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Luo L, Pan Y, Chen F, Zhang Z. Exploring the potential mechanism of Polygonatum sibiricum for Alzheimer's disease based on network pharmacology and molecular docking: An observational study. Medicine (Baltimore) 2024; 103:e40726. [PMID: 39969345 PMCID: PMC11688029 DOI: 10.1097/md.0000000000040726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 11/08/2024] [Indexed: 02/20/2025] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease, and there have been no systematic studies of Polygonatum against Alzheimer's disease. Therefore, our study will elucidate the mechanism of Polygonatum against AD based on network pharmacology and molecular docking. The active ingredients and corresponding targets of Polygonatum were identified using the traditional Chinese medicine systematic pharmacology database and analysis platform. Disease targets of AD were retrieved from the therapeutic target database, Online Mendelian Inheritance in Man, GeneCards, and Disgenet databases. Using the STRING database, we constructed protein interaction networks and performed gene ontology functional enrichment analysis as well as Kyoto encyclopedia of genes and genomes pathway enrichment analysis on common targets. We then drew drug-component-target-pathway-disease network maps using Cytoscape 3.10.1 software and validated the molecular docking using AutoDock4. A total of 10 active ingredients and 108 common targets were screened from Polygonatum, 29 genes (including AKT1 and STAT3) were identified as core genes. According to gene ontology analysis, the core targets were found to be mainly involved in signal transduction, positive regulation of gene expression, negative regulation of the apoptotic process, and so on. The Kyoto encyclopedia of genes and genomes analysis revealed that the signaling pathways comprised pathways in cancer, pathways of neurodegeneration - multiple diseases, and PI3K-Akt signaling pathway. The molecular docking results indicated that 10 of active ingredients from Polygonatum exhibited strong binding affinity with the 6 core targets that were screened before. The activity of Polygonatum against AD could be attributed to the regulation of multiple biological effects via multi-pathways (pathways in cancer, pathways of neurodegeneration - multiple diseases, and PI3K-Akt signaling pathway). The binding activities were estimated as good level by molecular docking. These discoveries disclosed the multi-component, multi-target, and multi-pathway characteristics of Polygonatum against AD, providing a new strategy for such medical problem.
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Affiliation(s)
- Liangliang Luo
- School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Yao Pan
- School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, China
| | - Fang Chen
- School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, China
| | - Zhihong Zhang
- School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, China
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Hossain R, Noonong K, Nuinoon M, Majima HJ, Eawsakul K, Sompol P, Rahman MA, Tangpong J. Network Pharmacology, Molecular Docking, and In Vitro Insights into the Potential of Mitragyna speciosa for Alzheimer's Disease. Int J Mol Sci 2024; 25:13201. [PMID: 39684911 DOI: 10.3390/ijms252313201] [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: 11/05/2024] [Revised: 12/02/2024] [Accepted: 12/06/2024] [Indexed: 12/18/2024] Open
Abstract
Mitragyna speciosa Korth. Havil (MS) has a traditional use in relieving pain, managing hypertension, treating cough, and diarrhea, and as a morphine substitute in addiction recovery. Its potential in addressing Alzheimer's disease (AD), a neurodegenerative condition with no effective treatments, is under investigation. This study aims to explore MS mechanisms in treating AD through network pharmacology, molecular docking, and in vitro studies. Using network pharmacology, we identified 19 MS components that may affect 60 AD-related targets. The compound-target network highlighted significant interactions among 60 nodes and 470 edges, with an average node degree of 15.7. The KEGG enrichment analysis revealed Alzheimer's disease (hsa05010) as a relevant pathway. We connected 20 targets to tau and β-amyloid proteins through gene expression data from the AlzData database. Docking studies demonstrated high binding affinities of MS compounds like acetylursolic acid, beta-sitosterol, isomitraphylline, and speciophylline to AD-related proteins, such as AKT1, GSK3B, NFκB1, and BACE1. In vitro studies showed that ethanolic (EE), distilled water (DWE), and pressurized hot water (PHWE) extracts of MS-treated 100 μM H2O2-induced SH-SY5Y cells significantly reduced oxidative damage. This research underscores the multi-component, multi-target, and multi-pathway effects of MS on AD, providing insights for future research and potential clinical applications.
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Affiliation(s)
- Rahni Hossain
- College of Graduate Studies, Walailak University, Nakhon Si Thammarat 80160, Thailand
- School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- Research Excellence Center for Innovation and Health Product (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Kunwadee Noonong
- School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- Research Excellence Center for Innovation and Health Product (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Manit Nuinoon
- School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- Research Excellence Center for Innovation and Health Product (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand
- Hematology and Transfusion Science Research Center, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Hideyuki J Majima
- School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- Research Excellence Center for Innovation and Health Product (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Komgrit Eawsakul
- Research Excellence Center for Innovation and Health Product (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand
- School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Pradoldej Sompol
- Department of Pharmacology & Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
| | - Md Atiar Rahman
- Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong 4331, Bangladesh
| | - Jitbanjong Tangpong
- School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- Research Excellence Center for Innovation and Health Product (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand
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Cui T, Yu P, Feng X, Song Q, Yang D, Li M, Feng L. Elucidation of the inhibitory effects of Jiedu Yizhi formula on neuronal apoptosis in the treatment of Alzheimer's disease based on network pharmacology and in vivo experiments. Metab Brain Dis 2024; 40:38. [PMID: 39576427 DOI: 10.1007/s11011-024-01444-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 10/14/2024] [Indexed: 11/24/2024]
Abstract
OBJECTIVE This study aimed to investigate the mechanism of action of Jiedu Yizhi formula (JDYZF) in the treatment of Alzheimer's disease (AD) through network pharmacology, molecular docking technology, and in vivo experiments. METHOD The main active ingredients of seven herbs in the Chinese Medicine compound JDYZF were identified by searching the TCMSP database, PubChem database, CNKI, and other sources. Disease targets of AD were obtained from databases such as OMIM, TDD, DisGeNET, and DrugBank. A protein‒protein interaction (PPI) network was constructed using the STRING platform, and core targets were identified through topological analysis using Cytoscape software. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the relevant targets were performed using the Metascape database. The main active ingredients of JDYZF and potential core targets were identified based on degree values. Molecular docking technology was used to verify the interactions between the main active ingredients and potential core targets. Furthermore, water maze tests and hematoxylin-eosin (HE) staining of brain and liver tissues were performed to evaluate the effects of JDYZF on cognitive dysfunction in AD mice and neuronal damage in hippocampal brain tissue and to assess drug toxicity. PCR was performed to determine the expression levels of the apoptosis-related genes Bcl-2, Bax, and caspase-3 and to investigate the effect of JDYZF on hippocampal apoptosis in AD mice. Results. One hundred twelve core PPI target proteins, including CASP3, TP53, and VEGFA, were found between JDYZF and AD. The KEGG pathway enrichment analysis showed significant enrichment of the MAPK signaling pathway, PI3K/AKT signaling pathway and so on. Water maze tests revealed that the high-dose JDYZF treatment significantly improved the escape latency of AD model mice. The HE staining results showed that JDYZF exerted a protective effect on neuronal damage in the hippocampus of AD mice. JDYZF could upregulate the expression of the anti-apoptotic factor Bcl-2 while downregulating the expression of the proapoptotic factors Bax and caspase-3. Conclusion. JDYZF can improve the cognitive function of AD mice by suppressing cell apoptosis.
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Affiliation(s)
- Tingting Cui
- Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, Jilin Province, China
| | - Ping Yu
- Department of Neurology, People's Hospital of Linyi, Linyi, Shandong Province, China
| | - Xiaotong Feng
- Shandong Key Laboratory of TCM Multi-Targets Intervention and Disease Control, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, China
| | - Qile Song
- Shandong Key Laboratory of TCM Multi-Targets Intervention and Disease Control, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, China
| | - Deyan Yang
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, 250017, Shandong, China.
| | - Mingquan Li
- Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
| | - Lina Feng
- Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
- Shandong Key Laboratory of TCM Multi-Targets Intervention and Disease Control, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, China.
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Brañes MC, Gillet R, Valenzuela R. Nuclear receptors behind the therapeutic effects of plant sterols on metabolism: A review. Lipids 2024; 59:169-180. [PMID: 39077818 DOI: 10.1002/lipd.12409] [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: 04/03/2024] [Revised: 07/14/2024] [Accepted: 07/15/2024] [Indexed: 07/31/2024]
Abstract
Plant sterols are known for their hypocholesterolemic action, and the molecular mechanisms behind this within the gut have been extensively discussed and demonstrated to the point that there is a degree of consensus. However, recent studies show that these molecules exert an additional umbrella of therapeutic effects in other tissues, which are related to immune function, lipid metabolism, and glucose metabolism. A strong hypothesis to explain these effects is the structural relationship between plant sterols and the ligands of a group of nuclear receptors. This review delves into the molecular aspects of therapeutic effects related with lipid and energy metabolism that have been observed and demonstrated for plant sterols, and turns the perspective to explore the involvement of nuclear receptors as part of these mechanisms.
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Affiliation(s)
| | | | - Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago, Chile
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Vafaei A, Vafaeian A, Iranmehr A, Nassireslami E, Hasannezhad B, Hosseini Y. Effects of β-sitosterol on anxiety in migraine-induced rats: The role of oxidative/nitrosative stress and mitochondrial function. CNS Neurosci Ther 2024; 30:e14892. [PMID: 39301958 PMCID: PMC11413762 DOI: 10.1111/cns.14892] [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: 01/08/2024] [Revised: 07/09/2024] [Accepted: 07/18/2024] [Indexed: 09/22/2024] Open
Abstract
AIMS Anxiety often coexists with migraine, and both conditions share a commonality in oxidative/nitrosative stress and mitochondrial dysfunction contributing to their pathogenesis. β-Sitosterol, a plant sterol, has shown promise in mitigating oxidative/nitrosative stress, enhancing mitochondrial function, and exerting neuroprotective effects. In this study, we investigated the impact of β-sitosterol on migraine-associated anxiety and whether this effect was associated with alleviation of oxidative/nitrosative stress and improvement in mitochondrial function. METHODS Nitroglycerin was used to induce migraine in adult male Wistar rats. β-Sitosterol treatment consisted of daily intraperitoneal injections (10 mg/kg) for 10 days following migraine induction. Anxiety levels were evaluated using open-field test (OFT) and hole-board test (HBT). Frontal cortex samples were analyzed for malondialdehyde (MDA), glutathione (GSH), reactive oxygen/nitrogen species, nitric oxide (NO) (markers of oxidative/nitrosative stress), and ATP (indicator of mitochondrial function). RESULTS Migraine induction led to impaired performance in both the OFT and the HBT. Concurrently, it elevated MDA, reactive oxygen/nitrogen species, and NO levels while diminishing GSH levels in the frontal cortex, signifying heightened oxidative/nitrosative stress. Moreover, ATP levels decreased, indicating mitochondrial dysfunction. Treatment with β-sitosterol significantly restored performance in both behavioral assays and normalized the levels of MDA, GSH, reactive oxygen/nitrogen species, NO, and ATP. CONCLUSION β-Sitosterol exerted anxiolytic effects in migraine, which can be attributed to its ability to ameliorate oxidative/nitrosative stress and enhance mitochondrial function.
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Affiliation(s)
- Ali Vafaei
- Toxicology Research CenterAJA University of Medical SciencesTehranIran
| | | | - Arad Iranmehr
- Neurosurgery Department, Sina HospitalTehran University of Medical SciencesTehranIran
- Gammaknife Center, Yas HospitalTehran University of Medical SciencesTehranIran
| | | | - Behnam Hasannezhad
- Cognitive and Behavioral Research CenterAJA University of Medical SciencesTehranIran
| | - Yasaman Hosseini
- Cognitive and Behavioral Research CenterAJA University of Medical SciencesTehranIran
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Singh M, Verma H, Gera N, Baddipadige R, Choudhary S, Bhandu P, Silakari O. Evaluation of Cordyceps militaris steroids as anti-inflammatory agents to combat the Covid-19 cytokine storm: a bioinformatics and structure-based drug designing approach. J Biomol Struct Dyn 2024; 42:5159-5177. [PMID: 37551029 DOI: 10.1080/07391102.2023.2245039] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 06/08/2023] [Indexed: 08/09/2023]
Abstract
Since the SARS-CoV-2 epidemic, researchers have been working on figuring out ways to tackle multi-organ failure and hyperinflation, which are brought on by a cytokine storm. Angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike glycoprotein's cellular receptor, is involved in complicated molecular processes that result in hyperinflammation. Cordyceps militaris is one of the traditional Chinese medicines that is used as an immune booster, and it has exhibited efficacy in lowering blood glucose levels, seminal emissions, and infertility. In the current study, we explored the potential of Cordyceps militaris steroids as key agents in managing the anger of cytokine storm in Covid-19 using network ethnopharmacological techniques and structure-based drug designing approaches. The steroids present in Cordyceps militaris were initially screened against the targets involved in inflammatory pathways. The results revealed that out of 16 steroids, 5 may be effective against 17 inflammatory pathways by targeting 11 pathological proteins. Among the five steroids, beta-sitosterol, Cholest-5-en-3β-ol, 3β, and 7α-Dihydroxycholest-5-ene were found to interact with thrombin (F2), an important protein reported to reduce the severity of inflammatory mediators and Cholest-4-en-3-one was found to target Glucocorticoid receptor (NR3C1). The top docked steroid displayed key interactions with both targets, which retained key interactions throughout the 100 ns simulation period. These compounds were also shown high binding free energy scores in water swap studies. Based on obtained results the current study suggests the use of Cordyceps militaris as an add-on therapy that may reduce the progression of inflammatory co-morbidities among patients infected with SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Manmeet Singh
- Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
| | - Himanshu Verma
- Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
| | - Narendra Gera
- Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
| | - Raju Baddipadige
- Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
| | - Shalki Choudhary
- Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
| | - Priyanka Bhandu
- Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
| | - Om Silakari
- Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India
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El Omari N, Bakrim S, Khalid A, Abdalla AN, Iesa MAM, El Kadri K, Tang SY, Goh BH, Bouyahya A. Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases. NATURAL PRODUCTS AND BIOPROSPECTING 2024; 14:27. [PMID: 38722432 PMCID: PMC11082103 DOI: 10.1007/s13659-024-00451-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 04/22/2024] [Indexed: 05/12/2024]
Abstract
Until recently, the main pharmaceuticals used to control cholesterol and prevent cardiovascular disease (CVD) were statin-related drugs, known for their historical side effects. Therefore, there is growing interest in exploring alternatives, such as nutritional and dietary components, that could play a central role in CVD prevention. This review aims to provide a comprehensive understanding of how natural phytosterols found in various diets combat CVDs. We begin with a description of the overall approach, then we explore in detail the different direct and indirect mechanisms that contribute to reducing cardiovascular incidents. Phytosterols, including stigmasterol, β-sitosterol, ergosterol, and fucosterol, emerge as promising molecules within nutritional systems for protection against CVDs due to their beneficial effects at different levels through direct or indirect cellular, subcellular, and molecular mechanisms. Specifically, the mentioned phytosterols exhibit the ability to diminish the generation of various radicals, including hydroperoxides and hydrogen peroxide. They also promote the activation of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, while inhibiting lipid peroxidation through the activation of Nrf2 and Nrf2/heme oxygenase-1 (HO-1) signaling pathways. Additionally, they demonstrate a significant inhibitory capacity in the generation of pro-inflammatory cytokines, thus playing a crucial role in regulating the inflammatory/immune response by inhibiting the expression of proteins involved in cellular signaling pathways such as JAK3/STAT3 and NF-κB. Moreover, phytosterols play a key role in reducing cholesterol absorption and improving the lipid profile. These compounds can be used as dietary supplements or included in specific diets to aid control cholesterol levels, particularly in individuals suffering from hypercholesterolemia.
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Affiliation(s)
- Nasreddine El Omari
- High Institute of Nursing Professions and Health Techniques of Tetouan, Tetouan, Morocco
| | - Saad Bakrim
- Geo-Bio-Environment Engineering and Innovation Laboratory, Molecular Engineering, Biotechnology and Innovation Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, 80000, Agadir, Morocco
| | - Asaad Khalid
- Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box: 114, 45142, Jazan, Saudi Arabia.
- Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, P. O. Box 2404, Khartoum, Sudan.
| | - Ashraf N Abdalla
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, 21955, Makkah, Saudi Arabia
| | - Mohamed A M Iesa
- Department of Physiology, Al Qunfudah Medical College, Umm Al Qura University, Mecca, Saudi Arabia
| | - Kawtar El Kadri
- Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University in Rabat, 10106, Rabat, Morocco
| | - Siah Ying Tang
- Department of Chemical Engineering, School of Engineering, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia
| | - Bey Hing Goh
- Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, 47500, Bandar Sunway, Malaysia.
- Sunway Biofunctional Molecules Discovery Centre (SBMDC), School of Medical and Life Sciences, Sunway University, 47500, Sunway City, Malaysia.
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University in Rabat, 10106, Rabat, Morocco.
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Zou X, Xu T, Zhao T, Xia J, Zhu F, Hou Y, Lu B, Zhang Y, Yang X. Phytosterol organic acid esters: Characterization, anti-inflammatory properties and a delivery strategy to improve mitochondrial function. Curr Res Food Sci 2024; 8:100702. [PMID: 38487178 PMCID: PMC10937313 DOI: 10.1016/j.crfs.2024.100702] [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: 11/12/2023] [Revised: 01/16/2024] [Accepted: 02/15/2024] [Indexed: 03/17/2024] Open
Abstract
Phytosterol organic acid esters are important food resources and the components of biomembrane structure. Due to the lack of extraction and synthesis techniques, more research has been focused on phytosterols, and the research on phytosterol acid esters have encountered a bottleneck, but phytosterol acid esters confer substantial benefits to human health. In this study, stigmasteryl vanillate (VAN), stigmasteryl protocatechuate (PRO) and stigmasteryl sinapate (SIN) were prepared through the Steglich reaction. The processes are promotable and the products reach up to 95% purity. In addition, their stability was evaluated by differential scanning calorimetry and thermogravimetric analysis. HPLC analysis revealed an enhancement in water solubility after esterification with phenolic acid. In an in vitro digestion model, the bioaccessibility of stigmasteryl phenolates was significantly higher than that of stigmasterols (STIs). Regarding the anti-inflammatory properties, VAN, PRO, and SIN exhibit superior effects against TNF-α induced pro-inflammatory responses compared to STI. All stigmasteryl phenolates supplementation increased the ATP production, the basal, and maximal oxygen consumption rate in mitochondrial stress test. Overall, we present a synthesis method for stigmasteryl phenolates. It will contribute to the development and research of phytosterol acid ester analysis, functions and utilization in food. Moreover, the nutrient-stigmasterol hybrids tactic we have constructed is practical and can become a targeted mitochondrial delivery strategy with enhanced anti-inflammatory effects.
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Affiliation(s)
- Xinyue Zou
- Department of Chemistry, China Agricultural University, Beijing, 100193, China
| | - Ting Xu
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products, Ministry of Agriculture and Rural Affair, Interdisciplinary Research Center on Optical Agricultural and Food Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China
| | - Tian Zhao
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products, Ministry of Agriculture and Rural Affair, Interdisciplinary Research Center on Optical Agricultural and Food Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China
| | - Jing Xia
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products, Ministry of Agriculture and Rural Affair, Interdisciplinary Research Center on Optical Agricultural and Food Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China
| | - Feifan Zhu
- Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
| | - Yu Hou
- Liangzhu Laboratory, Zhejiang University, No. 1369 West Wenyi Road, Hangzhou, 311121, China
| | - Baiyi Lu
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products, Ministry of Agriculture and Rural Affair, Interdisciplinary Research Center on Optical Agricultural and Food Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China
| | - Yunfei Zhang
- Department of Chemistry, China Agricultural University, Beijing, 100193, China
| | - Xuan Yang
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products, Ministry of Agriculture and Rural Affair, Interdisciplinary Research Center on Optical Agricultural and Food Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China
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Shi Y, Chen Z, Huang L, Gong Y, Shi L. A network pharmacology approach to reveal the key ingredients in Scrophulariae Radix (SR) and their effects against Alzheimer's disease. Heliyon 2024; 10:e24785. [PMID: 38322920 PMCID: PMC10844110 DOI: 10.1016/j.heliyon.2024.e24785] [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: 10/04/2023] [Revised: 12/20/2023] [Accepted: 01/15/2024] [Indexed: 02/08/2024] Open
Abstract
Background Scrophulariae Radix (SR) is a commonly used medicinal plant. Alzheimer's disease (AD) is a neurodegenerative disease for which there is no effective treatment. This study aims to initially clarify the potential mechanism of SR in the treatment of AD based on network pharmacology and molecular docking techniques. Methods The principal components and corresponding protein targets of SR were conducted by HPLC analysis and searched on TCMSP. AD targets were searched on DrugBank, Chemogenomics, TTD, OMIM and GeneCards databases. The compound-target network was constructed by Cytoscape3.8.2. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a PPI network. We further performed GO and KEGG enrichment analysis on the targets. Meanwhile, molecular docking study and cell experiments were approved for the core target and the active compound. Results Through multidatabase retrieval and integration, it was found that 17 components of SR could exert anti-AD effects against 40 targets. KEGG enrichment analysis indicated that Alzheimer's disease (hsa05010) was one of the most significant AD enrichment signalling pathways. Combined with the gene expression profile information in the AlzData database, 15 targets were found to be associated with tau or beta-amyloid protein (Aβ). GO analysis indicated that the primary molecular functions of SR in the treatment of AD were neurotransmitter receptor activity (GO:0007268), postsynaptic neurotransmitter receptor activity (GO:0070997), and acetylcholine receptor activity (GO:0050435). Moreover, we explored the anti-AD effects of SR extract and ursolic acid (UA) using SH-SY5Y cells. Treatment of SH-SY5Y cells with 20 μM UA significantly reduced the oxidative damage to these neuronal cells. Conclusion This study reveals the active ingredients and potential molecular mechanism of SR in the treatment of AD, and provides a theoretical basis for further basic research and clinical application.
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Affiliation(s)
- Yingying Shi
- Department of Immunology, School of Medicine, Jianghan University, Wuhan, Hubei, 430056, China
| | - Zhongqiang Chen
- Department of Pharmacy, School of Medicine, Jianghan University, Wuhan, Hubei, 430056, China
| | - Lixia Huang
- Department of Immunology, School of Medicine, Jianghan University, Wuhan, Hubei, 430056, China
| | - Yeli Gong
- Department of Immunology, School of Medicine, Jianghan University, Wuhan, Hubei, 430056, China
| | - Lu Shi
- Department of Pharmacy, School of Medicine, Jianghan University, Wuhan, Hubei, 430056, China
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Micek A, Jagielski P, Bolesławska I, Witkowska AM, Waśkiewicz A, Wajda Z, Kamińska A, Cebula A, Godos J. Negative Association of Lignan and Phytosterol Intake with Stress Perception during the COVID-19 Pandemic-A Polish Study on Young Adults. Nutrients 2024; 16:445. [PMID: 38337729 PMCID: PMC10857242 DOI: 10.3390/nu16030445] [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: 12/29/2023] [Revised: 01/24/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND There has been an increasing global prevalence of depression and other psychiatric diseases in recent years. Perceived stress has been proven to be associated with psychiatric and somatic symptoms. Some animal and human studies have suggested that consuming foods abundant in lignans and phytosterols may be associated with lower levels of stress, depression, and anxiety. Still, the evidence is not yet strong enough to draw firm conclusions. Thus, we investigated the association between dietary intake of these phytochemicals and the level of stress experienced by adult individuals. METHODS Diet was assessed using self-reported 7-day dietary records. The intakes of lignans and phytosterols were estimated using databases with their content in various food products. The Perceived Stress Scale (PSS) was implemented to measure the level of perceived stress. A logistic regression analysis was used to test for associations. RESULTS The odds of elevated PSS were negatively associated with dietary intake of total phytosterols, stigmasterol, and β-sitosterol, with evidence of a decreasing trend across tertiles of phytochemicals. The analysis for doubling the intake reinforced the aforementioned relationships and found protective effects against PSS for total lignans, pinoresinol, and campesterol. CONCLUSIONS Habitual inclusion of lignans and phytosterols in the diet may play a role in psychological health. To address the global outbreak of depression and other mental health issues triggered by stress, it is important to take a holistic approach. There is a need to develop effective strategies for prevention and treatment, among which certain dietary interventions such as consumption of products abundant in lignans and phytosterols may play a substantial role.
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Affiliation(s)
- Agnieszka Micek
- Statistical Laboratory, Jagiellonian University Medical College, 31-126 Kraków, Poland
| | - Paweł Jagielski
- Department of Nutrition and Drug Research, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, 31-066 Kraków, Poland;
| | - Izabela Bolesławska
- Department of Bromatology, Poznan University of Medical Sciences, 60-806 Poznań, Poland;
| | - Anna Maria Witkowska
- Department of Food Biotechnology, Medical University of Bialystok, 15-295 Bialystok, Poland;
| | - Anna Waśkiewicz
- Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, National Institute of Cardiology, 04-628 Warszawa, Poland;
| | - Zbigniew Wajda
- Faculty of Management and Social Communication, Institute of Applied Psychology, Jagiellonian University, 30-348 Kraków, Poland;
| | - Anna Kamińska
- Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 31-121 Kraków, Poland; (A.K.); (A.C.)
| | - Aneta Cebula
- Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 31-121 Kraków, Poland; (A.K.); (A.C.)
| | - Justyna Godos
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy;
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11
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Vigne S, Pot C. Implication of Oxysterols and Phytosterols in Aging and Human Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1440:231-260. [PMID: 38036883 DOI: 10.1007/978-3-031-43883-7_12] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/02/2023]
Abstract
Cholesterol is easily oxidized and can be transformed into numerous oxidation products, among which oxysterols. Phytosterols are plant sterols related to cholesterol. Both oxysterols and phytosterols can have an impact on human health and diseases.Cholesterol is a member of the sterol family that plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized into several molecules including bile acids, hormones, and oxysterols. On the other hand, phytosterols are plant-derived compounds structurally related to cholesterol, which can also have an impact on human health. Here, we review the current knowledge about the role of oxysterols and phytosterols on human health and focus on the impact of their pathways on diseases of the central nervous system (CNS), autoimmune diseases, including inflammatory bowel diseases (IBD), vascular diseases, and cancer in both experimental models and human studies. We will first discuss the implications of oxysterols and then of phytosterols in different human diseases.
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Affiliation(s)
- Solenne Vigne
- Laboratories of Neuroimmunology, Service of Neurology and Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Epalinges, Lausanne, Switzerland
| | - Caroline Pot
- Laboratories of Neuroimmunology, Service of Neurology and Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Epalinges, Lausanne, Switzerland.
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12
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H S S, V G, T M N, Setlur AS, K C, Kumar J, Niranjan V. Comprehending interaction mechanism of natural actives of Colchicum autumnale L. for rheumatoid arthritis using integrative chemoinformatic approaches. J Biomol Struct Dyn 2023:1-20. [PMID: 38116745 DOI: 10.1080/07391102.2023.2294177] [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: 08/10/2023] [Accepted: 12/01/2023] [Indexed: 12/21/2023]
Abstract
This research delves into the realm of therapeutic potential within natural compounds derived from Colchicum autumnale L., emphasizing a holistic perspective on medications used in human therapy. Rather than confining the study to their primary actions, the research endeavors to unveil molecular targets for these natural compounds, with a specific focus on their potential applicability in the treatment of rheumatoid arthritis (RA). The study focuses on understanding interactions between specific natural actives that target RA. Fifteen RA target proteins were identified from OMIM, GeneScan and PharmaGKB. Their structures were downloaded from RCSB PDB. Two active components of C. autumnale L. were chosen for mass spectrometry investigation. Ligand characteristics were determined using the ADMETlab and SwissADME software tools. Molecular docking was performed, and the top three complexes were simulated for 200 ns, along with identification of free binding energies. The compounds β-sitosterol-IL-10 (-6.50 kcal/mol), colchicine-IL-10 (-6.01 kcal/mol), linoleic acid-IL-10 (-7.22 kcal/mol) and linoleic acid-IL-10 (-7.22 kcal/mol) exhibited best binding energies. β-Sitosterol and colchicine showed the highest stability in simulations, confirmed by molecular mechanics free energy binding calculations. This work provides insights into the molecular interaction of natural compounds against RA targets, offering potential therapeutic anti-RA medications.
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Affiliation(s)
- Sowmya H S
- Bangalore Bio-innovation Centre (BBC), Helix Biotech Park, Electronic City Phase-I, Bangalore, Karnataka, India
| | - Guruprasad V
- Homeopathic medical college and Hospital Bangalore, Bangalore, Karnataka, India
| | - Ningaraju T M
- University of Agricultural science Bangalore, Bangalore, Karnataka, India
| | - Anagha S Setlur
- Department of Biotechnology, RV College of Engineering, Bangalore, Karnataka, India
| | - Chandrashekar K
- Department of Biotechnology, RV College of Engineering, Bangalore, Karnataka, India
| | - Jitendra Kumar
- Biotechnology Industry Research Assistance Council (BIRAC), CGO complex Lodhi Road, New Delhi, India
| | - Vidya Niranjan
- Department of Biotechnology, RV College of Engineering, Bangalore, Karnataka, India
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13
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Zahid S, Malik A, Waqar S, Zahid F, Tariq N, Khawaja AI, Safir W, Gulzar F, Iqbal J, Ali Q. Countenance and implication of Β-sitosterol, Β-amyrin and epiafzelechin in nickel exposed Rat: in-silico and in-vivo approach. Sci Rep 2023; 13:21351. [PMID: 38049552 PMCID: PMC10695965 DOI: 10.1038/s41598-023-48772-4] [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: 12/23/2022] [Accepted: 11/30/2023] [Indexed: 12/06/2023] Open
Abstract
The detrimental impact of reactive oxygen species on D.N.A. repair processes is one of the contributing factors to colon cancer. The idea that oxidative stress may be a significant etiological element for carcinogenesis is currently receiving more and more support. The goal of the current study is to evaluate the anti-inflammatory and anticancer activity of three powerful phytocompounds-sitosterol, amyrin, and epiafzelechin-alone and in various therapeutic combinations against colon cancer to identify the critical mechanisms that mitigate nickel's carcinogenic effect. To evaluate the ligand-protein interaction of four selected components against Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-9 (MMP9) inhibitor and Interleukin-10 (IL-10) molecular docking approach was applied using PyRx bioinformatics tool. For in vivo analysis, hundred albino rats were included, divided into ten groups, each containing ten rats of weight 160-200 g. All the groups were injected with 1 ml/kg nickel intraperitoneally per week for three months, excluding the negative control group. Three of the ten groups were treated with β-sitosterol (100 mg/kg b wt), β-amyrin (100 mg/kg b wt), and epiafzelechin (200 mg/kg b wt), respectively, for one month. The later four groups were fed with combinatorial treatments of the three phyto compounds for one month. The last group was administered with commercial drug Nalgin (500 mg/kg b wt). The biochemical parameters Creatinine, Protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), VEGF, MMP-9 Inhibitor, and IL-10 were estimated using ELISA kits and Glutathione (G.S.H.), Superoxide dismutase (S.O.D.), Catalase (C.A.T.) and Nitric Oxide (NO) were analyzed manually. The correlation was analyzed through Pearson's correlation matrix. All the parameters were significantly raised in the positive control group, indicating significant inflammation. At the same time, the levels of the foresaid biomarkers were decreased in the serum in all the other groups treated with the three phytocompounds in different dose patterns. However, the best recovery was observed in the group where the three active compounds were administered concomitantly. The correlation matrix indicated a significant positive correlation of IL-10 vs VEGF (r = 0.749**, p = 0.009), MMP-9 inhibitor vs SOD (r = 0.748**, p = 0.0 21). The study concluded that the three phytocompounds β-sitosterol, β-amyrin, and epiafzelechin are important anticancer agents which can target the cancerous biomarkers and might be used as a better therapeutic approach against colon cancer soon.
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Affiliation(s)
- Sara Zahid
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan
| | - Arif Malik
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan.
| | - Suleyman Waqar
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan
| | - Fatima Zahid
- Ibadat International University (IIUI), Islamabad, Pakistan
| | - Nusrat Tariq
- M. Islam Medical and Dental College, Gujranwala, Pakistan
| | - Ali Imran Khawaja
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan
| | - Waqas Safir
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Sciences and Technology, Xinjiang University, Urumqi, 830046, Xinjiang, China
| | - Faisal Gulzar
- Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
| | - Javeid Iqbal
- School of Pharmacy, Minhaj University Lahore, Lahore, Pakistan
| | - Qurban Ali
- Department of Plant Breeding and Genetics, Faculty of Agricultural Sciences, University of the Punjab, Lahore, Pakistan.
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14
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Yang L, Jian Y, Zhang ZY, Qi BW, Li YB, Long P, Yang Y, Wang X, Huang S, Huang J, Zhou LF, Ma J, Jiang CQ, Hu YH, Xiao WJ. Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes. World J Diabetes 2023; 14:1057-1076. [PMID: 37547579 PMCID: PMC10401449 DOI: 10.4239/wjd.v14.i7.1057] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/14/2023] [Accepted: 05/05/2023] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear.
AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.
METHODS This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments.
RESULTS According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.
CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.
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Affiliation(s)
- Ling Yang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
| | - Yang Jian
- Department of Clinical Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Zai-Yuan Zhang
- College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Bao-Wen Qi
- South China Hospital of Shenzhen University, Shenzhen 518116, Guangdong Province, China
| | - Yu-Bo Li
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
| | - Pan Long
- Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Yao Yang
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Xue Wang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
| | - Shuo Huang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
| | - Jing Huang
- College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Long-Fu Zhou
- Department of Biomedical Engineering, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Jie Ma
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Chang-Qing Jiang
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Yong-He Hu
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
- College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Wen-Jing Xiao
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
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15
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Begcevic Brkovic I, Reinicke M, Chey S, Bechmann I, Ceglarek U. Characterization of Non-Cholesterol Sterols in Microglia Cell Membranes Using Targeted Mass Spectrometry. Cells 2023; 12:cells12070974. [PMID: 37048046 PMCID: PMC10093698 DOI: 10.3390/cells12070974] [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: 12/09/2022] [Revised: 03/09/2023] [Accepted: 03/20/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Non-cholesterol sterols, as well as plant sterols, cross the blood-brain barrier and, thus, can be incorporated into cell membranes, affecting the cell's inflammatory response. The aim of our work was to develop an analytical protocol for a quantitative assessment of the sterol composition within the membrane microdomains of microglia. METHODS A protocol for cell membrane isolation using OptiPrepTM gradient ultracentrifugation, in combination with a targeted mass spectrometry (LC-MS/MS)-based assay, was developed and validated for the quantitative analysis of free sterols in microglia cell membranes. RESULTS Utilizing an established LC-MS/MS assay, cholesterol and seven non-cholesterol sterols were analyzed with a limit of detection from 0.001 to 0.05 mg/L. Applying the detergent-free isolation of SIM-A9 microglia cell membranes, cholesterol (CH), desmosterol (DE), lanosterol (LA) stigmasterol (ST), beta-sitosterol (SI) and campesterol (CA) were quantified with coefficients of variations between 6 and 29% (fractions 4-6, n = 5). The highest concentrations of non-CH sterols within the microglia plasma membranes were found in the microdomain region (DE>LA>SI>ST>CA), with ratios to CH ranging from 2.3 to 435 lower abundancies. CONCLUSION By applying our newly developed and validated analytical protocol, we show that the non-CH sterol concentration is about 38% of the total sterol content in microglia membrane microdomains. Further investigations must clarify how changes in the non-sterol composition influence membrane fluidity and cell signaling.
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Affiliation(s)
- Ilijana Begcevic Brkovic
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig Medical Center, 04103 Leipzig, Germany
| | - Madlen Reinicke
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig Medical Center, 04103 Leipzig, Germany
| | - Soroth Chey
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig Medical Center, 04103 Leipzig, Germany
| | - Ingo Bechmann
- Institute of Anatomy, Faculty of Medicine, University of Leipzig, 04103 Leipzig, Germany
| | - Uta Ceglarek
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig Medical Center, 04103 Leipzig, Germany
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16
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Refaey MS, Shah MA, Fayed MA, Rasul A, Siddiqui MF, Qasim M, Althobaiti NA, Saleem U, Malik A, Blundell R, Eldahshan OA. Neuroprotective effects of steroids. PHYTONUTRIENTS AND NEUROLOGICAL DISORDERS 2023:283-304. [DOI: 10.1016/b978-0-12-824467-8.00005-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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17
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Mechanistic Insights into the Neuroprotective Potential of Sacred Ficus Trees. Nutrients 2022; 14:nu14224731. [PMID: 36432418 PMCID: PMC9695857 DOI: 10.3390/nu14224731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/16/2022] [Accepted: 11/05/2022] [Indexed: 11/11/2022] Open
Abstract
Ficus religiosa (Bo tree or sacred fig) and Ficus benghalensis (Indian banyan) are of immense spiritual and therapeutic importance. Various parts of these trees have been investigated for their antioxidant, antimicrobial, anticonvulsant, antidiabetic, anti-inflammatory, analgesic, hepatoprotective, dermoprotective, and nephroprotective properties. Previous reviews of Ficus mostly discussed traditional usages, photochemistry, and pharmacological activities, though comprehensive reviews of the neuroprotective potential of these Ficus species extracts and/or their important phytocompounds are lacking. The interesting phytocompounds from these trees include many bengalenosides, carotenoids, flavonoids (leucopelargonidin-3-O-β-d-glucopyranoside, leucopelargonidin-3-O-α-l-rhamnopyranoside, lupeol, cetyl behenate, and α-amyrin acetate), flavonols (kaempferol, quercetin, myricetin), leucocyanidin, phytosterols (bergapten, bergaptol, lanosterol, β-sitosterol, stigmasterol), terpenes (α-thujene, α-pinene, β-pinene, α-terpinene, limonene, β-ocimene, β-bourbonene, β-caryophyllene, α-trans-bergamotene, α-copaene, aromadendrene, α-humulene, alloaromadendrene, germacrene, γ-cadinene, and δ-cadinene), and diverse polyphenols (tannin, wax, saponin, leucoanthocyanin), contributing significantly to their pharmacological effects, ranging from antimicrobial action to neuroprotection. This review presents extensive mechanistic insights into the neuroprotective potential, especially important phytochemicals from F. religiosa and F. benghalensis. Owing to the complex pathophysiology of neurodegenerative disorders (NDDs), the currently existing drugs merely alleviate the symptoms. Hence, bioactive compounds with potent neuroprotective effects through a multitarget approach would be of great interest in developing pharmacophores for the treatment of NDDs.
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Khan Z, Nath N, Rauf A, Emran TB, Mitra S, Islam F, Chandran D, Barua J, Khandaker MU, Idris AM, Wilairatana P, Thiruvengadam M. Multifunctional roles and pharmacological potential of β-sitosterol: Emerging evidence toward clinical applications. Chem Biol Interact 2022; 365:110117. [PMID: 35995256 DOI: 10.1016/j.cbi.2022.110117] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/12/2022] [Accepted: 08/16/2022] [Indexed: 12/17/2022]
Abstract
Currently, available therapeutic medications are both costly as well as not entirely promising in terms of potency. So, new candidates from natural resources are of research interest to find new alternative therapeutics. A well-known combination is a β-sitosterol, a plant-derived nutrient with anticancer properties against breast, prostate, colon, lung, stomach, and leukemia. Studies have shown that β-sitosterol interferes with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis, anti-inflammatory, anticancer, hepatoprotective, antioxidant, cardioprotective, and antidiabetic effects have been discovered during pharmacological screening without significant toxicity. The pharmacokinetic profile of β-sitosterol has also been extensively investigated. However, a comprehensive review of the pharmacology, phytochemistry and analytical methods of β-sitosterol is desired. Because β-sitosterol is a significant component of most plant materials, humans use it for various reasons, and numerous β-sitosterol-containing products have been commercialized. To offset the low efficacy of β-sitosterol, designing β-sitosterol delivery for "cancer cell-specific" therapy holds great potential. Delivery of β-sitosterol via liposomes is a demonstration that has shown great promise. But further research has not progressed on the drug delivery of β-sitosterol or how it can enhance β-sitosterol mediated anti-inflammatory activity, thus making β-sitosterol an orphan nutraceutical. Therefore, extensive research on β-sitosterol as an anticancer nutraceutical is recommended.
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Affiliation(s)
- Zidan Khan
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
| | - Nikhil Nath
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23430, Khyber Pakhtunkhwa, Pakistan.
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4381, Bangladesh; Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh.
| | - Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore, Tamil Nadu, 642109, India
| | - Jackie Barua
- Department of Biology, University of Louisiana at Lafayette, 410 East Saint Mary Boulevard, Lafayette, LA, 70503, USA
| | - Mayeen Uddin Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, 47500, Bandar Sunway, Selangor, Malaysia
| | - Abubakr M Idris
- Department of Chemistry, College of Science, King Khalid University, Abha, 62529, Saudi Arabia; Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha, 62529, Saudi Arabia
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand
| | - Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Sciences, Konkuk University, Seoul, 05029, South Korea; Department of Microbiology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai 600077, India.
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19
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Xie T, Liu W, Chen Y, Zhou Y. An evaluation of graded levels of beta-sitosterol supplementation on growth performance, antioxidant status, and intestinal permeability-related parameters and morphology in broiler chickens at an early age. Poult Sci 2022; 101:102108. [PMID: 36099659 PMCID: PMC9472065 DOI: 10.1016/j.psj.2022.102108] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 07/16/2022] [Accepted: 08/01/2022] [Indexed: 11/29/2022] Open
Abstract
This study was designed to examine the effects of different levels of beta-sitosterol (BS) supplementation on growth performance, serum biochemical indices, redox status, and intestinal permeability-related parameters and morphology of young broilers. Two hundred and forty male Arbor Acres broiler chicks were allocated into 5 groups of 6 replicates with 8 birds each, and fed a basal diet supplemented with 0, 25, 50, 75, and 100 mg/kg BS for 21-d, respectively. The BS quadratically decreased feed conversion ratio during 1 to 14 d and 1 to 21 d, with its effect being more prominent at 25 or 50 mg/kg (P < 0.05). The BS linearly and quadratically reduced 14-d plasma diamine oxidase activity and D-lactate level, and this effect was more pronounced when its supplemental level was 25 or 50 mg/kg (P < 0.05). The BS linearly increased duodenal villus height (VH) and quadratically increased jejunal VH and ratio of VH and crypt depth (CD) at 14 d, and these effects in 25 mg/kg group were more remarkable (P < 0.05). Similarly, BS linearly or quadratically increased VH and ratio of VH and CD, but decreased CD in the jejunum and ileum at 21 d, with these effects being more pronounced at 50 mg/kg (P < 0.05). The BS supplementation especially at 50 or 75 mg/kg linearly or quadratically reduced 14-d serum and 21-d hepatic malondialdehyde concentration, and increased serum glutathione peroxidase and catalase activities at 14 and 21 d (P < 0.05). Moreover, the BS administration linearly and/or quadratically increased glutathione peroxidase, catalase, and superoxide dismutase activities and glutathione level, and reduced malondialdehyde accumulation in the intestinal mucosa at 14 and/or 21 d, and these consequences were more significant in 50 to 100 mg/kg BS-supplemented groups (P < 0.05). The results demonstrated that BS administration could improve growth performance, intestinal barrier function, and antioxidant status of broilers at an early age, with these effects being more pronounced at a level of 50 mg/kg.
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Affiliation(s)
- Ting Xie
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China
| | - Wenhan Liu
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China
| | - Yueping Chen
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
| | - Yanmin Zhou
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China
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Oyeyinka BO, Afolayan AJ. Suitability of Banana and Plantain Fruits in Modulating Neurodegenerative Diseases: Implicating the In Vitro and In Vivo Evidence from Neuroactive Narratives of Constituent Biomolecules. Foods 2022; 11:foods11152263. [PMID: 35954031 PMCID: PMC9367880 DOI: 10.3390/foods11152263] [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: 11/20/2021] [Revised: 12/12/2021] [Accepted: 12/14/2021] [Indexed: 12/04/2022] Open
Abstract
Active principles in plant-based foods, especially staple fruits, such as bananas and plantains, possess inter-related anti-inflammatory, anti-apoptotic, antioxidative, and neuromodulatory activities. Neurodegenerative diseases affect the functionality of the central and peripheral nervous system, with attendant cognitive deficits being hallmarks of these conditions. The dietary constitution of a wide range of bioactive compounds identified in this review further iterates the significance of the banana and plantain in compromising, halting, or preventing the pathological mechanisms of neurological disorders. The neuroprotective mechanisms of these biomolecules have been identified by using protein expression regulation and specific gene/pathway targeting, such as the nuclear and tumor necrosis factors, extracellular signal-regulated and mitogen-activated protein kinases, activator protein-1, and the glial fibrillary acidic protein. This review establishes the potential double-edged neuro-pharmacological fingerprints of banana and plantain fruits in their traditionally consumed pulp and less utilized peel component for human nutrition.
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21
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Han M, Li H, Ke D, Tian LM, Hong Y, Zhang C, Tian DZ, Chen L, Zhan LR, Zong SQ. Mechanism of Ba Zhen Tang Delaying Skin Photoaging Based on Network Pharmacology and Molecular Docking. CLINICAL, COSMETIC AND INVESTIGATIONAL DERMATOLOGY 2022; 15:763-781. [PMID: 35510223 PMCID: PMC9058032 DOI: 10.2147/ccid.s344138] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 04/11/2022] [Indexed: 11/26/2022]
Abstract
Purpose To study the efficacy of Ba Zhen Tang in delaying skin photoaging and its potential mechanism based on network pharmacology and molecular docking. Methods First, we screened the active components and targets of Ba Zhen Tang by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and The Universal Protein Resource (UniProt). The target genes of skin photoaging were obtained from GeneCards and GeneMap database. Then, we analyzed the protein–protein interaction (PPI) by STRING database. The network map was constructed by Cytoscape. Finally, we performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis by Metascape database. The molecular docking via Autodock Vina and Pymol. Furthermore, skin photoaging cellular models were established, and the effects of Ba Zhen Tang on ameliorating skin photoaging were investigated. Results A total of 160 active ingredients in Ba Zhen Tang and 60 targets of Ba Zhen Tang for delaying skin photoaging were identified. By GO enrichment analysis, 1153 biological process entries, 45 cellular component entries and 89 molecular functional entries were obtained. A total of 155 signal pathways were obtained by KEGG analysis. Ba Zhen Tang is related to MAPK signaling pathway, TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc., which directly affect the key nodes of photoaging. The molecular docking results showed that there was a certain affinity between the main compounds (kaempferol, quercetin, β-sitosterol, naringenin) and core target genes (PTGS2, CASP3, MAPK1, MAPK3, TP53). Ba Zhen Tang-treated mouse serum inhibited the senescence and p16INK4a expression of human immortalized keratinocyte (HaCaT) cells irradiated by ultraviolet-B (UVB). Conclusion Our study elucidated the potential pharmacological mechanism of Ba Zhen Tang in the treatment of photoaging through multiple targets and pathways. The therapeutic effects of Ba Zhen Tang on skin photoaging were validated in cellular models.
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Affiliation(s)
- Miao Han
- Department of Dermatology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Heng Li
- Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Hospital Affiliated to Hubei University of Chinese Medicine, Wuhan, People's Republic of China
| | - Dan Ke
- Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People's Republic of China
| | - Li-Ming Tian
- Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Tongji Medicine College of Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Yi Hong
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, People's Republic of China
| | - Chong Zhang
- Institute of Geriatrics, Hubei University of Chinese Medicine, Wuhan, People's Republic of China
| | - Dai-Zhi Tian
- Institute of Geriatrics, Hubei University of Chinese Medicine, Wuhan, People's Republic of China
| | - Long Chen
- Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Tongji Medicine College of Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Li-Rui Zhan
- Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Tongji Medicine College of Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Shi-Qin Zong
- Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Tongji Medicine College of Huazhong University of Science and Technology, Wuhan, People's Republic of China
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22
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ZHANG BY, ZHENG YF, ZHAO J, KANG D, WANG Z, XU LJ, LIU AL, DU GH. Identification of multi-target anti-cancer agents from TCM formula by in silico prediction and in vitro validation. Chin J Nat Med 2022; 20:332-351. [DOI: 10.1016/s1875-5364(22)60180-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Indexed: 11/03/2022]
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Tundis R, Passalacqua NG, Bonesi M, Loizzo MR. An Insight into Salvia haematodes L. (Lamiaceae) Bioactive Extracts Obtained by Traditional and Green Extraction Procedures. PLANTS 2022; 11:plants11060781. [PMID: 35336663 PMCID: PMC8956035 DOI: 10.3390/plants11060781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/28/2022] [Accepted: 03/14/2022] [Indexed: 12/01/2022]
Abstract
Even though Salvia is one of the most known genera of the Lamiaceae family, some traditionally used Salvia species are still now less investigated. To that end, the present study aims to evaluate the chemical profile and the potential bioactivities of extracts and related fractions obtained from the endemic sage Salvia haematodes L. by applying a traditional extraction method such as Soxhlet apparatus (SHS) and the rapid solid–liquid dynamic extraction (RSLDE) by Naviglio extractor® (SHN), considered among the “green techniques” operating at room temperature and with minimum solvent employment and minimum energy. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity was measured by a modified Ellman’s method. The antioxidant activity was investigated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing ability power (FRAP), and β-carotene bleaching tests. The SHN methanol fraction resulted the most active in all assays in particular in inhibiting lipid peroxidation with IC50 of 1.7 and 1.6 μg/mL, respectively, after 30 and 60 min of incubation. The SHN n-hexane fraction exhibited a selective activity against AChE with half-maximal inhibitory concentration (IC50) of 22.9 μg/mL, while the SHS n-hexane extract was more active against BChE (IC50 of 30.9 μg/mL). Based on these results, these fractions were subjected to further bio-fractionation by Medium Pressure Liquid Chromatography (MPLC) and the relative obtained fractions were investigated for their AChE and BChE inhibitory activity. A comparative analysis with bio-activity and chemical profile was performed. The observed biological effects provided us with a good starting point for further studies on S. haematodes extracts and fractions such as agents beneficial for the treatment of AD.
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Affiliation(s)
- Rosa Tundis
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy; (M.B.); (M.R.L.)
- Correspondence: ; Tel.: +39-0984-493246
| | | | - Marco Bonesi
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy; (M.B.); (M.R.L.)
| | - Monica Rosa Loizzo
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy; (M.B.); (M.R.L.)
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Reinicke M, Leyh J, Zimmermann S, Chey S, Brkovic IB, Wassermann C, Landmann J, Lütjohann D, Isermann B, Bechmann I, Ceglarek U. Plant Sterol-Poor Diet Is Associated with Pro-Inflammatory Lipid Mediators in the Murine Brain. Int J Mol Sci 2021; 22:ijms222413207. [PMID: 34948003 PMCID: PMC8707069 DOI: 10.3390/ijms222413207] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/02/2021] [Accepted: 12/03/2021] [Indexed: 11/16/2022] Open
Abstract
Plant sterols (PSs) cannot be synthesized in mammals and are exclusively diet-derived. PSs cross the blood-brain barrier and may have anti-neuroinflammatory effects. Obesity is linked to lower intestinal uptake and blood levels of PSs, but its effects in terms of neuroinflammation—if any—remain unknown. We investigated the effect of high-fat diet-induced obesity on PSs in the brain and the effects of the PSs campesterol and β-sitosterol on in vitro microglia activation. Sterols (cholesterol, precursors, PSs) and polyunsaturated fatty acid-derived lipid mediators were measured in the food, blood, liver and brain of C57BL/6J mice. Under a PSs-poor high-fat diet, PSs levels decreased in the blood, liver and brain (>50%). This effect was reversible after 2 weeks upon changing back to a chow diet. Inflammatory thromboxane B2 and prostaglandin D2 were inversely correlated to campesterol and β-sitosterol levels in all brain regions. PSs content was determined post mortem in human cortex samples as well. In vitro, PSs accumulate in lipid rafts isolated from SIM-A9 microglia cell membranes. In summary, PSs levels in the blood, liver and brain were associated directly with PSs food content and inversely with BMI. PSs dampen pro-inflammatory lipid mediators in the brain. The identification of PSs in the human cortex in comparable concentration ranges implies the relevance of our findings for humans.
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Affiliation(s)
- Madlen Reinicke
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany; (M.R.); (S.Z.); (S.C.); (I.B.B.); (C.W.); (B.I.)
| | - Judith Leyh
- Institute of Anatomy, Leipzig University, Liebigstr. 13, 04103 Leipzig, Germany; (J.L.); (J.L.); (I.B.)
| | - Silke Zimmermann
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany; (M.R.); (S.Z.); (S.C.); (I.B.B.); (C.W.); (B.I.)
| | - Soroth Chey
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany; (M.R.); (S.Z.); (S.C.); (I.B.B.); (C.W.); (B.I.)
| | - Ilijana Begcevic Brkovic
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany; (M.R.); (S.Z.); (S.C.); (I.B.B.); (C.W.); (B.I.)
| | - Christin Wassermann
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany; (M.R.); (S.Z.); (S.C.); (I.B.B.); (C.W.); (B.I.)
| | - Julia Landmann
- Institute of Anatomy, Leipzig University, Liebigstr. 13, 04103 Leipzig, Germany; (J.L.); (J.L.); (I.B.)
| | - Dieter Lütjohann
- Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany;
| | - Berend Isermann
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany; (M.R.); (S.Z.); (S.C.); (I.B.B.); (C.W.); (B.I.)
| | - Ingo Bechmann
- Institute of Anatomy, Leipzig University, Liebigstr. 13, 04103 Leipzig, Germany; (J.L.); (J.L.); (I.B.)
| | - Uta Ceglarek
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany; (M.R.); (S.Z.); (S.C.); (I.B.B.); (C.W.); (B.I.)
- Correspondence: ; Tel.: +0049-341-97-2-2200
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Sharma N, Tan MA, An SSA. Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases. Int J Mol Sci 2021; 22:ijms222212255. [PMID: 34830148 PMCID: PMC8618769 DOI: 10.3390/ijms222212255] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 11/03/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022] Open
Abstract
Phytosterols constitute a class of natural products that are an important component of diet and have vast applications in foods, cosmetics, and herbal medicines. With many and diverse isolated structures in nature, they exhibit a broad range of biological and pharmacological activities. Among over 200 types of phytosterols, stigmasterol and β-sitosterol were ubiquitous in many plant species, exhibiting important aspects of activities related to neurodegenerative diseases. Hence, this mini-review presented an overview of the reported studies on selected phytosterols related to neurodegenerative diseases. It covered the major phytosterols based on biosynthetic considerations, including other phytosterols with significant in vitro and in vivo biological activities.
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Affiliation(s)
- Niti Sharma
- Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 461-701, Gyeonggi-do, Korea;
| | - Mario A. Tan
- Research Center for the Natural and Applied Sciences, College of Science, University of Santo Tomas, Manila 1015, Philippines;
| | - Seong Soo A. An
- Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 461-701, Gyeonggi-do, Korea;
- Correspondence: ; Tel.: +82-31-750-8755
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26
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Synthesis, Cytotoxicity, and α-glucosidase Inhibitory Activity of Triterpenic and Sitosterol Tetrazole Derivatives. Chem Heterocycl Compd (N Y) 2021. [DOI: 10.1007/s10593-021-03001-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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27
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Dash R, Mitra S, Ali MC, Oktaviani DF, Hannan MA, Choi SM, Moon IS. Phytosterols: Targeting Neuroinflammation in Neurodegeneration. Curr Pharm Des 2021; 27:383-401. [PMID: 32600224 DOI: 10.2174/1381612826666200628022812] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 05/02/2020] [Indexed: 11/22/2022]
Abstract
Plant-derived sterols, phytosterols, are well known for their cholesterol-lowering activity in serum and their anti-inflammatory activities. Recently, phytosterols have received considerable attention due to their beneficial effects on various non-communicable diseases, and recommended use as daily dietary components. The signaling pathways mediated in the brain by phytosterols have been evaluated, but little is known about their effects on neuroinflammation, and no clinical studies have been undertaken on phytosterols of interest. In this review, we discuss the beneficial roles of phytosterols, including their attenuating effects on inflammation, blood cholesterol levels, and hallmarks of the disease, and their regulatory effects on neuroinflammatory disease pathways. Despite recent advancements made in phytosterol pharmacology, some critical questions remain unanswered. Therefore, we have tried to highlight the potential of phytosterols as viable therapeutics against neuroinflammation and to direct future research with respect to clinical applications.
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Affiliation(s)
- Raju Dash
- Department of Anatomy, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Korea
| | - Sarmistha Mitra
- Plasma Bioscience Research Center, Plasma Bio-display, Kwangwoon University, Seoul-01897, Korea
| | - Md Chayan Ali
- Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia-7003, Bangladesh
| | - Diyah Fatimah Oktaviani
- Department of Anatomy, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Korea
| | - Md Abdul Hannan
- Department of Anatomy, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Korea
| | - Sung Min Choi
- Department of Pediatrics, Dongguk University College of Medicine, Gyeongju-38066, Korea
| | - Il Soo Moon
- Department of Anatomy, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Korea
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β-Sitosterol 3-O-D-glucoside increases ceramide levels in the stratum corneum via the up-regulated expression of ceramide synthase-3 and glucosylceramide synthase in a reconstructed human epidermal keratinization model. PLoS One 2021; 16:e0248150. [PMID: 33684145 PMCID: PMC7939263 DOI: 10.1371/journal.pone.0248150] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 01/31/2021] [Indexed: 11/19/2022] Open
Abstract
β-Sitosterol 3-O-d-glucoside (BSG) is known to act as an agonist by binding to estrogen receptors, and estrogen has been reported to enhance the activity of β-glucocerebrosidase, an epidermal ceramide metabolizing enzyme. In this study, we determined whether BSG up-regulates ceramide levels in the stratum corneum (SC) of a reconstructed human epidermal keratinization (RHEK) model. Treatment with BSG significantly increased the total ceramide content by 1.2-fold compared to that in the control in the SC of the RHEK model, accompanied by a significant increase of the ceramide species, Cer[EOS] by 2.1-fold compared to that in the control. RT-PCR analysis demonstrated that BSG significantly up-regulated the mRNA expression levels of serine palmitoyltransferase (SPT)2, ceramide synthase (CerS)3, glucosylceramide synthase (GCS) and acid sphingomyelinase by 1.41-1.89, 1.35-1.44, 1.19 and 2.06-fold, respectively, compared to that in the control in the RHEK model. Meanwhile, BSG significantly down-regulated the mRNA expression levels of sphingomyelin synthase (SMS)2 by 0.87-0.89-fold. RT-PCR analysis also demonstrated that BSG significantly up-regulated the mRNA expression levels of CerS3 and GCS by 1.19-1.55 and 1.20-fold, respectively, but not of SPT2 and significantly down-regulated that of SMS2 by 0.74-fold in HaCaT keratinocytes. Western blotting analysis revealed that BSG significantly increased the protein expression levels of CerS3 and GCS by 1.78 and 1.28-1.32-fold, respectively, compared to that in the control in HaCaT cells. These findings indicate that BSG stimulates ceramide synthesis via the up-regulated expression levels of CerS3 and GCS in the glucosylceramide pathway, which results in a significantly increased level of total ceramides in the SC accompanied by significantly increased levels of acylceramide species such as Cer[EOS].
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Shathviha PC, Ezhilarasan D, Rajeshkumar S, Selvaraj J. β-sitosterol Mediated Silver Nanoparticles Induce Cytotoxicity in Human Colon Cancer HT-29 Cells. Avicenna J Med Biotechnol 2021; 13:42-46. [PMID: 33680372 PMCID: PMC7903430 DOI: 10.18502/ajmb.v13i1.4577] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Background: Silver nanoparticles (AgNP) are commonly used metallic nanoparticles in health care systems. Colon cancer incidence is increasing worldwide. In this study, AgNP was synthesized using β-sitosterol and its cytotoxic potential was evaluated in human colon cancer (HT-29) cells. Methods: Characterization of AgNP was analyzed by TEM and spectrophotometry analysis. HT-29 cells were treated with different concentrations (2, 4, 6, 8 and 10 ng/ml) of AgNPs and cytotoxicity was evaluated by MTT assay. The apoptosis was analyzed by the flow cytometry. The expression of p53 protein was analyzed by western blotting. Results: β-sitosterol mediated AgNP are spherical in shape and induced concentration-dependent cytotoxicity in HT-29 cells. AgNP caused apoptosis related morphological changes as evidenced by annexin positive staining. AgNP treatments also induced the p53 expression in HT-29 cells. Conclusion: Our present result suggests that β-sitosterol mediated AgNP induce apoptosis in colon cancer cells and this finding may pave the way for further experimental analysis in vivo.
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Affiliation(s)
- Palaniappan Chithambara Shathviha
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India
| | - Devaraj Ezhilarasan
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India
| | - Shanmugam Rajeshkumar
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India
| | - Jayaraman Selvaraj
- Department of Biochemistry, Saveetha Dental College (SDC), Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
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Koc K, Geyikoglu F, Cakmak O, Koca A, Kutlu Z, Aysin F, Yilmaz A, Aşkın H. The targets of β-sitosterol as a novel therapeutic against cardio-renal complications in acute renal ischemia/reperfusion damage. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2021; 394:469-479. [PMID: 33048170 DOI: 10.1007/s00210-020-01984-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 09/30/2020] [Indexed: 01/17/2023]
Abstract
This research is the first to use β-sitosterol on myocardial and renal tissues in renal ischemia/reperfusion (IR) damage. Female Wistar rats were randomly divided into three groups: control (sham), renal IR (50 min ischemia - 3 h reperfusion), and renal IR + 150 mg/kg/p.o. β-sitosterol (the rats were treated with β-sitosterol orally once 1 h before the IR procedure). β-Sitosterol pretreatment caused an increase in superoxide dismutase and glutathione activities and a decrease in malondialdehyde levels in the kidney and heart. Moreover, it alleviated histopathological changes and downregulated the levels of tumor necrosis factor-alpha and interleukin-6 and upregulated the levels of endothelial nitric oxide synthase. As conclusion, the potential of β-sitosterol for renal and cardiac necrosis and apoptosis appears to act by limiting inflammatory response and oxidative stress. Thus, the potential of this compound is noteworthy and may serve as a potential therapeutic in the treatment of acute organ damages due to renal IR.
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Affiliation(s)
- Kubra Koc
- Department of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey
| | - Fatime Geyikoglu
- Department of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey
| | - Ozge Cakmak
- Department of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey.
| | - Aynur Koca
- Department of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey
| | - Zerrin Kutlu
- Department of Biochemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
| | - Ferhunde Aysin
- Department of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey
- East Anatolian High Technology Research and Application Center (DAYTAM), Ataturk University, Erzurum, Turkey
| | - Asli Yilmaz
- Department of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey
- East Anatolian High Technology Research and Application Center (DAYTAM), Ataturk University, Erzurum, Turkey
| | - Hakan Aşkın
- Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, Erzurum, Turkey
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Salgado-Román JM, Loza-Cornejo S, Hernández-Soto R, Hernández-Maldonado JA, Márquez-Villalobos FA, Pérez-Vázquez V, Franco-Robles E, Ramírez-Emiliano J. Phytosterol Extract Decreases the Oxidative Damage in the Brains of Diabetic db/db Mice. Metab Syndr Relat Disord 2021; 19:305-311. [PMID: 33646054 DOI: 10.1089/met.2020.0081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Introduction: Hypercaloric diets induce oxidative stress, and consequently induce hyperglycemia and type 2 diabetes mellitus (T2DM). Thus, oxidative stress is significantly increased in T2DM, leading to oxidative damage to brain, which might contribute to cognitive deficits and neurodegenerative diseases. Therefore, reducing the oxidative stress is important to preserving cognitive functions, and it has been suggested that phytosterols may reduce the oxidative stress. Objective: The objective of the present study was to determine the effects of phytosterols derived from corn on oxidative damage in the cerebellum, frontal cortex, and hippocampus of diabetic db/db mice. Materials and Methods: A phytosterol extract was isolated from yellow corn (Zea mays L.) and 100 mg/kg of the extract was administrated daily to diabetic mice for 8 weeks. At the end of the treatment period, tissues were isolated to determine the levels of oxidized lipid and protein. Results: The phytosterol treatment increased body weight in diabetic db/db mice, but this treatment did not have any effects on body weight in wild-type mice. Moreover, the phytosterol treatment decreased levels of oxidized lipids in the cerebellum, frontal cortex, and hippocampus, and also decreased the levels of oxidized proteins in the cerebellum and frontal cortex in diabetic db/db mice. Conclusion: These important results show that phytosterol treatment can reduce oxidative damage in the brains of diabetic mice.
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Affiliation(s)
- Juan Manuel Salgado-Román
- Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno, México.,Instituto Politécnico Nacional-UPIIG, Silao de la Victoria, México
| | - Sofía Loza-Cornejo
- Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno, México
| | | | | | | | - Victoriano Pérez-Vázquez
- División de Ciencias de la Salud, Departamento de Ciencias Médicas, Campus León, Universidad de Guanajuato, León, México
| | - Elena Franco-Robles
- División de Ciencias de la Vida, Departamento de Veterinaria y Zootecnia, Campus Irapuato-Salamanca, Universidad de Guanajuato, Irapuato, México
| | - Joel Ramírez-Emiliano
- División de Ciencias de la Salud, Departamento de Ciencias Médicas, Campus León, Universidad de Guanajuato, León, México
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Bai X, Tang Y, Li Q, Chen Y, Liu D, Liu G, Fan X, Ma R, Wang S, Li L, Zhou K, Zheng Y, Liu Z. Network pharmacology integrated molecular docking reveals the bioactive components and potential targets of Morinda officinalis-Lycium barbarum coupled-herbs against oligoasthenozoospermia. Sci Rep 2021; 11:2220. [PMID: 33500463 PMCID: PMC7838196 DOI: 10.1038/s41598-020-80780-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 12/28/2020] [Indexed: 02/06/2023] Open
Abstract
Oligoasthenozoospermia (OA) is one of the most common types of male infertility affecting sperm count and sperm motility. Unfortunately, it is difficult for existing drugs to fundamentally improve the sperm quality of OA patients, because the pathological mechanism of OA has not been fully elucidated yet. Morinda officinalis-Lycium barbarum coupled-herbs (MOLBCH), as traditional Chinese Medicines, has been widely used for treating OA over thousands of years, but its molecular mechanism is still unclear. For this purpose, we adopted a comprehensive approach integrated network pharmacology and molecular docking to reveal the bioactive components and potential targets of MOLBCH against OA. The results showed that MOLBCH alleviated apoptosis, promoted male reproductive function, and reduced oxidant stress in the treatment of OA. Ohioensin-A, quercetin, beta-sitosterol and sitosterol were the key bioactive components. Androgen receptor (AR), Estrogen receptor (ESR1), Mitogen-activated protein kinase 3 (MAPK3), RAC-alpha serine/threonine-protein kinase (AKT1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were the core potential targets. PI3K/Akt signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications were the most representative pathways. Moreover, molecular docking was performed to validate the strong binding interactions between the obtained core components and targets. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic instructions to treat OA.
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Affiliation(s)
- Xue Bai
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yibo Tang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Qiang Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yafei Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Dan Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Guimin Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xiaolei Fan
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Ru Ma
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Shuyan Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Lingru Li
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Kailin Zhou
- School of Humanities, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yanfei Zheng
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Zhenquan Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
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Naik B, Maurya VK, Kumar V, Kumar V, Upadhyay S, Gupta S. Phytochemical Analysis of Diplazium esculentum Reveals the Presence of Medically Important Components. CURRENT NUTRITION & FOOD SCIENCE 2021. [DOI: 10.2174/1573401316999200614162834] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background:
Diplazium esculentum is found throughout Asia growing along with water
channels and is used for many purposes. In India, the rhizomes are used to control insects and pests
while the young fronds are used as a vegetable and salad. But very few reports on phytochemicals of
young fronds and its anti-oxidant activity is available.
Objective:
The present study was undertaken to assess the antioxidant, antimicrobial and phytochemical
analysis of D. esculentum.
Methods:
Proximate analysis was done according to the standard protocol while antioxodant and antimicrobial
activity was performed by DDPH. and well diffusion method respectivity. Phytochemical
analysis was performed by GC-MS.
Results:
The present study revealed that the young fronds of D. esculentum contain high amount of
carbohydrate followed by protein, crude fibre, and fat. The free radical scavenging activity of methanolic
extract was 87.93 ± 0.3% reduction, which shows it have potential antioxidant activity. The antioxidant
property may be contributed by the presence of phytochemicals such as Phosphoric acid,
phytol, 2,6,10-Trimethyl,14 ethylene-14-pentadecene, Hexadecanoic acid methyl ester, Pentadecanoic
acid, Stigmasta-5,22-dien-3-ol, acetate, (3.beta.). It showed promising antimicrobial activity against
S. aureus and B. subtilis. The antimicrobial activity may be due to the presence of Phytochemicals
such as beta-Ocimene, 2,6,10-Trimethyl,14 ethylene-14-pentadecene, 1,2-Benzenedicarboxylic acid,
BIS(2-Methylpropyl)ester, Hexadecanoic acid, methyl ester, 1-Heneicosanol, Phytol, 5,8,11,14-
Eicosatetraenoic acid, methyl ester(all Z), 1,2-benzenedicarboxylic acid, Ergost-5-en-3-ol, (3.beta),
Stigmasta-5,22-dien-3-ol, acetate, (3.beta.), stigmast-5-EN-3-OL, (3.beta).
Conclusion:
From the present study, it can be deduced that D. Esculentum is a rich source of
medically important phytochemicals. Further work is required, so that these phytochemicals can be
explored in the management of various chronic diseases.
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Affiliation(s)
- Bindu Naik
- Department of Food Technology, UCALS, Uttaranchal University, Dehradun, Uttarakhand-248001, India
| | - Vinay K. Maurya
- Department of Food Technology, Doon (P.G.) College of Agriculture Science and Technology, Selaqui, Uttarakhand- 248011, India
| | - Vijay Kumar
- Department of Biosciences, Swami Rama Himalayan University, Jollygrant, Uttarakhand-248014, India
| | - Vivek Kumar
- Department of Biosciences, Swami Rama Himalayan University, Jollygrant, Uttarakhand-248014, India
| | - Sweta Upadhyay
- Department of Biosciences, Swami Rama Himalayan University, Jollygrant, Uttarakhand-248014, India
| | - Sanjay Gupta
- Department of Biosciences, Swami Rama Himalayan University, Jollygrant, Uttarakhand-248014, India
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Jie F, Yang X, Wu L, Wang M, Lu B. Linking phytosterols and oxyphytosterols from food to brain health: origins, effects, and underlying mechanisms. Crit Rev Food Sci Nutr 2021; 62:3613-3630. [PMID: 33397124 DOI: 10.1080/10408398.2020.1867819] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Phytosterols and their oxidation products, namely oxyphytosterols, are natural compounds present in plant foods. With increased intake of phytosterol-enriched functional food products, the exposure of both phytosterols and oxyphytosterols is rising. Over the past ten years, researches have been focused on their absorption and metabolism in human body, as well as their biological effects. More importantly, recent studies showed that phytosterols and oxyphytosterols can traverse the blood-brain barrier and accumulate in the brain. As brain health problems resulting from ageing being more serious, attenuating central nervous system (CNS) disorders with active compounds in food are becoming a hot topic. Phytosterols and oxyphytosterols have been shown to implicated in cognition altering and the pathologies of several CNS disorders, including Alzheimer's disease and multiple sclerosis. We will overview these findings with a focus on the contents of phytosterols and oxyphytosterols in food and their dietary intake, as well as their origins in the brain, and illustrate molecular pathways through which they affect brain health, in terms of inflammation, cholesterol homeostasis, oxidative stress, and mitochondria function. The existing scientific gaps of phytosterols and oxyphytosterols to brain health in knowledge are also discussed, highlighting research directions in the future.
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Affiliation(s)
- Fan Jie
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou, China.,Fuli Institute of Food Science, Zhejiang University, Hangzhou, China.,Ningbo Research Institute, Zhejiang University, Ningbo, China
| | - Xuan Yang
- Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
| | - Lipeng Wu
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou, China.,Fuli Institute of Food Science, Zhejiang University, Hangzhou, China.,Ningbo Research Institute, Zhejiang University, Ningbo, China
| | - Mengmeng Wang
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou, China.,Fuli Institute of Food Science, Zhejiang University, Hangzhou, China.,Ningbo Research Institute, Zhejiang University, Ningbo, China
| | - Baiyi Lu
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou, China.,Fuli Institute of Food Science, Zhejiang University, Hangzhou, China.,Ningbo Research Institute, Zhejiang University, Ningbo, China
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35
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Li W, Lu P, Lu Y, Wei H, Niu X, Xu J, Wang K, Zhang H, Li R, Qiu Z, Wang N, Jia P, Zhang Y, Zhang S, Lu H, Chen X, Liu Y, Zhang P. 17β-Estradiol Protects Neural Stem/Progenitor Cells Against Ketamine-Induced Injury Through Estrogen Receptor β Pathway. Front Neurosci 2020; 14:576813. [PMID: 33100963 PMCID: PMC7556164 DOI: 10.3389/fnins.2020.576813] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 09/04/2020] [Indexed: 02/06/2023] Open
Abstract
Ketamine inhibits neural stem/progenitor cell (NSPC) proliferation and disrupts normal neurogenesis in the developing brain. 17β-Estradiol alleviates neurogenesis damage and enhances behavioral performance after ketamine administration. However, the receptor pathway of 17β-estradiol that protects NSPCs from ketamine-induced injury remains unknown. In the present study, we investigated the role of estrogen receptor α (ER-α) and estrogen receptor β (ER-β) in 17β-estradiol’s protection against ketamine-exposed NSPCs and explored its potential mechanism. The primary cultured NSPCs were identified by immunofluorescence and then treated with ketamine and varying doses of ER-α agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) or ER-β agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) for 24 h. NSPC proliferation was analyzed by 5-bromo-2-deoxyuridine incorporation test. The expression of phosphorylated glycogen synthase kinase-3β (p-GSK-3β) was quantified by western blotting. It was found that treatment with different concentrations of PPT did not alter the inhibition of ketamine on NSPC proliferation. However, treatment with DPN attenuated the inhibition of ketamine on NSPC proliferation at 24 h after their exposure (P < 0.05). Furthermore, treatment with DPN increased p-GSK-3β expression in NSPCs exposed to ketamine. These findings indicated that ER-β mediates probably the protective effects of 17β-estradiol on ketamine-damaged NSPC proliferation and GSK-3β is involved in this process
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Affiliation(s)
- Weisong Li
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Pan Lu
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yang Lu
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Haidong Wei
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Xiaoli Niu
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Jing Xu
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Kui Wang
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Hong Zhang
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Rong Li
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Zhengguo Qiu
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Ning Wang
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Pengyu Jia
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yan Zhang
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Shuyue Zhang
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Haixia Lu
- Institute of Neurobiology, National Key Academic Subject of Physiology, Xi'an Jiaotong University, Xi'an, China
| | - Xinlin Chen
- Institute of Neurobiology, National Key Academic Subject of Physiology, Xi'an Jiaotong University, Xi'an, China
| | - Yong Liu
- Institute of Neurobiology, National Key Academic Subject of Physiology, Xi'an Jiaotong University, Xi'an, China
| | - Pengbo Zhang
- Department of Anesthesiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
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36
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Rodrigues CI, Costa DMD, Santos ACV, Batatinha MJM, Souza FVD, Souza EHD, Botura MB, Alves CQ, Soares TL, Brandão HN. Assessment of in vitro anthelmintic activity and bio-guided chemical analysis of BRS Boyrá pineapple leaf extracts. Vet Parasitol 2020; 285:109219. [PMID: 32889401 DOI: 10.1016/j.vetpar.2020.109219] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 08/11/2020] [Accepted: 08/15/2020] [Indexed: 11/29/2022]
Abstract
Species of the Bromeliaceae are known for their pharmacological actions, including anthelmintic effects. The aim of this study was to investigate the in vitro anthelmintic activity of extracts and fractions of BRS Boyrá pineapple leaf against the eggs and infective larvae of gastrointestinal nematodes (Trichostrongylidae) of goats and to identify the compounds involved in this activity. Crude methanol, hexane, dichloromethane, ethyl acetate and residual hydromethanol extracts were investigated by quantitative analysis of phenolic and flavonoid contents, antioxidant activity, anthelmintic activity against gastrointestinal nematodes of goats. The extracts were submitted to chromatographic methods for substance isolation and spectrometric techniques to identify their structures. The anthelmintic activity was performed by in vitro assays with eggs and larvae of nematodes obtained from naturally infected donor goats. All extracts contained phenolic (2.22-14.12 g of gallic acid equivalent per 100 g of dry extract) and flavonoid compounds (0.13-1.45 g of quercetin equivalent per 100 g of dry extract). Bio-guided fractionation of the BRS Boyrá pineapple leaves showed high antioxidant activity (EC50 for DPPH of 2.16-21.38 mg mL-1 and inhibition of co-oxidation of β-carotene of 36.40-74.86%) and anthelmintic activity (15.69-100% inhibition of egg hatching). The ethyl acetate extract exhibited greatest activity in all assays. Through chromatographic column analysis it was possible to isolate three substances: β-sitosterol and stigmasterol mixture in dichloromethane and hexane extracts, identified by NMR and p-coumaric acid in the ethyl acetate extract, identified by HPLC-DAD. The isolated p-coumaric acid exhibited high ovicidal effect against goat gastrointestinal nematodes (IC50: 0.12 mg mL-1) and can be considered the active substance of the ethyl acetate extract. This study revealed for the first time that the pineapple BRS Boyrá possesses inhibitory activity against gastrointestinal nematodes (Haemonchus spp., Oesophagostomum spp. and Trichostrongylus spp.), and that p-coumaric acid is an important bioactive.
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Affiliation(s)
- Caroline Issler Rodrigues
- Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, Novo Horizonte, Feira de Santana, 44036-900, Bahia, Brazil.
| | - Diego Mota da Costa
- Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, Novo Horizonte, Feira de Santana, 44036-900, Bahia, Brazil.
| | | | | | - Fernanda Vidigal Duarte Souza
- Embrapa Mandioca e Fruticultura, Rua Embrapa, s/n, Chapadinha, P.O. Box 007, Cruz das Almas, 44380-000, Bahia, Brazil.
| | - Everton Hilo de Souza
- Universidade Federal do Recôncavo da Bahia, Rua Rui Barbosa, 710, Cruz das Almas, 44380-000, Bahia, Brazil.
| | - Mariana Borges Botura
- Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, Novo Horizonte, Feira de Santana, 44036-900, Bahia, Brazil
| | - Clayton Queiroz Alves
- Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, Novo Horizonte, Feira de Santana, 44036-900, Bahia, Brazil.
| | - Taliane Leila Soares
- Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, Novo Horizonte, Feira de Santana, 44036-900, Bahia, Brazil.
| | - Hugo Neves Brandão
- Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, Novo Horizonte, Feira de Santana, 44036-900, Bahia, Brazil.
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37
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Zhang S, Wang X, Cheng F, Ma C, Fan S, Xu W, Jin N, Liu S, Lv K, Wang Q. Network Pharmacology-Based Approach to Revealing Biological Mechanisms of Qingkailing Injection against IschemicStroke: Focusing on Blood-Brain Barrier. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2020; 2020:2914579. [PMID: 32908557 PMCID: PMC7474352 DOI: 10.1155/2020/2914579] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 06/18/2020] [Accepted: 07/30/2020] [Indexed: 12/13/2022]
Abstract
Ischemic stroke is the most common type of cerebrovascular accident worldwide. It causes long-term disability and death. Qingkailing (QKL) injection is a traditional Chinese patent medicine which has been clinically applied in the treatment of ischemic stroke for nearly thirty years. In the present study, network pharmacology combined with experimentation was used to elucidate the mechanisms of QKL. ADME screening and target prediction identified 62 active compounds and 275 targets for QKL. Topological screening of the protein-protein interaction (PPI) network was used to build a core PPI network consisting of 408 nodes and 17,830 edges. KEGG enrichment indicated that the main signaling pathway implicated in ischemic stroke involved hypoxia-inducible factor-1 (HIF-1). Experimentation showed that QKL alleviated neurological deficits, brain infraction, blood-brain barrier (BBB) leakage, and tight junction degeneration in a mouse ischemic stroke model. Two-photon laser scanning microscopy was used to evaluate BBB permeability and cerebral microvessel structure in living mice. HIF-1α, matrix metalloproteinase-9 (MMP-9), and tight junction proteins such as occludin, zonula occludins-1 (ZO-1), claudin-5, and VE-Cadherin were measured by western blotting. QKL upregulated ZO-1 and downregulated HIF-1α and MMP-9. QKL has a multiapproach, multitarget, and synergistic effect against ischemic stroke.
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Affiliation(s)
- Shuang Zhang
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
| | - Xueqian Wang
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
| | - Fafeng Cheng
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
| | - Chongyang Ma
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
- School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Shuning Fan
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
| | - Wenxiu Xu
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
| | - Na Jin
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
| | - Shuling Liu
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
| | - Kai Lv
- The Third Affiliated Hospital of Beijing University of Chinese Medicine, 51 An Wai Xiaoguan Street, Chaoyang District, Beijing 100029, China
| | - Qingguo Wang
- Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China
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38
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Blanco-Vaca F, Cedó L, Julve J. Phytosterols in Cancer: From Molecular Mechanisms to Preventive and Therapeutic Potentials. Curr Med Chem 2020; 26:6735-6749. [PMID: 29874991 DOI: 10.2174/0929867325666180607093111] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Revised: 02/13/2018] [Accepted: 02/24/2018] [Indexed: 12/17/2022]
Abstract
Cancer is the second leading cause of death worldwide. Compelling evidence supports the hypothesis that the manipulation of dietary components, including plant compounds termed as phytochemicals, demonstrates certain important health benefits in humans, including those in cancer. In fact, beyond their well-known cardiovascular applications, phytosterols may also possess anticancer properties, as has been demonstrated by several studies. Although the mechanism of action by which phytosterols (and derivatives) may prevent cancer development is still under investigation, data from multiple experimental studies support the hypothesis that they may modulate proliferation and apoptosis of tumor cells. Phytosterols are generally considered safe for human consumption and may also be added to a broad spectrum of food matrices; further, they could be used in primary and secondary prevention. However, few interventional studies have evaluated the relationship between the efficacy of different types and forms of phytosterols in cancer prevention. In this context, the purpose of this review was to revisit and update the current knowledge on the molecular mechanisms involved in the anticancer action of phytosterols and their potential in cancer prevention or treatment.
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Affiliation(s)
- Francisco Blanco-Vaca
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau [IRHSCSP] i Institut d'Investigacio Biomedica Sant Pau [IIB-Sant Pau], Barcelona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Madrid, Spain.,Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Lídia Cedó
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau [IRHSCSP] i Institut d'Investigacio Biomedica Sant Pau [IIB-Sant Pau], Barcelona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Madrid, Spain
| | - Josep Julve
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau [IRHSCSP] i Institut d'Investigacio Biomedica Sant Pau [IIB-Sant Pau], Barcelona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Madrid, Spain
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Dierckx T, Bogie JFJ, Hendriks JJA. The Impact of Phytosterols on the Healthy and Diseased Brain. Curr Med Chem 2020; 26:6750-6765. [PMID: 29984647 DOI: 10.2174/0929867325666180706113844] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 02/28/2018] [Accepted: 03/07/2018] [Indexed: 02/07/2023]
Abstract
The central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of cholesterol metabolism can lead to neurological problems. Multiple sclerosis (MS) and Alzheimer's disease (AD) are examples of neurological diseases that are characterized by a disturbed cholesterol metabolism. Phytosterols (PS) are plant-derived components that structurally and functionally resemble cholesterol. PS are known for their cholesterol-lowering properties. Due to their ability to reach the brain, researchers have started to investigate the physiological role of PS in the CNS. In this review, the metabolism and function of PS in the diseased and healthy CNS are discussed.
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Affiliation(s)
- Tess Dierckx
- Biomedical Research Institute, Hasselt University, Diepenbeek, Hassett, Belgium
| | - Jeroen F J Bogie
- Biomedical Research Institute, Hasselt University, Diepenbeek, Hassett, Belgium
| | - Jerome J A Hendriks
- Biomedical Research Institute, Hasselt University, Diepenbeek, Hassett, Belgium
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40
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Lin M, Han P, Li Y, Wang W, Lai D, Zhou L. Quinoa Secondary Metabolites and Their Biological Activities or Functions. Molecules 2019; 24:E2512. [PMID: 31324047 PMCID: PMC6651730 DOI: 10.3390/molecules24132512] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 07/03/2019] [Accepted: 07/03/2019] [Indexed: 02/07/2023] Open
Abstract
Quinoa (Chenopodium quinoa Willd.) was known as the "golden grain" by the native Andean people in South America, and has been a source of valuable food over thousands of years. It can produce a variety of secondary metabolites with broad spectra of bioactivities. At least 193 secondary metabolites from quinoa have been identified in the past 40 years. They mainly include phenolic acids, flavonoids, terpenoids, steroids, and nitrogen-containing compounds. These metabolites exhibit many physiological functions, such as insecticidal, molluscicidal and antimicrobial activities, as well as various kinds of biological activities such as antioxidant, cytotoxic, anti-diabetic and anti-inflammatory properties. This review focuses on our knowledge of the structures, biological activities and functions of quinoa secondary metabolites. Biosynthesis, development and utilization of the secondary metabolites especially from quinoa bran were prospected.
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Affiliation(s)
- Minyi Lin
- Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China
| | - Peipei Han
- Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China
| | - Yuying Li
- Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China
| | - Weixuan Wang
- Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China
| | - Daowan Lai
- Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China
| | - Ligang Zhou
- Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
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Kiyama R. Estrogenic Activity of Coffee Constituents. Nutrients 2019; 11:E1401. [PMID: 31234352 PMCID: PMC6628280 DOI: 10.3390/nu11061401] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 06/14/2019] [Accepted: 06/18/2019] [Indexed: 02/06/2023] Open
Abstract
Here, the constituents of coffee with estrogenic activity are summarized by a comprehensive literature search, and their mechanisms of action for their physiological effects are discussed at the molecular and cellular levels. The estrogenic activity of coffee constituents, such as acids, caramelized products, carbohydrates, lignin, minerals, nitrogenous compounds, oil (lipids), and others, such as volatile compounds, was first evaluated by activity assays, such as animal tests, cell assay, ligand-binding assay, protein assay, reporter-gene assay, transcription assay, and yeast two-hybrid assay. Second, the health benefits associated with the estrogenic coffee constituents, such as bone protection, cancer treatment/prevention, cardioprotection, neuroprotection, and the improvement of menopausal syndromes, were summarized, including their potential therapeutic/clinical applications. Inconsistent results regarding mixed estrogenic/anti-estrogenic/non-estrogenic or biphasic activity, and unbeneficial effects associated with the constituents, such as endocrine disruption, increase the complexity of the effects of estrogenic coffee constituents. However, as the increase of the knowledge about estrogenic cell signaling, such as the types of specific signaling pathways, selective modulations of cell signaling, signal crosstalk, and intercellular/intracellular networks, pathway-based assessment will become a more realistic means in the future to more reliably evaluate the beneficial applications of estrogenic coffee constituents.
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Affiliation(s)
- Ryoiti Kiyama
- Dept. of Life Science, Faculty of Life Science, Kyushu Sangyo Univ. 2-3-1 Matsukadai, Higashi-ku, Fukuoka 813-8503, Japan.
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Li W, Li H, Wei H, Lu Y, Lei S, Zheng J, Lu H, Chen X, Liu Y, Zhang P. 17β-Estradiol Treatment Attenuates Neurogenesis Damage and Improves Behavior Performance After Ketamine Exposure in Neonatal Rats. Front Cell Neurosci 2019; 13:251. [PMID: 31263401 PMCID: PMC6585163 DOI: 10.3389/fncel.2019.00251] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 05/20/2019] [Indexed: 12/23/2022] Open
Abstract
Ketamine exposure disturbed normal neurogenesis in the developing brain and resulted in subsequent neurocognitive deficits. 17β-estradiol provides robust neuroprotection in a variety of brain injury models in animals of both sexes and attenuates neurodegeneration induced by anesthesia agents. In the present study, we aimed to investigate whether 17β-estradiol could attenuate neonatal ketamine exposure-disturbed neurogenesis and behavioral performance. We treated 7-day-old (Postnatal day 7, PND 7) Sprague-Dawley rats and neural stem cells (NSCs) with either normal saline, ketamine, or 17β-estradiol before/after ketamine exposure, respectively. At PND 14, the rats were decapitated to detect neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampus by immunofluorescence staining. The proliferation, neuronal differentiation, and apoptosis of NSCs were assessed by immunohistochemistry method and TUNEL assay, respectively. The protein levels of cleaved caspase-3 in vivo in addition to GSK-3β and p-GSK-3β in vitro were examined by western blotting. Spatial learning and memory abilities were assessed by Morris water maze (MWM) test at PND 42–47. Ketamine exposure decreased cell proliferation in the SVZ and SGZ, inhibited NSC proliferation and neuronal differentiation, promoted NSC apoptosis and led to adult cognitive deficits. Furthermore, ketamine increased cleaved caspase-3 in vivo and decreased the expression of p-GSK-3β in vitro. Treatment with 17β-estradiol could attenuate ketamine-induced changes both in vivo and in vitro. For the first time we showed that 17β-estradiol alleviated ketamine-induced neurogenesis inhibition and cognitive dysfunction in the developing rat brain. Moreover, the protection of 17β-estradiol was associated with GSK-3β.
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Affiliation(s)
- Weisong Li
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Huixian Li
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Haidong Wei
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yang Lu
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shan Lei
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Juan Zheng
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Haixia Lu
- Institute of Neurobiology, National Key Academic Subject, Physiology of Xi'an Jiaotong University, Xi'an, China
| | - Xinlin Chen
- Institute of Neurobiology, National Key Academic Subject, Physiology of Xi'an Jiaotong University, Xi'an, China
| | - Yong Liu
- Institute of Neurobiology, National Key Academic Subject, Physiology of Xi'an Jiaotong University, Xi'an, China
| | - Pengbo Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Li X, Shen Y, Wu G, Qi X, Zhang H, Wang L, Qian H. Determination of Key Active Components in Different Edible Oils Affecting Lipid Accumulation and Reactive Oxygen Species Production in HepG2 Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:11943-11956. [PMID: 30350970 DOI: 10.1021/acs.jafc.8b04563] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Owing to the poor ability of cells to decompose triglycerides, most studies of edible oil have depended on animal or clinical trials. However, such trials are expensive and time-consuming, and the results are limited to considerable individual differences. This is the first study to comprehensively investigate the effect of different oils on the lipid accumulation and reactive oxygen species (ROS) production in HepG2 cells by hydrolyzing oil to fatty acids with integrated fat content. In addition, the key components of fatty acid composition, phytosterol, polyphenols, and tocopherol/tocotrienol in different oils, contributing to a decrease in content of lipid accumulation, cholesterol, ROS, and malondialdehyde (MDA), were analyzed using multivariate analysis. The results showed that the lipid accumulation content of coconut oil, Pu'er tea oil, olive oil, and flaxseed oil at a concentration of 200 μM decreased by 45.98 ± 0.75, 50.35 ± 1.37, 40.43 ± 2.44, and 42.76 ± 1.88%, respectively, compared with the lard. In addition, the ROS contents of Pu'er tea oil, olive oil, and flaxseed oil had no significant difference from that of control cells ( p < 0.05). In the results, (3β,5α)-stigmastan-3-yl, cholane-5,20(22)-diene-3b-ph, and β-sitosterol were determined to be the key components in edible oils associated with lipid accumulation and ROS production.
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Affiliation(s)
- Xiaojing Li
- State Key Laboratory of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
- School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
| | - Yingbin Shen
- Department of Food Science and Engineering, School of Science and Engineering , Jinan University , Guangzhou 510632 , Guangdong , China
| | - Gangcheng Wu
- State Key Laboratory of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
- School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
| | - Xiguang Qi
- State Key Laboratory of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
- School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
| | - Hui Zhang
- State Key Laboratory of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
- School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
| | - Li Wang
- State Key Laboratory of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
- School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
| | - Haifeng Qian
- State Key Laboratory of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
- School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
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Hydroxypropyl-Beta-Cyclodextrin Reduces Inflammatory Signaling from Monocytes: Possible Implications for Suppression of HIV Chronic Immune Activation. mSphere 2018; 3:3/6/e00497-18. [PMID: 30404938 PMCID: PMC6222057 DOI: 10.1128/msphere.00497-18] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Monocytes from HIV-infected patients produce increased levels of inflammatory cytokines, which are associated with chronic immune activation and AIDS progression. Chronic immune activation is often not restored even in patients showing viral suppression under ART. Therefore, new therapeutic strategies to control inflammation and modulate immune activation are required. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent that has been reported to be safe for human use in numerous pharmaceutical applications and that has been shown to inactivate HIV in vitro and to control SIV infection in vivo Since cellular cholesterol content or metabolism has been related to altered cellular activation, we evaluated whether HP-BCD treatment could modulate monocyte response to inflammatory stimuli. Treatment of monocytes isolated from HIV-positive and HIV-negative donors with HP-BCD inhibited the expression of CD36 and TNF-α after LPS stimulation, independent of raft disruption. Accordingly, HP-BCD-treated cells showed significant reduction of TNF-α and IL-10 secretion, which was associated with lower mRNA expression. LPS-induced p38MAPK phosphorylation was dampened by HP-BCD treatment, indicating this pathway as a target for HP-BCD-mediated anti-inflammatory response. The expression of HLA-DR was also reduced in monocytes and dendritic cells treated with HP-BCD, which could hinder T cell activation by these cells. Our data suggest that, besides its well-known antiviral activity, HP-BCD could have an immunomodulatory effect, leading to decreased inflammatory responses mediated by antigen-presenting cells, which may impact HIV pathogenesis and AIDS progression.IMPORTANCE Chronic immune activation is a hallmark of HIV infection and is often not controlled even in patients under antiretroviral therapy. Indeed, chronic diseases with inflammatory pathogenesis are being reported as major causes of death for HIV-infected persons. Hydroxypropyl-beta cyclodextrin (HP-BCD) is a cholesterol-sequestering drug that inhibits HIV replication and infectivity in vitro and in vivo Recent studies have demonstrated the importance of cholesterol metabolism and content in different inflammatory conditions; therefore, we investigated the potential of HP-BCD as an immunomodulatory drug, regulating the activation of cells from HIV-infected patients. Treatment of monocytes with HP-BCD inhibited the expression and secretion of receptors and mediators that are usually enhanced in HIV patients. Furthermore, we investigated the molecular mechanisms associated with the immunomodulatory effect of HP-BCD. Our results indicate that, besides reducing viral replication, HP-BCD treatment may contribute to modulation of chronic immune activation associated with AIDS.
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Catani MV, Gasperi V, Bisogno T, Maccarrone M. Essential Dietary Bioactive Lipids in Neuroinflammatory Diseases. Antioxid Redox Signal 2018; 29:37-60. [PMID: 28637354 PMCID: PMC5984567 DOI: 10.1089/ars.2016.6958] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 06/19/2017] [Accepted: 06/20/2017] [Indexed: 12/13/2022]
Abstract
SIGNIFICANCE Under physiological conditions, neurons and glia are in a healthy, redox-balanced environment; when injury perturbs this equilibrium, a neuroinflammatory state is established by activated microglia that triggers pro-inflammatory responses and alters the oxidant/antioxidant balance, thus leading to neuronal loss and neurodegeneration. In neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease, amyothrophic lateral sclerosis, and multiple sclerosis), the brain is in a constitutively self-sustaining cycle of inflammation and oxidative stress that prompts and amplifies brain damage. Recent Advances: Recently, an increasing amount of scientific data highlight the ability of specific nutrients to cross the blood-brain barrier, and to modulate inflammatory and oxidative pathways. Therefore, nutritional approaches may contribute to restore the lost equilibrium among factors accounting for neurodegeneration. CRITICAL ISSUES Herein, we critically examine how essential lipids (including fatty acids, liposoluble vitamins and phytosterols) might contribute to accelerate or prevent the onset and progression of such pathologies. In particular, we highlight that experimental and clinical findings, although promising, are still inadequate to draw definitive conclusions. FUTURE DIRECTIONS More research is warranted in order to establish the real impact of lipid intake on brain health, especially when redox balance and inflammatory responses have been already compromised. In the future, it would be hoped to gain a detailed knowledge of chemical modifications and dynamic properties of such nutrients, before planning to exploit them as potential therapeutics. Antioxid. Redox Signal. 29, 37-60.
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Affiliation(s)
- Maria Valeria Catani
- Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| | - Valeria Gasperi
- Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| | - Tiziana Bisogno
- Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Italy
- Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy
| | - Mauro Maccarrone
- Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy
- European Center for Brain Research/Santa Lucia Foundation IRCCS, Rome, Italy
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Agrawal M, Saraf S, Saraf S, Antimisiaris SG, Hamano N, Li SD, Chougule M, Shoyele SA, Gupta U, Ajazuddin, Alexander A. Recent advancements in the field of nanotechnology for the delivery of anti-Alzheimer drug in the brain region. Expert Opin Drug Deliv 2018; 15:589-617. [DOI: 10.1080/17425247.2018.1471058] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Mukta Agrawal
- Department of Pharmaceutics, Rungta College of Pharmaceutical Sciences and Research, Bhilai, Chhattisgarh, India
| | - Swarnlata Saraf
- Department of Pharmaceutics, University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India
| | - Shailendra Saraf
- Department of Pharmaceutics, University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India
- Durg University, Govt. Vasudev Vaman Patankar Girls’ P.G. College Campus, Raipur Naka, Durg, Chhattisgarh, India
| | - Sophia G. Antimisiaris
- Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio, 26510, Greece
- Department of Pharmacy, FORTH/ICE-HT, Institute of Chemical Engineering, Rio, Patras, 25104, Greece
| | - Nobuhito Hamano
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British columbia V6T 1Z3, Canada
| | - Shyh-Dar Li
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British columbia V6T 1Z3, Canada
| | - Mahavir Chougule
- Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, Oxford, MS, 38677, USA
- Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS, USA
| | - Sunday A. Shoyele
- Department of Pharmaceutical Sciences, College of Pharmacy, Thomas Jefferson University, Philadelphia, PA, 19107, USA
| | - Umesh Gupta
- Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Kishangarh, Ajmer – 305817, India
| | - Ajazuddin
- Department of Pharmaceutics, Rungta College of Pharmaceutical Sciences and Research, Bhilai, Chhattisgarh, India
| | - Amit Alexander
- Department of Pharmaceutics, Rungta College of Pharmaceutical Sciences and Research, Bhilai, Chhattisgarh, India
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Song X, Liu B, Cui L, Zhou B, Liu L, Liu W, Yao G, Xia M, Hayashi T, Hattori S, Ushiki-Kaku Y, Tashiro SI, Ikejima T. Estrogen Receptors Are Involved in the Neuroprotective Effect of Silibinin in Aβ 1-42-Treated Rats. Neurochem Res 2018; 43:796-805. [PMID: 29397533 DOI: 10.1007/s11064-018-2481-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 01/18/2018] [Accepted: 01/19/2018] [Indexed: 02/06/2023]
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by a cascade of pathologic changes. A widely discussed theory indicates that amyloid β (Aβ) peptides are the causative agents of AD. Silibinin, a flavonoid derived from milk thistle, is well known for its hepato-protective activities and we have reported the neuroprotective effects of silibinin. In this study, we investigated the role of estrogen receptors (ERs) in silibinin's neuroprotective effect on Aβ1-42-injected rats. Results of Morris water maze and novel object-recognition tests demonstrated that silibinin significantly attenuated Aβ1-42-induced memory impairment. Silibinin attenuated ERs and PI3K-Akt pathways, as well as modulated mitogen-activated protein kinases in the hippocampus of Aβ1-42-injected rats. Taken together, silibinin is a potential candidate in the treatment of Alzheimer's disease.
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Affiliation(s)
- Xiaoyu Song
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.,Medical Research Center, Shenzhen University Health Science Center, Shenzhen, 518060, China
| | - Bo Liu
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Lingyu Cui
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Biao Zhou
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Lu Liu
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Weiwei Liu
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Guodong Yao
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.,School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Mingyu Xia
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Toshihiko Hayashi
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Shunji Hattori
- Nippi Research Institute of Biomatrix, Toride, Ibaraki, 302-0017, Japan
| | - Yuko Ushiki-Kaku
- Nippi Research Institute of Biomatrix, Toride, Ibaraki, 302-0017, Japan
| | - Shin-Ichi Tashiro
- Department of Medical Education & Primary Care, Kyoto Prefectural University of Medicine, Kajiicho 465, Kamikyo-ku, Kyoto City, Kyoto, 602-8566, Japan
| | - Takashi Ikejima
- China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
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Cyclodextrin-Steroid Interactions and Applications to Pharmaceuticals, Food, Biotechnology and Environment. ENVIRONMENTAL CHEMISTRY FOR A SUSTAINABLE WORLD 2018. [DOI: 10.1007/978-3-319-76162-6_2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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49
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Thomford AK, Ahmed Abdelhameed RF, Yamada K. Chemical studies on the parasitic plant Thonningia sanguinea Vahl. RSC Adv 2018; 8:21002-21011. [PMID: 35542344 PMCID: PMC9080861 DOI: 10.1039/c8ra03913e] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 06/01/2018] [Indexed: 11/21/2022] Open
Abstract
A detailed first-time report on plant sterols and one flavanone characterized from Thonningia sanguinea provides significant evidence for its ethnomedicinal usage.
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Affiliation(s)
- Ama Kyeraa Thomford
- Graduate School of Biomedical Sciences
- Nagasaki University
- Nagasaki 852-8521
- Japan
- Department of Biomedical Sciences
| | | | - Koji Yamada
- Graduate School of Biomedical Sciences
- Nagasaki University
- Nagasaki 852-8521
- Japan
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50
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Ayaz M, Junaid M, Ullah F, Subhan F, Sadiq A, Ali G, Ovais M, Shahid M, Ahmad A, Wadood A, El-Shazly M, Ahmad N, Ahmad S. Anti-Alzheimer's Studies on β-Sitosterol Isolated from Polygonum hydropiper L. Front Pharmacol 2017; 8:697. [PMID: 29056913 PMCID: PMC5635809 DOI: 10.3389/fphar.2017.00697] [Citation(s) in RCA: 157] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 09/19/2017] [Indexed: 12/22/2022] Open
Abstract
The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer's disease (AD). In search of new anti-AD drugs, β-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer's agent. The in vitro AChE, BChE inhibitory potentials of β-sitosterol were investigated following Ellman's assay. The antioxidant activity was tested using DPPH, ABTS and H2O2 assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. β-sitosterol was tested for in vivo inhibitory potentials against cholinesterase's and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of β-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo cholinesterase inhibitory effects were observed in the β-sitosterol treated groups. β-sitosterol exhibited an IC50 value of 55 and 50 μg/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of β-sitosterol with the target enzyme and further support the in vitro and in vivo results. In the antioxidant assays, the IC50 values were observed as 140, 120, and 280 μg/ml in the DPPH, ABTS and H2O2 assays respectively. The free radicals load in the brain tissues was significantly declined in the β-sitosterol treated animals as compared to the transgenic-saline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, β-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that β-sitosterol is a potential compound for the management of memory deficit disorders like AD.
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Affiliation(s)
- Muhammad Ayaz
- Department of Pharmacy, University of Malakand, Chakdara, Pakistan
| | - Muhammad Junaid
- Department of Pharmacy, University of Malakand, Chakdara, Pakistan
| | - Farhat Ullah
- Department of Pharmacy, University of Malakand, Chakdara, Pakistan
| | - Fazal Subhan
- Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
| | - Abdul Sadiq
- Department of Pharmacy, University of Malakand, Chakdara, Pakistan
| | - Gowhar Ali
- Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
| | - Muhammad Ovais
- Cancer Biology Lab, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muhammad Shahid
- Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
- Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan
| | - Ashfaq Ahmad
- Department of Pharmacy, University of Malakand, Chakdara, Pakistan
- Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan
| | - Abdul Wadood
- Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakistan
| | - Mohamed El-Shazly
- Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
| | - Nisar Ahmad
- Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
| | - Sajjad Ahmad
- Department of Pharmacy, University of Malakand, Chakdara, Pakistan
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