conclusions This study showed that C. rotundus extract, repaired spatial memory impairment in the Aβ rats, through increased neurogenesis in the hippocampus, which could be related to the flavonoid components in the extract.
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Affiliation(s)
- Zeinab Shakerin
- Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ebrahim Esfandiari
- Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shahnaz Razavi
- Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hojjatallah Alaei
- Department of Physiological Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mustafa Ghanadian
- Department of Pharmacognosy, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Dashti
- Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Ginsenoside Rg5 relieves type 2 diabetes by improving hepatic insulin resistance in db/db mice. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104014] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Nasseri B, Zareian P, Alizade H. Apelin attenuates streptozotocin-induced learning and memory impairment by modulating necroptosis signaling pathway. Int Immunopharmacol 2020; 84:106546. [PMID: 32413735 DOI: 10.1016/j.intimp.2020.106546] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 04/03/2020] [Accepted: 04/26/2020] [Indexed: 12/17/2022]
Abstract
Apelin is a neuropeptide that plays an important role in neuronal protection. In this study, we investigated the effects of apelin intracerebroventricular administration on spatial learning and memory-related behaviors, and necroptosis signaling pathways in the hippocampus of streptozotocin (STZ) -injected rats. Apelin treatment was implemented following STZ-induced dementia for 15 days. After conducting a behavioral test (Morris Water Maze), the cellular and molecular aspects were examined to detect the apelin effect on the necroptosis signaling pathway. We demonstrated that STZ administration significantly slowed down the learning capability. However apelin treatment notably reversed this neuroinflammation induced behavioral impairment. Furthermore, molecular investigations showed that apelin treatment reduced the hippocampal RIP1, RIP3, and TNF-α level. Our results suggest that apelin treatment attenuates STZ-induced dementia. This effect may be mediated by inhibition of the necroptosis signaling pathway which seems to be associated with the ability of apelin to reduce central TNF-α level. This data provides evidence of the neuroprotective effect of apelin on STZ-induced learning and memory impairment and characterize some of the underlying mechanisms.
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Affiliation(s)
- Behzad Nasseri
- Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Parvin Zareian
- Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran.
| | - Hadi Alizade
- Department of Pharmacology &Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
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Bocharova OA, Karpova RV, Bocharov EV, Vershinskaya AA, Baryshnikova MA, Kazeev IV, Kucheryanu VG, Kiselevskiy MV. PHYTOADAPTOGENS IN THE TUMOURS BIOTHERAPY AND GERIATRICS (PART 1). ACTA ACUST UNITED AC 2020. [DOI: 10.17650/1726-9784-2019-19-2-13-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The review reflects the history of phytoadaptogens studies (ginseng, eleutherococcus, etc.), which are considered to be geroprotectors by Eastern medicine for centures. They have a complex of protective effects on the body, as well as increasing its antitumor resistance. The first part of the review describes the antistress, immuno- and hormone-modulating, cognitive and neuroprotective properties of adapto gens. Together with the synchronizing effects on biorthms adaptogens are essential for preventive oncology.
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Affiliation(s)
- O. A. Bocharova
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
| | - R. V. Karpova
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
| | - E. V. Bocharov
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
| | - A. A. Vershinskaya
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
| | - M. A. Baryshnikova
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
| | - I. V. Kazeev
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
| | | | - M. V. Kiselevskiy
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
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Hibiscus sabdariffa L.: A potent natural neuroprotective agent for the prevention of streptozotocin-induced Alzheimer's disease in mice. Biomed Pharmacother 2020; 128:110303. [PMID: 32480228 DOI: 10.1016/j.biopha.2020.110303] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/17/2020] [Accepted: 05/19/2020] [Indexed: 12/24/2022] Open
Abstract
Hibiscus sabdariffa L. (Malvaceae) is one of the well-known traditionally used remedy worldwide. It exhibited numerous pharmacological properties including antioxidant, antidepressant, sedative, anti-inflammatory, antiproliferative, antimicrobial and neuroprotective activities. The aim of this study is to highlight the mechanisms underlying the neuroprotective effects of anthocyanin-enriched extracts of two Hibiscus varieties (white and red calyces) in the management of Alzheimer's disease (AD) in addition to their metabolic profiling. The anthocyanin contents were determined quantitatively using the pH-differential technique and qualitatively by LC/MS/MS. The extracts were tested in vitro for their antioxidant potential as well as acetylcholinesterase inhibition activity and both showed promising activities. The LC/MS/MS analysis allowed the tentative identification of 26 and 24 metabolites in red and white calyces, respectively, represented by anthocyanins, flavonoids, aliphatic and phenolic acids. In vivo, streptozotocin induced AD in mice model was established and Hibiscus extracts were tested at a dose of 200 mg kg-1 compared to celecoxib (30 mg/kg). Histopathology of cerebral cortex and hippocampus, immunohistochemistry for tau- protein and caspase-3 with behavioral tests and measurement of several biochemical parameters were done. Hibiscus prevented memory impairment, and this could be attributed to the amelioration of STZ-induced neuroinflammation and amyloidogenesis. Consequently, Hibiscus represents a promising safe agent that can be repurposed for AD through exerting anti-inflammatory, anti-acetylcholinesterase, antioxidant, and anti-amyloidogenic activities.
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Ginsenoside Rh3 activates Nrf2 signaling and protects endometrial cells from oxygen and glucose deprivation-reoxygenation. Aging (Albany NY) 2020; 12:6109-6119. [PMID: 32259797 PMCID: PMC7185134 DOI: 10.18632/aging.103009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 02/05/2020] [Indexed: 01/08/2023]
Abstract
Oxygen and glucose deprivation (OGD)-reoxygenation (OGDR) induces oxidative injury to endometrial cells in vitro. We tested the potential effect of ginsenoside Rh3 (GRh3) in the process. Our results show that GRh3 activated Nrf2 signaling in T-HESC cells and primary murine endometrial cells. GRh3 induced Nrf2 Ser-40 phosphorylation and Keap1-Nrf2 disassociation, causing Nrf2 protein stabilization and nuclear translocation, which led to transcription and expression of antioxidant response element-dependent genes (HO1, NQO1 and GCLC). In T-HESC cells and primary murine endometrial cells, GRh3 potently attenuated OGDR-induced reactive oxygen species production, lipid peroxidation and mitochondrial depolarization, as well as cell viability reduction and necrosis. Activation of Nrf2 is required for GRh3-induced anti-OGDR actions in endometrial cells. Nrf2 inhibition, by Nrf2 shRNA, knockout (through CRISPR-Cas9-editing) or S40T mutation, abolished GRh3-induced endometrial cell protection against OGDR. Additionally, forced activation of Nrf2, by Keap1 knockout, mimicked and nullified GRh3-induced anti-OGDR actions in T-HESC cells. Together, we conclude that GRh3 protects endometrial cells from OGDR via activation of Nrf2 signaling.
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Jang SA, Namkoong S, Lee SR, Lee JW, Park Y, So G, Kim SH, Kim MJ, Jang KH, Avolio AP, Gangoda SVS, Koo HJ, Kim MK, Kang SC, Sohn EH. Multi-tissue lipotoxicity caused by high-fat diet feeding is attenuated by the supplementation of Korean red ginseng in mice. Mol Cell Toxicol 2019. [DOI: 10.1007/s13273-019-00056-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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