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Zhao X, Zheng I, Huang W, Tang D, Zhao M, Hou R, Huang Y, Shi Y, Zhu W, Wang S. Research Progress on the Mechanism of Bile Acids and Their Receptors in Depression. Int J Mol Sci 2025; 26:4023. [PMID: 40362260 PMCID: PMC12071821 DOI: 10.3390/ijms26094023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/17/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
Depression, a highly prevalent mental disorder worldwide, arises from multifaceted interactions involving neurotransmitter imbalances, inflammatory responses, and gut-brain axis dysregulation. Emerging evidence highlights the pivotal role of bile acids (BAs) and their receptors, including farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), and liver X receptors (LXRs) in depression pathogenesis through modulation of neuroinflammation, gut microbiota homeostasis, and neural plasticity. Clinical investigations demonstrated altered BA profiles in depressed patients, characterized by decreased primary BAs (e.g., chenodeoxycholic acid (CDCA)) and elevated secondary BAs (e.g., lithocholic acid (LCA)), correlating with symptom severity. Preclinical studies revealed that BAs ameliorate depressive-like behaviors via dual mechanisms: direct CNS receptor activation and indirect gut-brain signaling, regulating neuroinflammation, oxidative stress, and BDNF/CREB pathways. However, clinical translation faces challenges including species-specific BA metabolism, receptor signaling complexity, and pharmacological barriers (e.g., limited blood-brain barrier permeability). While FXR/TGR5 agonists exhibit neuroprotective and anti-inflammatory potential, their adverse effects (pruritus, dyslipidemia) require thorough safety evaluation. Future research should integrate multiomics approaches and interdisciplinary strategies to develop personalized BA-targeted therapies, advancing novel treatment paradigms for depression.
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Affiliation(s)
- Xue Zhao
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Iin Zheng
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Wenjing Huang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Dongning Tang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Meidan Zhao
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
- School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
| | - Ruiling Hou
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Ying Huang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Yun Shi
- Hebei Key Laboratory of Early Life Health Promotion, Hebei Medical University, Shijiazhuang 050031, China;
| | - Weili Zhu
- National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence Research, Peking University, Beijing 100191, China
| | - Shenjun Wang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
- School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
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Idahosa SO, Diarra R, Ranu HK, Nasiri RH, Higuchi S. Evidence and Mechanism of Bile Acid-Mediated Gut-Brain Axis in Anxiety and Depression. THE AMERICAN JOURNAL OF PATHOLOGY 2025; 195:163-173. [PMID: 39566821 DOI: 10.1016/j.ajpath.2024.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 09/19/2024] [Accepted: 10/29/2024] [Indexed: 11/22/2024]
Abstract
Bidirectional communication between the brain and gastrointestinal tract, called the gut-brain axis, is linked with our emotions. Intestinal lipids, hormones, and molecules, such as bile acids (BAs), impact our mood, motivation, and emotions via the gut-brain axis. BAs are synthesized from cholesterol in the liver and serve as a regulator of lipid metabolism and hormonal secretion in the intestine. Human studies have indicated that the alteration of plasma BA levels is associated with depression and anxiety. Several possible mechanisms, such as BA receptor-dependent and receptor-independent mechanisms, have been reported for emotional control. Animal studies have indicated that the deletion of BA receptors shows behavioral abnormalities. BAs regulate gut hormones, glucagon-like peptide-1 secretion, bioactive lipids, oleoylethanolamide, and the immune system function, which influences neural activities. Thus, BAs act as an emotional regulator. This review aims to summarize the following: clinical evidence of BA concentration linked to mental disorders, including depression and anxiety; and animal studies of BA-related signaling correlated with its neurobehavioral effect supporting its mechanism. We will also discuss future research required for further neurobehavioral treatment.
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Affiliation(s)
- Sydney O Idahosa
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York
| | - Rokia Diarra
- Department of Biology, St. John's University, Queens, New York
| | - Hernoor K Ranu
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York
| | - Raidah H Nasiri
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York
| | - Sei Higuchi
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York.
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Fang RY, Pan XR, Zeng XX, Li ZZ, Chen BF, Zeng HM, Peng J. Gut-brain axis as a bridge in obesity and depression: Mechanistic exploration and therapeutic prospects. World J Psychiatry 2025; 15:101134. [PMID: 39831021 PMCID: PMC11684226 DOI: 10.5498/wjp.v15.i1.101134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 11/02/2024] [Accepted: 11/18/2024] [Indexed: 12/18/2024] Open
Abstract
A recent study by Wang et al, published in the World Journal of Psychiatry, provided preventative and therapeutic strategies for the comorbidity of obesity and depression. The gut-brain axis, which acts as a two-way communication system between the gastrointestinal tract and the central nervous system, plays a pivotal role in the pathogenesis of these conditions. Evidence suggests that metabolic byproducts, such as short-chain fatty acids, lipopolysaccharide and bile acids, which are generated by the gut microbiota, along with neurotransmitters and inflammatory mediators within the gut-brain axis, modulate the host's metabolic processes, neuronal regulation, and immune responses through diverse mechanisms. The interaction between obesity and depression via the gut-brain axis involves disruptions in the gut microbiota balance, inflammatory immune responses, and alterations in the neuroendocrine system. Modulating the gut-brain axis, for example, through a ketogenic diet, the use of probiotics, and the supplementation of antioxidants, offers new remedial approaches for obesity and depression. Future research that explores the mechanisms of the gut-brain axis is needed to provide more evidence for clinical treatment.
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Affiliation(s)
- Rui-Ying Fang
- The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Xiao-Rui Pan
- The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Xin-Xing Zeng
- The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zheng-Zheng Li
- The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Bo-Fan Chen
- The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Hai-Min Zeng
- The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Jie Peng
- The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
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Frumuzachi O, Kieserling H, Rohn S, Mocan A. The impact of oleuropein, hydroxytyrosol, and tyrosol on cardiometabolic risk factors: a meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr 2025:1-21. [PMID: 39828996 DOI: 10.1080/10408398.2025.2453090] [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: 01/22/2025]
Abstract
The so-called Mediterranean diet, with olive oil as a key component, is effective in reducing cardiometabolic disease risk. Olive oil consumption improves blood pressure, insulin levels and resistance, supporting heart health and glycemic control. Its phenolic compounds, including oleuropein (OLE), hydroxytyrosol (HT), and tyrosol (TYR) are hypothesized to likely contribute to these benefits. Thus, this meta-analysis evaluated the clinical effects of dietary supplementation with OLE, HT, and TYR on cardiometabolic outcomes. Fourteen human intervention studies with 594 participants were included. The analysis using a random-effects model showed that OLE, HT, and TYR significantly reduced total cholesterol (SMD = -0.19, CI: -0.37 to -0.01, p = 0.04, I2 = 35%), triacylglycerol (SMD = -0.32, CI: -0.60 to -0.03, p = 0.03, I2 = 73%), and insulin (SMD = -0.42, CI: -0.82 to -0.01, p = 0.04, I2 = 78%). Subgroup analysis showed that, in certain contexts, interventions may be more beneficial for BMI <30, non-Mediterranean, and cardiometabolic disease individuals, while intervention compound, type of intervention, and duration might have differential effects regarding considered outcomes. Overall, the meta-analysis suggests that supplementation with OLE, HT, and TYR may beneficially impact some cardiometabolic parameters, though further studies are needed to confirm these findings.
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Affiliation(s)
- Oleg Frumuzachi
- Department of Food Chemistry and Analysis, Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Berlin, Germany
- Department of Pharmaceutical Botany, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Helena Kieserling
- Department of Food Chemistry and Analysis, Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Berlin, Germany
| | - Sascha Rohn
- Department of Food Chemistry and Analysis, Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Berlin, Germany
| | - Andrei Mocan
- Department of Pharmaceutical Botany, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Laboratory of Chromatography, Institute of Advanced Horticulture Research of Transylvania, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
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Lillis JB, Willmott AGB, Chichger H, Roberts JD. The Application of Olive-Derived Polyphenols on Exercise-Induced Inflammation: A Scoping Review. Nutrients 2025; 17:223. [PMID: 39861354 PMCID: PMC11767577 DOI: 10.3390/nu17020223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/06/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES There is current scientific interest pertaining to the therapeutic effects of olive-derived polyphenols (ODPs), in particular their associated anti-inflammatory properties, following the wealth of research surrounding the physiological impact of the Mediterranean Diet (MD). Despite this association, the majority of the current literature investigates ODPs in conjunction with metabolic diseases. There is limited research focusing on ODPs and acute inflammation following exercise, regardless of the knowledge surrounding the elevated inflammatory response during this time. Therefore, the aim of this scoping review is to understand the impact ODPs may have on exercise-induced inflammation. METHODS This scoping review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScRs). The literature searches were conducted in PubMed and EBSCOhost and considered for review if records reported original data, examined olives, olive-derived nutrients, food sources, or ODPs in conjunction with exercise-induced inflammation (including known causes, associations, and proxy measures). RESULTS Seven studies investigated ODPs and exercise-induced inflammation, providing commentary on reduced oxidative stress, inflammatory biomarkers, and immune biomarkers, enhanced antioxidant defenses and modulations in mitochondrial function, albeit in low numbers. An average of 100.9 mg∙d-1 ODPs were supplemented for an average of 40 days, with hydroxytyrosol (HT) being the primary ODP investigated. Six studies employed individual aerobic exercise as their stimulus, whilst one study investigated the impact of an acute dose of ODP. CONCLUSIONS There is a limited consensus on the direction of isolated HT in human models, whereas animal models suggest a reduced inflammatory response following ≥2 weeks HT supplementation in conjunction with chronic exercise. Future research should initially investigate the inflammatory response of ODP, with particular focus on HT, and aim to identify an optimum dose and time course for supplementation surrounding exercise to support acute recovery and exercise adaptations.
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Affiliation(s)
- Joseph B. Lillis
- Cambridge Centre for Sport and Exercise Sciences (CCSES), Faculty of Science and Engineering, Anglia Ruskin University, Cambridge CB1 1PT, UK; (A.G.B.W.); (J.D.R.)
| | - Ashley G. B. Willmott
- Cambridge Centre for Sport and Exercise Sciences (CCSES), Faculty of Science and Engineering, Anglia Ruskin University, Cambridge CB1 1PT, UK; (A.G.B.W.); (J.D.R.)
| | - Havovi Chichger
- School of Life Sciences, Faculty of Science and Engineering, Anglia Ruskin University, Cambridge CB1 1PT, UK;
| | - Justin D. Roberts
- Cambridge Centre for Sport and Exercise Sciences (CCSES), Faculty of Science and Engineering, Anglia Ruskin University, Cambridge CB1 1PT, UK; (A.G.B.W.); (J.D.R.)
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Eedy V, Aucoin M. The role of olive oil and its constituents in mental health: a scoping review. Br J Nutr 2024:1-11. [PMID: 39696776 DOI: 10.1017/s000711452400299x] [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: 12/20/2024]
Abstract
Mounting evidence suggests that the Mediterranean diet has a beneficial effect on mental health. It has been hypothesised that this effect is mediated by a variety of foods, nutrients and constituents; however, there is a need for research elucidating which of these components contribute to the therapeutic effect. This scoping review sought to systematically search for and synthesise the research on olive oil and its constituents and their impact on mental health, including the presence or absence of a mental illness or the severity or progression of symptoms. PubMed and OVID MEDLINE databases were searched. The following article types were eligible for inclusion: human experimental and observational studies, animal and preclinical studies. Abstracts were screened in duplicate, and data were extracted using a piloted template. Data were analysed qualitatively to assess trends and gaps for further study. The PubMed and OVID MEDLINE search yielded 544 and 152 results, respectively. After full-text screening, forty-nine studies were eligible for inclusion, including seventeen human experimental, eighteen observational and fourteen animal studies. Of these, thirteen human and four animal studies used olive oil as a comparator. Observational studies reported inconsistent results, specifically five reporting higher rates of mental illness, eight reporting lower and five reporting no association with higher olive oil intake. All human experimental studies and nine of ten animal studies that assess olive oil as an intervention reported an improvement of anxiety or depression symptoms. Olive oil may benefit mental health outcomes. However, more experimental research is needed.
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Affiliation(s)
- Vanessa Eedy
- Canadian College of Naturopathic Medicine, 1255 Sheppard Ave E, Toronto, ONM2K 1E2, Canada
| | - Monique Aucoin
- Canadian College of Naturopathic Medicine, 1255 Sheppard Ave E, Toronto, ONM2K 1E2, Canada
- University of Guelph, 50 Stone Rd E, Guelph, ONN1G 2W1, Canada
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Loukou S, Papantoniou G, Pantazaki A, Tsolaki M. The Role of Greek Olive Leaf Extract in Patients with Mild Alzheimer's Disease (the GOLDEN Study): A Randomized Controlled Clinical Trial. Neurol Int 2024; 16:1247-1265. [PMID: 39585054 PMCID: PMC11587000 DOI: 10.3390/neurolint16060095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 10/03/2024] [Accepted: 10/15/2024] [Indexed: 11/26/2024] Open
Abstract
Background: Olive leaves are a significant source of biophenols, which have a beneficial impact on cognitive performance. Objective: To examine, for the first time, in humans the effect of the daily consumption of a beverage containing olive leaf extract (OLE) versus a Mediterranean diet (MeDi) on patients diagnosed with mild Alzheimer's Disease (AD), in addition to their regular treatment. Methods: A randomized clinical trial compared OLE's effects on cognitive and functional performance in 55 mild AD patients. Each participant was randomly assigned to two groups: (1) Group 1 was given olive leaves for making a daily beverage and MeDi instructions through monthly diet programs; (2) Group 2 received only the MeDi instructions. After six months, all participants underwent a second neuropsychological evaluation. Results: Group 1 participants had statistically significantly higher MMSE scores compared to Group 2 with a p-value of 0.0135. Specifically, the mean MMSE difference in patients receiving OLE was close to 0, indicating no memory deterioration, whereas in controls it was -4.1, indicative of cognitive decline. The remaining neuropsychological assessments (FRSSD, FUCAS, ADAS-Cog, CDR, GDS, and NPI) revealed better results in the OLE group, except for GDS, which showed no change, but without statistically significant differences between the two groups.
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Affiliation(s)
- Sofia Loukou
- 1st Department of Neurology, Medical School, “AHEPA” General Hospital Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, 54124 Thessaloniki, Greece;
- Greek Association of Alzheimer’s Disease and Related Disorders—GAADRD, 54124 Thessaloniki, Greece
- Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.P.); (A.P.)
| | - Georgia Papantoniou
- Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.P.); (A.P.)
- Laboratory of Psychology, Department of Early Childhood Education, School of Education, University of Ioannina, 45110 Ioannina, Greece
| | - Anastasia Pantazaki
- Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.P.); (A.P.)
- Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Magdalini Tsolaki
- 1st Department of Neurology, Medical School, “AHEPA” General Hospital Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, 54124 Thessaloniki, Greece;
- Greek Association of Alzheimer’s Disease and Related Disorders—GAADRD, 54124 Thessaloniki, Greece
- Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.P.); (A.P.)
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Papadopoulou P, Polissidis A, Kythreoti G, Sagnou M, Stefanatou A, Theoharides TC. Anti-Inflammatory and Neuroprotective Polyphenols Derived from the European Olive Tree, Olea europaea L., in Long COVID and Other Conditions Involving Cognitive Impairment. Int J Mol Sci 2024; 25:11040. [PMID: 39456822 PMCID: PMC11507169 DOI: 10.3390/ijms252011040] [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: 07/16/2024] [Revised: 10/03/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
The European olive tree, Olea europaea L., and its polyphenols hold great therapeutic potential to treat neuroinflammation and cognitive impairment. This review examines the evidence for the anti-inflammatory and neuroprotective actions of olive polyphenols and their potential in the treatment of long COVID and neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Key findings suggest that olive polyphenols exhibit antioxidant, anti-inflammatory, neuroprotective, and antiviral properties, making them promising candidates for therapeutic intervention, especially when formulated in unique combinations. Recommendations for future research directions include elucidating molecular pathways through mechanistic studies, exploring the therapeutic implications of olive polyphenol supplementation, and conducting clinical trials to assess efficacy and safety. Investigating potential synergistic effects with other agents addressing different targets is suggested for further exploration. The evidence reviewed strengthens the translational value of olive polyphenols in conditions involving cognitive dysfunction and emphasizes the novelty of new formulations.
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Affiliation(s)
- Paraskevi Papadopoulou
- Department of Science and Mathematics, Deree-The American College of Greece, 15342 Athens, Greece; (P.P.)
| | - Alexia Polissidis
- Department of Science and Mathematics, Deree-The American College of Greece, 15342 Athens, Greece; (P.P.)
| | - Georgia Kythreoti
- Department of Science and Mathematics, Deree-The American College of Greece, 15342 Athens, Greece; (P.P.)
| | - Marina Sagnou
- Institute of Biosciences and Applications, National Centre for Scientific Research Demokritos, 15310 Athens, Greece;
| | - Athena Stefanatou
- School of Graduate & Professional Education, Deree–The American College of Greece, 15342 Athens, Greece
| | - Theoharis C. Theoharides
- Institute for Neuro-Immune Medicine-Clearwater, Clearwater, FL 33759, USA
- Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA
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Cao X, Gao T, Lv F, Wang Y, Li B, Wang X. ROS-triggered and macrophage-targeted micelles modulate mitochondria function and polarization in obesity. NANOTECHNOLOGY 2024; 35:475707. [PMID: 39240071 DOI: 10.1088/1361-6528/ad7034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 08/16/2024] [Indexed: 09/07/2024]
Abstract
Inflammation involving adipose macrophages is an important inducer of obesity. Regulating macrophages polarization and improving the inflammatory microenvironment of adipose tissue is a new strategy for the treatment of obesity. An amphiphilic chondroitin sulfate phenylborate derivative (CS-PBE) was obtained by modifying the main chain of chondroitin sulfate with the hydrophobic small molecule phenylborate. Using CS-PBE self-assembly, macrophage targeting, reactive oxygen species (ROS) release and celastrol (CLT) encapsulation were achieved. The cytotoxicity, cellular uptake, internalization pathways and transmembrane transport efficiency of CS-PBE micelles were studied in Caco-2 and RAW264.7 cells. Hemolysis and organotoxicity tests were performed to assess the safety of the platform, while its therapeutic efficacy was investigated in high-fat diet-induced obese mice. Multifunctional micelles with macrophage targeting and ROS clearance capabilities were developed to improve the efficacy of CLT in treating obesity.In vitrostudies indicated that CS-PBE micelles had better ability to target M1 macrophages, better protective effects on mitochondrial function, better ability to reduce the number of LPS-stimulated M1 macrophages, better ability to reduce the number of M2 macrophages, and better ability to scavenge ROS in inflammatory macrophages.In vivostudies have shown that CS-PBE micelles improve inflammation and significantly reduce toxicity of CLT in the treatment of obesity. In summary, CS-PBE micelles could significantly improve the ability to target inflammatory macrophages and scavenge ROS in adipose tissue to alleviate inflammation, suggesting that CS-PBE micelles are a highly promising approach for the treatment of obesity.
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Affiliation(s)
- Xi Cao
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, People's Republic of China
- The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, Anhui, People's Republic of China
| | - Tingting Gao
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, People's Republic of China
- The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, Anhui, People's Republic of China
| | - Fengwen Lv
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, People's Republic of China
- The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, Anhui, People's Republic of China
| | - Yongchun Wang
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, People's Republic of China
- The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, Anhui, People's Republic of China
| | - Bo Li
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, People's Republic of China
- The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, Anhui, People's Republic of China
| | - Xiaohua Wang
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, People's Republic of China
- The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, Anhui, People's Republic of China
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Pezzino S, Sofia M, Mazzone C, Litrico G, Greco LP, Gallo L, La Greca G, Latteri S. Innovative treatments for obesity and NAFLD: A bibliometric study on antioxidants, herbs, phytochemicals, and natural compounds. Heliyon 2024; 10:e35498. [PMID: 39220898 PMCID: PMC11365328 DOI: 10.1016/j.heliyon.2024.e35498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 07/19/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
The increasing scientific interest in antioxidants and naturally derived compounds as potential remedies for obesity and non-alcoholic fatty liver disease (NAFLD) has led to extensive research. The objective of this bibliometric analysis is to present an updated perspective on the topic of antioxidants, herbs, phytochemicals, and natural compounds, in the control of obesity and NAFLD, to identify new areas for future research. Publications from the years 2012-2022 were retrieved using the Scopus database. The research trends were analyzed using the Biblioshiny and VOSviewer tools. The field has seen a significant increase in research activity, as indicated by an annual growth rate of 10 % in the number of published manuscripts. China, Korea, and the USA emerged as the most prominent contributors in this specific field, supported by their notable volumes of publications and citations. The density analysis revealed that the most frequently occurring authors' keywords related to herbal species are, in rank order, Camelia sinensis, Momordica charantia, Curcuma longa, Ilex paraguariensis, Panax ginseng, Moringa oleifera, Garcinia cambogia, Garcinia mangostana, Zingiber officinale, and Cinnamomum verum. In the group of antioxidants, phytochemicals, and natural compounds, the top 10 were resveratrol, curcumin, quercetin, vitamin E, alpha-lipoic acid, vitamin C, chlorogenic acid, lycopene, fucoxanthin, and berberine. The co-occurrence analysis unveiled significant themes and potential trends, including a notable interest in the impact of herbal species, antioxidants, phytochemicals, and natural compounds on obesity and NAFLD through the modulation of the gut microbiome. Another recurring theme that arises, is the ongoing investigation of molecular targets that demonstrate anti-adipogenesis properties. The analysis presented in this study provides valuable insights for researchers investigating the efficacy of antioxidants, herbs, phytochemicals, and natural compounds in addressing obesity and NAFLD. Through the use of bibliometric methods, the study offers a comprehensive overview. Furthermore, the findings of this analysis can serve as a foundation for future research in this specific domain.
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Affiliation(s)
- Salvatore Pezzino
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Maria Sofia
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Chiara Mazzone
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Giorgia Litrico
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Luigi Piero Greco
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Luisa Gallo
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Gaetano La Greca
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Saverio Latteri
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
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11
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Frumuzachi O, Gavrilaș LI, Vodnar DC, Rohn S, Mocan A. Systemic Health Effects of Oleuropein and Hydroxytyrosol Supplementation: A Systematic Review of Randomized Controlled Trials. Antioxidants (Basel) 2024; 13:1040. [PMID: 39334699 PMCID: PMC11428715 DOI: 10.3390/antiox13091040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 08/14/2024] [Accepted: 08/23/2024] [Indexed: 09/30/2024] Open
Abstract
Non-communicable diseases (NCDs) cause 41 million deaths annually, accounting for 74% of global fatalities. The so-called Mediterranean diet, with its especially significant consumption of olive oil, has shown promising results in reducing the risk of developing NCDs, such as cardiovascular, liver, or bone diseases. In the context of the nutritional health benefits of foods, phenolic compounds such as olive oil's main components, oleuropein (OLE) and hydroxytyrosol (HT), have been shown to possess different beneficial effects. However, no systematic review has evaluated the health-promoting effects of OLE and HT until now. Consequently, this systematic review analyzed 12 human randomized controlled trials (RCTs), involving 683 participants, to assess the effects of supplements, pure compounds, or enriched foods containing OLE and HT regarding systemic health outcomes, including CVD risk factors, liver parameters, and bone, joint, and cognitive health. The review found contrasting but encouraging results, with some studies reporting significant modulation of body weight, lipid profile, and glucose metabolism, and improvements in bone, joint, and cognitive functions. The studies described different dosages and forms of supplementation, ranging from 5 mg/d HT to 990 mL/d olive leaf infusion (320.8 mg OLE and 11.9 mg HT), highlighting the need for further research to determine the optimal dosing and duration. Despite the mixed outcomes, OLE and HT supplementation show potential for improving some of the cardiometabolic health outcomes and bone, joint, and cognitive health. However, further studies are necessary to understand their benefits better and address existing limitations.
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Affiliation(s)
- Oleg Frumuzachi
- Department of Pharmaceutical Botany, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania; (O.F.); (A.M.)
- Department of Food Chemistry and Analysis, Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
| | - Laura Ioana Gavrilaș
- Department of Bromatology, Hygiene, Nutrition, “Iuliu Hațieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Dan Cristian Vodnar
- Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 3-5 Mănăştur Street, 400372 Cluj-Napoca, Romania;
| | - Sascha Rohn
- Department of Food Chemistry and Analysis, Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
| | - Andrei Mocan
- Department of Pharmaceutical Botany, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania; (O.F.); (A.M.)
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12
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Sharma P, Tandel N, Kumar R, Negi S, Sharma P, Devi S, Saxena K, Chaudhary NR, Saini S, Kumar R, Chandel BS, Sijwali PS, Tyagi RK. Oleuropein activates autophagy to circumvent anti-plasmodial defense. iScience 2024; 27:109463. [PMID: 38562521 PMCID: PMC10982566 DOI: 10.1016/j.isci.2024.109463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 02/27/2024] [Accepted: 03/07/2024] [Indexed: 04/04/2024] Open
Abstract
Antimalarial drug resistance and unavailability of effective vaccine warrant for newer drugs and drug targets. Hence, anti-inflammatory activity of phyto-compound (oleuropein; OLP) was determined in antigen (LPS)-stimulated human THP-1 macrophages (macrophage model of inflammation; MMI). Reduction in the inflammation was controlled by the PI3K-Akt1 signaling to establish the "immune-homeostasis." Also, OLP treatment influenced the cell death/autophagy axis leading to the modulated inflammation for extended cell survival. The findings with MII prompted us to detect the antimalarial activity of OLP in the wild type (3D7), D10-expressing GFP-Atg18 parasite, and chloroquine-resistant (Dd2) parasite. OLP did not show the parasite inhibition in the routine in vitro culture of P. falciparum whereas OLP increased the antimalarial activity of artesunate. The molecular docking of autophagy-related proteins, investigations with MMI, and parasite inhibition assays indicated that the host activated the autophagy to survive OLP pressure. The challenge model of P. berghei infection showed to induce autophagy for circumventing anti-plasmodial defenses.
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Affiliation(s)
- Praveen Sharma
- Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
| | - Nikunj Tandel
- Institute of Science, Nirma University, SG highway, Ahmedabad 382481, India
| | - Rajinder Kumar
- Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
| | - Sushmita Negi
- Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
- Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India
| | - Prakriti Sharma
- Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
| | - Sonia Devi
- Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
- Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India
| | - Kanika Saxena
- Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India
- CSIR-Centre for Cellular & Molecular Biology, Hyderabad, Telangana, India
| | - Neil Roy Chaudhary
- Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
| | - Sheetal Saini
- Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
| | - Reetesh Kumar
- Faculty of Agricultural Sciences, Institute of Applied Sciences & Humanities, GLA University, Mathura 281406, India
| | - Bharat Singh Chandel
- Department of Animal Biotechnology, College of Veterinary Science and AH, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Gujarat 385 506, India
| | - Puran S. Sijwali
- Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India
- CSIR-Centre for Cellular & Molecular Biology, Hyderabad, Telangana, India
| | - Rajeev K. Tyagi
- Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
- Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India
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13
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Lun W, Yan Q, Guo X, Zhou M, Bai Y, He J, Cao H, Che Q, Guo J, Su Z. Mechanism of action of the bile acid receptor TGR5 in obesity. Acta Pharm Sin B 2024; 14:468-491. [PMID: 38322325 PMCID: PMC10840437 DOI: 10.1016/j.apsb.2023.11.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 09/17/2023] [Accepted: 10/24/2023] [Indexed: 02/08/2024] Open
Abstract
G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research.
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Affiliation(s)
- Weijun Lun
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Qihao Yan
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Xinghua Guo
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Minchuan Zhou
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yan Bai
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China
| | - Jincan He
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China
| | - Hua Cao
- School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458, China
| | - Qishi Che
- Guangzhou Rainhome Pharm & Tech Co., Ltd., Science City, Guangzhou 510663, China
| | - Jiao Guo
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Zhengquan Su
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
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14
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Liu S, Chen X, He J, Luo Y, Zheng P, Yu B, Chen D, Huang Z. Oleanolic acid promotes skeletal muscle fiber type transformation by activating TGR5-mediated CaN signaling pathway. J Nutr Biochem 2024; 123:109507. [PMID: 37890712 DOI: 10.1016/j.jnutbio.2023.109507] [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: 07/18/2023] [Revised: 09/27/2023] [Accepted: 10/24/2023] [Indexed: 10/29/2023]
Abstract
In recent years, the impact of bile acids and their representative G protein-coupled bile acid receptor 1 Takeda-G-protein-receptor-5 (TGR5) signaling pathway on muscle function and metabolic health has gained considerable interest. Increasing the content of slow muscle fibers has been recognized as an effective strategy to improve metabolic health. Oleanolic acid (OA) is a naturally occurring triterpenoid compound derived from plants, which can activate TGR5. The aim of this study was to investigate the effect of OA and TGR5 on muscle fiber types and further explore the underlying TGR5-dependent mechanisms. In this study, mice were divided into three groups and dietary supplementation with 0, 50, or 100 mg/kg OA. In addition, C2C12 cells were treated with OA at concentrations of 0, 5, 10, and 20 µM. Our studies revealed that OA promoted the conversion of fast to slow muscle fibers. In addition, it was found that OA activated the TGR5-mediated calcineurin (CaN)/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Further mechanistic investigations demonstrated that inhibiting TGR5 and CaN abolished the effects of OA on muscle fiber types transformation. In conclusion, this study found that OA promotes the transformation of fast muscle fibers to slow muscle fibers through the TGR5-mediated CaN/NFATc1 signaling pathway.
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Affiliation(s)
- Shuang Liu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Xiaoling Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Jun He
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Yuheng Luo
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Ping Zheng
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Bing Yu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Daiwen Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Zhiqing Huang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China.
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15
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Shumnalieva R, Kotov G, Ermencheva P, Monov S. Pathogenic Mechanisms and Therapeutic Approaches in Obesity-Related Knee Osteoarthritis. Biomedicines 2023; 12:9. [PMID: 38275369 PMCID: PMC10812969 DOI: 10.3390/biomedicines12010009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 12/10/2023] [Accepted: 12/14/2023] [Indexed: 01/27/2024] Open
Abstract
The knee is the joint most frequently involved in osteoarthritis, a common joint disorder in the adult population that is associated with significant chronic joint pain, reduced mobility and quality of life. Recent studies have established an association between obesity and the development of knee osteoarthritis that goes beyond the increased mechanical load on the knees as weight-bearing joints. This link is based on the maintenance of a chronic low-grade inflammation, altered secretion of adipokines by the adipose tissue and development of sarcopenia. Major adipokines involved in the pathogenesis of obesity-related knee osteoarthritis include adiponectin, which appears to have a protective effect, as well as leptin, resistin and visfatin, which are associated with higher pain scores and more severe structural damage. Joint pain in knee osteoarthritis may be both nociceptive and neuropathic and is the result of complex mechanisms driven by nerve growth factor, calcitonin gene-related peptide and pro-inflammatory cytokines. The role of endogenous cannabinoids and gut microbiota in common mechanisms between obesity and knee pain has recently been studied. The aim of the present review is to highlight major pathogenic mechanisms in obesity-related knee osteoarthritis with special attention on pain and to comment on possible therapeutic approaches.
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Affiliation(s)
- Russka Shumnalieva
- Department of Rheumatology, Medical University of Sofia, 1431 Sofia, Bulgaria; (R.S.); (S.M.)
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 1612 Sofia, Bulgaria;
| | - Georgi Kotov
- Department of Rheumatology, Medical University of Sofia, 1431 Sofia, Bulgaria; (R.S.); (S.M.)
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 1612 Sofia, Bulgaria;
| | - Plamena Ermencheva
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 1612 Sofia, Bulgaria;
| | - Simeon Monov
- Department of Rheumatology, Medical University of Sofia, 1431 Sofia, Bulgaria; (R.S.); (S.M.)
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 1612 Sofia, Bulgaria;
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Guo W, Xu Y, Yang Y, Xiang J, Chen J, Luo D, Xie Q. Antibiofilm Effects of Oleuropein against Staphylococcus aureus: An In Vitro Study. Foods 2023; 12:4301. [PMID: 38231779 DOI: 10.3390/foods12234301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 01/19/2024] Open
Abstract
Staphylococcus aureus has posed a huge threat to human health and the economy. Oleuropein has antibacterial activities against various microorganisms but research on its effect on the S. aureus biofilm is limited. This research aimed to estimate the antibiofilm activities of oleuropein against S. aureus. The results suggest that the minimum inhibitory concentration of oleuropein against S. aureus ATCC 25923 was 3 mg/mL. The biomass of biofilms formed on the microplates and coverslips and the viability of bacteria were significantly reduced after the treatment with oleuropein. The scanning electron microscopy observation results indicated that the stacking thickness and density of the biofilm decreased when S. aureus was exposed to oleuropein. It had a bactericidal effect on biofilm bacteria and removed polysaccharides and proteins from mature biofilms. The effects of oleuropein on the biofilm could be explained by a reduction in bacterial secretion of extracellular polymeric substances and a change in bacterial surface hydrophobicity. Based on the above findings, oleuropein has the potential to be used against food pollution caused by S. aureus biofilms.
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Affiliation(s)
- Weiping Guo
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Yunfeng Xu
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Yangyang Yang
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Jinle Xiang
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Junliang Chen
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Denglin Luo
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Qinggang Xie
- Heilongjiang Feihe Dairy Co., Ltd., Beijing 100015, China
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17
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Liu Y, Huang K, Zhang Y, Cao H, Guan X. Dietary polyphenols maintain homeostasis via regulating bile acid metabolism: a review of possible mechanisms. Food Funct 2023; 14:9486-9505. [PMID: 37815149 DOI: 10.1039/d3fo02471g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
The synthesis and metabolism of bile acids (BAs) have been implicated in various metabolic diseases, including obesity and diabetes. Dietary polyphenols, as natural antioxidants, play a vital role in synthesizing and metabolizing bile acids. This paper reviews the mechanism of dietary polyphenols involved in bile acid (BA) synthesis and metabolism. The impact of different gut microorganisms on BA profiles is discussed in detail. The regulation of BA metabolism by dietary polyphenols can be divided into two modes: (1) dietary polyphenols directly activate/inhibit farnesol X receptor (FXR) and Takeda G protein-coupled receptor (TGR5); (2) dietary polyphenols regulate BA synthesis and metabolism through changes in intestinal microorganisms. Research on direct activation/inhibition of FXR and TGR5 by polyphenols should be ramped up. In addition, the effect of dietary polyphenols on intestinal microorganisms has been paid more and more attention and has become a target that cannot be ignored.
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Affiliation(s)
- Yongyong Liu
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
| | - Kai Huang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, PR China
| | - Yu Zhang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, PR China
| | - Hongwei Cao
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, PR China
| | - Xiao Guan
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, PR China
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18
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de la Peña I, Afable T, Dahilig-Talan VR, Cruz P. Review of Plant Extracts and Active Components: Mechanisms of Action for the Treatment of Obesity-Induced Cognitive Impairment. Brain Sci 2023; 13:929. [PMID: 37371407 DOI: 10.3390/brainsci13060929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/05/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
Obesity has been shown to negatively impact cognitive functions, but effective treatments for obesity-induced cognitive impairment are lacking. Natural dietary and plant products, functional foods, and plant-derived compounds have gained attention as potential remedies in part due to the nootropic properties of plants and certain plant-derived agents. This review discusses plant extracts and plant-derived substances that have been shown to ameliorate obesity-induced cognitive impairment in animal models. Mechanistic evaluations of their therapeutic effects are also summarized. A literature search was conducted using PubMed and Google Scholar databases, resulting in the review of 27 English language articles meeting the inclusion criteria. The nine plants (e.g., Ashwagandha, Adzuki bean, and olive) and 18 plant-derived substances (e.g., curcumin, Huperzine A, and Roxburgh's jewel orchid polysaccharides) included in this review improved obesity-induced cognitive impairment through several mechanisms, including attenuation of neuroinflammation, improvement in both central and peripheral insulin resistance, enhancement of neuroprotection and neurogenesis, and modulation of the synthesis and release of cognition-associated neurotransmitters. Based on these findings, plants and plant-derived substances may hold promise for the prevention and treatment of obesity-induced cognitive impairment. Further research is warranted to explore the clinical potential of these plant-derived treatments and to elucidate their underlying molecular mechanisms.
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Affiliation(s)
- Ike de la Peña
- Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Loma Linda University, Loma Linda, CA 92350, USA
| | - Timothy Afable
- Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Loma Linda University, Loma Linda, CA 92350, USA
| | | | - Philip Cruz
- Herbanext Laboratories, Inc., Negros South Road, Bago City 6101, Philippines
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Naomi R, Yazid MD, Teoh SH, Balan SS, Shariff H, Kumar J, Bahari H, Embong H. Dietary Polyphenols as a Protection against Cognitive Decline: Evidence from Animal Experiments; Mechanisms and Limitations. Antioxidants (Basel) 2023; 12:antiox12051054. [PMID: 37237920 DOI: 10.3390/antiox12051054] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 04/27/2023] [Accepted: 05/03/2023] [Indexed: 05/28/2023] Open
Abstract
Emerging evidence suggests that cognitive impairments may result from various factors, such as neuroinflammation, oxidative stress, mitochondrial damage, impaired neurogenesis, synaptic plasticity, blood-brain barrier (BBB) disruption, amyloid β protein (Aβ) deposition, and gut dysbiosis. Meanwhile, dietary polyphenol intake in a recommended dosage has been suggested to reverse cognitive dysfunction via various pathways. However, excessive intake of polyphenols could trigger unwanted adverse effects. Thus, this review aims to outline possible causes of cognitive impairments and how polyphenols alleviate memory loss via various pathways based on in vivo experimental studies. Thus, to identify potentially relevant articles, the keywords (1) nutritional polyphenol intervention NOT medicine AND neuron growth OR (2) dietary polyphenol AND neurogenesis AND memory impairment OR (3) polyphenol AND neuron regeneration AND memory deterioration (Boolean operators) were used in the Nature, PubMed, Scopus, and Wiley online libraries. Based on the inclusion and exclusion criteria, 36 research papers were selected to be further reviewed. The outcome of all the studies included supports the statement of appropriate dosage by taking into consideration gender differences, underlying conditions, lifestyle, and causative factors for cognitive decline, which will significantly boost memory power. Therefore, this review recapitulates the possible causes of cognitive decline, the mechanism of polyphenols involving various signaling pathways in modulating the memory, gut dysbiosis, endogenous antioxidants, bioavailability, dosage, and safety efficacy of polyphenols. Hence, this review is expected to provide a basic understanding of therapeutic development for cognitive impairments in the future.
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Affiliation(s)
- Ruth Naomi
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Muhammad Dain Yazid
- Centre for Tissue Engineering and Regenerative Medicine (CTERM), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Soo Huat Teoh
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia
| | - Santhra Segaran Balan
- Department of Diagnostic and Allied Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Shah Alam 40100, Malaysia
| | - Halim Shariff
- Faculty of Health Sciences, University Technology Mara (UITM) Pulau Pinang, Bertam Campus, Kepala Batas 13200, Malaysia
| | - Jaya Kumar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Hasnah Bahari
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Hashim Embong
- Department of Emergency Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
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20
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Quan Z, Li H, Quan Z, Qing H. Appropriate Macronutrients or Mineral Elements Are Beneficial to Improve Depression and Reduce the Risk of Depression. Int J Mol Sci 2023; 24:7098. [PMID: 37108261 PMCID: PMC10138658 DOI: 10.3390/ijms24087098] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/06/2023] [Accepted: 04/09/2023] [Indexed: 04/29/2023] Open
Abstract
Depression is a common mental disorder that seriously affects the quality of life and leads to an increasing global suicide rate. Macro, micro, and trace elements are the main components that maintain normal physiological functions of the brain. Depression is manifested in abnormal brain functions, which are considered to be tightly related to the imbalance of elements. Elements associated with depression include glucose, fatty acids, amino acids, and mineral elements such as lithium, zinc, magnesium, copper, iron, and selenium. To explore the relationship between these elements and depression, the main literature in the last decade was mainly searched and summarized on PubMed, Google Scholar, Scopus, Web of Science, and other electronic databases with the keywords "depression, sugar, fat, protein, lithium, zinc, magnesium, copper, iron, and selenium". These elements aggravate or alleviate depression by regulating a series of physiological processes, including the transmission of neural signals, inflammation, oxidative stress, neurogenesis, and synaptic plasticity, which thus affect the expression or activity of physiological components such as neurotransmitters, neurotrophic factors, receptors, cytokines, and ion-binding proteins in the body. For example, excessive fat intake can lead to depression, with possible mechanisms including inflammation, increased oxidative stress, reduced synaptic plasticity, and decreased expression of 5-Hydroxytryptamine (5-HT), Brain Derived Neurotrophic Factor (BDNF), Postsynaptic density protein 95(PSD-95), etc. Supplementing mineral elements, such as selenium, zinc, magnesium, or lithium as a psychotropic medication is mostly used as an auxiliary method to improve depression with other antidepressants. In general, appropriate nutritional elements are essential to treat depression and prevent the risk of depression.
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Affiliation(s)
| | | | - Zhenzhen Quan
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
| | - Hong Qing
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
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21
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Romero-Márquez JM, Forbes-Hernández TY, Navarro-Hortal MD, Quirantes-Piné R, Grosso G, Giampieri F, Lipari V, Sánchez-González C, Battino M, Quiles JL. Molecular Mechanisms of the Protective Effects of Olive Leaf Polyphenols against Alzheimer's Disease. Int J Mol Sci 2023; 24:ijms24054353. [PMID: 36901783 PMCID: PMC10001635 DOI: 10.3390/ijms24054353] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/14/2023] [Accepted: 02/16/2023] [Indexed: 02/25/2023] Open
Abstract
Alzheimer's Disease (AD) is the cause of around 60-70% of global cases of dementia and approximately 50 million people have been reported to suffer this disease worldwide. The leaves of olive trees (Olea europaea) are the most abundant by-products of the olive grove industry. These by-products have been highlighted due to the wide variety of bioactive compounds such as oleuropein (OLE) and hydroxytyrosol (HT) with demonstrated medicinal properties to fight AD. In particular, the olive leaf (OL), OLE, and HT reduced not only amyloid-β formation but also neurofibrillary tangles formation through amyloid protein precursor processing modulation. Although the isolated olive phytochemicals exerted lower cholinesterase inhibitory activity, OL demonstrated high inhibitory activity in the cholinergic tests evaluated. The mechanisms underlying these protective effects may be associated with decreased neuroinflammation and oxidative stress via NF-κB and Nrf2 modulation, respectively. Despite the limited research, evidence indicates that OL consumption promotes autophagy and restores loss of proteostasis, which was reflected in lower toxic protein aggregation in AD models. Therefore, olive phytochemicals may be a promising tool as an adjuvant in the treatment of AD.
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Affiliation(s)
- Jose M. Romero-Márquez
- Department of Physiology, Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Centre, University of Granada, 18016 Armilla, Spain
| | - Tamara Y. Forbes-Hernández
- Department of Physiology, Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Centre, University of Granada, 18016 Armilla, Spain
| | - María D. Navarro-Hortal
- Department of Physiology, Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Centre, University of Granada, 18016 Armilla, Spain
| | - Rosa Quirantes-Piné
- Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Avenida del Conocimiento 37, 18016 Granada, Spain
| | - Giuseppe Grosso
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
- Center for Human Nutrition and Mediterranean Foods (NUTREA), University of Catania, 95123 Catania, Italy
| | - Francesca Giampieri
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21, 39011 Santander, Spain
| | - Vivian Lipari
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21, 39011 Santander, Spain
- Department of Project Management, Universidad Internacional Iberoamericana, Campeche 24560, Mexico
- Department of Prohect Management, Universidade Internacional do Cuanza, Cuito 250, Bié, Angola
| | - Cristina Sánchez-González
- Department of Physiology, Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Centre, University of Granada, 18016 Armilla, Spain
- Sport and Health Research Centre, University of Granada, C/Menéndez Pelayo 32, 18016 Granada, Spain
| | - Maurizio Battino
- Department of Clinical Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
- International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu University, Zhenjiang 212013, China
| | - José L. Quiles
- Department of Physiology, Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Centre, University of Granada, 18016 Armilla, Spain
- Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Avenida del Conocimiento 37, 18016 Granada, Spain
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21, 39011 Santander, Spain
- Correspondence:
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22
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Angeloni C, Malaguti M, Prata C, Freschi M, Barbalace MC, Hrelia S. Mechanisms Underlying Neurodegenerative Disorders and Potential Neuroprotective Activity of Agrifood By-Products. Antioxidants (Basel) 2022; 12:94. [PMID: 36670956 PMCID: PMC9854890 DOI: 10.3390/antiox12010094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/23/2022] [Accepted: 12/25/2022] [Indexed: 01/03/2023] Open
Abstract
Neurodegenerative diseases, characterized by progressive loss in selected areas of the nervous system, are becoming increasingly prevalent worldwide due to an aging population. Despite their diverse clinical manifestations, neurodegenerative diseases are multifactorial disorders with standard features and mechanisms such as abnormal protein aggregation, mitochondrial dysfunction, oxidative stress and inflammation. As there are no effective treatments to counteract neurodegenerative diseases, increasing interest has been directed to the potential neuroprotective activities of plant-derived compounds found abundantly in food and in agrifood by-products. Food waste has an extremely negative impact on the environment, and recycling is needed to promote their disposal and overcome this problem. Many studies have been carried out to develop green and effective strategies to extract bioactive compounds from food by-products, such as peel, leaves, seeds, bran, kernel, pomace, and oil cake, and to investigate their biological activity. In this review, we focused on the potential neuroprotective activity of agrifood wastes obtained by common products widely produced and consumed in Italy, such as grapes, coffee, tomatoes, olives, chestnuts, onions, apples, and pomegranates.
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Affiliation(s)
- Cristina Angeloni
- Department for Life Quality Studies, Alma Mater Studiorum–University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy
| | - Marco Malaguti
- Department for Life Quality Studies, Alma Mater Studiorum–University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy
| | - Cecilia Prata
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum–University of Bologna, Via Irnerio 48, 40126 Bologna, Italy
| | - Michela Freschi
- Department for Life Quality Studies, Alma Mater Studiorum–University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy
| | - Maria Cristina Barbalace
- Department for Life Quality Studies, Alma Mater Studiorum–University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy
| | - Silvana Hrelia
- Department for Life Quality Studies, Alma Mater Studiorum–University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy
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23
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Kou Y, Li Z, Yang T, Shen X, Wang X, Li H, Zhou K, Li L, Xia Z, Zheng X, Zhao Y. Therapeutic potential of plant iridoids in depression: a review. PHARMACEUTICAL BIOLOGY 2022; 60:2167-2181. [PMID: 36300881 PMCID: PMC9621214 DOI: 10.1080/13880209.2022.2136206] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 08/23/2022] [Accepted: 09/25/2022] [Indexed: 05/29/2023]
Abstract
CONTEXT Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases. OBJECTIVE The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication. METHODS The following key phrases were sought in PubMed, Google Scholar, Web of Science, and China National Knowledge Internet (CNKI) without time limitation to search all relevant articles with in vivo or in vitro experimental studies as comprehensively as possible: ('iridoid' or 'seciridoid' or 'depression'). This review extracted the experimental data on the therapeutic potential and molecular mechanism of plant-derived iridoids for depression. RESULTS Plant iridoids (i.e., catalpol, geniposide, loganin), and secoiridoids (i.e., morroniside, gentiopicroside, oleuropein, swertiamarin), all showed significant improvement effects on depression. DISCUSSION AND CONCLUSIONS Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications.
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Affiliation(s)
- Yaoyao Kou
- Three level Scientific Research Laboratory of National Administration of Traditional Chinese Medicine, Northwest University, Xi’an, PR China
| | - Zhihao Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR China
| | - Tong Yang
- Three level Scientific Research Laboratory of National Administration of Traditional Chinese Medicine, Northwest University, Xi’an, PR China
| | - Xue Shen
- Three level Scientific Research Laboratory of National Administration of Traditional Chinese Medicine, Northwest University, Xi’an, PR China
| | - Xin Wang
- Three level Scientific Research Laboratory of National Administration of Traditional Chinese Medicine, Northwest University, Xi’an, PR China
| | - Haopeng Li
- Three level Scientific Research Laboratory of National Administration of Traditional Chinese Medicine, Northwest University, Xi’an, PR China
| | - Kun Zhou
- Three level Scientific Research Laboratory of National Administration of Traditional Chinese Medicine, Northwest University, Xi’an, PR China
| | - Luyao Li
- Three level Scientific Research Laboratory of National Administration of Traditional Chinese Medicine, Northwest University, Xi’an, PR China
| | - Zhaodi Xia
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR China
| | - Xiaohui Zheng
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR China
| | - Ye Zhao
- Three level Scientific Research Laboratory of National Administration of Traditional Chinese Medicine, Northwest University, Xi’an, PR China
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24
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Ren ZL, Li CX, Ma CY, Chen D, Chen JH, Xu WX, Chen CA, Cheng FF, Wang XQ. Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling. Int J Mol Sci 2022; 23:13045. [PMID: 36361829 PMCID: PMC9654021 DOI: 10.3390/ijms232113045] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/21/2022] [Accepted: 10/25/2022] [Indexed: 11/01/2023] Open
Abstract
A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world's population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood-brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.
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Affiliation(s)
- Zi-Lin Ren
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chang-Xiang Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chong-Yang Ma
- School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Dan Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jia-Hui Chen
- Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing 100700, China
| | - Wen-Xiu Xu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Cong-Ai Chen
- Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing 100700, China
| | - Fa-Feng Cheng
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xue-Qian Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
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25
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Park J, Kim J, Mikami T. Exercise hormone irisin prevents physical inactivity-induced cognitive decline in mice. Behav Brain Res 2022; 433:114008. [PMID: 35850397 DOI: 10.1016/j.bbr.2022.114008] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/29/2022] [Accepted: 07/14/2022] [Indexed: 11/29/2022]
Abstract
We previously reported that physical inactivity (PI) induces cognitive decline and depressive states, which were ameliorated by regular exercise. However, the mechanism underlying the preventive effect of exercise remains unelucidated. Irisin has recently been identified as an exercise-inducible myokine that improves cognitive impairment. Plasma irisin levels increase during physical exercise; therefore, PI could lead to a decline in cognitive function by reducing plasma irisin. Therefore, this study aimed to examine whether irisin is associated with cognitive decline and mental deterioration altered by PI and exercise. The mice were housed for eight weeks in the PI cage, whose living space was one-sixth that of a standard cage. Simultaneously, the mice were subjected to regular exercise in the presence or absence of an irisin-neutralizing antibody. PI increased the epididymal fat mass without increasing body weight, muscle mass, or plasma corticosterone levels. Additionally, PI induced anxiety, depressive states, and a decline in working memory. In contrast, regular exercise after PI elevated irisin levels in plasma and increased fibronectin type III domain-containing 5 (FNDC5) and peroxisome proliferator-activated receptor gammacoactivator 1α expression in skeletal muscle. Regular exercise also increased hippocampal brain-derived neurotrophic factor (BDNF) expression and BrdU-positive cells, alleviating cognitive decline and mental deterioration induced by PI. The beneficial effects of exercise were compromised by the administration of an irisin-neutralizing antibody. Moreover, plasma irisin level was positively correlated with working memory, hippocampal BDNF levels, and hippocampal cell proliferation. These findings suggest that exercise-inducible irisin is critical for maintaining cognitive function in the PI state.
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Affiliation(s)
- Jonghyuk Park
- Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
| | - Jimmy Kim
- Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
| | - Toshio Mikami
- Department of Health and Sports Science, Nippon Medical School, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-0023, Japan.
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Park J, Kim J, Mikami T. Exercise-Induced Lactate Release Mediates Mitochondrial Biogenesis in the Hippocampus of Mice via Monocarboxylate Transporters. Front Physiol 2021; 12:736905. [PMID: 34603087 PMCID: PMC8481603 DOI: 10.3389/fphys.2021.736905] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/17/2021] [Indexed: 12/25/2022] Open
Abstract
Regular exercise training induces mitochondrial biogenesis in the brain via activation of peroxisome proliferator-activated receptor gamma-coactivator 1α (PGC-1α). However, it remains unclear whether a single bout of exercise would increase mitochondrial biogenesis in the brain. Therefore, we first investigated whether mitochondrial biogenesis in the hippocampus is affected by a single bout of exercise in mice. A single bout of high-intensity exercise, but not low- or moderate-intensity, increased hippocampal PGC-1α mRNA and mitochondrial DNA (mtDNA) copy number at 12 and 48h. These results depended on exercise intensity, and blood lactate levels observed immediately after exercise. As lactate induces mitochondrial biogenesis in the brain, we examined the effects of acute lactate administration on blood and hippocampal extracellular lactate concentration by in vivo microdialysis. Intraperitoneal (I.P.) lactate injection increased hippocampal extracellular lactate concentration to the same as blood lactate level, promoting PGC-1α mRNA expression in the hippocampus. However, this was suppressed by administering UK5099, a lactate transporter inhibitor, before lactate injection. I.P. UK5099 administration did not affect running performance and blood lactate concentration immediately after exercise but attenuated exercise-induced hippocampal PGC-1α mRNA and mtDNA copy number. In addition, hippocampal monocarboxylate transporters (MCT)1, MCT2, and brain-derived neurotrophic factor (BDNF) mRNA expression, except MCT4, also increased after high-intensity exercise, which was abolished by UK5099 administration. Further, injection of 1,4-dideoxy-1,4-imino-D-arabinitol (glycogen phosphorylase inhibitor) into the hippocampus before high-intensity exercise suppressed glycogen consumption during exercise, but hippocampal lactate, PGC-1α, MCT1, and MCT2 mRNA concentrations were not altered after exercise. These results indicate that the increased blood lactate released from skeletal muscle may induce hippocampal mitochondrial biogenesis and BDNF expression by inducing MCT expression in mice, especially during short-term high-intensity exercise. Thus, a single bout of exercise above the lactate threshold could provide an effective strategy for increasing mitochondrial biogenesis in the hippocampus.
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Affiliation(s)
- Jonghyuk Park
- Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Jimmy Kim
- Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Toshio Mikami
- Department of Health and Sports Science, Nippon Medical School, Tokyo, Japan
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