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Warias P, Plewa P, Poniewierska-Baran A. Resveratrol, Piceatannol, Curcumin, and Quercetin as Therapeutic Targets in Gastric Cancer-Mechanisms and Clinical Implications for Natural Products. Molecules 2024; 30:3. [PMID: 39795061 PMCID: PMC11721033 DOI: 10.3390/molecules30010003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/14/2024] [Accepted: 12/21/2024] [Indexed: 01/13/2025] Open
Abstract
Gastric cancer remains a significant global health challenge, driving the need for innovative therapeutic approaches. Natural polyphenolic compounds such as resveratrol, piceatannol, curcumin, and quercetin currently show promising results in the prevention and treatment of various cancers, due to their diverse biological activities. This review presents the effects of natural compounds on important processes related to cancer, such as apoptosis, proliferation, migration, invasion, angiogenesis, and autophagy. Resveratrol, naturally found in red grapes, has been shown to induce apoptosis and inhibit the proliferation, migration, and invasion of gastric cancer cells. Piceatannol, a metabolite of resveratrol, shares similar anticancer properties, particularly in modulating autophagy. Curcumin, derived from turmeric, is known for its anti-inflammatory and antioxidant properties, and its ability to inhibit tumor growth and metastasis. Quercetin, a flavonoid found in various fruits and vegetables, induces cell cycle arrest and apoptosis while enhancing the efficacy of conventional therapies. Despite their potential, challenges such as low bioavailability limit their clinical application, necessitating further research into novel delivery systems. Collectively, these compounds represent a promising avenue for enhancing gastric cancer treatment and improving patient outcomes through their multifaceted biological effects.
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Affiliation(s)
- Paulina Warias
- Doctoral School, University of Szczecin, Mickiewicza 18, 70-384 Szczecin, Poland;
| | - Paulina Plewa
- Department of Physiology, Pomeranian Medical University in Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland;
| | - Agata Poniewierska-Baran
- Department of Physiology, Pomeranian Medical University in Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland;
- Institute of Biology, University of Szczecin, Felczaka 3c, 71-412 Szczecin, Poland
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Owjfard M, Rahimian Z, Karimi F, Borhani-Haghighi A, Mallahzadeh A. A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke. Heliyon 2024; 10:e34121. [PMID: 39082038 PMCID: PMC11284444 DOI: 10.1016/j.heliyon.2024.e34121] [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: 10/09/2023] [Revised: 06/07/2024] [Accepted: 07/03/2024] [Indexed: 08/02/2024] Open
Abstract
Stroke is the second leading cause of death and the third leading cause of disability worldwide. Globally, 68 % of all strokes are ischemic, with 32 % being hemorrhagic. Ischemic stroke (IS) poses significant challenges globally, necessitating the development of effective therapeutic strategies. IS is among the deadliest illnesses. Major functions are played by neuroimmunity, inflammation, and oxidative stress in the multiple intricate pathways of IS. Secondary brain damage is specifically caused by the early pro-inflammatory activity that follows cerebral ischemia, which is brought on by excessive activation of local microglia and the infiltration of circulating monocytes and macrophages. Resveratrol, a natural polyphenol found in grapes and berries, has shown promise as a neuroprotective agent in IS. This review offers a comprehensive overview of resveratrol's neuroprotective role in IS, focusing on its mechanisms of action and therapeutic potential. Resveratrol exerts neuroprotective effects by activating nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) pathways. SIRT1 activation by resveratrol triggers the deacetylation and activation of downstream targets like peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and forkhead box protein O (FOXO), regulating mitochondrial biogenesis, antioxidant defense, and cellular stress response. Consequently, resveratrol promotes cellular survival and inhibits apoptosis in IS. Moreover, resveratrol activates the NRF2 pathway, a key mediator of the cellular antioxidant response. Activation of NRF2 through resveratrol enhances the expression of antioxidant enzymes, like heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), which neutralize reactive oxygen species and mitigate oxidative stress in the ischemic brain. Combined, the activation of SIRT1 and NRF2 pathways contributes to resveratrol's neuroprotective effects by reducing oxidative stress, inflammation, and apoptosis in IS. Preclinical studies demonstrate that resveratrol improves functional outcomes, reduces infarct size, regulates cerebral blood flow and preserves neuronal integrity. Gaining a comprehensive understanding of these mechanisms holds promise for the development of targeted therapeutic interventions aimed at promoting neuronal survival and facilitating functional recovery in IS patients and to aid future studies in this matter.
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Affiliation(s)
- Maryam Owjfard
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Rahimian
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | | | - Arashk Mallahzadeh
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Islam F, Roy S, Zehravi M, Paul S, Sutradhar H, Yaidikar L, Kumar BR, Dogiparthi LK, Prema S, Nainu F, Rab SO, Doukani K, Emran TB. Polyphenols Targeting MAP Kinase Signaling Pathway in Neurological Diseases: Understanding Molecular Mechanisms and Therapeutic Targets. Mol Neurobiol 2024; 61:2686-2706. [PMID: 37922063 DOI: 10.1007/s12035-023-03706-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 10/10/2023] [Indexed: 11/05/2023]
Abstract
Polyphenols are a class of secondary metabolic products found in plants that have been extensively studied for how well they regulate biological processes, such as the proliferation of cells, autophagy, and apoptosis. The mitogen-activated protein kinase (MAPK)-mediated signaling cascade is currently identified as a crucial pro-inflammatory pathway that plays a significant role in the development of neuroinflammation. This process has been shown to contribute to the pathogenesis of several neurological conditions, such as Alzheimer's disease (AD), Parkinson's disease (PD), CNS damage, and cerebral ischemia. Getting enough polyphenols through eating habits has resulted in mitigating the effects of oxidative stress (OS) and lowering the susceptibility to associated neurodegenerative disorders, including but not limited to multiple sclerosis (MS), AD, stroke, and PD. Polyphenols possess significant promise in dealing with the root cause of neurological conditions by modulating multiple therapeutic targets simultaneously, thereby attenuating their complicated physiology. Several polyphenolic substances have demonstrated beneficial results in various studies and are presently undergoing clinical investigation to treat neurological diseases (NDs). The objective of this review is to provide a comprehensive summary of the different aspects of the MAPK pathway involved in neurological conditions, along with an appraisal of the progress made in using polyphenols to regulate the MAPK signaling system to facilitate the management of NDs.
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Affiliation(s)
- Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Sumon Roy
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Mehrukh Zehravi
- Department of Clinical Pharmacy, College of Dentistry & Pharmacy, Buraydah Private Colleges, Buraydah, 51418, Kingdom of Saudi Arabia.
| | - Shyamjit Paul
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Hriday Sutradhar
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Lavanya Yaidikar
- Department of Pharmacology, Seven Hills College of Pharmacy, Tirupati, India
| | - B Raj Kumar
- Department of Pharmaceutical Analysis, Moonray Institute of Pharmaceutical Sciences, Raikal (V), Farooq Nagar (Tlq), Shadnagar (M), R.R Dist., Telangana, 501512, India
| | - Lakshman Kumar Dogiparthi
- Department of Pharmacognosy, MB School of Pharmaceutical Sciences, MBU, Tirupati, Andhra Pradesh, India
| | - S Prema
- Crescent School of Pharmacy, BS Abdur Rahman Crescent Institute of Science and Technology, Vandalur, Chennai, 600048, India
| | - Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia
| | - Safia Obaidur Rab
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Koula Doukani
- Faculty of Nature and Life Sciences, University of Ibn Khaldoun-Tiaret, Tiaret, Algeria
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh.
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI, 02912, USA.
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Guarnieri L, Bosco F, Leo A, Citraro R, Palma E, De Sarro G, Mollace V. Impact of micronutrients and nutraceuticals on cognitive function and performance in Alzheimer's disease. Ageing Res Rev 2024; 95:102210. [PMID: 38296163 DOI: 10.1016/j.arr.2024.102210] [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: 07/31/2023] [Revised: 01/10/2024] [Accepted: 01/25/2024] [Indexed: 02/13/2024]
Abstract
Alzheimer's disease (AD) is a major global health problem today and is the most common form of dementia. AD is characterized by the formation of β-amyloid (Aβ) plaques and neurofibrillary clusters, leading to decreased brain acetylcholine levels in the brain. Another mechanism underlying the pathogenesis of AD is the abnormal phosphorylation of tau protein that accumulates at the level of neurofibrillary aggregates, and the areas most affected by this pathological process are usually the cholinergic neurons in cortical, subcortical, and hippocampal areas. These effects result in decreased cognitive function, brain atrophy, and neuronal death. Malnutrition and weight loss are the most frequent manifestations of AD, and these are also associated with greater cognitive decline. Several studies have confirmed that a balanced low-calorie diet and proper nutritional intake may be considered important factors in counteracting or slowing the progression of AD, whereas a high-fat or hypercholesterolemic diet predisposes to an increased risk of developing AD. Especially, fruits, vegetables, antioxidants, vitamins, polyunsaturated fatty acids, and micronutrients supplementation exert positive effects on aging-related changes in the brain due to their antioxidant, anti-inflammatory, and radical scavenging properties. The purpose of this review is to summarize some possible nutritional factors that may contribute to the progression or prevention of AD, understand the role that nutrition plays in the formation of Aβ plaques typical of this neurodegenerative disease, to identify some potential therapeutic strategies that may involve some natural compounds, in delaying the progression of the disease.
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Affiliation(s)
- Lorenza Guarnieri
- Section of Pharmacology, Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Francesca Bosco
- Section of Pharmacology, Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
| | - Antonio Leo
- Section of Pharmacology, Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy; Research Center FAS@UMG, Department of Health Science, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Rita Citraro
- Section of Pharmacology, Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy; Research Center FAS@UMG, Department of Health Science, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Ernesto Palma
- Department of Health Sciences, Institute of Research for Food Safety and Health (IRC-FSH), University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Giovambattista De Sarro
- Section of Pharmacology, Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy; Research Center FAS@UMG, Department of Health Science, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Vincenzo Mollace
- Department of Health Sciences, Institute of Research for Food Safety and Health (IRC-FSH), University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
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Pisoschi AM, Iordache F, Stanca L, Cimpeanu C, Furnaris F, Geicu OI, Bilteanu L, Serban AI. Comprehensive and critical view on the anti-inflammatory and immunomodulatory role of natural phenolic antioxidants. Eur J Med Chem 2024; 265:116075. [PMID: 38150963 DOI: 10.1016/j.ejmech.2023.116075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 12/29/2023]
Abstract
The immune response encompasses innate and adaptive immunity, each with distinct and specific activities. The innate immune system is constituted by phagocytic cells, macrophages, monocytes and neutrophils, the cascade system, and different classes of receptors such as toll-like receptors that are exploited by the innate immune cells. The adaptive immune system is antigen-specific, encompassing memory lymphocytes and the corresponding specific receptors. Inflammation is understood as an activation of different signaling pathways such as toll-like receptors or nuclear factor kappa-light-chain-enhancer of activated B cells, with an increase in nitric oxide, inflammatory cytokines and chemokines. Increased oxidative stress has been identified as main source of chronic inflammation. Phenolic antioxidants modulate the activities of lymphocytes and macrophages by impacting cytokines and nitric oxide release, exerting anti-inflammatory effect. The nuclear-factor kappa-light-chain-enhancer of activated B cells signaling pathway and the mitogen-activated protein kinase pathway are targeted, alongside an increase in nuclear factor erythroid 2-related factor mediated antioxidant response, triggering the activity of antioxidant enzymes. The inhibitive potential on phospholipase A2, cyclooxygenase and lipoxygenase in the arachidonic acid pathway, and the subsequent reduction in prostaglandin and leukotriene generation, reveals the potential of phenolics as inflammation antagonists. The immunomodulative potential encompasses the capacity to interfere with proinflammatory cytokine synthesis and with the expression of the corresponding genes. A diet rich in antioxidants can result in prevention of inflammation-related pathologies. More investigations are necessary to establish the role of these antioxidants in therapy. The appropriate delivery system and the prooxidant effects exhibited at large doses, or in the presence of heavy metal cations should be regarded.
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Affiliation(s)
- Aurelia Magdalena Pisoschi
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania.
| | - Florin Iordache
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Loredana Stanca
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Carmen Cimpeanu
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Land Reclamation and Environmental Engineering, 59 Marasti Blvd, 011464, Bucharest, Romania
| | - Florin Furnaris
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Ovidiu Ionut Geicu
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania; University of Bucharest, Faculty of Biology, Department Biochemistry and Molecular Biology, 91-95 Splaiul Independentei, 050095, Bucharest, Romania
| | - Liviu Bilteanu
- Molecular Nanotechnology Laboratory, National Institute for Research and Development in Microtechnologies, 126A, Erou Iancu Nicolae Street, 077190, Bucharest, Romania
| | - Andreea Iren Serban
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania; University of Bucharest, Faculty of Biology, Department Biochemistry and Molecular Biology, 91-95 Splaiul Independentei, 050095, Bucharest, Romania
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Zhang B, Xi Y, Huang Y, Zhang Y, Guo F, Yang H. Integration of single-nucleus RNA sequencing and network disturbance to elucidate crosstalk between multicomponent drugs and trigeminal ganglia cells in migraine. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117286. [PMID: 37838292 DOI: 10.1016/j.jep.2023.117286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 10/02/2023] [Accepted: 10/04/2023] [Indexed: 10/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Migraine is caused by hyperactivity of the trigeminovascular system, where trigeminal ganglia (TG) plays an important role. TG is composed of multiple neuronal and non-neuronal cell types, which is related to "neuro-inflammation-vascular" disorder in migraine. Tou Tong Ning capsule (TTNC), a CFDA-approved traditional Chinese medicine for treating migraine, has the characteristics of "multicomponents, multitargets, multipathways". AIM OF THE STUDY To clarify the mechanism of TTNC and elucidate crosstalk between multicomponent drugs and neuronal and non-neuronal functions and cells in migraine. MATERIALS AND METHODS We integrated single-nucleus RNA sequencing and a quantitative evaluation algorithm of the disturbance of multitarget drugs on the disease network and explored the specific pathology of migraine and corresponding compounds. A cerebrovascular smooth muscle spasmolytic activity experiment was carried out to verify the results of the bioinformatics analysis. RESULTS TTNC exhibited its regulation activities in neuronal and non-neuronal aspects based on drugs attack to four subnetworks and cell specific networks, which explored the MoA of TTNC in comprehensive and refined perspectives. Compared to neuronal regulation, TTNC showed more significant attack score on non-neuronal biological function (smooth muscle and vessel). And TTNC compound clusters C1, C6 and C7, targeting non-neuronal function and cells, had larger group area than C10, C4 and C6 for neuronal function and cell, which implied that TTNC may mainly regulate the non-neuronal function, e.g., vessel smooth muscle contraction. Contraction of cerebrovascular smooth muscle of mice ex vivo confirmed the vasodilation activity of TTNC and active compounds from C1, C6, C9 (Emodin, Luteolin and Levistilide A). Literature mining confirmed the vasospasmodolytic activity and neuroprotective effect of TTNC. CONCLUSIONS The study found that TTNC may primarily alleviate non-neuronal functional disorders in migraine by relaxing cerebral vascular smooth muscle cell spasm to alleviate migraine. Integrating single-nucleus RNA sequencing data and network disturbance tools provides a new strategy for the pharmacological mechanism of multicomponent drugs through cell subtyping.
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Affiliation(s)
- Bo Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yujie Xi
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China; Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ying Huang
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yi Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Feifei Guo
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Hongjun Yang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China; Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China; China Academy of Chinese Medical Sciences, Beijing, China.
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Sovrani V, Bobermin LD, Sesterheim P, Rezena E, Cioccari MS, Netto CA, Gonçalves CA, Leipnitz G, Quincozes-Santos A. Glioprotective effects of resveratrol in hypothalamic astrocyte cultures obtained from interferon receptor knockout (IFNα/βR -/-) mice. In Vitro Cell Dev Biol Anim 2023:10.1007/s11626-023-00777-z. [PMID: 37353697 DOI: 10.1007/s11626-023-00777-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 05/12/2023] [Indexed: 06/25/2023]
Abstract
Astrocytes play essential roles in the central nervous system (CNS), such as the regulation of glutamate metabolism, antioxidant defenses, and inflammatory/immune responses. Moreover, hypothalamic astrocytes seem to be crucial in the modulation of inflammatory processes, including those related to type I interferon signaling. In this regard, the polyphenol resveratrol has emerged as an important glioprotective molecule to regulate astrocyte functions. Therefore, this study aimed to investigate the immunomodulatory and protective effects of resveratrol in hypothalamic astrocyte cultures obtained from mouse depleted of type I interferon receptors (INF-α/β-/-), a condition that can impair immune and inflammatory functions. Resveratrol upregulated glutamate transporter and glutamine synthetase gene expression, as well as modulated the release of wide range of cytokines and genes involved in the control of inflammatory response, besides the expression of adenosine receptors, which display immunomodulatory functions. Resveratrol also increased genes associated with redox balance, mitochondrial processes, and trophic factors signaling. The putative genes associated with glioprotective effects of resveratrol, including nuclear factor erythroid derived 2 like 2 (Nrf2), heme oxygenase 1 (HO-1), sirtuin 1 (SIRT1), and phosphoinositide 3-kinase (PI3K)/Akt, were further upregulated by resveratrol. Thus, our data show that resveratrol was able to modulate key genes associated with glial functionality and inflammatory response in astrocyte cultures derived from IFNα/βR-/- mice. These data are in agreement with previous results, reinforcing its glioprotective effects even in hypothalamic astrocytes with altered inflammatory and immune signaling. Finally, this polyphenol can prepare astrocytes to better respond to injuries, including those associated with neuroimmunology defects.
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Affiliation(s)
- Vanessa Sovrani
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Larissa Daniele Bobermin
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Patrícia Sesterheim
- Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Instituto de Cardiologia/Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil
| | - Ester Rezena
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Matheus Sinhorelli Cioccari
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Carlos Alexandre Netto
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Laboratório de Neurotoxicidade e Glioproteção (LABGLIO), Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600 - Anexo, Porto Alegre, RS, 90035-003, Brazil
| | - Carlos-Alberto Gonçalves
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Laboratório de Neurotoxicidade e Glioproteção (LABGLIO), Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600 - Anexo, Porto Alegre, RS, 90035-003, Brazil
| | - Guilhian Leipnitz
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Laboratório de Neurotoxicidade e Glioproteção (LABGLIO), Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600 - Anexo, Porto Alegre, RS, 90035-003, Brazil
| | - André Quincozes-Santos
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
- Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
- Laboratório de Neurotoxicidade e Glioproteção (LABGLIO), Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600 - Anexo, Porto Alegre, RS, 90035-003, Brazil.
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Monmai C, Kim JS, Baek SH. Use of Germination to Enhance Resveratrol Content and Its Anti-Inflammatory Activity in Lipopolysaccharide-Stimulated RAW264.7 Cells. Molecules 2023; 28:4898. [PMID: 37446559 DOI: 10.3390/molecules28134898] [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: 05/19/2023] [Revised: 06/17/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Inflammation is triggered by a variety of danger signals and is now a worldwide concern. Resveratrol, a natural nonflavonoid polyphenol found in naturally consumed plants and foods, has a wide spectrum of bioactive potency. We successfully generated resveratrol-enriched rice by introducing the resveratrol biosynthesis gene into Dongjin rice. In this study, resveratrol- and piceid-enriched rice (DJ526) was investigated for its anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells compared to normal rice (DJ). In addition, the 5-day-old germinated DJ526 (DJ526_5) was tested for its anti-inflammatory effects. The piceid and resveratrol amounts increased in DJ526_5 by germination. Treatment of LPS-stimulated RAW264.7 cells with resveratrol-enriched rice seed extracts (DJ526_0 and DJ526_5) significantly decreased the production of nitric oxide (NO) and the inflammatory mediator prostaglandin E2 (PGE2), downregulated proinflammatory gene expression, and inhibited nuclear factor kappa B (NF-κB) p65, p38 mitogen-activated protein kinase, and extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation. These findings demonstrated the anti-inflammatory mechanisms of resveratrol-enriched rice in LPS-stimulated RAW264.7 cells. Furthermore, resveratrol-enriched rice could be a potential source of anti-inflammatory agents.
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Affiliation(s)
- Chaiwat Monmai
- Department of Agricultural Life Science, Sunchon National University, Suncheon 59722, Republic of Korea
| | - Jin-Suk Kim
- Department of Agricultural Life Science, Sunchon National University, Suncheon 59722, Republic of Korea
| | - So-Hyeon Baek
- Department of Agricultural Life Science, Sunchon National University, Suncheon 59722, Republic of Korea
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Shaito A, Al-Mansoob M, Ahmad SM, Haider MZ, Eid AH, Posadino AM, Pintus G, Giordo R. Resveratrol-Mediated Regulation of Mitochondria Biogenesis-associated Pathways in Neurodegenerative Diseases: Molecular Insights and Potential Therapeutic Applications. Curr Neuropharmacol 2023; 21:1184-1201. [PMID: 36237161 PMCID: PMC10286596 DOI: 10.2174/1570159x20666221012122855] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 09/22/2022] [Accepted: 10/09/2022] [Indexed: 11/22/2022] Open
Abstract
Neurodegenerative disorders include different neurological conditions that affect nerve cells, causing the progressive loss of their functions and ultimately leading to loss of mobility, coordination, and mental functioning. The molecular mechanisms underpinning neurodegenerative disease pathogenesis are still unclear. Nonetheless, there is experimental evidence to demonstrate that the perturbation of mitochondrial function and dynamics play an essential role. In this context, mitochondrial biogenesis, the growth, and division of preexisting mitochondria, by controlling mitochondria number, plays a vital role in maintaining proper mitochondrial mass and function, thus ensuring efficient synaptic activity and brain function. Mitochondrial biogenesis is tightly associated with the control of cell division and variations in energy demand in response to extracellular stimuli; therefore, it may represent a promising therapeutic target for developing new curative approaches to prevent or counteract neurodegenerative disorders. Accordingly, several inducers of mitochondrial biogenesis have been proposed as pharmacological targets for treating diverse central nervous system conditions. The naturally occurring polyphenol resveratrol has been shown to promote mitochondrial biogenesis in various tissues, including the nervous tissue, and an ever-growing number of studies highlight its neurotherapeutic potential. Besides preventing cognitive impairment and neurodegeneration through its antioxidant and anti-inflammatory properties, resveratrol has been shown to be able to enhance mitochondria biogenesis by acting on its main effectors, including PGC-1α, SIRT1, AMPK, ERRs, TERT, TFAM, NRF-1 and NRF-2. This review aims to present and discuss the current findings concerning the impact of resveratrol on the machinery and main effectors modulating mitochondrial biogenesis in the context of neurodegenerative diseases.
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Affiliation(s)
- Abdullah Shaito
- Biomedical Research Center, College of Medicine, Qatar University, Doha, 2713, Qatar
- Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha, 2713, Qatar
| | - Maryam Al-Mansoob
- Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, 2713, Qatar
| | - Salma M.S. Ahmad
- Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, 2713, Qatar
| | | | - Ali H. Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, 2713, Qatar
| | - Anna Maria Posadino
- Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy
| | - Gianfranco Pintus
- Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy
- Department of Medical Laboratory Sciences, College of Health Sciences and Sharjah Institute for Medical Research, University of Sharjah, University City Rd, Sharjah, 27272, United Arab Emirates
| | - Roberta Giordo
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, 505055, United Arab Emirates
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10
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Harwansh RK, Yadav P, Deshmukh R. Current Insight into Novel Delivery Approaches of Resveratrol for Improving Therapeutic Efficacy and Bioavailability with its Clinical Updates. Curr Pharm Des 2023; 29:2921-2939. [PMID: 38053352 DOI: 10.2174/0113816128282713231129094715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/22/2023] [Accepted: 11/02/2023] [Indexed: 12/07/2023]
Abstract
Resveratrol (RSV) is a polyphenolic phytoalexin, and belongs to the stilbene family. RSV has several therapeutic activities such as cardioprotective, anticancer, and antioxidant. Apart from its therapeutic benefits, its pharmacological uses are limited due to low solubility, poor bioavailability, and short biological halflife. A researcher continuously focuses on overcoming the limitations of RSV through nanotechnology platforms to get the optimum health benefits. In this context, nanocarriers are pioneering to overcome these drawbacks. Nanocarriers possess high drug loading capacity, thermal stability, low production cost, longer shelflife, etc. Fortunately, scientists were proficient in delivering resveratrol-based nanocarriers in the present scenario. Nanocarriers can deliver drugs to the target sites without compromising the bioavailability. Thus, this review highlights how the latest nanocarrier systems overcome the shortcomings of RSV, which will be good for improving therapeutic efficacy and bioavailability. Moreover, recent updates on resveratrol-based novel formulations and their clinical trials have been addressed to manage several health-related problems.
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Affiliation(s)
- Ranjit K Harwansh
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Paras Yadav
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Rohitas Deshmukh
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
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11
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Cerebral Ischemia/Reperfusion Injury and Pharmacologic Preconditioning as a Means to Reduce Stroke-induced Inflammation and Damage. Neurochem Res 2022; 47:3598-3614. [DOI: 10.1007/s11064-022-03789-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 10/09/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022]
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12
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Chiang MC, Nicol CJB, Lo SS, Hung SW, Wang CJ, Lin CH. Resveratrol Mitigates Oxygen and Glucose Deprivation-Induced Inflammation, NLRP3 Inflammasome, and Oxidative Stress in 3D Neuronal Culture. Int J Mol Sci 2022; 23:ijms231911678. [PMID: 36232980 PMCID: PMC9570351 DOI: 10.3390/ijms231911678] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/16/2022] [Accepted: 09/26/2022] [Indexed: 11/21/2022] Open
Abstract
Oxygen glucose deprivation (OGD) can produce hypoxia-induced neurotoxicity and is a mature in vitro model of hypoxic cell damage. Activated AMP-activated protein kinase (AMPK) regulates a downstream pathway that substantially increases bioenergy production, which may be a key player in physiological energy and has also been shown to play a role in regulating neuroprotective processes. Resveratrol is an effective activator of AMPK, indicating that it may have therapeutic potential as a neuroprotective agent. However, the mechanism by which resveratrol achieves these beneficial effects in SH-SY5Y cells exposed to OGD-induced inflammation and oxidative stress in a 3D gelatin scaffold remains unclear. Therefore, in the present study, we investigated the effect of resveratrol in 3D gelatin scaffold cells to understand its neuroprotective effects on NF-κB signaling, NLRP3 inflammasome, and oxidative stress under OGD conditions. Here, we show that resveratrol improves the expression levels of cell viability, inflammatory cytokines (TNF-α, IL-1β, and IL-18), NF-κB signaling, and NLRP3 inflammasome, that OGD increases. In addition, resveratrol rescued oxidative stress, nuclear factor-erythroid 2 related factor 2 (Nrf2), and Nrf2 downstream antioxidant target genes (e.g., SOD, Gpx GSH, catalase, and HO-1). Treatment with resveratrol can significantly normalize OGD-induced changes in SH-SY5Y cell inflammation, oxidative stress, and oxidative defense gene expression; however, these resveratrol protective effects are affected by AMPK antagonists (Compounds C) blocking. These findings improve our understanding of the mechanism of the AMPK-dependent protective effect of resveratrol under 3D OGD-induced inflammation and oxidative stress-mediated cerebral ischemic stroke conditions.
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Affiliation(s)
- Ming-Chang Chiang
- Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei 242304, Taiwan
| | - Christopher J. B. Nicol
- Departments of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
- Departments of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada
- Cancer Biology and Genetics Division, Cancer Research Institute, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Shy-Shyong Lo
- Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei 242304, Taiwan
| | - Shiang-Wei Hung
- Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei 242304, Taiwan
| | - Chieh-Ju Wang
- Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei 242304, Taiwan
| | - Chien-Hung Lin
- Division of Pediatric Immunology and Nephrology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- Department of Pediatrics, Zhongxing Branch, Taipei City Hospital, Taipei 10341, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
- College of Science and Engineering, Fu Jen Catholic University, New Taipei 242304, Taiwan
- Correspondence:
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13
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Noori T, Shirooie S, Sureda A, Sobarzo-Sanchez E, Dehpour AR, Saldías M, Akkol EK. Regulation of DAPK1 by Natural Products: An Important Target in Treatment of Stroke. Neurochem Res 2022; 47:2142-2157. [PMID: 35674928 DOI: 10.1007/s11064-022-03628-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 05/01/2022] [Accepted: 05/05/2022] [Indexed: 12/12/2022]
Abstract
Stroke is a sudden neurological disorder that occurs due to impaired blood flow to an area of the brain. Stroke can be caused by the blockage or rupture of a blood vessel in the brain, called ischemic stroke and hemorrhagic stroke, respectively. Stroke is more common in men than women. Atrial fibrillation, hypertension, kidney disease, high cholesterol and lipids, genetic predisposition, inactivity, poor nutrition, diabetes mellitus, family history and smoking are factors that increase the risk of stroke. Restoring blood flow by repositioning blocked arteries using thrombolytic agents or endovascular therapy are the most effective treatments for stroke. However, restoring circulation after thrombolysis can cause fatal edema or intracranial hemorrhage, and worsen brain damage in a process known as ischemia-reperfusion injury. Therefore, there is a pressing need to find and develop more effective treatments for stroke. In the past, the first choice of treatment was based on natural compounds. Natural compounds are able to reduce the symptoms and reduce various diseases including stroke that attract the attention of the pharmaceutical industry. Nowadays, as a result of the numerous studies carried out in the field of herbal medicine, many useful and valuable effects of plants have been identified. The death-associated protein kinase (DAPK) family is one of the vital families of serine/threonine kinases involved in the regulation of some biological functions in human cells. DAPK1 is the most studied kinase within the DAPKs family as it is involved in neuronal and recovery processes. Dysregulation of DAPK1 in the brain is involved in the developing neurological diseases such as stroke. Natural products can function in a variety of ways, including reducing cerebral edema, reducing brain endothelial cell death, and inhibiting TNFα and interleukin-1β (IL-1β) through regulating the DAPK1 signal against stroke. Due to the role of DAPK1 in neurological disorders, the aim of this article was to investigate the role of DAPK1 in stroke and its modulation by natural compounds.
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Affiliation(s)
- Tayebeh Noori
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Samira Shirooie
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress (NUCOX) and Health Research Institute of Balearic Islands (IdISBa), University of Balearic Islands, 07122, Palma de Mallorca, Balearic Islands, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain
| | - Eduardo Sobarzo-Sanchez
- Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago, Chile
| | - Ahmad Reza Dehpour
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Marianela Saldías
- Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago, Chile
| | - Esra Küpeli Akkol
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330, Ankara, Turkey
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14
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Abd Aziz NAW, Iezhitsa I, Agarwal R, Bakar NS, Abd Latiff A, Ismail NM. Neuroprotection by Trans-Resveratrol in Rats With Intracerebral Hemorrhage: Insights into the Role of Adenosine A1 Receptors. J Neuropathol Exp Neurol 2022; 81:596-613. [PMID: 35799401 DOI: 10.1093/jnen/nlac047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Given the neuroprotective effects of trans-resveratrol (RV), this study aimed to investigate the involvement of the adenosine A1 receptor (A1R) in RV-mediated neuroprotection in a rat intracerebral hemorrhage (ICH) model induced by intrastriatal injection of collagenase. Rats were divided into 5 groups: (1) control, (2) sham-operated, (3) ICH pretreated with vehicle, (4) ICH pretreated with RV, and (5) ICH pretreated with RV and the A1R antagonist DPCPX. At 48 hours after ICH, the rats were subjected to neurological testing. Brain tissues were assessed for neuronal density and morphological features using routine and immunohistochemical staining. Expression of tumor necrosis factor-α (TNF-α), caspase-3, and RIPK3 proteins was examined using ELISA. A1R, MAPK P38, Hsp90, TrkB, and BDNF genes were examined using RT-qPCR. RV protected against neurological deficits and neuronal depletion, restored the expression of TNF-α, CASP3, RIPK3, A1R, and Hsp90, and increased BDNF/TrkB. DPCPX abolished the effects of RV on neurological outcomes, neuronal density, CASP3, RIPK3, A1R, Hsp90, and BDNF. These data indicate that the neuroprotection by RV involves A1R and inhibits CASP3-dependent apoptosis and RIPK3-dependent necroptosis in the perihematoma region; this is likely to be mediated by crosstalk between A1R and the BDNF/TrkB pathway.
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Affiliation(s)
- Noor Azliza Wani Abd Aziz
- From the Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA, NSB, NMI); Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA); School of Medicine, International Medical University, Kuala Lumpur, Malaysia (II, RA); Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Volgograd, Russia (II); and Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (AAL)
| | - Igor Iezhitsa
- From the Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA, NSB, NMI); Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA); School of Medicine, International Medical University, Kuala Lumpur, Malaysia (II, RA); Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Volgograd, Russia (II); and Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (AAL)
| | - Renu Agarwal
- From the Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA, NSB, NMI); Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA); School of Medicine, International Medical University, Kuala Lumpur, Malaysia (II, RA); Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Volgograd, Russia (II); and Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (AAL)
| | - Nor Salmah Bakar
- From the Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA, NSB, NMI); Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA); School of Medicine, International Medical University, Kuala Lumpur, Malaysia (II, RA); Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Volgograd, Russia (II); and Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (AAL)
| | - Azian Abd Latiff
- From the Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA, NSB, NMI); Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA); School of Medicine, International Medical University, Kuala Lumpur, Malaysia (II, RA); Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Volgograd, Russia (II); and Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (AAL)
| | - Nafeeza Mohd Ismail
- From the Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA, NSB, NMI); Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia (NAWAA); School of Medicine, International Medical University, Kuala Lumpur, Malaysia (II, RA); Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Volgograd, Russia (II); and Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia (AAL)
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15
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Yan W, Ren D, Feng X, Huang J, Wang D, Li T, Zhang D. Neuroprotective and Anti-Inflammatory Effect of Pterostilbene Against Cerebral Ischemia/Reperfusion Injury via Suppression of COX-2. Front Pharmacol 2021; 12:770329. [PMID: 34795593 PMCID: PMC8593399 DOI: 10.3389/fphar.2021.770329] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 10/13/2021] [Indexed: 01/07/2023] Open
Abstract
Background: The incidence of cerebral ischemia disease leading cause of death in human population worldwide. Treatment of cerebral ischemia remains a clinical challenge for researchers and mechanisms of cerebral ischemia remain unknown. During the cerebral ischemia, inflammatory reaction and oxidative stress plays an important role. The current investigation scrutinized the neuroprotective and anti-inflammatory role of pterostilbene against cerebral ischemia in middle cerebral artery occlusion (MCAO) rodent model and explore the underlying mechanism. Methods: The rats were divided into following groups viz., normal, sham, MCAO and MCAO + pterostilbene (25 mg/kg) group, respectively. The groups received the oral administration of pterostilbene for 30 days followed by MCAO induction. The neurological score, brain water content, infarct volume and Evan blue leakage were estimated. Hepatic, renal, heart, inflammatory cytokines and inflammatory mediators were estimated. Results: Pterostilbene treatment significantly (p < 0.001) improved the body weight and suppressed the glucose level and brain weight. Pterostilbene significantly (p < 0.001) reduced the hepatic, renal and heart parameters. Pterostilbene significantly (p < 0.001) decreased the level of glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and decreased the level of malonaldehyde (MDA), 8-Hydroxy-2′-deoxyguanosine (8-OHdG). Pterostilbene significantly (p < 0.001) inflammatory cytokines and inflammatory parameters such as cyclooxygenase-2 (COX-2), inducible nitric oxidase synthase (iNOS) and prostaglandin (PGE2). Pterostilbene significantly (p < 0.001) down-regulated the level of metalloproteinases (MMP) such as MMP-2 and MMP-9. Pterostilbene suppressed the cellular swelling, cellular disintegration, macrophage infiltration, monocyte infiltration and polymorphonuclear leucocyte degranulation in the brain. Conclusion: In conclusion, Pterostilbene exhibited the neuroprotective effect against cerebral ischemia in rats via anti-inflammatory mechanism.
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Affiliation(s)
- Wenjun Yan
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, China
| | - Dongqing Ren
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, China
| | - Xiaoxue Feng
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, China
| | - Jinwen Huang
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, China
| | - Dabin Wang
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, China
| | - Ting Li
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, China
| | - Dong Zhang
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, China
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16
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Khan MM, Badruddeen, Mujahid M, Akhtar J, Khan MI, Ahmad U. An Overview of Stroke: Mechanism, In vivo Experimental Models Thereof, and Neuroprotective Agents. Curr Protein Pept Sci 2021; 21:860-877. [PMID: 32552641 DOI: 10.2174/1389203721666200617133903] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 05/22/2019] [Accepted: 07/30/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Stroke is one of the causes of death and disability globally. Brain attack is because of the acute presentation of stroke, which highlights the requirement for decisive action to treat it. OBJECTIVE The mechanism and in-vivo experimental models of stroke with various neuroprotective agents are highlighted in this review. METHOD The damaging mechanisms may proceed by rapid, nonspecific cell lysis (necrosis) or by the active form of cell death (apoptosis or necroptosis), depending upon the duration and severity and of the ischemic insult. RESULTS Identification of injury mediators and pathways in a variety of experimental animal models of global cerebral ischemia has directed to explore the target-specific cytoprotective strategies, which are critical to clinical brain injury outcomes. CONCLUSION The injury mechanism, available encouraging medicaments thereof, and outcomes of natural and modern medicines for ischemia have been summarized. In spite of available therapeutic agents (thrombolytics, calcium channel blockers, NMDA receptor antagonists and antioxidants), there is a need for an ideal drug for strokes.
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Affiliation(s)
- Mohd Muazzam Khan
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Badruddeen
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Mohd Mujahid
- Department of Pharmacology, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia
| | - Juber Akhtar
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | | | - Usama Ahmad
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
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17
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Miziak B, Błaszczyk B, Czuczwar SJ. Some Candidate Drugs for Pharmacotherapy of Alzheimer's Disease. PHARMACEUTICALS (BASEL, SWITZERLAND) 2021; 14:ph14050458. [PMID: 34068096 PMCID: PMC8152728 DOI: 10.3390/ph14050458] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/07/2021] [Accepted: 05/10/2021] [Indexed: 12/12/2022]
Abstract
Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.
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Affiliation(s)
- Barbara Miziak
- Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Barbara Błaszczyk
- Faculty of Health Sciences, High School of Economics, Law and Medical Sciences, 25-734 Kielce, Poland;
| | - Stanisław J. Czuczwar
- Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland;
- Correspondence: ; Tel.: +48-81-448-65-00; Fax: +48-81-65-00-01
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18
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Xie Q, Li H, Lu D, Yuan J, Ma R, Li J, Ren M, Li Y, Chen H, Wang J, Gong D. Neuroprotective Effect for Cerebral Ischemia by Natural Products: A Review. Front Pharmacol 2021; 12:607412. [PMID: 33967750 PMCID: PMC8102015 DOI: 10.3389/fphar.2021.607412] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 03/08/2021] [Indexed: 12/12/2022] Open
Abstract
Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. Stroke is a disease with high prevalence and incidence, the pathogenesis is a complex cascade reaction. In recent years, it’s reported that a vast number of natural products have demonstrated beneficial effects on stroke worldwide. Natural products have been discovered to modulate activities with multiple targets and signaling pathways to exert neuroprotection via direct or indirect effects on enzymes, such as kinases, regulatory receptors, and proteins. This review provides a comprehensive summary of the established pharmacological effects and multiple target mechanisms of natural products for cerebral ischemic injury in vitro and in vivo preclinical models, and their potential neuro-therapeutic applications. In addition, the biological activity of natural products is closely related to their structure, and the structure-activity relationship of most natural products in neuroprotection is lacking, which should be further explored in future. Overall, we stress on natural products for their role in neuroprotection, and this wide band of pharmacological or biological activities has made them suitable candidates for the treatment of stroke.
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Affiliation(s)
- Qian Xie
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hongyan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Danni Lu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jianmei Yuan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Rong Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinxiu Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mihong Ren
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yong Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hai Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jian Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Daoyin Gong
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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19
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Zhou J, Yang Z, Shen R, Zhong W, Zheng H, Chen Z, Tang J, Zhu J. Resveratrol Improves Mitochondrial Biogenesis Function and Activates PGC-1α Pathway in a Preclinical Model of Early Brain Injury Following Subarachnoid Hemorrhage. Front Mol Biosci 2021; 8:620683. [PMID: 33968980 PMCID: PMC8100450 DOI: 10.3389/fmolb.2021.620683] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 03/17/2021] [Indexed: 12/11/2022] Open
Abstract
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) has been shown to play a pivotal role in the regulation of mitochondrial biogenesis in diseases. Resveratrol (RSV), a natural polyphenolic reagent, has powerful antioxidant properties and the ability to scavenge mitochondrial reactive oxygen species (ROS) in a variety of central nervous system diseases. However, the underlying molecular mechanisms of RSV on mitochondrial biogenesis in early brain injury (EBI) following subarachnoid hemorrhage (SAH) remain poorly understood. This study aimed to explore the potential neuroprotective effects of RSV on mitochondrial biogenesis and function by activation of the PGC-1α signaling pathway in a prechiasmatic cistern SAH model. PGC-1α expression and related mitochondrial biogenesis were detected. Amounts of nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) were determined to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis after SAH were observed in the temporal cortex. Resveratrol increased the expression of PGC-1α, NRF1, and TFAM, and promoted PGC-1α nuclear translocation. Moreover, RSV could scavenge excess ROS, increase the activity of superoxide dismutase (SOD), enhance the potential of mitochondrial membrane and ATP levels, reduce the number of mitochondrial DNA copy, and decrease the level of malondialdehyde (MDA). RSV significantly ameliorated the release of apoptosis-related cytokines, namely P53, cleaved caspase-3, cytochrome c, and BAX, leading to the amelioration of neuronal apoptosis, brain edema, and neurological impairment 24 h after SAH. These results indicate that resveratrol promotes mitochondrial biogenesis and function by activation of the PGC-1α signaling pathway in EBI following SAH.
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Affiliation(s)
- Jian Zhou
- Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Zaijia Yang
- School of Medical Management, Hainan Medical University, Haikou, China
| | - Ruiming Shen
- Department of Rheumatology, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Wangwang Zhong
- Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Huiduan Zheng
- Department of Neurology, Hainan Provincial People's Hospital, Haikou, China
| | - Zhenggang Chen
- Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Jianjian Tang
- Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Juan Zhu
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, China
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20
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Meng T, Xiao D, Muhammed A, Deng J, Chen L, He J. Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules 2021; 26:molecules26010229. [PMID: 33466247 PMCID: PMC7796143 DOI: 10.3390/molecules26010229] [Citation(s) in RCA: 333] [Impact Index Per Article: 83.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 12/31/2020] [Accepted: 12/31/2020] [Indexed: 02/07/2023] Open
Abstract
Resveratrol (3,4',5-trihy- droxystilbene), a natural phytoalexin polyphenol, exhibits anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. This phytoalexin is well-absorbed and rapidly and extensively metabolized in the body. Inflammation is an adaptive response, which could be triggered by various danger signals, such as invasion by microorganisms or tissue injury. In this review, the anti-inflammatory activity and the mechanism of resveratrol modulates the inflammatory response are examined. Multiple experimental studies that illustrate regulatory mechanisms and the immunomodulatory function of resveratrol both in vivo and in vitro. The data acquired from those studies are discussed.
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Affiliation(s)
- Tiantian Meng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
| | - Dingfu Xiao
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
- Correspondence: (D.X.); (J.H.)
| | - Arowolo Muhammed
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
| | - Juying Deng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
| | - Liang Chen
- Huaihua Institute of Agricultural Sciences, No.140 Yingfeng East Road, Hecheng District, Huaihua 418000, China;
| | - Jianhua He
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (T.M.); (A.M.); (J.D.)
- Correspondence: (D.X.); (J.H.)
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21
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Huang J, Huang N, Xu S, Luo Y, Li Y, Jin H, Yu C, Shi J, Jin F. Signaling mechanisms underlying inhibition of neuroinflammation by resveratrol in neurodegenerative diseases. J Nutr Biochem 2020; 88:108552. [PMID: 33220405 DOI: 10.1016/j.jnutbio.2020.108552] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 11/07/2020] [Accepted: 11/09/2020] [Indexed: 12/20/2022]
Abstract
Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), and Parkinson's disease (PD), are characterized by the progressive loss of the structure and function of neurons and most commonly occur in the elderly population. Microglia are resident macrophages of the central nervous system (CNS). The neuroinflammation caused by excessive microglial activation is closely related to the onset and progression of many NDs. Therefore, inhibiting excessive microglial activation is a potential drug target for controlling neuroinflammation. In recent years, natural products as modulators of microglial polarization have attracted considerable attention in the field of NDs therapy. Furthermore, resveratrol (RES) has been found to have a protective effect in NDs through the inhibition of microglial activation and the regulation of neuroinflammation. In this review, we mainly summarize the therapeutic potential of RES and its various molecular mechanisms in the treatment of NDs through the modulation of microglial activation.
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Affiliation(s)
- Juan Huang
- Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Guizhou, China; School of Public Health, Zunyi Medical University, Guizhou, China
| | - Nanqu Huang
- Drug Clinical Trial Institution, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou, China
| | - Shangfu Xu
- Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Guizhou, China
| | - Yong Luo
- Drug Clinical Trial Institution, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou, China
| | - Yan Li
- School of Public Health, Zunyi Medical University, Guizhou, China
| | - Hai Jin
- Institute of Digestive Diseases of Affiliated Hospital, Zunyi Medical University, Guizhou, China
| | - Changyin Yu
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Jingshan Shi
- Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Guizhou, China
| | - Feng Jin
- Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Guizhou, China.
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22
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Effects of resveratrol on mitochondrial biogenesis and physiological diseases. ADVANCES IN TRADITIONAL MEDICINE 2020. [DOI: 10.1007/s13596-020-00492-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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23
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Youn K, Jun M. Geraniin Protects PC12 Cells Against Aβ 25-35-Mediated Neuronal Damage: Involvement of NF-κB and MAPK Signaling Pathways. J Med Food 2020; 23:928-937. [PMID: 32744877 DOI: 10.1089/jmf.2019.4613] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
β-amyloid peptide (Aβ) has been considered a critical factor that is associated with the development of oxidative stress and neuroinflammation in the pathogenesis of Alzheimer's disease. This study was performed to evaluate the effect of geraniin on Aβ25-35-caused oxidative damage and neuroinflammatory response, and its underlying mechanism. Geraniin protected pheochromocytoma12 (PC12) cells from Aβ25-35-mediated cell death by reducing oxidative stress and restoring cell cycle dysregulation. Moreover, geraniin markedly attenuated Aβ-triggered DNA injury that was partially associated with decreases in caspase-3 activity. Moreover, the compound significantly downregulated the release of neuroinflammatory factors. Upregulation of nuclear factor-κB activity was suppressed by geraniin, which was due to suppression of JNK, ERK1/2, and the p38 mitogen-activated protein kinase (MAPK) pathway. This was the first study to support further understanding of geraniin as a promising agent against neurotoxicity in the reduction of oxidative stress and neuroinflammation.
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Affiliation(s)
- Kumju Youn
- Department of Food Science and Nutrition, College of Health Sciences, Dong-A University, Busan, Korea
| | - Mira Jun
- Department of Food Science and Nutrition, College of Health Sciences, Dong-A University, Busan, Korea.,Brain Busan 21 Plus Program, Center for Silver-Targeted Biomaterials, Graduate School, Dong-A University, Busan, Korea
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24
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Yu L, Su X, Li S, Zhao F, Mu D, Qu Y. Microglia and Their Promising Role in Ischemic Brain Injuries: An Update. Front Cell Neurosci 2020; 14:211. [PMID: 32754016 PMCID: PMC7365911 DOI: 10.3389/fncel.2020.00211] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 06/16/2020] [Indexed: 12/14/2022] Open
Abstract
Ischemic brain injuries are common diseases with high morbidity, disability, and mortality rates, which have significant impacts on human health and life. Microglia are resident cells of the central nervous system (CNS). The inflammatory responses mediated by microglia play an important role in the occurrence and development of ischemic brain injuries. This article summarizes the activation, polarization, depletion, and repopulation of microglia after ischemic brain injuries, proposing new treatment strategies for such injuries through the modulation of microglial function.
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Affiliation(s)
- Luting Yu
- Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Xiaojuan Su
- Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Shiping Li
- Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Fengyan Zhao
- Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Dezhi Mu
- Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Yi Qu
- Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
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25
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Yessenkyzy A, Saliev T, Zhanaliyeva M, Masoud AR, Umbayev B, Sergazy S, Krivykh E, Gulyayev A, Nurgozhin T. Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research. Nutrients 2020; 12:E1344. [PMID: 32397145 PMCID: PMC7285205 DOI: 10.3390/nu12051344] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 04/16/2020] [Accepted: 04/16/2020] [Indexed: 02/06/2023] Open
Abstract
It has been thought that caloric restriction favors longevity and healthy aging where autophagy plays a vital role. However, autophagy decreases during aging and that can lead to the development of aging-associated diseases such as cancer, diabetes, neurodegeneration, etc. It was shown that autophagy can be induced by mechanical or chemical stress. In this regard, various pharmacological compounds were proposed, including natural polyphenols. Apart from the ability to induce autophagy, polyphenols, such as resveratrol, are capable of modulating the expression of pro- and anti-apoptotic factors, neutralizing free radical species, affecting mitochondrial functions, chelating redox-active transition metal ions, and preventing protein aggregation. Moreover, polyphenols have advantages compared to chemical inducers of autophagy due to their intrinsic natural bio-compatibility and safety. In this context, polyphenols can be considered as a potential therapeutic tool for healthy aging either as a part of a diet or as separate compounds (supplements). This review discusses the epigenetic aspect and the underlying molecular mechanism of polyphenols as an anti-aging remedy. In addition, the recent advances of studies on NAD-dependent deacetylase sirtuin-1 (SIRT1) regulation of autophagy, the role of senescence-associated secretory phenotype (SASP) in cells senescence and their regulation by polyphenols have been highlighted as well. Apart from that, the review also revised the latest information on how polyphenols can help to improve mitochondrial function and modulate apoptosis (programmed cell death).
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Affiliation(s)
- Assylzhan Yessenkyzy
- Research Institute of Fundamental and Applied Medicine named after B. Atchabarov, S.D. Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan; (A.Y.); (T.N.)
| | - Timur Saliev
- Research Institute of Fundamental and Applied Medicine named after B. Atchabarov, S.D. Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan; (A.Y.); (T.N.)
| | - Marina Zhanaliyeva
- Department of Human Anatomy, NSC “Medical University of Astana”, Nur-Sultan 010000, Kazakhstan;
| | - Abdul-Razak Masoud
- Department of Biological Sciences, Louisiana Tech University, Ruston, LA 71270, USA;
| | - Bauyrzhan Umbayev
- National Laboratory Astana, Nazarbayev University, Nur-Sultan 010000, Kazakhstan; (B.U.); (S.S.); (A.G.)
| | - Shynggys Sergazy
- National Laboratory Astana, Nazarbayev University, Nur-Sultan 010000, Kazakhstan; (B.U.); (S.S.); (A.G.)
| | - Elena Krivykh
- Khanty-Mansiysk State Medical Academy, Tyumen Region, Khanty-Mansiysk Autonomous Okrug—Ugra, Khanty-Mansiysk 125438, Russia;
| | - Alexander Gulyayev
- National Laboratory Astana, Nazarbayev University, Nur-Sultan 010000, Kazakhstan; (B.U.); (S.S.); (A.G.)
| | - Talgat Nurgozhin
- Research Institute of Fundamental and Applied Medicine named after B. Atchabarov, S.D. Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan; (A.Y.); (T.N.)
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26
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Neuroprotective Mechanisms of Resveratrol in Alzheimer's Disease: Role of SIRT1. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:8152373. [PMID: 30510627 PMCID: PMC6232815 DOI: 10.1155/2018/8152373] [Citation(s) in RCA: 248] [Impact Index Per Article: 35.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 07/21/2018] [Accepted: 08/15/2018] [Indexed: 02/07/2023]
Abstract
Alzheimer's disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence of β-amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβ peptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβ peptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.
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27
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Anti-Inflammatory Effects of Resveratrol: Mechanistic Insights. Int J Mol Sci 2018; 19:ijms19061812. [PMID: 29925765 PMCID: PMC6032205 DOI: 10.3390/ijms19061812] [Citation(s) in RCA: 174] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 06/10/2018] [Accepted: 06/12/2018] [Indexed: 12/14/2022] Open
Abstract
Inflammation is the principal response invoked by the body to address injuries. Despite inflammation constituting a crucial component of tissue repair, it is well known that unchecked or chronic inflammation becomes deleterious, leading to progressive tissue damage. Studies over the past years focused on foods rich in polyphenols with anti-inflammatory and immunomodulatory properties, since inflammation was recognized to play a central role in several diseases. In this review, we discuss the beneficial effects of resveratrol, the most widely investigated polyphenol, on cancer and neurodegenerative, respiratory, metabolic, and cardiovascular diseases. We highlight how resveratrol, despite its unfavorable pharmacokinetics, can modulate the inflammatory pathways underlying those diseases, and we identify future opportunities for the evaluation of its clinical feasibility.
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28
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Khaleel EF, Abdel-Aleem GA, Mostafa DG. Resveratrol improves high-fat diet induced fatty liver and insulin resistance by concomitantly inhibiting proteolytic cleavage of sterol regulatory element-binding proteins, free fatty acid oxidation, and intestinal triglyceride absorption. Can J Physiol Pharmacol 2018; 96:145-157. [DOI: 10.1139/cjpp-2017-0001] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Resveratrol (RES) has the ability to ameliorate nonalcoholic fatty liver disease (NAFLD) and the mechanism remains unclear. Hence, using high-fat diet (HFD) obese rat model, we investigated the effect of a low dose of RES (20 mg/kg) on the hepatic sterol regulatory element-binding protein (SREBPs) – lipogenesis pathway, enzymes involved in β-oxidation and activity of pancreatic lipase. Four groups of rats (n = 8) of control (12% of calories as fat) and HFD (40% of calories as fat) were administered orally with either normal saline as a vehicle or RES as a concomitant treatment for 8 weeks on a daily basis. Then, various biochemical, histological, and molecular experiments were carried out. RES prevented the development and progression of NAFLD and significantly improved insulin sensitivity through (1) inhibiting the proteolytic cleavage of SREBPs-1 and SREBPs-2 without affecting their precursor mRNA or protein levels, (2) inhibiting free fatty acid β-oxidation and generation of reactive oxygen species through significant inhibition of CPT-1 and UCP-2, and (3) decreasing activity of pancreatic lipase in vivo and in vitro. In conclusion, our findings are the first in the literature to show new mechanisms of the hepatoprotective effect of RES against HFD induced NAFLD in rats.
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Affiliation(s)
- Eman F. Khaleel
- Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Medical Physiology, College of Medicine, King Khalid University, P.O. Box 3340, Abha 61421, Saudi Arabia
| | - Ghada A. Abdel-Aleem
- Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt
- Department of Medical Biochemistry, College of Medicine, King Khalid University, P.O. Box 3340, Abha 61421, Saudi Arabia
| | - Dalia G. Mostafa
- Department of Medical Physiology, College of Medicine, King Khalid University, P.O. Box 3340, Abha 61421, Saudi Arabia
- Department of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt
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29
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Bernier M, Wahl D, Ali A, Allard J, Faulkner S, Wnorowski A, Sanghvi M, Moaddel R, Alfaras I, Mattison JA, Tarantini S, Tucsek Z, Ungvari Z, Csiszar A, Pearson KJ, de Cabo R. Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet. Aging (Albany NY) 2017; 8:899-916. [PMID: 27070252 PMCID: PMC4931843 DOI: 10.18632/aging.100942] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 03/30/2016] [Indexed: 01/19/2023]
Abstract
Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-κB activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress.
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Affiliation(s)
- Michel Bernier
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Devin Wahl
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Ahmed Ali
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Joanne Allard
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.,Department of Physiology and Biophysics, Howard University, College of Medicine, Washington, DC 20059, USA
| | - Shakeela Faulkner
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Artur Wnorowski
- Department of Biopharmacy, Medical University of Lublin, 20-093 Lublin, Poland.,Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Mitesh Sanghvi
- Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Ruin Moaddel
- Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Irene Alfaras
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Julie A Mattison
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
| | - Stefano Tarantini
- University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
| | - Zsuzsanna Tucsek
- University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
| | - Zoltan Ungvari
- University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
| | - Anna Csiszar
- University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
| | - Kevin J Pearson
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.,Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA
| | - Rafael de Cabo
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
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30
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Wang X, Ma S, Yang B, Huang T, Meng N, Xu L, Xing Q, Zhang Y, Zhang K, Li Q, Zhang T, Wu J, Yang GL, Guan F, Wang J. Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer's disease. Behav Brain Res 2017; 339:297-304. [PMID: 29102593 DOI: 10.1016/j.bbr.2017.10.032] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 10/23/2017] [Accepted: 10/30/2017] [Indexed: 02/06/2023]
Abstract
Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer's disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD.
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Affiliation(s)
- Xinxin Wang
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
| | - Shanshan Ma
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Bo Yang
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
| | - Tuanjie Huang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Nan Meng
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ling Xu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Qu Xing
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Yanting Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Kun Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Qinghua Li
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Tao Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Junwei Wu
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | | | - Fangxia Guan
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
| | - Jian Wang
- Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD,USA
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Abd El-Aal SA, Abd El-Fattah MA, El-Abhar HS. CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues. Front Pharmacol 2017; 8:735. [PMID: 29081748 PMCID: PMC5645536 DOI: 10.3389/fphar.2017.00735] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 09/29/2017] [Indexed: 12/12/2022] Open
Abstract
Statins were reported to lower the Coenzyme Q10 (CoQ10) content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg), CoQ10 (10 mg/kg) and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase. They also opposed the upregulation of gp91phox, and p47phox subunits of NADPH oxidase. Meanwhile, both agents reduced content/expression of TNF-α, iNOS, NF-κBp65, ICAM-1, and MPO. Besides, all regimens abated cytochrome c, caspase-3 and Bax, but increased Bcl-2 in favor of cell survival. On the molecular level, they increased p-Akt and its downstream target p-FOXO3A, with the inhibition of the nuclear content of FOXO3A to downregulate the expression of Bim, a pro-apoptotic gene. Additionally, both treatments downregulate the JNK3/c-Jun signaling pathway. The effect of the combination regimen overrides that of either treatment alone. These effects were reflected on the alleviation of the hippocampal damage in CA1 region inflicted by I/R. Together, these findings accentuate the neuroprotective potentials of both treatments against global I/R by virtue of their rigorous multi-pronged actions, including suppression of hippocampal oxidative stress, inflammation, and apoptosis with the involvement of the Akt/FOXO3A/Bim and JNK3/c-Jun/Bax signaling pathways. The study also nominates CoQ10 as an adds-on therapy with statins.
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Affiliation(s)
- Sarah A Abd El-Aal
- Department of Pharmacology and Toxicology, October 6 University, Cairo, Egypt
| | - Mai A Abd El-Fattah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Hanan S El-Abhar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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Ziemka-Nalecz M, Jaworska J, Zalewska T. Insights Into the Neuroinflammatory Responses After Neonatal Hypoxia-Ischemia. J Neuropathol Exp Neurol 2017; 76:644-654. [DOI: 10.1093/jnen/nlx046] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Wang Y, Sherchan P, Huang L, Akyol O, McBride DW, Zhang JH. Naja sputatrix Venom Preconditioning Attenuates Neuroinflammation in a Rat Model of Surgical Brain Injury via PLA2/5-LOX/LTB4 Cascade Activation. Sci Rep 2017; 7:5466. [PMID: 28710425 PMCID: PMC5511148 DOI: 10.1038/s41598-017-05770-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 06/02/2017] [Indexed: 01/30/2023] Open
Abstract
Inflammatory preconditioning is a mechanism in which exposure to small doses of inflammatory stimuli prepares the body against future massive insult by activating endogenous protective responses. Phospholipase A2/5-lipoxygenase/leukotriene-B4 (PLA2/5-LOX/LTB4) axis is an important inflammatory signaling pathway. Naja sputatrix (Malayan spitting cobra) venom contains 15% secretory PLA2 of its dry weight. We investigated if Naja sputatrix venom preconditioning (VPC) reduces surgical brain injury (SBI)-induced neuroinflammation via activating PLA2/5-LOX/LTB4 cascade using a partial frontal lobe resection SBI rat model. Naja sputatrix venom sublethal dose was injected subcutaneously for 3 consecutive days prior to SBI. We observed that VPC reduced brain edema and improved neurological function 24 h and 72 h after SBI. The expression of pro-inflammatory mediators in peri-resection brain tissue was reduced with VPC. Administration of Manoalide, a PLA2 inhibitor or Zileuton, a 5-LOX inhibitor with VPC reversed the protective effects of VPC against neuroinflammation. The current VPC regime induced local skin inflammatory reaction limited to subcutaneous injection site and elicited no other toxic effects. Our findings suggest that VPC reduces neuroinflammation and improves outcomes after SBI by activating PLA2/5-LOX/LTB4 cascade. VPC may be beneficial to reduce post-operative neuroinflammatory complications after brain surgeries.
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Affiliation(s)
- Yuechun Wang
- Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, California, 92354, USA
- Department of Physiology, Jinan University School of Medicine, Guangzhou, Guangdong Province, China
| | - Prativa Sherchan
- Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, California, 92354, USA
| | - Lei Huang
- Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, California, 92354, USA
- Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, 92354, USA
| | - Onat Akyol
- Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, California, 92354, USA
| | - Devin W McBride
- Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, California, 92354, USA
| | - John H Zhang
- Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, California, 92354, USA.
- Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, 92354, USA.
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Isac S, Panaitescu AM, Spataru A, Iesanu M, Totan A, Udriste A, Cucu N, Peltecu G, Zagrean L, Zagrean AM. Trans-resveratrol enriched maternal diet protects the immature hippocampus from perinatal asphyxia in rats. Neurosci Lett 2017; 653:308-313. [PMID: 28595952 DOI: 10.1016/j.neulet.2017.06.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 05/10/2017] [Accepted: 06/04/2017] [Indexed: 01/20/2023]
Abstract
Trans-resveratrol (tRESV), a polyphenol with antioxidant properties, is common in many food sources, hence easily accessible for study as a maternal dietary supplement in perinatal asphyxia (PA). Hypoxic-ischemic encephalopathy secondary to PA affects especially vulnerable brain areas such as hippocampus and is a leading cause of neonatal morbidity. The purpose of this study is to identify new epigenetic mechanisms of brain inflammation and injury related to PA and to explore the benefit of tRESV enriched maternal diet. The hippocampal interleukin 1 beta (IL-1b), tumour necrosis factor alpha (TNFα) and S-100B protein, at 24-48h after 90min of asphyxia were assessed in postnatal day 6 rats whose mothers received either standard or tRESV enriched diet. The expression of non-coding microRNAs miR124, miR132, miR134, miR146 and miR15a as epigenetic markers of hippocampus response to PA was determined 24h post-asphyxia. Our results indicate that neural response to PA could be epigenetically controlled and that tRESV reduces asphyxia-related neuroinflammation and neural injury. Moreover, tRESV could increase, through epigenetic mechanisms, the tolerance to asphyxia, with possible impact on the neuronal maturation. Our data support the neuroprotective quality of tRESV when used as a supplement in the maternal diet on the offspring's outcome in PA.
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Affiliation(s)
- Sebastian Isac
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Anca Maria Panaitescu
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; Filantropia Clinical Hospital, 011171 Bucharest, Romania
| | - Ana Spataru
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Mara Iesanu
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Alexandra Totan
- Division of Biochemistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Amalia Udriste
- Association for Epigenetics and Metabolomics, Bucharest, Romania; Research Center for Studies of Food Quality and Agricultural Products, Bucharest, Romania
| | - Natalia Cucu
- Association for Epigenetics and Metabolomics, Bucharest, Romania
| | | | - Leon Zagrean
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Ana-Maria Zagrean
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
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Ramagiri S, Taliyan R. Remote limb ischemic post conditioning during early reperfusion alleviates cerebral ischemic reperfusion injury via GSK-3β/CREB/ BDNF pathway. Eur J Pharmacol 2017; 803:84-93. [DOI: 10.1016/j.ejphar.2017.03.028] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 03/06/2017] [Accepted: 03/15/2017] [Indexed: 01/07/2023]
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Abstract
Disturbance of cerebral redox homeostasis is the primary cause of human neurodegenerative disorders, such as Parkinson's disease or Alzheimer's disease. Well known experimental research demonstrates that oxidative stress is a main cause of cell death. A high concentration of reactive oxygen and nitrogen species leads to damage of a lot of proteins, lipids and also DNA. Synthetic compounds used for the treatment in the neurodegenerative diseases failed to meet the hopes they had raised and often exhibit a number of side effects. Therefore, in recent years interest in natural compounds derived from plants appears to be on the rise. This review describes a few natural compounds (1MeTIQ, resveratrol, curcumin, vitamin C and Gingko biloba) which revealed neuroprotective potential both in experimental studies and clinical trials. 1MeTIQ has a privileged position because, as opposed to the remaining compounds, it is an endogenous amine synthesized in human and animal brain. Based on evidence from research, it seems that a common protective mechanism for all the above-mentioned natural compounds relies on their ability to inhibit or even scavenge the excess of free radicals generated in oxidative and neurotoxin-induced processes in nerve cells of the brain. However, it was demonstrated that further different molecular processes connected with neurotoxicity (e.g. the inhibition of mitochondrial complex I, activation of caspase-3, apoptosis) follow later and are initiated by the reactive oxygen species. What is more, these natural compounds are able to inhibit further stages of apoptosis triggered by neurotoxins in the brain.
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Affiliation(s)
- Agnieszka Wąsik
- Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Kraków, Poland.
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Pineda-Ramírez N, Gutiérrez Aguilar GF, Espinoza-Rojo M, Aguilera P. Current evidence for AMPK activation involvement on resveratrol-induced neuroprotection in cerebral ischemia. Nutr Neurosci 2017; 21:229-247. [DOI: 10.1080/1028415x.2017.1284361] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Narayana Pineda-Ramírez
- Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía ‘Manuel Velasco Suárez’, Ciudad de México, 14269, México
| | - Germán Fernando Gutiérrez Aguilar
- Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía ‘Manuel Velasco Suárez’, Ciudad de México, 14269, México
| | - Mónica Espinoza-Rojo
- Laboratorio de Biología Molecular y Genómica, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, 39087, México
| | - Penélope Aguilera
- Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía ‘Manuel Velasco Suárez’, Ciudad de México, 14269, México
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Abdel-Aleem GA, Khaleel EF, Mostafa DG, Elberier LK. Neuroprotective effect of resveratrol against brain ischemia reperfusion injury in rats entails reduction of DJ-1 protein expression and activation of PI3K/Akt/GSK3b survival pathway. Arch Physiol Biochem 2016; 122:200-213. [PMID: 27109835 DOI: 10.1080/13813455.2016.1182190] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
In the current study, we aimed to investigate the mechanistic role of DJ-1/PI3K/Akt survival pathway in ischemia/reperfusion (I/R) induced cerebral damage and to investigate if the resveratrol (RES) mediates its ischemic neuroptotection through this pathway. RES administration to Sham rats boosted glutathione level and superoxide dismutase activity and downregulated inducible nitric oxide synthase expression without affecting redox levels of DJ-1 forms or components of PI3K/Akt pathway including PTEN, p-Akt or p/p-GSK3b. However, RES pre-administration to I/R rats reduced infarction area, oxidative stress, inflammation and apoptosis. Concomitantly, RES ameliorated the decreased levels of oxidized forms of DJ-1 and enhancing its reduction, increased the nuclear protein expression of Nfr-2 and led to activation of PI3K/Akt survival pathway. In conclusion, overoxidation of DJ-1 is a major factor that contributes to post-I/R cerebral damage and its reduction by RES could explain the neuroprotection offered by RES.
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Affiliation(s)
- Ghada A Abdel-Aleem
- a Department of Medical Biochemistry , Faculty of Medicine, Tanta University , Tanta , Egypt
- b Department of Medical Biochemistry , College of Medicine, King Khalid University , Abha , Saudi Arabia
| | - Eman F Khaleel
- c Department of Medical Physiology , Faculty of Medicine, Cairo University , Cairo , Egypt
- d Department of Medical Physiology , College of Medicine, King Khalid University , Abha , Saudi Arabia
| | - Dalia G Mostafa
- d Department of Medical Physiology , College of Medicine, King Khalid University , Abha , Saudi Arabia
- e Department of Medical Physiology , Faculty of Medicine, Assiut University , Assiut , Egypt
| | - Lydia K Elberier
- f Department of Histopathology , College of Medical Laboratory Technology, University of Science and Technology , Khartoum , Sudan , and
- g Department of Pathology , College of Medicine, King Khalid University , Abha , Saudi Arabia
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Zhang XS, Li W, Wu Q, Wu LY, Ye ZN, Liu JP, Zhuang Z, Zhou ML, Zhang X, Hang CH. Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway. Int J Mol Sci 2016; 17:ijms17081331. [PMID: 27529233 PMCID: PMC5000728 DOI: 10.3390/ijms17081331] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 08/02/2016] [Accepted: 08/08/2016] [Indexed: 12/13/2022] Open
Abstract
Toll-like receptor 4 (TLR4) has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH). Resveratrol (RSV), a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI) after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway.
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Affiliation(s)
- Xiang-Sheng Zhang
- Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Wei Li
- Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Qi Wu
- Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Ling-Yun Wu
- Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Zhen-Nan Ye
- Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Jing-Peng Liu
- Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Zong Zhuang
- Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Meng-Liang Zhou
- Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Xin Zhang
- Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
- Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
| | - Chun-Hua Hang
- Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
- Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
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Hyatt JPK, Nguyen L, Hall AE, Huber AM, Kocan JC, Mattison JA, de Cabo R, LaRocque JR, Talmadge RJ. Muscle-Specific Myosin Heavy Chain Shifts in Response to a Long-Term High Fat/High Sugar Diet and Resveratrol Treatment in Nonhuman Primates. Front Physiol 2016; 7:77. [PMID: 26973542 PMCID: PMC4773583 DOI: 10.3389/fphys.2016.00077] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Accepted: 02/15/2016] [Indexed: 01/14/2023] Open
Abstract
Shifts in myosin heavy chain (MHC) expression within skeletal muscle can be induced by a host of stimuli including, but not limited to, physical activity, alterations in neural activity, aging, and diet or obesity. Here, we hypothesized that both age and a long-term (2 year) high fat/high sugar diet (HFS) would induce a slow to fast MHC shift within the plantaris, soleus, and extensor digitorum longus (EDL) muscles from rhesus monkeys. Furthermore, we tested whether supplementation with resveratrol, a naturally occurring compound that has been attributed with augmenting aerobic potential through mitochondrial proliferation, would counteract any diet-induced MHC changes by promoting a fast to slow isoform switch. In general, we found that MHC isoforms were not altered by aging during mid-life. The HFS diet had the largest impact within the soleus muscle where the greatest slow to fast isoform shifts were observed in both mRNA and protein indicators. As expected, long-term resveratrol treatment counteracted, or blunted, these diet-induced shifts within the soleus muscle. The plantaris muscle also demonstrated a fast-to-slow phenotypic response to resveratrol treatment. In conclusion, diet or resveratrol treatment impacts skeletal muscle phenotype in a muscle-specific manner and resveratrol supplementation may be one approach for promoting the fatigue-resistant MHC (type I) isoform especially if its expression is blunted as a result of a long-term high fat/sugar diet.
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Affiliation(s)
| | - Lisa Nguyen
- Department of Biological Sciences, California State Polytechnic University Pomona, CA, USA
| | - Allison E Hall
- Department of Human Science, Georgetown University Washington, DC, USA
| | - Ashley M Huber
- Department of Human Science, Georgetown University Washington, DC, USA
| | - Jessica C Kocan
- Department of Human Science, Georgetown University Washington, DC, USA
| | - Julie A Mattison
- Translational Gerontology Branch, National Institute on Aging, National Institutes of Health Baltimore, MD, USA
| | - Rafael de Cabo
- Translational Gerontology Branch, National Institute on Aging, National Institutes of Health Baltimore, MD, USA
| | | | - Robert J Talmadge
- Department of Biological Sciences, California State Polytechnic University Pomona, CA, USA
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Revuelta M, Arteaga O, Alvarez A, Martinez-Ibargüen A, Hilario E. Characterization of Gene Expression in the Rat Brainstem After Neonatal Hypoxic–Ischemic Injury and Antioxidant Treatment. Mol Neurobiol 2016; 54:1129-1143. [DOI: 10.1007/s12035-016-9724-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 01/13/2016] [Indexed: 11/29/2022]
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Lopez MS, Dempsey RJ, Vemuganti R. Resveratrol neuroprotection in stroke and traumatic CNS injury. Neurochem Int 2015; 89:75-82. [PMID: 26277384 DOI: 10.1016/j.neuint.2015.08.009] [Citation(s) in RCA: 118] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 08/07/2015] [Accepted: 08/08/2015] [Indexed: 02/02/2023]
Abstract
Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection.
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Affiliation(s)
- Mary S Lopez
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA
| | - Robert J Dempsey
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA
| | - Raghu Vemuganti
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA.
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Potter-Baker KA, Stewart WG, Tomaszewski WH, Wong CT, Meador WD, Ziats NP, Capadona JR. Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes. J Neural Eng 2015; 12:046002. [PMID: 26015427 PMCID: PMC4510031 DOI: 10.1088/1741-2560/12/4/046002] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
OBJECTIVE Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. APPROACH Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg(-1). The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. MAIN RESULTS Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. SIGNIFICANCE Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.
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Affiliation(s)
- Kelsey A. Potter-Baker
- Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Bldg., Cleveland, OH 44106, USA
- Advanced Platform Technology Center, L. Stokes Cleveland VA Medical Center, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland, OH 44106-1702, USA
| | - Wade G. Stewart
- Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Bldg., Cleveland, OH 44106, USA
| | - William H. Tomaszewski
- Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Bldg., Cleveland, OH 44106, USA
| | - Chun T. Wong
- Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Bldg., Cleveland, OH 44106, USA
| | - William D. Meador
- Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Bldg., Cleveland, OH 44106, USA
| | - Nicholas P. Ziats
- Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Bldg., Cleveland, OH 44106, USA
- Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Bldg., Cleveland, OH 44106, USA
| | - Jeffrey R. Capadona
- Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Bldg., Cleveland, OH 44106, USA
- Advanced Platform Technology Center, L. Stokes Cleveland VA Medical Center, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland, OH 44106-1702, USA
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Organ-Protective Effects of Red Wine Extract, Resveratrol, in Oxidative Stress-Mediated Reperfusion Injury. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2015:568634. [PMID: 26161238 PMCID: PMC4487914 DOI: 10.1155/2015/568634] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 10/09/2014] [Indexed: 12/25/2022]
Abstract
Resveratrol, a polyphenol extracted from red wine, possesses potential antioxidative and anti-inflammatory effects, including the reduction of free radicals and proinflammatory mediators overproduction, the alteration of the expression of adhesion molecules, and the inhibition of neutrophil function. A growing body of evidence indicates that resveratrol plays an important role in reducing organ damage following ischemia- and hemorrhage-induced reperfusion injury. Such protective phenomenon is reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed.
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Resveratrol downregulates type-1 glutamate transporter expression and microglia activation in the hippocampus following cerebral ischemia reperfusion in rats. Brain Res 2015; 1608:203-14. [DOI: 10.1016/j.brainres.2015.02.038] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Revised: 02/17/2015] [Accepted: 02/18/2015] [Indexed: 01/04/2023]
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Sun K, Fan J, Han J. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage. Acta Pharm Sin B 2015; 5:8-24. [PMID: 26579420 PMCID: PMC4629119 DOI: 10.1016/j.apsb.2014.11.002] [Citation(s) in RCA: 176] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Revised: 10/22/2014] [Accepted: 10/28/2014] [Indexed: 01/22/2023] Open
Abstract
Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage.
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Key Words
- 8-OHdG, 8-hydroxydeoxyguanosine
- AIF, apoptosis inducing factor
- AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- AP-1, activator protein-1
- Antioxidant
- Asp, aspartate
- BBB, brain blood barrier
- BMEC, brain microvascular endothelial cell
- BNDF, brain-derived neurotrophic factor
- Brain blood barrier
- CAT, catalase
- CBF, cerebral blood flow
- COX-2, cyclooxygenase-2
- Cav-1, caveolin-1
- DHR, dihydrorhodamine 123
- DPPH, 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl
- ERK, extracellular signal-regulated kinase
- GABA, γ-aminobutyric acid
- GRK2, G protein-coupled receptor kinase 2
- GSH, glutathione
- GSH-Px, glutathione peroxidase
- GSSH, glutathione disulfide
- Glu, glutamate
- Gly, glysine
- HE, hematoxylin and eosin
- HIF, hypoxia-inducible factor
- HPLC, high performance liquid chromatography
- Hyperpermeability
- I-κBα, Inhibitory κBα
- I/R, ischemia-reperfusion
- ICAM-1, intercellular adhesion molecule-1
- IL-10, interleukin-10
- IL-1β, interleukin-1β
- IL-8, interleukin-8
- Ischemia/reperfusion
- JAM-1, junctional adhesion molecule-1
- JNK, Jun N-terminal kinase
- LDH, lactate dehydrogenase
- Leukocyte adhesion
- MAPK, mitogen activated protein kinase
- MCAO, middle cerebral artery occlusion
- MDA, malondialdehyde
- MMPs, matrix metalloproteinases
- MPO, myeloperoxidase
- MRI, magnetic resonance imaging
- NADPH, nicotinamide adenine dinucleotide phosphate
- NF-κB, nuclear factor κ-B
- NGF, nerve growth factor
- NMDA, N-methyl-d-aspartic acid
- NO, nitric oxide
- NSC, neural stem cells
- Neuron
- OGD, oxygen-glucose deprivation
- PARP, poly-ADP-ribose polymerase
- PMN, polymorphonuclear
- RANTES, regulated upon activation normal T-cell expressed and secreted
- ROS, reactive oxygen species
- SFDA, state food and drug administration
- SOD, superoxide dismutase
- TBARS, thiobarbituric acid reactive substance
- TCM, traditional Chinese medicine
- TGF-β1, transforming growth factor β1
- TIMP-1, tissue inhibitor of metalloproteinase-1
- TNF-α, tissue necrosis factor-α
- TTC, 2,3,5-triphenyltetrazolium chloride
- TUNEL, terminal-deoxynucleoitidyl transferase mediated nick end labeling
- Tuj-1, class III β-tublin
- VCAM-1, vascular adhesion molecule-1
- VEGF, vascular endothelial growth factor
- ZO-1, zonula occludens-1
- bFGF, basic fibroblast growth factor
- cAMP, cyclic adenosine monophosphate
- hs-CRP, high-sensitivity C-reactive protein
- iNOS, inducible nitric oxide synthase
- rtPA, recombinant tissue plasminogen activator
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Agrawal T, Gupta GK, Rai V, Carroll JD, Hamblin MR. Pre-conditioning with low-level laser (light) therapy: light before the storm. Dose Response 2014; 12:619-49. [PMID: 25552961 DOI: 10.2203/dose-response.14-032.agrawal] [Citation(s) in RCA: 273] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance.
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Affiliation(s)
- Tanupriya Agrawal
- The Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114; ; Department of Dermatology, Harvard Medical School, Boston, MA 02115
| | - Gaurav K Gupta
- The Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114; ; Department of Dermatology, Harvard Medical School, Boston, MA 02115; ; Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, 02111
| | - Vikrant Rai
- Wilf Family Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
| | - James D Carroll
- THOR Photomedicine Ltd, 18A East Street, Chesham, HP5 1HQ, UK
| | - Michael R Hamblin
- The Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114; ; Department of Dermatology, Harvard Medical School, Boston, MA 02115; ; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139
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Rege SD, Geetha T, Griffin GD, Broderick TL, Babu JR. Neuroprotective effects of resveratrol in Alzheimer disease pathology. Front Aging Neurosci 2014; 6:218. [PMID: 25309423 PMCID: PMC4161050 DOI: 10.3389/fnagi.2014.00218] [Citation(s) in RCA: 157] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Accepted: 08/04/2014] [Indexed: 01/11/2023] Open
Abstract
Alzheimer's disease is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4'-trihydroxy-trans-stilbene) when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogs aimed at increasing the bioavailability in plasma is also discussed.
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Affiliation(s)
- Shraddha D Rege
- Department of Nutrition, Dietetics, and Hospitality Management, Auburn University Auburn, AL, USA
| | - Thangiah Geetha
- Department of Chemistry, Auburn University at Montgomery Montgomery, AL, USA
| | - Gerald D Griffin
- Department of Biology, Tuskegee Institute, Tuskegee University AL, USA
| | - Tom L Broderick
- Laboratory of Diabetes and Exercise Metabolism, Department of Physiology, Midwestern University Glendale, AZ, USA
| | - Jeganathan Ramesh Babu
- Department of Nutrition, Dietetics, and Hospitality Management, Auburn University Auburn, AL, USA
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Zholobenko A, Modriansky M. Silymarin and its constituents in cardiac preconditioning. Fitoterapia 2014; 97:122-32. [DOI: 10.1016/j.fitote.2014.05.016] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 05/21/2014] [Accepted: 05/22/2014] [Indexed: 01/28/2023]
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Ghosh N, Ghosh R, Bhat ZA, Mandal V, Bachar SC, Nima ND, Sunday OO, Mandal SC. Advances in Herbal Medicine for Treatment of Ischemic Brain Injury. Nat Prod Commun 2014. [DOI: 10.1177/1934578x1400900739] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Ischemic brain injury is one of the leading causes of death worldwide and has attracted a lot of attention in the field of drug discovery. Cerebral ischemia is a complex pathological process involving a series of mechanisms, including generation of free radicals, oxidative stress, disruption of the membrane function, release of neurotransmitters and apoptosis. Thrombolytic therapy is the most effective therapeutic strategy, but the benefits are far from being absolute. Increased attention in the field of drug discovery has been focused on using natural compounds from traditional medicinal herbs for neuroprotection, which appears to be a promising therapeutic option for cerebral ischemia with minimal systemic adverse effects that could limit their long term use. The scenario calls for extensive investigations which can result in the development of lead molecules for neuroprotection in the future. In this context, the present review focuses on possible mechanisms underlying the beneficial effects of herbal drugs in patients with cerebral ischemic injury. Natural compounds have been demonstrated to have neurofunctional regulatory actions with antioxidative, anti-inflammatory, calcium antagonizing and anti-apoptotic activities. Among the several leads obtained from plant sources as potential neuroprotective agents, resveratrol, EGb761, curcumin and epigallocatechin-3-gallate have shown significant therapeutic benefits in cerebral ischemic conditions. However, ligustilide, tanshinone, scutellarin and shikonin are the few lead molecules which are under investigation for treatment of cerebral ischemia.
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Affiliation(s)
- Nilanjan Ghosh
- Dr B.C. Roy College of Pharmacy and Allied Health Sciences, Durgapur, India 713206
| | - Rituparna Ghosh
- Dr B.C. Roy College of Pharmacy and Allied Health Sciences, Durgapur, India 713206
| | - Zulfiqar A Bhat
- Department of Pharmaceutical Sciences, University of Kashmir, Srinagar, India 190006
| | - Vivekananda Mandal
- Institute of Pharmacy, Guru Ghasidas University, Bilaspur, India, 495009
| | - Sitesh C. Bachar
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Bangladesh
| | - Namsa D. Nima
- Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, India 784028
| | - Otimenyin O. Sunday
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Jos, Jos, Plateau State, Nigeria
| | - Subhash C. Mandal
- Pharmacognosy and Phytotherapy Research Laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India 700032
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