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Guo Y, Wang Y, Xu B, Li Y. The prospective therapeutic benefits of sesamol: neuroprotection in neurological diseases. Nutr Neurosci 2025:1-14. [PMID: 39881218 DOI: 10.1080/1028415x.2025.2457051] [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: 01/31/2025]
Abstract
Oxidative stress is recognized as a critical contributor to the advancement of neurological diseases, thereby rendering the alleviation of oxidative stress a pivotal strategy in the therapeutic management of such conditions. Sesamol, the principal constituent of sesame oil, has been the subject of extensive research due to its significant antioxidant properties, especially its ability to effectively counteract oxidative stress within the central nervous system and confer neuroprotection. While sesamol demonstrates potential in the treatment and prevention of neurological diseases, its modulation of oxidative stress is complex and not yet fully understood. This review delves into the neuroprotective effects arising from sesamol's antioxidant properties, analyzing how its antioxidative capabilities impact neurological diseases. It provides a theoretical foundation and unveils potential novel therapeutic applications of sesamol in the treatment of neurological disorders through the modulation of oxidative stress.
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Affiliation(s)
- Yuchao Guo
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Yaqing Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China
| | - Boyang Xu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China
| | - Yue Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China
- Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macau, People's Republic of China
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2
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Tu W, Xu F, Li J, Tian X, Cao L, Wang L, Qu Y. Studying targeted oxidation in diabetic cognitive dysfunction based on scientometrics analysis: research progress of natural product approaches. Front Endocrinol (Lausanne) 2024; 15:1445750. [PMID: 39758348 PMCID: PMC11695123 DOI: 10.3389/fendo.2024.1445750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 11/12/2024] [Indexed: 01/07/2025] Open
Abstract
PURPOSE The aim is to provide new insights for researchers studying the pathogenesis of diabetic cognitive dysfunction and promoting the wider use of natural products in their treatment. METHOD First, the Web of Science Core Collection was selected as the data source for a computerized literature search on oxidative stress and diabetic cognitive dysfunction (DCD). Next, Biblimetrix and VOSviewer performed statistical analysis focusing on publication countries, institutions, authors, research hotspots, and emerging directions in the field. Then, through the analysis of keywords and key articles, the forefront of the field is identified. Finally, we discussed the pathogenesis of DCD, the influence of oxidative stress on DCD and the antioxidant effect of natural products on DCD. RESULT 293 valid papers were obtained. Bibliometrics showed that oxidative stress, diabetes, Alzheimer's disease (AD), cognitive decline, insulin resistance and quercetin were the key words of the symbiotic network. CONCLUSION The antioxidant effects of natural products in improving DCD have been extensively studied in preclinical studies, providing potential for their treatment in DCD, but their evaluation in clinical trials is currently uncommon.
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Affiliation(s)
| | | | | | | | | | - Lei Wang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University,
Hangzhou, China
| | - Yiqian Qu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University,
Hangzhou, China
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3
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Jadon N, Tomar P, Shrivastava S, Hosseinzadeh B, Kaya SI, Ozkan SA. Monitoring of Specific Phytoestrogens by Dedicated Electrochemical Sensors: A Review. Food Chem 2024; 460:140404. [PMID: 39068721 DOI: 10.1016/j.foodchem.2024.140404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 07/05/2024] [Accepted: 07/07/2024] [Indexed: 07/30/2024]
Abstract
Phytoestrogens are non-steroidal estrogens produced from plants that can bind with the human body's estrogenic receptor site and be used as a substitute for maintaining hormonal balance. They are mainly classified as flavonoids, phenolic acids, lignans, stilbenes, and coumestans; some are resocyclic acids of lactones, which are mycotoxins and not natural phytoestrogen. Phytoestrogens have many beneficial medicinal properties, making them an important part of the daily diet. Electrochemical sensors are widely used analytical tools for analysing various pharmaceuticals, chemicals, pollutants and food items. Electrochemical sensors provide an extensive platform for highly sensitive and rapid analysis. Several reviews have been published on the importance of the biological and medicinal properties of phytoestrogens. However, this review provides an overview of recent work performed through electrochemical measurements with electrochemical sensors and biosensors for all the classes of phytoestrogens done so far since 2019.
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Affiliation(s)
- Nimisha Jadon
- Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, 06560 Ankara, Türkiye; School of Studies in Environmental Chemistry, Jiwaji University, Gwalior, M.P., 474011, India.
| | - Puja Tomar
- School of Studies in Environmental Chemistry, Jiwaji University, Gwalior, M.P., 474011, India
| | - Swati Shrivastava
- School of Studies in Environmental Chemistry, Jiwaji University, Gwalior, M.P., 474011, India
| | - Batoul Hosseinzadeh
- Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, 06560 Ankara, Türkiye
| | - S Irem Kaya
- University of Health Sciences, Gulhane Faculty of Pharmacy, Department of Analytical Chemistry, Ankara, Türkiye
| | - Sibel A Ozkan
- Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, 06560 Ankara, Türkiye.
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4
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Pradhan SP, Behera A, Sahu PK. Effect of selenium nanoparticles conjugated Vildagliptin on cognitive dysfunction associated with Diabetes mellitus. J Drug Deliv Sci Technol 2024; 98:105907. [DOI: 10.1016/j.jddst.2024.105907] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Javed H, Meeran MFN, Jha NK, Ashraf GM, Ojha S. Sesamol: A Phenolic Compound of Health Benefits and Therapeutic Promise in Neurodegenerative Diseases. Curr Top Med Chem 2024; 24:797-809. [PMID: 38141184 DOI: 10.2174/0115680266273944231213070916] [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: 08/12/2023] [Revised: 10/22/2023] [Accepted: 10/25/2023] [Indexed: 12/25/2023]
Abstract
Sesamol, one of the key bioactive ingredients of sesame seeds (Sesamum indicum L.), is responsible for many of its possible nutritional benefits. Both the Chinese and Indian medical systems have recognized the therapeutic potential of sesame seeds. It has been shown to have significant therapeutic potential against oxidative stress, inflammatory diseases, metabolic syndrome, neurodegeneration, and mental disorders. Sesamol is a benign molecule that inhibits the expression of inflammatory indicators like numerous enzymes responsible for inducing inflammation, protein kinases, cytokines, and redox status. This review summarises the potential beneficial effects of sesamol against neurological diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Recently, sesamol has been shown to reduce amyloid peptide accumulation and attenuate cognitive deficits in AD models. Sesamol has also been demonstrated to reduce the severity of PD and HD in animal models by decreasing oxidative stress and inflammatory pathways. The mechanism of sesamol's pharmacological activities against neurodegenerative diseases will also be discussed in this review.
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Affiliation(s)
- Hayate Javed
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates
| | - Mohamed Fizur Nagoor Meeran
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, 201310, UP, India
- Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, 248007, India
- Department of Biotechnology Engineering and Food Technology, Chandigarh University, Mohali, 140413, India
| | - Ghulam Md Ashraf
- Department of Medical Laboratory Sciences, College of Health Sciences, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Shreesh Ojha
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates
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6
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Majdalawieh AF, Ahari SH, Yousef SM, Nasrallah GK. Sesamol: A lignan in sesame seeds with potent anti-inflammatory and immunomodulatory properties. Eur J Pharmacol 2023; 960:176163. [PMID: 37925135 DOI: 10.1016/j.ejphar.2023.176163] [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: 07/05/2023] [Revised: 10/24/2023] [Accepted: 10/25/2023] [Indexed: 11/06/2023]
Abstract
Inflammation is associated with the development and progression of a plethora of diseases including joint, metabolic, neurological, hepatic, and renal disorders. Sesamol, derived from the seeds of Sesamum indicum L., has received considerable attention due to its well-documented multipotent phytotherapeutic effects, including its anti-inflammatory and immunomodulatory properties. However, to date, no comprehensive review has been established to highlight or summarize the anti-inflammatory and immunomodulatory properties of sesamol. Herein, we aim to address this gap in the literature by presenting a thorough review encapsulating evidence surrounding the range of inflammatory mediators and cytokines shown to be targeted by sesamol in modulating its anti-inflammatory actions against a range of inflammatory disorders. Additionally, evidence highlighting the role that sesamol has in modulating components of adaptive immunity including cellular immune responses and Th1/Th2 balance is underscored. Moreover, the molecular mechanisms and the signaling pathways underlying such effects are also highlighted. Findings indicate that this seemingly potent lignan mediates its anti-inflammatory actions, at least in part, via suppression of various pro-inflammatory cytokines like IL-1β and TNFα, and downregulation of a multitude of signaling pathways including NF-κB and MAPK. In conclusion, we anticipate that sesamol may be employed in future therapeutic regimens to aid in more effective drug development to alleviate immune-related and inflammatory conditions.
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Affiliation(s)
- Amin F Majdalawieh
- Department of Biology, Chemistry, and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, P.O. Box 26666, United Arab Emirates.
| | - Sogand H Ahari
- Department of Biology, Chemistry, and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, P.O. Box 26666, United Arab Emirates
| | - Sarah M Yousef
- Department of Psychology, College of Arts and Sciences, American University of Sharjah, Sharjah, P.O. Box 26666, United Arab Emirates
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, Doha, Qatar; Biomedical Research Center, Qatar University, Doha, Qatar
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7
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Kim MY, Kim S, Lee J, Kim JI, Oh E, Kim SW, Lee E, Cho KS, Kim CS, Lee MH. Lignan-Rich Sesame ( Sesamum indicum L.) Cultivar Exhibits In Vitro Anti-Cholinesterase Activity, Anti-Neurotoxicity in Amyloid-β Induced SH-SY5Y Cells, and Produces an In Vivo Nootropic Effect in Scopolamine-Induced Memory Impaired Mice. Antioxidants (Basel) 2023; 12:antiox12051110. [PMID: 37237976 DOI: 10.3390/antiox12051110] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 04/28/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
Alzheimer's disease, a major cause of dementia, is characterized by impaired cholinergic function, increased oxidative stress, and amyloid cascade induction. Sesame lignans have attracted considerable attention owing to their beneficial effects on brain health. This study investigated the neuroprotective potential of lignan-rich sesame cultivars. Among the 10 sesame varieties studied, Milyang 74 (M74) extracts exhibited the highest total lignan content (17.71 mg/g) and in vitro acetylcholinesterase (AChE) inhibitory activity (66.17%, 0.4 mg/mL). M74 extracts were the most effective in improving cell viability and inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) generation in amyloid-β25-35 fragment-treated SH-SY5Y cells. Thus, M74 was used to evaluate the nootropic effects of sesame extracts and oil on scopolamine (2 mg/kg)-induced memory impairment in mice compared to the control cultivar (Goenback). Pretreatment with the M74 extract (250 and 500 mg/kg) and oil (1 and 2 mL/kg) effectively improved memory disorder in mice (demonstrated by the passive avoidance test), inhibited AChE, and enhanced acetylcholine (Ach) levels. Moreover, immunohistochemistry and Western blot results showed that the M74 extract and oil reversed the scopolamine-induced increase in APP, BACE-1, and presenilin expression levels in the amyloid cascade and decreased BDNF and NGF expression levels in neuronal regeneration.
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Affiliation(s)
- Min-Young Kim
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Sungup Kim
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Jeongeun Lee
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Jung-In Kim
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Eunyoung Oh
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Sang-Woo Kim
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Eunsoo Lee
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Kwang-Soo Cho
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Choon-Song Kim
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
| | - Myoung-Hee Lee
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Milyang 50424, Republic of Korea
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8
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Borovcanin MM, Vesic K, Petrovic I, Jovanovic IP, Mijailović NR. Diabetes mellitus type 2 as an underlying, comorbid or consequent state of mental disorders. World J Diabetes 2023; 14:481-493. [PMID: 37273248 PMCID: PMC10236997 DOI: 10.4239/wjd.v14.i5.481] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/21/2023] [Accepted: 04/12/2023] [Indexed: 05/15/2023] Open
Abstract
Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice. Various factors contribute to the development of mental and somatic disorders. Type 2 diabetes mellitus (T2DM) is a significant health burden worldwide, and the prevalence of diabetes in adults is increasing. The comorbidity of diabetes and mental disorders is very common. By sharing a bidirectional link, both T2DM and mental disorders influence each other in various manners, but the exact mechanisms underlying this link are not yet elucidated. The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction, oxidative stress, endothelial dysfunction, and metabolic disturbances. Moreover, diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetes-associated cognitive decline to pre-dementia and dementia. A complex re-lationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production. The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders, emphasizing their complexity and interweaving. We also focused on the cognitive performances and changes in neurodegenerative disorders. The importance of implementing integrated approaches in treating both of these states is highlighted, along with the need for individual therapeutic strategies.
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Affiliation(s)
- Milica M Borovcanin
- Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Katarina Vesic
- Department of Neurology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Ivica Petrovic
- Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Ivan P Jovanovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Nataša R Mijailović
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
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9
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Dutta BJ, Singh S, Seksaria S, Das Gupta G, Singh A. Inside the diabetic brain: Insulin resistance and molecular mechanism associated with cognitive impairment and its possible therapeutic strategies. Pharmacol Res 2022; 182:106358. [PMID: 35863719 DOI: 10.1016/j.phrs.2022.106358] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 07/02/2022] [Accepted: 07/15/2022] [Indexed: 01/21/2023]
Abstract
Type 2 diabetes mellitus (T2DM) the most prevalent metabolic disease that has evolved into a major public health issue. Concerning about its secondary complications, a growing body of evidence links T2DM to cognitive impairment and neurodegenerative disorders. The underlying pathology behind this secondary complication disease is yet to be fully known. Nonetheless, they are likely to be associated with poor insulin signaling as a result of insulin resistance. We have combed through a rising body of literature on insulin signaling in the normal and diabetic brains along with various factors like insulin resistance, hyperglycemia, obesity, oxidative stress, neuroinflammation and Aβ plaques which can act independently or synergistically to link T2DM with cognitive impairments. Finally, we explored several pharmacological and non-pharmacological methods in the hopes of accelerating the rational development of medications for cognitive impairment in T2DM by better understanding these shared pathways.
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Affiliation(s)
- Bhaskar Jyoti Dutta
- Department of Pharmacology, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga 142001, Punjab, India
| | - Shamsher Singh
- Department of Pharmacology, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga 142001, Punjab, India
| | - Sanket Seksaria
- Department of Pharmacology, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga 142001, Punjab, India
| | - Ghanshyam Das Gupta
- Department of Pharmacology, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga 142001, Punjab, India
| | - Amrita Singh
- Department of Pharmacology, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga 142001, Punjab, India.
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Joshi P, Bisht A, Joshi S, Semwal D, Nema NK, Dwivedi J, Sharma S. Ameliorating potential of curcumin and its analogue in central nervous system disorders and related conditions: A review of molecular pathways. Phytother Res 2022; 36:3143-3180. [PMID: 35790042 DOI: 10.1002/ptr.7522] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Revised: 04/26/2022] [Accepted: 05/25/2022] [Indexed: 12/12/2022]
Abstract
Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti-inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis-mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF-kB, Nrf2-ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions.
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Affiliation(s)
- Priyanka Joshi
- Department of Pharmacy, Banasthali Vidyapith, Rajasthan, India.,R & D, Patanjali Ayurved Ltd, Patanjali Food and Herbal Park, Haridwar, Uttarakhand, India
| | - Akansha Bisht
- Department of Pharmacy, Banasthali Vidyapith, Rajasthan, India
| | - Sushil Joshi
- R & D, Patanjali Ayurved Ltd, Patanjali Food and Herbal Park, Haridwar, Uttarakhand, India
| | - Deepak Semwal
- Faculty of Biomedical Sciences, Uttarakhand Ayurved University, Dehradun, Uttarakhand, India
| | - Neelesh Kumar Nema
- Paramount Kumkum Private Limited, Prestige Meridian-1, Bangalore, Karnataka, India
| | - Jaya Dwivedi
- Department of Chemistry, Banasthali Vidyapith, Rajasthan, India
| | - Swapnil Sharma
- Department of Pharmacy, Banasthali Vidyapith, Rajasthan, India
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Jing FY, Zhou YZ, Wang HY, Yin XL, Zhang YQ. Enhancing antioxidant and anti-hyperglycaemic functions of gingko biloba L. seeds using thermal detoxification. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104819] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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12
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Ogunlabi OO, Adegbesan BO, Ezima EN, Adebisi AA. Cellgevity® attenuates liver distruption, oxidative stress and inflammation in STZ-diabetic male rats. SCIENTIFIC AFRICAN 2021. [DOI: 10.1016/j.sciaf.2021.e01055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
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13
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Abou-Zeid SM, Elkhadrawey BA, Anis A, AbuBakr HO, El-Bialy BE, Elsabbagh HS, El-Borai NB. Neuroprotective effect of sesamol against aluminum nanoparticle-induced toxicity in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:53767-53780. [PMID: 34037932 DOI: 10.1007/s11356-021-14587-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/21/2021] [Indexed: 06/12/2023]
Abstract
Alumina nanoparticles (ALNPs) are widely used causing neurobehavioral impairment in intoxicated animals and humans. Sesamol (SML) emerged as a natural phytochemical with potent antioxidant and anti-inflammatory properties. However, no study has directly tested the potential of SML to protect against AlNP-induced detrimental effects on the brain. AlNPs (100 mg/kg) were orally administered to rats by gavage with or without oral sesamol (100 mg/kg) for 28 days. In AlNP-intoxicated group, the brain AChE activity was elevated. The concentrations of MDA and 8-OHdG were increased suggesting lipid peroxidation and oxidative DNA damage. GSH depletion with inhibited activities of CAT and SOD were demonstrated. Serum levels of IL-1β and IL-6 were elevated. The expressions of GST, TNF-α, and caspase-3 genes in the brain were upregulated. Histopathologically, AlNPs induced hemorrhages, edema, neuronal necrosis, and/or apoptosis in medulla oblongata. The cerebellum showed loss of Purkinje cells, and the cerebrum showed perivascular edema, neuronal degeneration, necrosis, and neuronal apoptosis. However, concomitant administration of SML with AlNPs significantly ameliorated the toxic effects on the brain, reflecting antioxidant, anti-inflammatory, and anti-apoptotic effects of SML. Considering these results, sesamol could be a promising phytochemical with neuroprotective activity against AlNP-induced neurotoxicity.
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Affiliation(s)
- Shimaa M Abou-Zeid
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City, Sadat, 32897, Egypt.
| | - Basma A Elkhadrawey
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City, Sadat, 32897, Egypt
| | - Anis Anis
- Department of Pathology, Faculty of Veterinary Medicine, University of Sadat City, Sadat, 32897, Egypt
| | - Huda O AbuBakr
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Badr E El-Bialy
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City, Sadat, 32897, Egypt
| | - Hesham S Elsabbagh
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City, Sadat, 32897, Egypt
| | - Nermeen B El-Borai
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City, Sadat, 32897, Egypt
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Xie YD, Xu YH, Liu JP, Wang B, Shi YH, Wang W, Wang XP, Sun M, Xu XY, Bian XL. 1,3-Benzodioxole-based fibrate derivatives as potential hypolipidemic and hepatoprotective agents. Bioorg Med Chem Lett 2021; 43:127898. [PMID: 33684440 DOI: 10.1016/j.bmcl.2021.127898] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/12/2021] [Accepted: 02/16/2021] [Indexed: 01/21/2023]
Abstract
A series of target compounds 1,3-benzodioxole-based fibrate derivatives were designed and synthesized. All the target compounds were preliminarily evaluated by hyperlipidemia mice induced by Triton WR-1339, in which compound 12 displayed a greater anti-hyperlipidemia activity than other compounds as well as positive drug fenofibrate (FF). 12 showed a significant reduction of plasma lipids, such as triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterin (LDL-C), in high fat diet (HFD) induced hyperlipidemic mice. In addition, hepatic transaminases (AST and ALT) were ameliorated after administration of 12, in particular the AST, and the histopathological examination showed that 12 improved the hepatic lipid accumulation. The expression of PPAR-α involved in lipids metabolism was up-regulated in the liver tissues of 12-treated group. Other significant activity such as antioxidant, and anti-inflammation was confirmed and reinforced the effects of 12 as a potential hypolipidemia and hepatoprotective agent.
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Affiliation(s)
- Yun-Dong Xie
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China
| | - Yan-Hong Xu
- The People's Hospital of Yongcheng, 888 Ouya Road, Yongcheng City, Shangqiu City, Henan Province 476600, China
| | - Ji-Ping Liu
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, China; Subject Innovation Team of Shaanxi University of Chinese Medicine, China
| | - Bin Wang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, China; Subject Innovation Team of Shaanxi University of Chinese Medicine, China
| | - Yong-Heng Shi
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, China; Subject Innovation Team of Shaanxi University of Chinese Medicine, China
| | - Wei Wang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China
| | - Xiao-Ping Wang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China
| | - Meng Sun
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China
| | - Xin-Ya Xu
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China
| | - Xiao-Li Bian
- Department of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
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15
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Rahmati M, Keshvari M, Mirnasouri R, Chehelcheraghi F. Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats. Biomed Pharmacother 2021; 139:111577. [PMID: 33839493 DOI: 10.1016/j.biopha.2021.111577] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/24/2021] [Accepted: 03/31/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Diabetes mellitus is related to cognitive impairments and molecular abnormalities of the hippocampus. A growing body of evidence suggests that Urtica dioica (Ud) and exercise training (ET) have potential therapeutic effects on diabetes and its related complications. Therefore, we hypothesized that the combined effect of exercise training (ET) and Ud might play an important role in insulin signaling pathway, oxidative stress, neuroinflammation, and cognitive impairment in diabetic rats. METHODS Forty animals were divided into five groups (N = 8): healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-exercise training (D-ET), diabetes-Urtica dioica (D-Ud), diabetes-exercise training-Urtica dioica (D-ET-Ud). Streptozotocin (STZ) (Single dosage; 45 mg/kg, i.p.) was used to induce diabetes. Then, ET (moderate intensity/5day/week) and Ud extract (50 mg/kg, oral/daily) were administered for six weeks. We also investigated the effects of ET and Ud on cognitive performance (assessed through Morris Water Maze tests), antioxidant capacity, and lipid peroxidation markers in hippocampus. Furthermore, we measured levels of insulin sensitivity and signaling factors (insulin-Ins, insulin receptor-IR and insulin-like growth factor-1 receptor-IGF-1R), and neuroinflammatory markers (IL-1 β, TNF-α). This was followed by TUNEL assessment of the apoptosis rate in all regions of the hippocampus. RESULTS D-sed rats compared to H-sed animals showed significant impairments (P < 0.001) in hippocampal insulin sensitivity and signaling, oxidative stress, neuroinflammation, and apoptosis, which resulted in cognitive dysfunction. Ud extract and ET treatment effectively improved these impairments in D-ET (P < 0.001), D-Ud (P < 0.05), and D-ET-Ud (P < 0.001) groups compared to D-sed rats. Moreover, diabetes mediated hippocampal oxidative stress, neuroinflammation, insulin signaling deficits, apoptosis, and cognitive dysfunction was further reversed by chronic Ud+ET administration in D-ET-Ud rats (P < 0.001) compared to D-sed animals. CONCLUSIONS Ud extract and ET ameliorate cognitive dysfunction via improvement in hippocampal oxidative stress, neuroinflammation, insulin signaling pathway, and apoptosis in STZ-induced diabetic rats. The results of this study provide new experimental evidence for using Ud+ET in the treatment of hippocampal complications and cognitive dysfunction caused by diabetes.
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Affiliation(s)
- Masoud Rahmati
- Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khorramabad, Iran.
| | - Maryam Keshvari
- Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khorramabad, Iran
| | - Rahim Mirnasouri
- Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khorramabad, Iran
| | - Farzaneh Chehelcheraghi
- Anatomical Sciences Department, School of Medicine, Lorestan University Medical of Sciences, Khorramabad, Iran
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16
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The impact of sesamol and exercise on striatal TNF-α level, motor behavior, aversive memory and oxidative stress status in 6-hydroxydopamine-lesioned rats. PHYSIOLOGY AND PHARMACOLOGY 2021. [DOI: 10.52547/phypha.26.1.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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17
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Wicha P, Das S, Mahakkanukrauh P. Blood-brain barrier dysfunction in ischemic stroke and diabetes: the underlying link, mechanisms and future possible therapeutic targets. Anat Cell Biol 2021; 54:165-177. [PMID: 33658432 PMCID: PMC8225477 DOI: 10.5115/acb.20.290] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 12/27/2020] [Accepted: 01/30/2021] [Indexed: 01/04/2023] Open
Abstract
Ischemic stroke caused by occlusion of cerebral artery is responsible for the majority of stroke that increases the morbidity and mortality worldwide. Diabetes mellitus (DM) is a crucial risk factor for ischemic stroke. Prolonged DM causes various microvascular and macrovascular changes, and blood-brain barrier (BBB) permeability that facilitates inflammatory response following stroke. In the acute phase following stroke, BBB disruption has been considered the initial step that induces neurological deficit and functional disabilities. Stroke outcomes are significantly worse among DM. In this article, we review stroke with diabetes-induce BBB damage, as well as underlying mechanism and possible therapeutic targets for stroke with diabetes.
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Affiliation(s)
- Piyawadee Wicha
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Srijit Das
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Pasuk Mahakkanukrauh
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Excellence in Osteology Research and Training Center (ORTC), Chiang Mai University, Chiang Mai, Thailand
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18
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Mazzocchi A, De Cosmi V, Risé P, Milani GP, Turolo S, Syrén ML, Sala A, Agostoni C. Bioactive Compounds in Edible Oils and Their Role in Oxidative Stress and Inflammation. Front Physiol 2021; 12:659551. [PMID: 33995124 PMCID: PMC8119658 DOI: 10.3389/fphys.2021.659551] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 04/12/2021] [Indexed: 12/13/2022] Open
Abstract
Diet and inflammatory response are recognized as strictly related, and interest in exploring the potential of edible fats and oils for health and chronic diseases is emerging worldwide. Polyunsaturated fatty acids (PUFAs) present in fish oil (FO), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be partly converted into oxygenated bioactive lipids with anti-inflammatory and/or pro-resolving activities. Moreover, the co-presence of phenolic compounds and vitamins in edible oils may prevent the development of chronic diseases by their anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory activities. Finally, a high content in mono-unsaturated fatty acids may improve the serum lipid profile and decrease the alterations caused by the oxidized low-density lipoproteins and free radicals. The present review aims to highlight the role of lipids and other bioactive compounds contained in edible oils on oxidative stress and inflammation, focusing on critical and controversial issues that recently emerged, and pointing to the opposing role often played by edible oils components and their oxidized metabolites.
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Affiliation(s)
- Alessandra Mazzocchi
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Valentina De Cosmi
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.,Pediatric Intermediate Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Patrizia Risé
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | - Gregorio Paolo Milani
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.,Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Stefano Turolo
- Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marie-Louise Syrén
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Angelo Sala
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.,Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche (CNR), Palermo, Italy
| | - Carlo Agostoni
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.,Pediatric Intermediate Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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19
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Sesame Oil-Based Nanostructured Lipid Carriers of Nicergoline, Intranasal Delivery System for Brain Targeting of Synergistic Cerebrovascular Protection. Pharmaceutics 2021; 13:pharmaceutics13040581. [PMID: 33921796 PMCID: PMC8072759 DOI: 10.3390/pharmaceutics13040581] [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: 03/19/2021] [Revised: 04/09/2021] [Accepted: 04/16/2021] [Indexed: 02/07/2023] Open
Abstract
Nicergoline (NIC) is a semisynthetic ergot alkaloid derivative applied for treatment of dementia and other cerebrovascular disorders. The efficacy of sesame oil to slow and reverse the symptoms of neurodegenerative cognitive disorders has been proven. This work aimed to formulate and optimize sesame oil-based NIC-nanostructured lipid carriers (NIC–NLCs) for intranasal (IN) delivery with expected synergistic and augmented neuroprotective properties. The NIC–NLC were prepared using sesame oil as a liquid lipid. A three-level, three-factor Box–Behnken design was applied to statistically optimize the effect of sesame oil (%) of the total lipid, surfactant concentration, and sonication time on particle size, zeta potential, and entrapment efficacy as responses. Solid-state characterization, release profile, and ex vivo nasal permeation in comparison to NIC solution (NIC–SOL) was studied. In vivo bioavailability from optimized NIC–NLC and NIC–SOL following IN and IV administration was evaluated and compared. The optimized NIC–NLC formula showed an average particle size of 111.18 nm, zeta potential of −15.4 mV, 95.11% entrapment efficacy (%), and 4.6% loading capacity. The NIC–NLC formula showed a biphasic, extended-release profile (72% after 48 h). Permeation of the NIC–NLC formula showed a 2.3 enhancement ratio. Bioavailability studies showed a 1.67 and 4.57 fold increase in plasma and brain following IN administration. The results also indicated efficient direct nose-to-brain targeting properties with the brain-targeting efficiency (BTE%) and direct transport percentage (DTP%) of 187.3% and 56.6%, respectively, after IN administration. Thus, sesame oil-based NIC–NLC can be considered as a promising IN delivery system for direct and efficient brain targeting with improved bioavailability and expected augmented neuroprotective action for the treatment of dementia.
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20
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Mohamed EA, Ahmed HI, Zaky HS, Badr AM. Sesame oil mitigates memory impairment, oxidative stress, and neurodegeneration in a rat model of Alzheimer's disease. A pivotal role of NF-κB/p38MAPK/BDNF/PPAR-γ pathways. JOURNAL OF ETHNOPHARMACOLOGY 2021; 267:113468. [PMID: 33049345 DOI: 10.1016/j.jep.2020.113468] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 10/05/2020] [Accepted: 10/08/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Sesame (Sesamum indicum, L., Family: Pedaliaceae) is a notable folk medicine in Middle East, Asia and Africa. Many traditional and pharmacological studies have documented the unique nature of sesame oil (SO). SO has been reported to have many pharmacological effects related to the anti-inflammatory and antioxidant capacity of its components. Neuroinflammation and oxidative stress have been the predominant pathogenic events in Alzheimer's disease (AD) which is one of the most common neurodegenerative diseases. AIM OF STUDY we aimed to explore the neuroprotective effect and the probable mechanisms of SO against aluminium chloride (AlCl3)-induced AD symptoms. MATERIALS AND METHODS Rats were treated daily with AlCl3 (100 mg/kg/i.p.) either alone or with SO (two different doses) for six weeks. Behavioral (Open-field and Morris water maze tests), histopathological, and biochemical examinations were used to evaluate the neuroprotective effect and the underlying mechanisms of SO against AlCl3-induced AD symptoms. RESULTS Our results indicated that SO significantly improved learning and memory impairments induced by AlCl3. Indeed, SO treatment significantly restored the elevated level of acetylcholinesterase (AChE) and amyloid beta (Aβ) overexpression. Moreover, AlCl3 treatment afforded histopathological changes, increase the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in addition to mitigation of oxidative stress status in the brain. SO abolished all these abnormalities. Meanwhile, AlCl3 induced activation of p38 mitogen-activated protein kinase (p38MAPK) and decreased brain-derived neurotrophic factor (BDNF) which were inhibited by SO. Furthermore, SO administration modulated the expression of the peroxisome proliferator-activated receptor gamma (PPAR-γ) and nuclear factor kappa B (NF-κB). CONCLUSIONS In conclusion, the neuroprotective effect of SO involved the modulation of different mechanisms targeting oxidative stress, neuroinflammation, and cognitive functions. SO may modulate different molecular targets involved in AD pathogenesis by alterations of NF-κB/p38MAPK/BDNF/PPAR-γ signalling and this may be attributed to the synergistic effect of their active components.
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Affiliation(s)
- Eman A Mohamed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
| | - Hebatalla I Ahmed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
| | - Heba S Zaky
- Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
| | - Amira M Badr
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Ain Shams University, Heliopolis, Cairo, Egypt
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21
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Khursheed R, Singh SK, Wadhwa S, Gulati M, Kapoor B, Awasthi A, Kr A, Kumar R, Pottoo FH, Kumar V, Dureja H, Anand K, Chellappan DK, Dua K, Gowthamarajan K. Opening eyes to therapeutic perspectives of bioactive polyphenols and their nanoformulations against diabetic neuropathy and related complications. Expert Opin Drug Deliv 2020; 18:427-448. [PMID: 33356647 DOI: 10.1080/17425247.2021.1846517] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation.Area covered: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues.Expert opinion: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.
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Affiliation(s)
- Rubiya Khursheed
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Sheetu Wadhwa
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Bhupinder Kapoor
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Ankit Awasthi
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Arya Kr
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Rajan Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Faheem Hyder Pottoo
- Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Vijay Kumar
- Department of Biotechnology, School of Bioengineering and Biosciences, Faculty of Technology and Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Harish Dureja
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India
| | - Krishnan Anand
- Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences and National Health Laboratory Service, University of the Free State, Bloemfontein, South Africa
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Australia
| | - K Gowthamarajan
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.,Centre of Excellence in Nanoscience & Technology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
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22
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Rahmani G, Farajdokht F, Mohaddes G, Babri S, Ebrahimi V, Ebrahimi H. Garlic ( Allium sativum) improves anxiety- and depressive-related behaviors and brain oxidative stress in diabetic rats. Arch Physiol Biochem 2020; 126:95-100. [PMID: 30169970 DOI: 10.1080/13813455.2018.1494746] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
This study investigated the effects of garlic on anxiety- and depression-related behaviors and brain oxidative markers in streptozotocin (STZ)-induced diabetes in rats. Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8/group): control, diabetic + saline, diabetic + garlic, diabetic + imipramine, and diabetic + diazepam groups. Animals received garlic homogenate (0.1, 0.25, and 0.5 g/kg) for 10 days. At the end of the treatments, anxiety- and depressive-related behaviors were evaluated by elevated plus maze (EPM) and forced swimming test (FST), respectively. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and malondialdehyde (MDA) levels were measured in the brain. Diabetic + garlic (0.5 g/kg) group showed lower anxiety- and- depressive-like behaviors as compared to the diabetic rats. Furthermore, garlic treatment (0.5 g/kg) attenuated MDA levels and enhanced SOD and GPx activities in the brain. Our findings indicate that garlic alleviates anxiety- and depression-related behaviors in the diabetic rats possibly by attenuation of brain oxidative stress.
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Affiliation(s)
- Ghazal Rahmani
- Neuroscience Research Center of Tabriz University of Medical Sciences (NSRC), Tabriz, Iran
| | - Fereshteh Farajdokht
- Neuroscience Research Center of Tabriz University of Medical Sciences (NSRC), Tabriz, Iran
| | - Gisou Mohaddes
- Neuroscience Research Center of Tabriz University of Medical Sciences (NSRC), Tabriz, Iran
| | - Shirin Babri
- Neuroscience Research Center of Tabriz University of Medical Sciences (NSRC), Tabriz, Iran
| | - Vida Ebrahimi
- Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hadi Ebrahimi
- Neuroscience Research Center of Tabriz University of Medical Sciences (NSRC), Tabriz, Iran
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23
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Castro-González L, Alvarez-Idaboy JR, Galano A. Computationally Designed Sesamol Derivatives Proposed as Potent Antioxidants. ACS OMEGA 2020; 5:9566-9575. [PMID: 32363309 PMCID: PMC7191856 DOI: 10.1021/acsomega.0c00898] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 04/03/2020] [Indexed: 05/14/2023]
Abstract
Oxidative stress has been recognized to play an important role in several diseases, such as Parkinson's and Alzheimer's disease, which justifies the beneficial effects of antioxidants in ameliorating the deleterious effects of these health disorders. Sesamol, in particular, has been investigated for the treatment of several conditions because of its antioxidant properties. This article reports a rational computational design of new sesamol derivatives. They were constructed by adding four functional groups (-OH, -NH2, -COOH, and -SH) in three different positions of the sesamol molecular framework. A total of 50 derivatives between mono-, di-, and trisubstituted compounds were obtained. All the derivatives were evaluated and compared with a reference set of commercial neuroprotective drugs. The estimated properties are absorption, distribution, metabolism, excretion, toxicity, and synthetic accessibility. Selection and elimination scores were used to choose a first set of promising candidates. Acid-based properties and reactivity indexes were then estimated using the density functional theory. Four sesamol derivatives were finally selected, which are hypothesized to be potent antioxidants, even better than sesamol and Trolox for that purpose.
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Affiliation(s)
- Laura
M. Castro-González
- Departamento
de Física y Química Teórica, Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, Mexico
| | - Juan Raúl Alvarez-Idaboy
- Departamento
de Física y Química Teórica, Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, Mexico
| | - Annia Galano
- Departamento
de Química, Universidad Autónoma
Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina. Iztapalapa. C. P., México DF 09340, Mexico
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24
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Ahmed A, Zeng G, Jiang D, Lin H, Azhar M, Farooq AD, Choudhary MI, Liu X, Wang Q. Time-dependent impairments in learning and memory in Streptozotocin-induced hyperglycemic rats. Metab Brain Dis 2019; 34:1431-1446. [PMID: 31286327 DOI: 10.1007/s11011-019-00448-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 06/10/2019] [Indexed: 12/17/2022]
Abstract
The sedentary lifestyle is responsible for the high prevalence of diabetes which also impairs cognition including learning and memory. Various studies have highlighted the learning and memory impairments in rodent models but data regarding the timeline of their development and their correlation to biochemical parameters are scarce. So, the present study was designed to investigate the type of memory which is more susceptible to hyperglycemia and its correlation with biochemical parameters such as inflammatory cytokines, cAMP response element binding (CREB) and protein kinase B (Akt) activation. Hyperglycemia was induced using streptozotocin (STZ, 45 mg/kg i.p.) and confirmed by measuring fasting blood glucose levels after 1 week of STZ injection. Learning and memory deficits were evaluated using the Novel Object Recognition Test (NORT) and Morris water maze (MWM), and correlated with biochemical parameters (TNF-α, IL-1β, and dopamine) at 3, 6 and 9 weeks. STZ-injected rats after 3 weeks of injection demonstrated moderate hyperglycemia (blood glucose = 7.99 ± 0.62 mM) with intact learning and reference memory; however, their working memory was impaired in MWM. Severe hyperglycemia (blood glucose = 11.51 ± 0.69 mM) accompanied by impaired short, long, and working memory was evident after 6 weeks whereas learning was intact. After 9 weeks of STZ injection, hyperglycemia was more pronounced (13.69 ± 1.43 mM) and accompanied by a learning deficit in addition to short, long, and working memory impairments. The extent of hyperglycemia either in terms of duration or severity resulted in enhanced inflammation, down-regulation of the level of dopamine, protein expression of AKT and CREB, which possibly affected learning and memory negatively.
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Affiliation(s)
- Ayaz Ahmed
- Affiliated TCM hospital/ Sino-Portugal TCM International Cooperation Center / Department of Physiology in School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, China
- Hunan Provincial Research Center for Safety Evaluation of Drugs, Changsha, China
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
| | - Guirong Zeng
- Hunan Provincial Research Center for Safety Evaluation of Drugs, Changsha, China
- Research Center for Pharmacology & Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dejiang Jiang
- Hunan Provincial Research Center for Safety Evaluation of Drugs, Changsha, China
| | - Haiying Lin
- Affiliated TCM hospital/ Sino-Portugal TCM International Cooperation Center / Department of Physiology in School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, China
| | - Mudassar Azhar
- Hunan Provincial Research Center for Safety Evaluation of Drugs, Changsha, China
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
| | - Ahsana Dar Farooq
- Hamdard Al-Majeed College of Eastern Medicine, Hamdard University, Karachi, 74600, Pakistan
| | - Muhammad Iqbal Choudhary
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
- Department of Biochemistry, College of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Xinmin Liu
- Affiliated TCM hospital/ Sino-Portugal TCM International Cooperation Center / Department of Physiology in School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, China.
- Hunan Provincial Research Center for Safety Evaluation of Drugs, Changsha, China.
- Research Center for Pharmacology & Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Qiong Wang
- Affiliated TCM hospital/ Sino-Portugal TCM International Cooperation Center / Department of Physiology in School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, China.
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25
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Aslışen B, Koçak ÇC, Koçak S. Electrochemical Determination of Sesamol in Foods by Square Wave Voltammetry at a Boron-Doped Diamond Electrode. ANAL LETT 2019. [DOI: 10.1080/00032719.2019.1650752] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Affiliation(s)
- Burak Aslışen
- Department of Chemistry, Science and Art Faculty, Manisa Celal Bayar University, Manisa, Turkey
| | - Çağrı C. Koçak
- Bergama Vocational School, Dokuz Eylul University, Izmir, Turkey
| | - Süleyman Koçak
- Department of Chemistry, Science and Art Faculty, Manisa Celal Bayar University, Manisa, Turkey
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26
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Yuan T, Chu C, Shi R, Cui T, Zhang X, Zhao Y, Shi X, Hui Y, Pan J, Qian R, Dai X, Liu Z, Liu X. ApoE-Dependent Protective Effects of Sesamol on High-Fat Diet-Induced Behavioral Disorders: Regulation of the Microbiome-Gut-Brain Axis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:6190-6201. [PMID: 31117496 DOI: 10.1021/acs.jafc.9b01436] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Sesamol, an antioxidant lignan from sesame oil, possesses neuroprotective bioactivities. The present work was aimed to elucidate the systemic protective effects of sesamol on cognitive deficits and to determine the possible link between gut and brain. Wildtype and ApoE-/- mice were treated with a high-fat diet and sesamol (0.05%, w/v, in drinking water) for 10 weeks. Behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype. Consistently, sesamol improved synapse ultrastructure and inhibited Aβ accumulation in an ApoE-dependent manner. Moreover, sesamol prevented dietary-induced gut barrier damages and systemic inflammation. Sesamol also reshaped gut microbiome and improved the generation of microbial metabolites short-chain fatty acids. To summarize, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and its beneficial effects on gut microbiota/metabolites could be translated into neurodegenerative diseases treatment.
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Affiliation(s)
- Tian Yuan
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
| | - Chuanqi Chu
- School of Food Science and Technology , Jiangnan University , Wuxi , China
| | - Rubing Shi
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
| | - Tianlin Cui
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
| | - Xinglin Zhang
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
| | - Yihang Zhao
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
| | - Xu Shi
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
| | - Yan Hui
- Department of Food Science , University of Copenhagen , Copenhagen , Denmark
| | - Junru Pan
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
| | - Rui Qian
- Food Analysis and Development Center , Beijing ZhiYunDa Technology, Co., LTD. , Beijing , China
| | - Xiaoshuang Dai
- BGI Institute of Applied Agriculture , BGI-Shenzhen , Shenzhen , China
| | - Zhigang Liu
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
| | - Xuebo Liu
- College of Food Science and Engineering , Northwest A&F University , Yangling , China
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Ci LY, Liu DS, Yang JQ, Liu YZ, Li CL, Zhang X, Ma CM, Hu RT. Expression of long non‑coding RNA and mRNA in the hippocampus of mice with type 2 diabetes. Mol Med Rep 2018; 18:4960-4968. [PMID: 30272307 PMCID: PMC6236254 DOI: 10.3892/mmr.2018.9504] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Accepted: 08/28/2018] [Indexed: 12/30/2022] Open
Abstract
Long non‑coding RNAs (lncRNAs) serve key roles in cell growth, development and various diseases associated with the central nervous system. However, differential expression profiles of lncRNAs in type 2 diabetes have not been reported. The present study aimed to analyze the expression pattern of lncRNA‑mRNA in a type 2 diabetic mouse model using microarray analysis. The mouse model of type 2 diabetes was established and the total RNAs were extracted from the hippocampus of the mice used in the present study. The total RNAs were then examined by the GeeDom human lncRNA + mRNA V4.0 expression profile and analyzed through comparing Gene Ontology (GO) enrichment analysis and signal pathway analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. There were statistically significant differences between the expression of IncRNAs and mRNA in the healthy mice and that of the diabetic mice. In the diabetic mice, 130 different lncRNAs were expressed with 126 significantly upregulated and 4 significantly downregulated and 49 different mRNAs were detected with 45 significantly upregulated and 4 downregulated. GO analysis indicated that the mRNAs that are affected are involved in transport, cell adhesion, ion transport and metabolic processes. KEGG and Reactome enrichment analysis indicated that mRNAs impact on cholinergic synapses, nuclear factor‑kB pathway, Toll like receptor 4 cascade and zinc transporter are correlated with cognitive dysfunction in type 2 diabetes. A dynamic lncRNA‑mRNA network was constructed containing 123 lncRNAs and 48 mRNAs, which can elucidate the interaction between lncRNA and mRNA. Overall, this is the first study to indicate that lncRNAs are differentially expressed in the type 2 diabetic mice.
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Affiliation(s)
- Li-Ya Ci
- Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - De-Shan Liu
- Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Jing-Qing Yang
- Department of Respiratory Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China
| | - Yu Zhao Liu
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Chang Ling Li
- Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Xi Zhang
- Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Chun Mei Ma
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Rui Ting Hu
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
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An inhibitor of soluble epoxide hydrolase ameliorates diabetes-induced learning and memory impairment in rats. Prostaglandins Other Lipid Mediat 2018; 136:84-89. [PMID: 29751149 DOI: 10.1016/j.prostaglandins.2018.05.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 04/29/2018] [Accepted: 05/07/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Pharmacological inhibition of soluble epoxide hydrolase (sEH) enhances the synaptic function in the CNS and has a protective role in cognitive decline. We hypothesized that the sEH inhibitor TPPU might prevent the diabetes-induced decline in learning and memory which is associated with an alteration in the level of neurotransmitters and oxidative stress. METHODS Type 1 diabetes was induced in rats and the animals were treated with TPPU for 8 weeks. The learning and memory functions were assessed by the Barnes maze and a step-down test. Indicators of oxidative stress, levels of neurotransmitters, and activity of acetylcholinesterase were measured in the discrete regions of the brain. RESULTS Our results revealed that treatment with TPPU significantly improves learning and memory performance in diabetic rats along with decreasing the level of blood sugar. Moreover, treatment with TPPU significantly prevented the diabetes-induced alteration in levels of neurotransmitters, the activity of acetylcholinesterase and preserved anti-oxidant defence system. CONCLUSION Inhibition of the sEH alleviates diabetes-induced decline in learning and memory.
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29
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Guo X, Zhang T, Shi L, Gong M, Jin J, Zhang Y, Liu R, Chang M, Jin Q, Wang X. The relationship between lipid phytochemicals, obesity and its related chronic diseases. Food Funct 2018; 9:6048-6062. [DOI: 10.1039/c8fo01026a] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This review focuses on phytochemicals in oils, and summarizes the mechanisms of the anti-obesity effects of these compounds in in vitro studies, animal models, and human trials.
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30
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The BET/BRD inhibitor JQ1 attenuates diabetes-induced cognitive impairment in rats by targeting Nox4-Nrf2 redox imbalance. Biochem Biophys Res Commun 2018; 495:204-211. [DOI: 10.1016/j.bbrc.2017.11.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 11/03/2017] [Indexed: 01/07/2023]
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31
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Mohamed N, Gawad HA. Taurine dietary supplementation attenuates brain, thyroid, testicular disturbances and oxidative stress in streptozotocin-induced diabetes mellitus in male rats. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2017. [DOI: 10.1016/j.bjbas.2017.04.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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32
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Kim JM, Park CH, Park SK, Seung TW, Kang JY, Ha JS, Lee DS, Lee U, Kim DO, Heo HJ. Ginsenoside Re Ameliorates Brain Insulin Resistance and Cognitive Dysfunction in High Fat Diet-Induced C57BL/6 Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2017; 65:2719-2729. [PMID: 28314104 DOI: 10.1021/acs.jafc.7b00297] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
The ameliorating effects of ginsenoside Re (G Re) on high fat diet (HFD)-induced insulin resistance in C57BL/6 mice were investigated to assess its physiological function. In the results of behavioral tests, G Re improved cognitive dysfunction in diabetic mice using Y-maze, passive avoidance, and Morris water maze tests. G Re also significantly recovered hyperglycemia and fasting blood glucose level. In the results of serum analysis, G Re decreased triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDLC), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) and increased the ratio of high-density lipoprotein cholesterol (HDLC). G Re regulated acetylcholine (ACh), acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), and oxidized glutathione (GSH)/total GSH by regulating the c-Jun N-terminal protein kinase (JNK) pathway. These findings suggest that G Re could be used to improve HFD-induced insulin resistance condition by ameliorating hyperglycemia via protecting the cholinergic and antioxidant systems in the mouse brains.
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Affiliation(s)
- Jong Min Kim
- Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University , Jinju 52828, Republic of Korea
| | - Chang Hyeon Park
- Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University , Jinju 52828, Republic of Korea
| | - Seon Kyeong Park
- Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University , Jinju 52828, Republic of Korea
| | - Tae Wan Seung
- Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University , Jinju 52828, Republic of Korea
| | - Jin Yong Kang
- Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University , Jinju 52828, Republic of Korea
| | - Jeong Su Ha
- Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University , Jinju 52828, Republic of Korea
| | - Du Sang Lee
- Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University , Jinju 52828, Republic of Korea
| | - Uk Lee
- Division of Special Purpose Trees, National Institute of Forest Science , Suwon 16631, Republic of Korea
| | - Dae-Ok Kim
- Department of Food Science and Biotechnology, Kyung Hee University , Yongin 17104, Republic of Korea
| | - Ho Jin Heo
- Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University , Jinju 52828, Republic of Korea
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33
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Ahmadi M, Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M. Crocin improves spatial learning and memory deficits in the Morris water maze via attenuating cortical oxidative damage in diabetic rats. Neurosci Lett 2017; 642:1-6. [PMID: 28137647 DOI: 10.1016/j.neulet.2017.01.049] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 01/11/2017] [Accepted: 01/19/2017] [Indexed: 01/29/2023]
Abstract
The purpose of the current study was to examine the influence of crocin on improving spatial memory deficits and cerebral oxidative damage in streptozotocin-induced diabetic rats. Crocin was administered intraperitoneally daily at doses of 15, 30 and 60mg/kg for 6 weeks. Spatial memory performance was measured in rats by the Morris water maze paradigm. Lipid peroxidation and total thiol levels as parameters of oxidative stress were assessed in the cerebral cortex at the end of week 6. Diabetic rats showed spatial learning and memory deficits in the Morris water maze which was accompanied by increased lipid peroxidation levels in the cerebral cortex. By contrast, chronic treatment with crocin (15, 30 and 60mg/kg, ip, 6 weeks) improved cognitive performance and lowered hyperglycaemia and oxidative stress in diabetic rats. In conclusion, the results suggest that beneficial effects of crocin on streptozotocin-induced memory dysfunction may be attributed to its antidiabetic and antioxidant activity, which could find clinical use in treating cognitive dysfunction in diabetics.
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Affiliation(s)
- M Ahmadi
- Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Isfahan, Iran
| | - Z Rajaei
- Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - M A Hadjzadeh
- Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Isfahan, Iran
| | - H Nemati
- Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Isfahan, Iran
| | - M Hosseini
- Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Isfahan, Iran
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34
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Novel indole-2-carboxylic acid linked 3-phenyl-2-alkoxy propanoic acids: Synthesis, molecular docking and in vivo antidiabetic studies. Med Chem Res 2017. [DOI: 10.1007/s00044-017-1791-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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35
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Liu Z, Sun Y, Qiao Q, Zhao T, Zhang W, Ren B, Liu Q, Liu X. Sesamol ameliorates high-fat and high-fructose induced cognitive defects via improving insulin signaling disruption in the central nervous system. Food Funct 2017; 8:710-719. [DOI: 10.1039/c6fo01562j] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The present study demonstrated that sesamol prevents high-fat and high-fructose diet induced systemic insulin resistance and cognitive defects via stimulating PI3K/Akt signaling, improving ERK/CREB/BDNF cascades, and preserving mitochondrial function.
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Affiliation(s)
- Zhigang Liu
- Laboratory of Functional Chemistry and Nutrition of Food
- College of Food Science and Engineering
- Northwest A&F University
- Yangling
- China
| | - Yali Sun
- Laboratory of Functional Chemistry and Nutrition of Food
- College of Food Science and Engineering
- Northwest A&F University
- Yangling
- China
| | - Qinglian Qiao
- Laboratory of Functional Chemistry and Nutrition of Food
- College of Food Science and Engineering
- Northwest A&F University
- Yangling
- China
| | - Tong Zhao
- Laboratory of Functional Chemistry and Nutrition of Food
- College of Food Science and Engineering
- Northwest A&F University
- Yangling
- China
| | - Wentong Zhang
- Laboratory of Functional Chemistry and Nutrition of Food
- College of Food Science and Engineering
- Northwest A&F University
- Yangling
- China
| | - Bo Ren
- Laboratory of Functional Chemistry and Nutrition of Food
- College of Food Science and Engineering
- Northwest A&F University
- Yangling
- China
| | - Qian Liu
- Laboratory of Functional Chemistry and Nutrition of Food
- College of Food Science and Engineering
- Northwest A&F University
- Yangling
- China
| | - Xuebo Liu
- Laboratory of Functional Chemistry and Nutrition of Food
- College of Food Science and Engineering
- Northwest A&F University
- Yangling
- China
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36
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Tian X, Liu Y, Ren G, Yin L, Liang X, Geng T, Dang H, An R. Resveratrol limits diabetes-associated cognitive decline in rats by preventing oxidative stress and inflammation and modulating hippocampal structural synaptic plasticity. Brain Res 2016; 1650:1-9. [DOI: 10.1016/j.brainres.2016.08.032] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 08/21/2016] [Accepted: 08/22/2016] [Indexed: 12/15/2022]
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Abstract
Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with reduced performance on multiple domains of cognitive function and with evidence of abnormal structural and functional brain magnetic resonance imaging (MRI). Cognitive deficits may occur at the very earliest stages of diabetes and are further exacerbated by the metabolic syndrome. The duration of diabetes and glycemic control may have an impact on the type and severity of cognitive impairment, but as yet we cannot predict who is at greatest risk of developing cognitive impairment. The pathophysiology of cognitive impairment is multifactorial, although dysfunction in each interconnecting pathway ultimately leads to discordance in metabolic signaling. The pathophysiology includes defects in insulin signaling, autonomic function, neuroinflammatory pathways, mitochondrial (Mt) metabolism, the sirtuin-peroxisome proliferator-activated receptor-gamma co-activator 1α (SIRT-PGC-1α) axis, and Tau signaling. Several promising therapies have been identified in pre-clinical studies, but remain to be validated in clinical trials.
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Affiliation(s)
- Lindsay A Zilliox
- Department of Neurology, Maryland VA Healthcare System and University of Maryland, 110 South Paca Street, Baltimore, MD, 21201, USA
| | - Krish Chadrasekaran
- Department of Neurology, Maryland VA Healthcare System and University of Maryland, 110 South Paca Street, Baltimore, MD, 21201, USA
| | - Justin Y Kwan
- Department of Neurology, Maryland VA Healthcare System and University of Maryland, 110 South Paca Street, Baltimore, MD, 21201, USA
| | - James W Russell
- Department of Neurology, Maryland VA Healthcare System and University of Maryland, 110 South Paca Street, Baltimore, MD, 21201, USA.
- School of Medicine, Department of Neurology, University of Maryland, 3S-129, 110 South Paca Street, Baltimore, MD, 21201-1595, USA.
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38
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Gerö D, Szabo C. Glucocorticoids Suppress Mitochondrial Oxidant Production via Upregulation of Uncoupling Protein 2 in Hyperglycemic Endothelial Cells. PLoS One 2016; 11:e0154813. [PMID: 27128320 PMCID: PMC4851329 DOI: 10.1371/journal.pone.0154813] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 04/19/2016] [Indexed: 11/19/2022] Open
Abstract
Diabetic complications are the leading cause of morbidity and mortality in diabetic patients. Elevated blood glucose contributes to the development of endothelial and vascular dysfunction, and, consequently, to diabetic micro- and macrovascular complications, because it increases the mitochondrial proton gradient and mitochondrial oxidant production. Therapeutic approaches designed to counteract glucose-induced mitochondrial reactive oxygen species (ROS) production in the vasculature are expected to show efficacy against all diabetic complications, but direct pharmacological targeting (scavenging) of mitochondrial oxidants remains challenging due to the high reactivity of some of these oxidant species. In a recent study, we have conducted a medium-throughput cell-based screening of a focused library of well-annotated pharmacologically active compounds and identified glucocorticoids as inhibitors of mitochondrial superoxide production in microvascular endothelial cells exposed to elevated extracellular glucose. The goal of the current study was to investigate the mechanism of glucocorticoids' action. Our findings show that glucocorticoids induce the expression of the mitochondrial UCP2 protein and decrease the mitochondrial potential. UCP2 silencing prevents the protective effect of the glucocorticoids on ROS production. UCP2 induction also increases the oxygen consumption and the "proton leak" in microvascular endothelial cells. Furthermore, glutamine supplementation augments the effect of glucocorticoids via further enhancing the expression of UCP2 at the translational level. We conclude that UCP2 induction represents a novel experimental therapeutic intervention in diabetic vascular complications. While direct repurposing of glucocorticoids may not be possible for the therapy of diabetic complications due to their significant side effects that develop during chronic administration, the UCP2 pathway may be therapeutically targetable by other, glucocorticoid-independent pharmacological means.
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Affiliation(s)
- Domokos Gerö
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America
- University of Exeter Medical School, Exeter, United Kingdom
- * E-mail:
| | - Csaba Szabo
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America
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39
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Zhou J, Du X, Long M, Zhang Z, Zhou S, Zhou J, Qian G. Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats. Eur J Pharmacol 2016; 774:87-94. [DOI: 10.1016/j.ejphar.2016.02.007] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Revised: 01/21/2016] [Accepted: 02/01/2016] [Indexed: 12/12/2022]
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40
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Gaspar JM, Baptista FI, Macedo MP, Ambrósio AF. Inside the Diabetic Brain: Role of Different Players Involved in Cognitive Decline. ACS Chem Neurosci 2016; 7:131-42. [PMID: 26667832 DOI: 10.1021/acschemneuro.5b00240] [Citation(s) in RCA: 120] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus is the most common metabolic disease, and its prevalence is increasing. A growing body of evidence, both in animal models and epidemiological studies, has demonstrated that metabolic diseases like obesity, insulin resistance, and diabetes are associated with alterations in the central nervous system (CNS), being linked with development of cognitive and memory impairments and presenting a higher risk for dementia and Alzheimer's disease. The rising prevalence of diabetes together with its increasing earlier onset suggests that diabetes-related cognitive dysfunction will increase in the near future, causing substantial socioeconomic impact. Decreased insulin secretion or action, dysregulation of glucose homeostasis, impairment in the hypothalamic-pituitary-adrenal axis, obesity, hyperleptinemia, and inflammation may act independently or synergistically to disrupt neuronal homeostasis and cause diabetes-associated cognitive decline. However, the crosstalk between those factors and the mechanisms underlying the diabetes-related CNS complications is still elusive. During the past few years, different strategies (neuroprotective and antioxidant drugs) have emerged as promising therapies for this complication, which still remains to be preventable or treatable. This Review summarizes fundamental past and ongoing research on diabetes-associated cognitive decline, highlighting potential contributors, mechanistic mediators, and new pharmacological approaches to prevent and/or delay this complication.
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Affiliation(s)
- Joana M. Gaspar
- CEDOC,
Chronic Diseases Research Centre, NOVA Medical School/Faculdade de
Ciências Médicas, Universidade Nova de Lisboa, Edifício
CEDOC - IIRua Câmara Pestana no. 6, 6A e 6B, 1150-082 Lisboa, Portugal
- Institute
for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Portuguese Diabetes Association (APDP), R. do Salitre 118-120, 1250-203 Lisboa, Portugal
| | - Filipa I. Baptista
- Institute
for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- CNC.IBILI
Consortium, University of Coimbra, 3004-517 Coimbra, Portugal
| | - M. Paula Macedo
- CEDOC,
Chronic Diseases Research Centre, NOVA Medical School/Faculdade de
Ciências Médicas, Universidade Nova de Lisboa, Edifício
CEDOC - IIRua Câmara Pestana no. 6, 6A e 6B, 1150-082 Lisboa, Portugal
- Portuguese Diabetes Association (APDP), R. do Salitre 118-120, 1250-203 Lisboa, Portugal
| | - António F. Ambrósio
- Institute
for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- CNC.IBILI
Consortium, University of Coimbra, 3004-517 Coimbra, Portugal
- AIBILI, 3000-548 Coimbra, Portugal
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41
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Anti-adipogenic effects of sesamol on human mesenchymal stem cells. Biochem Biophys Res Commun 2015; 469:49-54. [PMID: 26616060 DOI: 10.1016/j.bbrc.2015.11.070] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 11/16/2015] [Indexed: 01/09/2023]
Abstract
Human mesenchymal stem cells (hMSCs) from adult bone marrow are able to differentiate into adipocytes, osteoblasts, chondrocytes and neuronal cells. Adipocytes in bone marrow are primarily responsible for the maintenance of bone structure by maintaining cell number balance with other stromal cells. However, the number of adipocytes in the bone marrow increases with age, leading to an imbalance of the bone marrow microenvironment, which results in a disruption of bone structure. In addition, the excessive number of adipocytes in bone marrow can cause diseases, such as osteoporosis or anemia. In this study, we investigated the effect of sesamol, a major natural phenolic compound of sesame oil, on the adipogenic differentiation of hMSCs. Numerous studies have reported the anti-oxidant property of sesamol, but its effect on cell differentiation has not yet been shown. We first found that sesamol treatment during adipogenic differentiation of hMSCs reduced intracellular lipid accumulation, which was unrelated to lipolysis. Interestingly, sesamol diminished the expression of genes responsible for adipogenesis, but increased the expression of osteogenic genes. In addition, sesamol decreased the expression of genes necessary for adipocyte maturation without affecting the expression of hMSC-specific genes. Studies concerning intracellular signaling in hMSCs showed that the extracellular signal-regulated kinase 1/2 (ERK1/2) was decreased by sesamol, which was similar with the effect of an ERK1/2 inhibitor. Overall, this study demonstrates that sesamol can attenuate the adipogenic differentiation of hMSCs without affecting its characteristics through the inhibition of ERK1/2 pathway. Herein, this study reports for the first time the effect of sesamol on hMSC differentiation and suggests the possibility of using sesamol as a therapeutic agent to treat intraosseous disruption triggered by the excessive adipogenesis of hMSCs.
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42
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Yan BC, Jeon YH, Park JH, Kim IH, Cho JH, Ahn JH, Chen BH, Tae HJ, Lee JC, Ahn JY, Kim DW, Cho JH, Won MH, Hong S. Increased cyclooxygenase-2 and nuclear factor-κB/p65 expression in mouse hippocampi after systemic administration of tetanus toxin. Mol Med Rep 2015; 12:7837-44. [PMID: 26498481 PMCID: PMC4758276 DOI: 10.3892/mmr.2015.4490] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 10/01/2015] [Indexed: 12/21/2022] Open
Abstract
Brain inflammation has a crucial role in various diseases of the central nervous system. The hippocampus in the mammalian brain exerts an important memory function, which is sensitive to various insults, including inflammation induced by exo/endotoxin stimuli. Tetanus toxin (TeT) is an exotoxin with the capacity for neuronal binding and internalization. The present study investigated changes in inflammatory mediators in the mouse hippocampus proper (CA1‑3 regions) and dentate gyrus (DG) after TeT treatment. The experimental mice were intraperitoneally injected with TeT at a low dosage (100 ng/kg), while the control mice were injected with the same volume of saline. At 6, 12 and 24 h after TeT treatment, changes in the hippocampal levels of inflammatory mediators cyclooxygenase‑2 (COX‑2) and nuclear factor kappa‑B (NF‑κB/p65) were assessed using immunohistochemical and western blot analysis. In the control group, moderate COX‑2 immunoreactivity was observed in the stratum pyramidal (SP) of the CA2‑3 region, while almost no expression was identified in the CA1 region and the DG. COX‑2 immunoreactivity was increased by TeT in the SP and granule cell layer (GCL) of the DG in a time‑dependent manner. At 24 h post‑treatment, COX‑2 immunoreactivity in the SP of the CA1 region and in the GCL of the DG was high, and COX‑2 immunoreactivity in the SP of the CA2/3 region was highest. Furthermore, the present study observed that NF‑κB/p65 immunoreactivity was obviously increased in the SP and GCL at 6, 12 and 24 h after TeT treatment. In conclusion, the present study demonstrated that systemic treatment with TeT significantly increased the expression of COX-2 and NF-κB/p65 in the mouse hippocampus, suggesting that increased COX‑2 and NF-κB/65 expression may be associated with inflammation in the brain induced by exotoxins.
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Affiliation(s)
- Bing Chun Yan
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, P.R. China
| | - Yong Hwan Jeon
- Department of Radiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - Joon Ha Park
- Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - In Hye Kim
- Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - Jeong-Hwi Cho
- Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - Ji Hyeon Ahn
- Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - Bai Hui Chen
- Department of Physiology, College of Medicine, Hallym University, Chuncheon, Gangwon 200‑702, Republic of Korea
| | - Hyun-Jin Tae
- Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 200‑702, Republic of Korea
| | - Jae-Chul Lee
- Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - Ji Yun Ahn
- Department of Emergency Medicine, Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Gyeonggi 431‑796, Republic of Korea
| | - Dong Won Kim
- Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - Jun Hwi Cho
- Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - Moo-Ho Won
- Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
| | - Seongkweon Hong
- Department of Surgery, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
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Nabavi SF, Braidy N, Gortzi O, Sobarzo-Sanchez E, Daglia M, Skalicka-Woźniak K, Nabavi SM. Luteolin as an anti-inflammatory and neuroprotective agent: A brief review. Brain Res Bull 2015; 119:1-11. [PMID: 26361743 DOI: 10.1016/j.brainresbull.2015.09.002] [Citation(s) in RCA: 288] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 09/02/2015] [Accepted: 09/03/2015] [Indexed: 11/19/2022]
Abstract
According to the World Health Organization, two billion people will be aged 60 years or older by 2050. Aging is a major risk factor for a number of neurodegenerative disorders. These age-related disorders currently represent one of the most important and challenging health problems worldwide. Therefore, much attention has been directed towards the design and development of neuroprotective agents derived from natural sources. These phytochemicals have demonstrated high efficacy and low adverse effects in multiple in vitro and in vivo studies. Among these phytochemicals, dietary flavonoids are an important and common chemical class of bioactive products, found in several fruits and vegetables. Luteolin is an important flavone, which is found in several plant products, including broccoli, pepper, thyme, and celery. Numerous studies have shown that luteolin possesses beneficial neuroprotective effects both in vitro and in vivo. Despite this, an overview of the neuroprotective effects of luteolin has not yet been accomplished. Therefore, the aim of this paper is to provide a review of the available literature regarding the neuroprotective effects of luteolin and its molecular mechanisms of action. Herein, we also review the available literature regarding the chemistry of luteolin, its herbal sources, and bioavailability as a pharmacological agent for the treatment and management of age-related neurodegenerative disorders.
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Affiliation(s)
- Seyed Fazel Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Nady Braidy
- Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Australia
| | - Olga Gortzi
- Department of Food Technology, Technological Educational Institution of Thessaly, Terma N. Temponera Str., Greece
| | - Eduardo Sobarzo-Sanchez
- Laboratory of Pharmaceutical Chemistry, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostel, 15782 Santiago de Compostela, Spain
| | - Maria Daglia
- Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Italy
| | - Krystyna Skalicka-Woźniak
- Department of Pharmacognosy with Medicinal Plants Unit, Medical University of Lublin, Lublin, Poland
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Qi Z, Xu Y, Liang Z, Li S, Wang J, Wei Y, Dong B. Naringin ameliorates cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in a type 2 diabetic rat model. Mol Med Rep 2015; 12:7093-101. [PMID: 26300349 DOI: 10.3892/mmr.2015.4232] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 07/17/2015] [Indexed: 11/06/2022] Open
Abstract
Naringenin is a flavonoid polyphenolic compound, which facilitates the removal of free radicals, oxidative stress and inflammation. The present study aimed to obtain a better understanding of the effects of curcumin on the regulation of diabetes‑associated cognitive decline, and its underlying mechanisms. An experimental diabetes mellitus (DM) rat model was induced by streptozoticin (50 mg/kg). Following treatment with naringin (100 and 200 mg/kg) for 16 weeks, the body weight and blood glucose levels of the DM rats were measured. A morris water maze test was used to analyze the effects of naringin on the cognitive deficit of the DM rats. The levels of oxidative stress, proinflammatory factors, caspase‑3 and caspase‑9, and the protein expression of peroxisome proliferator‑activated receptor γ (PPARγ) were quantified in the DM rats using a commercially‑available kit and western blot assay, respectively. In addition, a GW9662 PPARγ inhibitor (0.3 mg/kg) was administered to the DM rats to determine whether PPARγ affected the effects of naringin on the cognitive deficit of the DM rats. The results demonstrated that naringin increased the body weight, blood glucose levels, and cognitive deficits of the DM rats. The levels of oxidative stress and proinflammatory factors in the naringin‑treated rats were significantly lower, compared with those of the DM rats. In addition, naringin activated the protein expression of PPARγ, and administration of the PPARγ inhibitor decreased the protein expression of PPARγ, and attenuated the effects of naringin on cognitive deficit. The results also demonstrated that naringin decreased the expression levels of caspase‑3 and caspase‑9 in the DM rats. These results suggested that naringin ameliorated cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in the type 2 diabetic rat model. Furthermore, oxidative stress, proinflammatory factors and PPARγ signaling may be involved in mediating these effects.
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Affiliation(s)
- Zhonghua Qi
- Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Yinghui Xu
- Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Zhanhua Liang
- Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Sheng Li
- Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Jie Wang
- Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Yi Wei
- Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Bin Dong
- Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
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Ma P, Mao XY, Li XL, Ma Y, Qiao YD, Liu ZQ, Zhou HH, Cao YG. Baicalin alleviates diabetes‑associated cognitive deficits via modulation of mitogen-activated protein kinase signaling, brain‑derived neurotrophic factor and apoptosis. Mol Med Rep 2015; 12:6377-83. [PMID: 26300488 DOI: 10.3892/mmr.2015.4219] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Accepted: 07/21/2015] [Indexed: 11/06/2022] Open
Abstract
Baicalin is an important active component of the medicinal herb Scutellaria baicalensis Georgi and has shown a variety of pharmacological actions. The present study aimed to evaluate the neuroprotective effects of baicalin against diabetes‑associated cognitive deficits (DACD) in rats and to elucidate the potential molecular mechanisms of action. A rat model of diabetes mellitus was prepared by intraperitoneal injection of streptozotocin. After the successful establishment of the diabetic rat model, baicalin (50, 100 and 200 mg/kg) or vehicle was administrated for seven weeks. Learning and memory function were assessed using the Morris water maze test. At the end of the experiment, the activities of acetylcholinesterase (AChE) and choline acetylase (ChAT) were determined using commercial kits. Furthermore, the expression of proteins involved in mitogen‑activated protein kinase (MAPK) cascades [extracellular signal‑regulated kinase (ERK), c‑Jun N‑terminal kinase (JNK) and p38], brain‑derived neurotrophic factor (BDNF) and apoptosis‑associated proteins [caspase‑3, B-cell lymphoma 2 (Bcl‑2) and Bcl-2-associated X protein (Bax)] were detected by western blot analysis. Caspase‑3 activity was also analyzed using a commercial kit. The results demonstrated that diabetic rats exhibited decreases in body weight, decreases in the percentage of time spent in the target quadrant and the number of times of crossing the platform in the water maze test, as well as decreases in neuronal survival, ChAT, phosphorylated (p)ERK, BDNF and Bcl‑2. Furthermore, diabetic rats showed increases in escape latency and mean path length in the water maze test, increases in the levels of hippocampal AChE, p‑JNK, p‑p38, caspase‑3 and Bax as well as plasma glucose. However, in diabetic rats treated with baicalin, all of the abovementioned observations were obviously reversed. The findings suggested that baicalin exerts neuroprotective effects against DACD via modulation of MAPK cascades, BDNF and apoptosis.
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Affiliation(s)
- Ping Ma
- Department of Anatomy, Daqing Campus of Harbin Medical University, Daqing, Heilongjiang 163319, P.R. China
| | - Xiao-Yuan Mao
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Xiao-Lei Li
- Department of Pathology, College of Basic Medical Sciences, Daqing Campus of Harbin Medical University, Daqing, Heilongjiang 163319, P.R. China
| | - Ying Ma
- Department of Pathology, College of Basic Medical Sciences, Daqing Campus of Harbin Medical University, Daqing, Heilongjiang 163319, P.R. China
| | - Yuan-Dong Qiao
- Department of Pharmacology, Daqing Campus of Harbin Medical University, Daqing, Heilongjiang 163319, P.R. China
| | - Zhao-Qian Liu
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Hong-Hao Zhou
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Yong-Gang Cao
- Department of Pharmacology, Daqing Campus of Harbin Medical University, Daqing, Heilongjiang 163319, P.R. China
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Hong BY, Kim JS, Lee KB, Lim SH. The effect of sesamol on rats with ischemic stroke. J Phys Ther Sci 2015; 27:1771-3. [PMID: 26180317 PMCID: PMC4499980 DOI: 10.1589/jpts.27.1771] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 02/14/2015] [Indexed: 11/24/2022] Open
Abstract
[Purpose] Although previous studies have demonstrated several effects of sesamol on
neurological diseases, its effects on ischemic stroke are unclear. We evaluated the direct
effects of sesamol on infarcts and efficacy in terms of functional improvement in rats
with transient middle cerebral artery occlusion (MCAO). [Subjects and Methods] Male
Sprague Dawley rats (n = 30) were randomly divided into two groups: an MCAO with sesamol
group and an MCAO group. MCAO was induced for 2 h, and sesamol was administered in the
treatment group just after reperfusion. Infarct size was calculated 5 days after MCAO.
Efficacy in function was assessed using a modified sticky-tape test (MST) and percent
weight borne on the paretic leg during 5 days. [Results] Infarct volumes did not differ
significantly between the two MCAO groups. The values of MST did not differ between the
two MCAO groups. Based on the values of percent weight borne on the paretic leg, function
of the hindlimb in the MCAO with sesamol group was significantly better than in the MCAO
group throughout the experimental period. [Conclusion] These results demonstrate that
sesamol induced functional improvements during 5 days after MCAO, and could be a useful
addition to the therapeutic regimen for the treatment of ischemic stroke.
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Affiliation(s)
- Bo Young Hong
- Department of Rehabilitation Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Joon Sung Kim
- Department of Rehabilitation Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Kyoung Bo Lee
- Department of Rehabilitation Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Seong Hoon Lim
- Department of Rehabilitation Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
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Effect of Ginseng (Panax ginseng) Berry EtOAc Fraction on Cognitive Impairment in C57BL/6 Mice under High-Fat Diet Inducement. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:316527. [PMID: 26161118 PMCID: PMC4486251 DOI: 10.1155/2015/316527] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Revised: 05/08/2015] [Accepted: 05/11/2015] [Indexed: 12/30/2022]
Abstract
High-fat diet-induced obesity leads to type 2 diabetes. Recently, there has been growing apprehension about diabetes-associated cognitive impairment (DACM). The effect of ginseng (Panax ginseng) berry ethyl acetate fraction (GBEF) on mice with high-fat diet-induced cognitive impairment was investigated to confirm its physiological function. C57BL/6 mice were fed a high-fat diet for 5 weeks and then a high-fat diet with GBEF (20 and 50 mg/kg of body weight) for 4 weeks. After three in vivo behavioral tests (Y-maze, passive avoidance, and Morris water maze tests), blood samples were collected from the postcaval vein for biochemical analysis, and whole brains were prepared for an ex vivo test. A method based on ultra-performance liquid chromatography (UPLC) accurate-mass quadrupole time-of-flight mass spectrometry (Q-TOF/MS) was used to determine major ginsenosides. GBEF decreased the fasting blood glucose levels of high-fat diet-induced diabetes mellitus (DM) mice and improved hyperglycemia. Cognitive behavior tests were examined after setting up the DM mice. The in vivo experiments showed that mice treated with GBEF exhibited more improved cognitive behavior than DM mice. In addition, GBEF effectively inhibited the acetylcholinesterase (AChE) activity and malondialdehyde (MDA) levels of DM mice brain tissues. Q-TOF UPLC/MS analyses of GBEF showed that ginsenoside Re was the major ginsenoside.
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Neuroprotective potential of sesamol and its loaded solid lipid nanoparticles in ICV-STZ-induced cognitive deficits: behavioral and biochemical evidence. Eur J Pharmacol 2014; 747:132-40. [PMID: 25449035 DOI: 10.1016/j.ejphar.2014.11.014] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 11/10/2014] [Accepted: 11/11/2014] [Indexed: 01/08/2023]
Abstract
Neuroinflammation is a prominent feature of Alzheimer disease (AD) and other chronic neurodegenerative disorders. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental paradigm of Alzheimer׳s disease. Sesamol is a potent inhibitor of cytokine production as well as an antioxidant. The present study was designed to evaluate the effectiveness of sesamol in ICV-STZ-induced cognitive deficits in rats by incorporating it into solid lipid nanoparticles (SLNs). ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced nitrodative stress, altered acetylcholinesterase in rat brain along with significantly increased serum TNF-α levels. Chronic treatment with sesamol and sesamol loaded SLNs dose dependently restored cognitive deficits in ICV-STZ rats along with mitigation of nitrodative stress and cytokine release. Effectiveness of SLNs to deliver sesamol to the brain was shown by a significantly better alleviation of the oxidative stress parameters. Our findings demonstrate that loading of sesamol in SLNs is an effective strategy to mitigate ICV-STZ-induced neuronal dysfunction and memory deficits.
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Fu X, Zhang J, Guo L, Xu Y, Sun L, Wang S, Feng Y, Gou L, Zhang L, Liu Y. Protective role of luteolin against cognitive dysfunction induced by chronic cerebral hypoperfusion in rats. Pharmacol Biochem Behav 2014; 126:122-30. [PMID: 25220684 DOI: 10.1016/j.pbb.2014.09.005] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Revised: 09/03/2014] [Accepted: 09/06/2014] [Indexed: 12/22/2022]
Abstract
Chronic cerebral hypoperfusion, a mild ischemic condition, is associated with the cognitive deficits of Alzheimer's disease (AD). Luteolin, a polyphenolic compound found in foods of plant origin, belonging to the flavone subclass of flavonoids, has been shown to possess antioxidant, anti-inflammatory and antitumorigenic properties. In the present study, the effects of luteolin on chronic cerebral hypoperfusion-associated neurocognitive pathologies were investigated by using rats with permanent bilateral common carotid artery occlusion, a rat model of chronic cerebral hypoperfusion. As expected, we found that luteolin could attenuate cognitive dysfunction in chronic cerebral hypoperfused rats, as assessed using Morris water maze tests. Daily oral administration of luteolin (50, 100 and 200mg/kg) significantly scavenged oxygen free radicals, enhanced antioxidant potential, decreased the lipid peroxide production and suppressed inflammatory reaction in the cerebral cortex and hippocampus induced by chronic cerebral hypoperfusion. Meanwhile, the results indicated that cerebral hypoperfusion activated nuclear factor-κB (NF-κB), increased the expression of β-site amyloid precursor protein cleaving enzyme (BACE1), as well as elevated amyloid beta (Aβ) levels in the cortex and hippocampus. However, long-term administration of luteolin significantly down-regulated the expression of NF-κB and BACE1, accompanied by diminishing the deposition of Aβ. Our results suggest a potential therapeutic use of luteolin for cerebral hypoperfusion associated cognitive dysfunction in AD.
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Affiliation(s)
- Xiaobin Fu
- School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China.
| | - Jingzheng Zhang
- School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China.
| | - Ling Guo
- Department of dermatological of People's hospital of Liaocheng, Liaocheng, 252000, Shandong Province, PR China.
| | - Yaguang Xu
- Department of nephrology of the Second People's hospital of Liaocheng affiliated to Taishan Meidical College, Linqing, 252600, Shandong Province, PR China.
| | - Lingyan Sun
- School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China.
| | - Shuaishuai Wang
- School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China.
| | - Yan Feng
- School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China.
| | - Lingshan Gou
- School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China.
| | - Ling Zhang
- School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China.
| | - Yi Liu
- School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China.
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50
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Yang RH, Lin J, Hou XH, Cao R, Yu F, Liu HQ, Ji AL, Xu XN, Zhang L, Wang F. Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition: involvement of PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways. Neuroscience 2014; 274:218-28. [PMID: 24881575 DOI: 10.1016/j.neuroscience.2014.05.042] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 05/17/2014] [Accepted: 05/21/2014] [Indexed: 12/01/2022]
Abstract
Accumulating evidence suggested that hyperglycemia played a critical role in hippocampus dysfunction in patients with diabetes mellitus. However, the multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown to enhance learning and memory and affect neural function in various experimental conditions. The present study investigated the effects of DHA on the lipid peroxidation, the level of inflammatory cytokines and neuron apoptosis in the hippocampal neurons in high-glucose condition. High-glucose administration increased the level of tumor necrosis factor α (TNF-α) and IL-6, induced oxidative stress and apoptosis of hippocampal neurons in vitro. DHA treatment reduced oxidative stress and TNF-α expression, protected the hippocampal neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9 expression. These results suggested that high-glucose exposure induced injury of hippocampal neurons in vitro, and the principle mechanisms involved in the neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential. DHA may thus be of use in preventing or treating neuron-degeneration resulting from hyperglycemia.
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Affiliation(s)
- R-H Yang
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
| | - J Lin
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China
| | - X-H Hou
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China
| | - R Cao
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China
| | - F Yu
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China
| | - H-Q Liu
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China
| | - A-L Ji
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China
| | - X-N Xu
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China
| | - L Zhang
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China
| | - F Wang
- Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
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