1
|
Akhter N, Rafiq I, Jamil A, Chauhdary Z, Mustafa A, Nisar A. Neuroprotective effect of Thymus vulgaris on paraquat induced Parkinson's disease. Biochem Biophys Res Commun 2025; 761:151740. [PMID: 40188599 DOI: 10.1016/j.bbrc.2025.151740] [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: 11/18/2024] [Revised: 03/17/2025] [Accepted: 03/31/2025] [Indexed: 04/08/2025]
Abstract
The dramatic surge of neurodegenerative disorders among elderly population underscore the pressing demand for development of optimal and evidence based noninvasive natural treatment strategies. Paraquat exposure in animal models used in scientific studies can cause a variety of clinical signs of Parkinson disease (PD). The health benefits of thyme include antioxidant, anti-inflammatory, pulmonary, and neurological benefits. Thyme and other herbal treatments are frequently used to treat a variety of conditions, including neurological issues. The primary factor in the etiology of neurodegeneration is oxidative stress. Conventional treatments are indicated to potentially have negative side effects. The primary phytochemicals of Thymus vulgaris (TV), which are responsible for its unique therapeutic property of neuro-protection, include hydrocarbon and phenolic compounds like thymol and carvacrol. The goal of the current investigation was to examine T. vulgaris' potential for neuroprotection while also ensuring its safety. Analyses of the plant's physicochemical and phytochemical composition were performed by liquid chromatographic analysis. Neuro-behavioral and biochemical parameters were evaluated to determine the impact of T. vulgaris in paraquat induced parkinsonian rodents model. The neurobehavioral tests include open field tests for movement and exploration, Y maze test and elevated plus maze test for natural behavior, memory, and anxiety, hole board tests for exploratory behavior, ladder climbing, foot printing, and wire hanging tests for estimating neuromuscular coordination. T. vulgaris treatment significantly improved neurobehavioral parameters dose-dependently, Biochemical analysis revealed that extract treatment mitigated the declined level of antioxidant enzymes. RT-PCR analysis showed that in paraquat treated group mRNA expression of IL-1α, IL-1β, Alpha-Synuclein, TNF-α, and IL-6 was upregulated markedly. However, T. vulgaris treatment dose dependently down-regulated the mRNA expression of these genes. The groundbreaking results of current study revealed that T. vulgaris restored the degenerative alterations, neuro-inflammation, and nerve loss in the brain structure, as evident by histopathological investigation. Particularly remarkable restoration in neuropsychological and biochemical markers emphasize the medicinal potential of T. vulgaris as a revolutionary treatment for neurodegenerative disorders, offering new hope for millions worldwide afflicted by these devastating conditions.
Collapse
Affiliation(s)
- Naheed Akhter
- Department of Biochemistry, Faculty of Life Sciences, Government College University, Faisalabad, 38000, Pakistan
| | - Iqra Rafiq
- Department of Biochemistry, University of Agriculture, Faisalabad, 38000, Pakistan
| | - Amer Jamil
- Department of Biochemistry, University of Agriculture, Faisalabad, 38000, Pakistan.
| | - Zunera Chauhdary
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan.
| | - Anum Mustafa
- Department of Biochemistry, University of Agriculture, Faisalabad, 38000, Pakistan
| | - Aqsa Nisar
- Department of Biochemistry, Faculty of Life Sciences, Government College University, Faisalabad, 38000, Pakistan
| |
Collapse
|
2
|
Tang Y, Gao Z, Yang J, Li C, Wang W, Wu C, Wu M, Li M, Wu H, Sun Y, Zhang H, Chai Y, Xie F, Qian J, Shen H, Wang D. Breaking the synergism of iron overload and miR-122 to rescue lipid accumulation and peroxidation in MASLD. Pharmacol Res 2025; 215:107728. [PMID: 40188979 DOI: 10.1016/j.phrs.2025.107728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/01/2025] [Accepted: 04/01/2025] [Indexed: 04/10/2025]
Abstract
MASLD is a multifactorial disease with specific subtypes being featured by hepatic iron overload and loss of miR-122, a liver-specific microRNA regulating hepatic lipid homeostasis. Previously we reported the mechanism of iron overload decreasing miR-122. Interestingly, we found that mice lacking miR-122 were highly sensitive to iron overload-induced steatosis and fibrosis. The present study aimed to disclose the downstream mechanisms and the preventive measures targeting miR-122. We first validated the decreases in iron-related genes and miR-122 in MASLD. By using LC-MS/MS and gas-chromatography, we found that the combination of miR-122 knockout and iron overload significantly increased the production and peroxidation of polyunsaturated fatty acids (PUFAs). However, miR-122 knockout itself only incurred lipid accumulation, suggesting a synergistic effect of miR-122 knockout and iron overload in lipid peroxidation. We then located the key enzymes involved in PUFA production and peroxidation by the transcriptome and proteome analysis. Mechanistically, miR-122 and iron regulated fatty acid synthesis through Aacs, fatty acid desaturation through Fads2, and PUFAs oxidation through CYPs. Re-supplementation of miR-122 by recombinant adeno-associated virus or agomir effectively broke the synergism of miR-122 knockout and iron overload in vivo. We further designed a miR-122 expression reporter cell model for high-throughput screening on 2543 natural compounds, and eventually found and validated that the dihydroberberine could upregulate miR-122 expression and correct iron overload-induced lipid disorders. These results identified the synergistic role of miR-122 and iron in PUFAs production and peroxidation, and also proposed the potential application of dihydroberberine as a preventive and therapeutic candidate for MASLD.
Collapse
Affiliation(s)
- Yuxiao Tang
- Department of Nutrition, Second Military Medical University, Shanghai, China.
| | - Zelong Gao
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Jianxin Yang
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Chenqi Li
- Department of Nutrition, Second Military Medical University, Shanghai, China; Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Weili Wang
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Jiangxi University of Chinese Medicine, Jiangxi, China
| | - Chenghua Wu
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengpu Wu
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Min Li
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Huiwen Wu
- Department of Clinical Nutrition, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Sun
- Department of Clinical Nutrition, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hongwei Zhang
- Department of Clinical Nutrition, Brain Disease Hospital, Zhengzhou University, Henan, China
| | - Yifeng Chai
- Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Feng Xie
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Jiangxi University of Chinese Medicine, Jiangxi, China
| | - Jianxin Qian
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Hui Shen
- Department of Nutrition, Second Military Medical University, Shanghai, China.
| | - Dongyao Wang
- Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai, China.
| |
Collapse
|
3
|
Kumari A, Rahaman A, Zeng XA, Baloch Z. Therapeutic potential and microRNA regulating properties of phytochemicals in Alzheimer's disease. MOLECULAR THERAPY. NUCLEIC ACIDS 2025; 36:102439. [PMID: 40114707 PMCID: PMC11925107 DOI: 10.1016/j.omtn.2024.102439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by the aggregation of Aβ (peptide) and neurofibrillary tangles along with inflammatory processes. Aging is a significant driver of these alterations, and dementia is a major cause of disability and mortality. Despite extensive clinical trials over the past two decades, no effective drug has been developed to improve AD symptoms or slow its progression, indicating the inefficiency of current treatment targets. In AD development, the molecular microenvironment plays a significant role. MicroRNAs (miRNAs) are a key component of this microenvironment, regulate post-transcriptional gene expression, and are expressed more abundantly in the brain than in other tissues. Several dysregulated miRNAs in AD have been linked to neuropathological changes, such as plaque and tangle accrual, as well as altered expression of notorious molecules. Preclinical studies have confirmed the efficacy of phytochemicals/food bioactive compounds (PCs/FBCs) in regulating miRNA expression, which makes them immensely beneficial for targeting miRNA-altered expression patterns in neuronal diseases. This review highlights the potential of miRNAs in driving AD pathology and its development. Furthermore, it discusses the therapeutic efficacy of PCs/FBCs and their miRNA-regulatory properties, especially focusing on antiinflammatory and antioxidant capacities for their development as effective AD agents.
Collapse
Affiliation(s)
- Ankita Kumari
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, Guangdong, China
- School of Food Science and Engineering, Foshan University, Foshan, Guangdong, China
| | - Abdul Rahaman
- Guangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, Guangdong, China
- School of Food Science and Engineering, Foshan University, Foshan, Guangdong, China
| | - Xin-An Zeng
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, Guangdong, China
- School of Food Science and Engineering, Foshan University, Foshan, Guangdong, China
| | - Zulqarnain Baloch
- Faculty of Science and Technology, Kunming University of Science and Technology, Kunming, Yunan, China
| |
Collapse
|
4
|
Wang L, Liu X, Lv H, Zhang H, Lin R, Xu S, Zhang C, Lou S, Qiu Z, Sun C, Cui N. Research Progress on Natural Products That Regulate miRNAs in the Treatment of Osteosarcoma. BIOLOGY 2025; 14:61. [PMID: 39857292 PMCID: PMC11759184 DOI: 10.3390/biology14010061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 01/07/2025] [Accepted: 01/09/2025] [Indexed: 01/27/2025]
Abstract
miRNAs are small non-coding RNA molecules that play critical roles in the regulation of gene expression and have been closely associated with various diseases, including cancer. These molecules significantly influence the cell cycle of tumor cells and control programmed cell death (apoptosis). Currently, research on miRNAs has become a major focus in developing cancer therapies. Osteosarcoma, a malignant neoplasm predominantly occurring during adolescence and later in life, is characterized by a high propensity for metastasis. This review explores the role of miRNAs in the initiation and progression of cancer, highlighting their potential as predictive biomarkers for disease. It discusses the mechanisms by which natural products modulate miRNA activity to influence apoptosis, ferroptosis, and autophagy in osteosarcoma cells, aiming to identify new strategies for osteosarcoma treatment. Recent studies on how natural products regulate miRNAs to reduce tumor cell resistance to chemotherapy are also reviewed. Furthermore, the review elaborates on how natural products regulate m6A modifications to influence miRNA expression, thereby exerting antitumor effects. In this process, interactions between m6A modifications and miRNAs have been identified, with both jointly influencing tumorigenesis and cancer progression, offering a new perspective in osteosarcoma treatment. These approaches could help uncover novel regulatory mechanisms in osteosarcoma pathways and provide a theoretical foundation for developing new drugs and identifying novel therapeutic targets.
Collapse
Affiliation(s)
- Lin Wang
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (L.W.); (X.L.); (H.L.); (H.Z.); (R.L.); (S.X.); (C.Z.); (Z.Q.)
| | - Xinyu Liu
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (L.W.); (X.L.); (H.L.); (H.Z.); (R.L.); (S.X.); (C.Z.); (Z.Q.)
| | - Haoze Lv
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (L.W.); (X.L.); (H.L.); (H.Z.); (R.L.); (S.X.); (C.Z.); (Z.Q.)
| | - Han Zhang
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (L.W.); (X.L.); (H.L.); (H.Z.); (R.L.); (S.X.); (C.Z.); (Z.Q.)
| | - Rimei Lin
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (L.W.); (X.L.); (H.L.); (H.Z.); (R.L.); (S.X.); (C.Z.); (Z.Q.)
| | - Shan Xu
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (L.W.); (X.L.); (H.L.); (H.Z.); (R.L.); (S.X.); (C.Z.); (Z.Q.)
| | - Chaojing Zhang
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (L.W.); (X.L.); (H.L.); (H.Z.); (R.L.); (S.X.); (C.Z.); (Z.Q.)
| | - Shilei Lou
- College of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130117, China;
| | - Zhidong Qiu
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (L.W.); (X.L.); (H.L.); (H.Z.); (R.L.); (S.X.); (C.Z.); (Z.Q.)
| | - Cong Sun
- College of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130117, China;
| | - Ning Cui
- Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China
| |
Collapse
|
5
|
Wang Z, Liu Y, Asemi Z. Quercetin and microRNA Interplay in Apoptosis Regulation: A New Therapeutic Strategy for Cancer? Curr Med Chem 2025; 32:939-957. [PMID: 38018191 DOI: 10.2174/0109298673259466231031050437] [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: 04/25/2023] [Revised: 07/06/2023] [Accepted: 10/09/2023] [Indexed: 11/30/2023]
Abstract
Cancer is known as a global problem for the health and economy. Following cancer onset, apoptosis is the primary mechanism countering the tumor cells' growth. Most anticancer agents initiate apoptosis to remove tumor cells. Phytochemicals have appeared as a beneficial treatment option according to their less adverse effects. In recent decades, quercetin has been highlighted due to its high pharmacological benefits, and various literature has suggested it as a potential anti-proliferative agent against different kinds of cancers. The microRNAs (miRNAs) play key roles in cancer treatment, progression, and apoptosis. This review reviewed the effect of quercetin on miRNAs contributing to the induction or inhibition of apoptosis in cancers.
Collapse
Affiliation(s)
- Zicheng Wang
- Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, 210000, Jiangsu, China
- Department of Pharmacology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu, China
| | - Yanqing Liu
- Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, 210000, Jiangsu, China
- Department of Pharmacology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu, China
| | - Zatollah Asemi
- Department of Nutrition, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I.R. Iran
| |
Collapse
|
6
|
Liu Y, Fang M, Tu X, Mo X, Zhang L, Yang B, Wang F, Kim YB, Huang C, Chen L, Fan S. Dietary Polyphenols as Anti-Aging Agents: Targeting the Hallmarks of Aging. Nutrients 2024; 16:3305. [PMID: 39408272 PMCID: PMC11478989 DOI: 10.3390/nu16193305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/20/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Aging is a natural biological process influenced by multiple factors and is a significant contributor to various chronic diseases. Slowing down the aging process and extending health span have been pursuits of the scientific field. Methods: Examination of the effects of dietary polyphenols on hallmarks of aging such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Results: Polyphenols, abundant in nature, exhibit numerous biological activities, including antioxidant effects, free radical scavenging, neuroprotection, and anti-aging properties. These compounds are generally safe and effective in potentially slowing aging and preventing age-related disorders. Conclusions: The review encourages the development of novel therapeutic strategies using dietary polyphenols to create holistic anti-aging therapies and nutritional supplements.
Collapse
Affiliation(s)
- Ying Liu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Minglv Fang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Xiaohui Tu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Xueying Mo
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Lu Zhang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Binrui Yang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Feijie Wang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Young-Bum Kim
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Cheng Huang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Liang Chen
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Shengjie Fan
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| |
Collapse
|
7
|
Chuang YT, Yen CY, Chien TM, Chang FR, Tsai YH, Wu KC, Tang JY, Chang HW. Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis. Int J Mol Sci 2024; 25:6083. [PMID: 38892270 PMCID: PMC11173094 DOI: 10.3390/ijms25116083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 05/22/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Ferroptosis, which comprises iron-dependent cell death, is crucial in cancer and non-cancer treatments. Exosomes, the extracellular vesicles, may deliver biomolecules to regulate disease progression. The interplay between ferroptosis and exosomes may modulate cancer development but is rarely investigated in natural product treatments and their modulating miRNAs. This review focuses on the ferroptosis-modulating effects of natural products and miRNAs concerning their participation in ferroptosis and exosome biogenesis (secretion and assembly)-related targets in cancer and non-cancer cells. Natural products and miRNAs with ferroptosis-modulating effects were retrieved and organized. Next, a literature search established the connection of a panel of ferroptosis-modulating genes to these ferroptosis-associated natural products. Moreover, ferroptosis-associated miRNAs were inputted into the miRNA database (miRDB) to bioinformatically search the potential targets for the modulation of ferroptosis and exosome biogenesis. Finally, the literature search provided a connection between ferroptosis-modulating miRNAs and natural products. Consequently, the connections from ferroptosis-miRNA-exosome biogenesis to natural product-based anticancer treatments are well-organized. This review sheds light on the research directions for integrating miRNAs and exosome biogenesis into the ferroptosis-modulating therapeutic effects of natural products on cancer and non-cancer diseases.
Collapse
Affiliation(s)
- Ya-Ting Chuang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Ching-Yu Yen
- School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan;
- Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan
| | - Tsu-Ming Chien
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan;
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Urology, Kaohsiung Gangshan Hospital, Kaohsiung Medical University, Kaohsiung 820111, Taiwan
| | - Fang-Rong Chang
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Yi-Hong Tsai
- Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung 907101, Taiwan;
| | - Kuo-Chuan Wu
- Department of Computer Science and Information Engineering, National Pingtung University, Pingtung 900391, Taiwan;
| | - Jen-Yang Tang
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Hsueh-Wei Chang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| |
Collapse
|
8
|
Salama RM, Eissa N, Doghish AS, Abulsoud AI, Abdelmaksoud NM, Mohammed OA, Abdel Mageed SS, Darwish SF. Decoding the secrets of longevity: unraveling nutraceutical and miRNA-Mediated aging pathways and therapeutic strategies. FRONTIERS IN AGING 2024; 5:1373741. [PMID: 38605867 PMCID: PMC11007187 DOI: 10.3389/fragi.2024.1373741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 03/04/2024] [Indexed: 04/13/2024]
Abstract
MicroRNAs (miRNAs) are short RNA molecules that are not involved in coding for proteins. They have a significant function in regulating gene expression after the process of transcription. Their participation in several biological processes has rendered them appealing subjects for investigating age-related disorders. Increasing data indicates that miRNAs can be influenced by dietary variables, such as macronutrients, micronutrients, trace minerals, and nutraceuticals. This review examines the influence of dietary factors and nutraceuticals on the regulation of miRNA in relation to the process of aging. We examine the present comprehension of miRNA disruption in age-related illnesses and emphasize the possibility of dietary manipulation as a means of prevention or treatment. Consolidating animal and human research is essential to validate the significance of dietary miRNA control in living organisms, despite the abundance of information already provided by several studies. This review elucidates the complex interaction among miRNAs, nutrition, and aging, offering valuable insights into promising areas for further research and potential therapies for age-related disorders.
Collapse
Affiliation(s)
- Rania M. Salama
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt
| | - Nermin Eissa
- Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates
| | - Ahmed S. Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, Egypt
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Egypt
| | - Ahmed I. Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Egypt
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | | | - Osama A. Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Sherif S. Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, Egypt
| | - Samar F. Darwish
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, Egypt
| |
Collapse
|
9
|
Toker Ç, Kuyucu Y, Şaker D, Kara S, Güzelel B, Mete UÖ. Investigation of miR-26b and miR-27b expressions and the effect of quercetin on fibrosis in experimental pulmonary fibrosis. J Mol Histol 2024; 55:25-35. [PMID: 37857923 DOI: 10.1007/s10735-023-10168-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 10/06/2023] [Indexed: 10/21/2023]
Abstract
In this study, investigation of the effects of Quercetin on Bleomycin-induced pulmonary fibrosis and fibrosis-associated molecules miR-26b and miR-27b was aimed. Control group was given 10% saline on the 0th day, and saline was administered for 21 days starting from the 8th day. Group 2 was given 50 mg/kg Quercetin for 21 days starting from the 8th day. Group 3 was given 10 mg/kg Bleomycin Sulfate on day 0, and sacrificed on the 22nd and 29th day. Group 4 was given 10 mg/kg Bleomycin Sulfate on the 0th day, and was given 50 mg/kg Quercetin for 14 days, and 21 days starting from day 8. Lung tissues were examined using light and electron microscopic, immunohistochemical and molecular biological methods. Injury groups revealed impaired alveolar structure, collagen accumulation and increased inflammatory cells in interalveolar septum. Fibrotic response was decreased and the alveolar structure was improved with Quercetin treatment. α-SMA expressions were higher in the injury groups, but lower in the treatment groups compared to the injury groups. E-cadherin expressions were decreased in the injury groups and showed stronger immunoreactivity in the treatment groups compared to the injury groups. miR-26b and miR-27b expressions were lower in the injury groups than the control groups, and higher in the treatment groups than the injury groups. Quercetin can be considered as a new treatment agent in the idiopathic pulmonary fibrosis, since it increases the expression levels of miR-26b and miR-27b which decrease in fibrosis, and has therapeutic effects on the histopathological changes.
Collapse
Affiliation(s)
- Çağrı Toker
- Department of Histology and Embryology, Faculty of Medicine, Çukurova University, 01330, Adana, Turkey
| | - Yurdun Kuyucu
- Department of Histology and Embryology, Faculty of Medicine, Çukurova University, 01330, Adana, Turkey.
| | - Dilek Şaker
- Department of Histology and Embryology, Faculty of Medicine, Çukurova University, 01330, Adana, Turkey
| | - Samet Kara
- Department of Histology and Embryology, Faculty of Medicine, Çukurova University, 01330, Adana, Turkey
| | - Bilge Güzelel
- Department of Histology and Embryology, Faculty of Medicine, Çukurova University, 01330, Adana, Turkey
| | - Ufuk Özgü Mete
- Department of Histology and Embryology, Faculty of Medicine, Çukurova University, 01330, Adana, Turkey
| |
Collapse
|
10
|
Esmaealzadeh N, Ram M, Abdolghaffari A, Marques AM, Bahramsoltani R. Toll-like receptors in inflammatory bowel disease: A review of the role of phytochemicals. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 123:155178. [PMID: 38007993 DOI: 10.1016/j.phymed.2023.155178] [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: 04/06/2023] [Revised: 10/18/2023] [Accepted: 10/31/2023] [Indexed: 11/28/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic inflammation within the gastrointestinal tract with a remarkable impact on patients' quality of life. Toll-like receptors (TLR), as a key contributor of immune system in inflammation, has a critical role in the pathogenesis of IBD and thus, can be a suitable target of therapeutic agents. Medicinal plants have long been considered as a source of bioactive agents for different diseases, including IBD. PURPOSE This review discusses current state of the art on the role of plant-derived compounds for the management of IBD with a focus on TLRs. METHODS Electronic database including PubMed, Web of Science, and Scopus were searched up to January 2023 and all studies in which anticolitis effects of a phytochemical was assessed via modulation of TLRs were considered. RESULTS Different categories of phytochemicals, including flavonoids, lignans, alkaloids, terpenes, saccharides, and saponins have demonstrated modulatory effects on TLR in different animal and cell models of bowel inflammation. Flavonoids were the most studied phytochemicals amongst others. Also, TLR4 was the most important type of TLRs which were modulated by phytochemicals. Other mechanisms such as inhibition of pro-inflammatory cytokines, nuclear factor-κB pathway, nitric oxide synthesis pathway, cyclooxygenase-2, lipid peroxidation, as well as induction of endogenous antioxidant defense mechanisms were also reported for phytochemicals in various IBD models. CONCLUSION Taken together, a growing body of pre-clinical evidence support the efficacy of herbal compounds for the treatment of IBD via modulation of TLRs. Future clinical studies are recommended to assess the safety and efficacy of these compounds in human.
Collapse
Affiliation(s)
- Niusha Esmaealzadeh
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahboobe Ram
- Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Amirhossein Abdolghaffari
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - André Mesquita Marques
- Department of Natural Products, Institute of Drug Technology (Farmanguinhos), FIOCRUZ, Rio de Janeiro, Brazil
| | - Roodabeh Bahramsoltani
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran; PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| |
Collapse
|
11
|
Zhang L, Kang Q, Kang M, Jiang S, Yang F, Gong J, Ou G, Wang S. Regulation of main ncRNAs by polyphenols: A novel anticancer therapeutic approach. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 120:155072. [PMID: 37714063 DOI: 10.1016/j.phymed.2023.155072] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 08/29/2023] [Accepted: 09/04/2023] [Indexed: 09/17/2023]
Abstract
BACKGROUND Plant polyphenols have shown promising applications in oncotherapy. Increasing evidence reveals that polyphenols possess the antitumor potential for multiple cancers. Non-coding RNAs (ncRNAs), mainly including small ncRNAs (microRNA) and long ncRNAs (lncRNAs), play critical roles in cancer initiation and progression. PURPOSE To establish the modulation of ncRNAs by polyphenols as a novel and promising approach in anticancer treatment. STUDY DESIGN The present research employed ncRNA, miRNA, lncRNA, and regulatory mechanism as keywords to retrieve the literature from PubMed, Web of Science, Science direct, and Google Scholar, in a 20-year period from 2003 to 2023. This study critically reviewed the current literature and presented the regulation of prominent ncRNAs by polyphenols. A comprehensive total of 169 papers were retrieved on polyphenols and their related ncRNAs in cancers. RESULTS NcRNAs, mainly including miRNA and lncRNA, play critical roles in cancer initiation and progression, which are potential modulatory targets of bioactive polyphenols, such as resveratrol, genistein, curcumin, EGCG, quercetin, in cancer management. The mechanism involved in polyphenol-mediated ncRNA regulation includes epigenetic and transcriptional modification, and post-transcriptional processing. CONCLUSION Regulatory ncRNAs are potential therapeutic targets of bioactive polyphenols, and these phytochemicals could modulate the level of these ncRNAs directly and indirectly. A better comprehension of the ncRNA regulation by polyphenols in cancers, their functional outcomes on tumor pathophysiology and regulatory molecular mechanisms, may be helpful to develop effective strategies to fight the devastating disease.
Collapse
Affiliation(s)
- Liang Zhang
- Hubei Superior Discipline Group of Exercise and Brain Science from Hubei Provincial, Wuhan Sports University, Wuhan 430079, China
| | - Qingzheng Kang
- Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory, Shenzhen University General Hospital, Shenzhen University, Shenzhen 518061, China
| | | | - Suwei Jiang
- School of Medicine, Shenzhen University, Shenzhen 518060, China
| | - Feng Yang
- BGI-Shenzhen, Shenzhen 518103, China
| | - Jun Gong
- Central Laboratory, Yunfu People's Hospital, Yunfu 527399, China
| | - Gaozhi Ou
- School of Physical Education, China University of Geosciences, Wuhan 430074, China
| | - Song Wang
- Hubei Superior Discipline Group of Exercise and Brain Science from Hubei Provincial, Wuhan Sports University, Wuhan 430079, China.
| |
Collapse
|
12
|
Zhou Y, Qian C, Tang Y, Song M, Zhang T, Dong G, Zheng W, Yang C, Zhong C, Wang A, Zhao Y, Lu Y. Advance in the pharmacological effects of quercetin in modulating oxidative stress and inflammation related disorders. Phytother Res 2023; 37:4999-5016. [PMID: 37491826 DOI: 10.1002/ptr.7966] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/27/2023] [Accepted: 07/07/2023] [Indexed: 07/27/2023]
Abstract
Numerous pharmacological effects of quercetin have been illustrated, including antiinflammation, antioxidation, and anticancer properties. In recent years, the antioxidant activity of quercetin has been extensively reported, in particular, its impacts on glutathione, enzyme activity, signaling transduction pathways, and reactive oxygen species (ROS). Quercetin has also been demonstrated to exert a striking antiinflammatory effect mainly by inhibiting the production of cytokines, reducing the expression of cyclooxygenase and lipoxygenase, and preserving the integrity of mast cells. By regulating oxidative stress and inflammation, which are regarded as two critical processes involved in the defense and regular physiological operation of biological systems, quercetin has been validated to be effective in treating a variety of disorders. Symptoms of these reactions have been linked to degenerative processes and metabolic disorders, including metabolic syndrome, cardiovascular, neurodegeneration, cancer, and nonalcoholic fatty liver disease. Despite that evidence demonstrates that antioxidants are employed to prevent excessive oxidative and inflammatory processes, there are still concerns regarding the expense, accessibility, and side effects of agents. Notably, natural products, especially those derived from plants, are widely accessible, affordable, and generally safe. In this review, the antioxidant and antiinflammatory abilities of the active ingredient quercetin and its application in oxidative stress-related disorders have been outlined in detail.
Collapse
Affiliation(s)
- Yueke Zhou
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Cheng Qian
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yu Tang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mengyao Song
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Teng Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guanglu Dong
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Weiwei Zheng
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chunmei Yang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chongjin Zhong
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Aiyun Wang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yang Zhao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yin Lu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| |
Collapse
|
13
|
Zhang JY, Ren CQ, Cao YN, Ren Y, Zou L, Zhou C, Peng LX. Role of MicroRNAs in Dietary Interventions for Obesity and Obesity-Related Diseases. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:14396-14412. [PMID: 37782460 DOI: 10.1021/acs.jafc.3c03042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
Obesity and related metabolic syndromes pose a serious threat to human health and quality of life. A proper diet is a safe and effective strategy to prevent and control obesity, thus maintaining overall health. However, no consensus exists on the connotations of proper diet, and it is attributed to various factors, including "nutritional dark matter" and the "matrix effect" of food. Accumulating evidence confirms that obesity is associated with the in vivo levels of miRNAs, which serve as potential markers and regulatory targets for obesity onset and progression; food-derived miRNAs can regulate host obesity by targeting the related genes or gut microbiota across the animal kingdom. Host miRNAs mediate food nutrient-gut microbiota-obesity interactions. Thus, miRNAs are important correlates of diet and obesity onset. This review outlines the recent findings on miRNA-mediated food interventions for obesity, thereby elucidating their potential applications. Overall, we provide new perspectives and views on the evaluation of dietary nutrition, which may bear important implications for dietary control and obesity prevention.
Collapse
Affiliation(s)
- Ji-Yue Zhang
- Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Sichuan Province Engineering Technology Research Center of Coarse Cereal Industrialization, Chengdu University, Chengdu 610106, People's Republic of China
| | - Chao-Qin Ren
- Aba Teachers University, Wenchuan, Sichuan 623002, People's Republic of China
| | - Ya-Nan Cao
- Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Sichuan Province Engineering Technology Research Center of Coarse Cereal Industrialization, Chengdu University, Chengdu 610106, People's Republic of China
| | - Yuanhang Ren
- Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Sichuan Province Engineering Technology Research Center of Coarse Cereal Industrialization, Chengdu University, Chengdu 610106, People's Republic of China
| | - Liang Zou
- Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Sichuan Province Engineering Technology Research Center of Coarse Cereal Industrialization, Chengdu University, Chengdu 610106, People's Republic of China
| | - Chuang Zhou
- Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Sichuan Province Engineering Technology Research Center of Coarse Cereal Industrialization, Chengdu University, Chengdu 610106, People's Republic of China
| | - Lian-Xin Peng
- Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Sichuan Province Engineering Technology Research Center of Coarse Cereal Industrialization, Chengdu University, Chengdu 610106, People's Republic of China
| |
Collapse
|
14
|
Yu XJ, Zhang T, Wei ZZ, Gu B, Guo T, Jiang WJ, Shen YQ, Wang D, Wang Q, Wang J. Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1. Clinics (Sao Paulo) 2023; 78:100199. [PMID: 37119591 PMCID: PMC10173405 DOI: 10.1016/j.clinsp.2023.100199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 02/21/2023] [Accepted: 03/08/2023] [Indexed: 05/01/2023] Open
Abstract
OBJECTIVE To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. METHOD A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People's Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. RESULT Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3'UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122. CONCLUSION Serum miRNA-122 increased significantly after ACI, which may be a diagnostic marker of ACI. miRNA-122 may be involved in the pathological process of ACI and is related to the degree of neurological impairment and short-term prognosis in patients with ACI. miRNA-122 may play a regulatory role in ACI by inhibiting cell proliferation, increasing apoptosis, and inhibiting vascular endothelial cell regeneration through the CCNG1 channel.
Collapse
Affiliation(s)
- Xiao-Juan Yu
- Emergency Department, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Tian Zhang
- Emergency Department, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Zeng-Zhen Wei
- Emergency Department, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Bin Gu
- Emergency Department, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Ting Guo
- Emergency Department, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Wen-Juan Jiang
- Emergency Department, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Yue-Qin Shen
- Emergency Department, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Dong Wang
- Clinical Laboratory, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Qian Wang
- Blood Purification Center, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China
| | - Jun Wang
- Emergency Department, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, P.R. China.
| |
Collapse
|
15
|
Sousa-Filho CPB, Silva V, Bolin AP, Rocha ALS, Otton R. Green tea actions on miRNAs expression – An update. Chem Biol Interact 2023; 378:110465. [PMID: 37004950 DOI: 10.1016/j.cbi.2023.110465] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/17/2023] [Accepted: 03/28/2023] [Indexed: 04/01/2023]
Abstract
Compounds derived from plants have been widely studied in the context of metabolic diseases and associated clinical conditions. In this regard, although the effects of Camellia sinensis plant, from which various types of teas, such as green tea, originate, have been vastly reported in the literature, the mechanisms underlying these effects remain elusive. A deep search of the literature showed that green tea's action in different cells, tissues, and diseases is an open field in the research of microRNAs (miRNAs). miRNAs are important communicator molecules between cells in different tissues implicated in diverse cellular pathways. They have emerged as an important linkage between physiology and pathophysiology, raising the issue of polyphenols can act also by changing miRNA expression. miRNAs are short, non-coding endogenous RNA, which silence the gene functions by targeting messenger RNA (mRNA) through degradation or translation repression. Therefore, the aim of this review is to present the studies that show the main compounds of green tea modulating the expression of miRNAs in inflammation, adipose tissue, skeletal muscle, and liver. We provide an overview of a few studies that have tried to demonstrate the role of miRNAs associated with the beneficial effects of compounds from green tea. We have emphasized that there is still a considerable gap in the literature investigating the role and likely involvement of miRNAs in the extensive beneficial health effects of green tea compounds already described, indicating miRNAs as potential polyphenols' mediators with a promising field to be investigated.
Collapse
Affiliation(s)
| | - Victoria Silva
- Interdisciplinary Post-graduate Program in Health Sciences, Cruzeiro do Sul University, São Paulo, Brazil
| | - Anaysa Paola Bolin
- Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil
| | | | - Rosemari Otton
- Interdisciplinary Post-graduate Program in Health Sciences, Cruzeiro do Sul University, São Paulo, Brazil.
| |
Collapse
|
16
|
Huang Y, Zhang X, Zou Y, Yuan Q, Xian YF, Lin ZX. Quercetin Ameliorates Neuropathic Pain after Brachial Plexus Avulsion via Suppressing Oxidative Damage through Inhibition of PKC/MAPK/ NOX Pathway. Curr Neuropharmacol 2023; 21:2343-2361. [PMID: 37533160 PMCID: PMC10556381 DOI: 10.2174/1570159x21666230802144940] [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: 11/07/2022] [Revised: 01/06/2023] [Accepted: 01/09/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Brachial plexus avulsion (BPA) animally involves the separation of spinal nerve roots themselves and the correlative spinal cord segment, leading to formidable neuropathic pain of the upper limb. METHODS The right seventh cervical (C7) ventral and dorsal roots were avulsed to establish a neuropathic pain model in rats. After operation, rats were treated with quercetin (QCN) by intragastric administration for 1 week. The effects of QCN were evaluated using mechanical allodynia tests and biochemical assay kits. RESULTS QCN treatment significantly attenuated the avulsion-provoked mechanical allodynia, elevated the levels of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and total antioxidant capacity (TAC) in the C7 spinal dorsal horn. In addition, QCN administration inhibited the activations of macrophages, microglia and astrocytes in the C6 dorsal root ganglion (DRG) and C6-8 spinal dorsal horn, as well as attenuated the release of purinergic 2X (P2X) receptors in C6 DRG. The molecular mechanism underlying the above alterations was found to be related to the suppression of the PKC/MAPK/NOX signal pathway. To further study the anti-oxidative effects of QCN, we applied QCN on the H2O2-induced BV-2 cells in vitro, and the results attested that QCN significantly ameliorated the H2O2-induced ROS production in BV-2 cells, inhibited the H2O2-induced activation of PKC/MAPK/NOX pathway. CONCLUSION Our study for the first time provided evidence that QCN was able to attenuate pain hypersensitivity following the C7 spinal root avulsion in rats, and the molecular mechanisms involve the reduction of both neuro-inflammatory infiltration and oxidative stress via suppression of P2X receptors and inhibition of the activation of PKC/MAPK/NOX pathway. The results indicate that QCN is a natural compound with great promise worthy of further development into a novel therapeutic method for the treatment of BPA-induced neuropathic pain.
Collapse
Affiliation(s)
- Yanfeng Huang
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
| | - Xie Zhang
- Research Center for Integrative Medicine of Guangzhou University of Chinese Medicine, Key Laboratory of Chinese Medicine Pathogenesis and Therapy Research, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong. P.R. China
- Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong. P.R. China
| | - Yidan Zou
- Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
| | - Qiuju Yuan
- Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Shatin, N.T., Hong Kong SAR, China
| | - Yan-Fang Xian
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
| | - Zhi-Xiu Lin
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| |
Collapse
|
17
|
Li S, Yin S, Ding H, Shao Y, Zhou S, Pu W, Han L, Wang T, Yu H. Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention. Cell Prolif 2023; 56:e13346. [PMID: 36229407 DOI: 10.1111/cpr.13346] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/19/2022] [Accepted: 09/29/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
Collapse
Affiliation(s)
- Shuangfeng Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Shuangshuang Yin
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Hui Ding
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yingying Shao
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Shiyue Zhou
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Weiling Pu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Lifeng Han
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Tao Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| | - Haiyang Yu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Haihe Laboratory of Modern Chinese Medicine, Tianjin, China
| |
Collapse
|
18
|
Huang Y, Zhang X, Huang Q, Dou Y, Qu C, Xu Q, Yuan Q, Xian YF, Lin ZX. Quercetin enhances survival and axonal regeneration of motoneurons after spinal root avulsion and reimplantation: experiments in a rat model of brachial plexus avulsion. Inflamm Regen 2022; 42:56. [PMID: 36456978 PMCID: PMC9714227 DOI: 10.1186/s41232-022-00245-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 11/23/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Brachial plexus avulsion (BPA) physically involves the detachment of spinal nerve roots themselves and the associated spinal cord segment, leading to permanent paralysis of motor function of the upper limb. Root avulsion induces severe pathological changes, including inflammatory reaction, oxidative damage, and finally massive motoneuron apoptosis. Quercetin (QCN), a polyphenolic flavonoid found in abundance in fruit and vegetables, has been reported to possess anti-oxidative, anti-inflammatory, and neuroprotective effects in many experimental models of both central nervous system (CNS) and peripheral nervous system (PNS) disorders. The purpose of this study was to investigate whether QCN could improve motor function recovery after C5-7 ventral root avulsion and C6 reimplantation in a rat model of BPA. METHODS The right fifth cervical (C5) to C7 ventral roots were avulsed followed by re-implantation of only C6 to establish the spinal root avulsion plus re-implantation model in rats. After surgery, rats were treated with QCN (25, 50, and 100 mg/kg) by gavage for 2 or 8 consecutive weeks. The effects of QCN were assessed using behavior test (Terzis grooming test, TGT) and histological evaluation. The molecular mechanisms were determined by immunohistochemistry analysis and western blotting. RESULTS Our results demonstrated that QCN significantly expedited motor function recovery in the forelimb as shown by the increased Terzis grooming test score, and accelerated motor axon regeneration as evidenced by the ascending number of Fluoro-Ruby-labeled and P75-positive regenerative motoneurons. The raised ChAT-immunopositive and cresyl violet-stained neurons indicated the enhanced survival of motoneurons by QCN administration. Furthermore, QCN treatment markedly alleviated muscle atrophy, restored functional motor endplates in biceps and inhibited the microglial and astroglia activation via modulating Nrf2/HO-1 and neurotrophin/Akt/MAPK signaling pathway. CONCLUSIONS Taken together, these findings have for the first time unequivocally indicated that QCN has promising potential for further development into a novel therapeutic in conjunction with reimplantation surgery for the treatment of BPA. .
Collapse
Affiliation(s)
- Yanfeng Huang
- grid.10784.3a0000 0004 1937 0482School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR China
| | - Xie Zhang
- grid.411866.c0000 0000 8848 7685School of Basic Medical Sciences, Department of Medical Biotechnology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong People’s Republic of China
| | - Qionghui Huang
- grid.10784.3a0000 0004 1937 0482School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR China
| | - Yaoxing Dou
- grid.411866.c0000 0000 8848 7685The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Chang Qu
- grid.10784.3a0000 0004 1937 0482School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR China
| | - Qingqing Xu
- grid.10784.3a0000 0004 1937 0482School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR China
| | - Qiuju Yuan
- grid.10784.3a0000 0004 1937 0482School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR China ,grid.9227.e0000000119573309Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Shatin, N.T., Hong Kong, SAR China
| | - Yan-Fang Xian
- grid.10784.3a0000 0004 1937 0482School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR China
| | - Zhi-Xiu Lin
- grid.10784.3a0000 0004 1937 0482School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR China ,grid.10784.3a0000 0004 1937 0482Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong, SAR China
| |
Collapse
|
19
|
Adelipour M, Cheraghzadeh M, Rashidi M. Polyphenols as epigenetic modulators in treating or preventing of cancers. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
20
|
Alam SB, Wagner A, Willows S, Kulka M. Quercetin and Resveratrol Differentially Decrease Expression of the High-Affinity IgE Receptor (FcεRI) by Human and Mouse Mast Cells. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27196704. [PMID: 36235240 PMCID: PMC9573482 DOI: 10.3390/molecules27196704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/24/2022] [Accepted: 09/28/2022] [Indexed: 11/05/2022]
Abstract
Mast cells (MC) synthesize and store proinflammatory mediators and are centrally important in atopic diseases such as asthma and atopic dermatitis. Quercetin a and resveratrol are plant derived polyphenolic compounds with anti-inflammatory properties that inhibit MC degranulation and mediator release. However, the underlying mechanism of these inhibitory effects on MC is poorly understood and it is unclear whether this is a general effect on all MC phenotypes. We have characterized and compared the effects of quercetin with resveratrol on human (LAD2) and mouse (MC/9 and BMMC) MC mediator release, receptor expression and FcεRI signaling to better understand the mechanisms involved in quercetin and resveratrol-mediated inhibition of MC activation. Quercetin significantly decreased the expression of FcεRI by BMMC and MC/9, although the effects on MC/9 were associated with a significant reduction in cell viability. Quercetin also inhibited antigen-stimulated TNF release by BMMC. Although neither quercetin nor resveratrol significantly altered antigen-stimulated BMMC degranulation or downstream signaling events such as phosphorylation of spleen tyrosine kinase (SYK) or extracellular signal-regulated kinase 1/2 (ERK), resveratrol inhibited ERK phosphorylation and FcεRI- stimulated degranulation in LAD2. Our data suggests that quercetin and resveratrol inhibit human and mouse MC differentially and that these effects are associated with modification of FcεRI expression, signaling (phosphorylation of SYK and ERK) and mediator release.
Collapse
Affiliation(s)
- Syed Benazir Alam
- Nanotechnology Research Center, National Research Council, Edmonton, AB T6G 2M9, Canada
- Correspondence:
| | - Ashley Wagner
- Nanotechnology Research Center, National Research Council, Edmonton, AB T6G 2M9, Canada
| | - Steven Willows
- Nanotechnology Research Center, National Research Council, Edmonton, AB T6G 2M9, Canada
| | - Marianna Kulka
- Nanotechnology Research Center, National Research Council, Edmonton, AB T6G 2M9, Canada
- Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada
| |
Collapse
|
21
|
Murata M, Marugame Y, Yamada S, Lin I, Yamashita S, Fujimura Y, Tachibana H. Circulating miRNA profiles in mice plasma following flavonoid intake. Mol Biol Rep 2022; 49:10399-10407. [PMID: 36098884 DOI: 10.1007/s11033-022-07918-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/03/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Polyphenols, including flavonoids, have been the focus of numerous studies that have revealed diverse health benefits. MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that function as posttranscriptional regulators of gene expression. miRNAs can be detected in the blood and these so-called circulating miRNAs are potential biomarkers of various diseases. This study aimed to explore circulating miRNAs in plasma as a means to predict the biological effects of functional food ingredients. METHODS AND RESULTS We used miRNA microarray analysis to compare plasma miRNA levels in mice orally administered three flavonoids (daidzein, quercetin, and delphinidin). Several miRNAs were differentially expressed in plasma from mice in each treatment group compared with the vehicle-treated group. The plasma levels of miR-25-5p, miR-146b-5p, and miR-501-3p were increased in the flavonoid-treated and the plasma levels of miR-148b-3p, miR-669e-5p, and miR-3962 were decreased. CONCLUSIONS Our findings suggested that flavonoids alter miRNA expression in plasma and identified promising plasma miRNAs for assessing the functionality of flavonoids.
Collapse
Affiliation(s)
- Motoki Murata
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan
- Advanced Research Support Center (ADRES), Ehime University, Matsuyama, Ehime, Japan
| | - Yuki Marugame
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan
| | - Shuhei Yamada
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan
| | - Ichian Lin
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan
| | - Shuya Yamashita
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan
| | - Yoshinori Fujimura
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
| |
Collapse
|
22
|
Mohanty JN, Sahoo S, Routray SP, Bhuyan R. Does the diverse source of miRNAs affect human health? An approach towards diagnosis and therapeutic management. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
|
23
|
Pandita D, Pandita A. Omics Technology for the Promotion of Nutraceuticals and Functional Foods. Front Physiol 2022; 13:817247. [PMID: 35634143 PMCID: PMC9136416 DOI: 10.3389/fphys.2022.817247] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 03/23/2022] [Indexed: 12/24/2022] Open
Abstract
The influence of nutrition and environment on human health has been known for ages. Phytonutrients (7,000 flavonoids and phenolic compounds; 600 carotenoids) and pro-health nutrients—nutraceuticals positively add to human health and may prevent disorders such as cancer, diabetes, obesity, cardiovascular diseases, and dementia. Plant-derived bioactive metabolites have acquired an imperative function in human diet and nutrition. Natural phytochemicals affect genome expression (nutrigenomics and transcriptomics) and signaling pathways and act as epigenetic modulators of the epigenome (nutri epigenomics). Transcriptomics, proteomics, epigenomics, miRNomics, and metabolomics are some of the main platforms of complete omics analyses, finding use in functional food and nutraceuticals. Now the recent advancement in the integrated omics approach, which is an amalgamation of multiple omics platforms, is practiced comprehensively to comprehend food functionality in food science.
Collapse
Affiliation(s)
- Deepu Pandita
- Government Department of School Education, Jammu, India
- *Correspondence: Deepu Pandita,
| | | |
Collapse
|
24
|
Medrano-Jiménez E, Meza-Sosa KF, Urbán-Aragón JA, Secundino I, Pedraza-Alva G, Pérez-Martínez L. Microglial activation in Alzheimer's disease: The role of flavonoids and microRNAs. J Leukoc Biol 2022; 112:47-77. [PMID: 35293018 DOI: 10.1002/jlb.3mr1021-531r] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 01/31/2022] [Indexed: 12/16/2022] Open
Abstract
Alzheimer's disease (AD) is the most common form of senile dementia and is characterized by progressive cognitive impairment and neuronal degeneration. Microglial activation is an important pathologic hallmark of AD. During disease progression, microglial cells switch from an alternative or anti-inflammatory and neuroprotective profile (M2) to a classic or proinflammatory and neurotoxic profile (M1). Phenotypically, M1 microglia is characterized by the activation of inflammatory signaling pathways that cause increased expression of proinflammatory genes, including those coding for cytokines and chemokines. This microglia-mediated neuroinflammation contributes to neuronal cell death. Recent studies in microglial cells have shown that a group of plant-derived compounds, known as flavonoids, possess anti-inflammatory properties and therefore exert a neuroprotective effect through regulating microglia activation. Here, we discuss how flavonoids can promote the switch from an inflammatory M1 phenotype to an anti-inflammatory M2 phenotype in microglia and how this represents a valuable opportunity for the development of novel therapeutic strategies to blunt neuroinflammation and boost neuronal recovery in AD. We also review how certain flavonoids can inhibit neuroinflammation through their action on the expression of microglia-specific microRNAs (miRNAs), which also constitute a key therapeutic approach in different neuropathologies involving an inflammatory component, including AD. Finally, we propose novel targets of microglia-specific miRNAs that may be considered for AD treatment.
Collapse
Affiliation(s)
- Elisa Medrano-Jiménez
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México
| | - Karla F Meza-Sosa
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México
| | - José A Urbán-Aragón
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México
| | - Ismael Secundino
- Universidad De La Salle Bajío, Facultad de Odontología y Escuela de Veterinaria, León-Guanajuato, México
| | - Gustavo Pedraza-Alva
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México
| | - Leonor Pérez-Martínez
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México
| |
Collapse
|
25
|
Nobiletin Protects Endothelial Cell Function via Upregulation of eNOS/ET-1 and Antioxidant Status-Related Genes under Nonstimulated and Inflammatory Conditions. J FOOD QUALITY 2022. [DOI: 10.1155/2022/9119547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Nobiletin, a natural polymethoxylated flavonoid compound, has been shown to exert a wide range of biological activities. However, there is limited evidence on the molecular mechanisms by which nobiletin modulates endothelial cell function. Our aim was to investigate the potential of nobiletin to enhance endothelial cell functionality under nonstimulated and inflammatory conditions. To this end, gene expression relevant to nitric oxide (NO) production, endothelin 1 (ET-1), and antioxidant status in human endothelial cells EA.hy926 was determined using real-time PCR. The fluorescence probe 4,5-diaminofluorescein (DAF-2) was used to measure NO production. The results demonstrated significant upregulation of eNOS and antioxidant genes as well as downregulation of ET-1 by nobiletin under nonstimulated and TNF-α-stimulated inflammatory conditions. These findings suggest a promising protective effect of nobiletin with relevance for cardiovascular health, likely through the NO/ET-1 dynamics and Nrf2 signaling pathway.
Collapse
|
26
|
Beigoli S, Behrouz S, Memarzia A, Ghasemi SZ, Boskabady M, Marefati N, Kianian F, Khazdair MR, El-Seedi H, Boskabady MH. Effects of Allium cepa and Its Constituents on Respiratory and Allergic Disorders: A Comprehensive Review of Experimental and Clinical Evidence. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:5554259. [PMID: 34552650 PMCID: PMC8452398 DOI: 10.1155/2021/5554259] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/10/2021] [Accepted: 08/30/2021] [Indexed: 11/27/2022]
Abstract
The health benefits of Allium cepa (A. cepa) have been proclaimed for centuries. Various pharmacological and therapeutic effects on respiratory, allergic, and immunologic disorders are shown by A. cepa and its constituents. Flavonoids such as quercetin and kaempferol, alk(en)yl cysteine sulfoxides including S-methyl cysteine sulfoxide and S-propyl cysteine sulfoxide, cycloalliin, thiosulfinates, and sulfides are the main compounds of the plant. A. cepa displays broad-spectrum pharmacological activities including antioxidant, anti-inflammatory, antihypertensive, and antidiabetic effects. Our objective in this review is to present the effects of A. cepa and its constituents on respiratory, allergic, and immunologic disorders. Different online databases were searched to find articles related to the effect of A. cepa extracts and its constituents on respiratory, allergic, and immunologic disorders until the end of December 2020 using keywords such as onion, A. cepa, constituents of A. cepa, therapeutic effects and pharmacological effects, and respiratory, allergic, and immunologic disorders. Extracts and constituents of A. cepa showed tracheal smooth muscle relaxant effects, indicating possible bronchodilator activities or relieving effects on obstructive respiratory diseases. In experimental animal models of different respiratory diseases, the preventive effect of various extracts and constituents of A. cepa was induced by their antioxidant, immunomodulatory, and anti-inflammatory effects. The preventive effects of the plant and its components on lung disorders induced by exposure to noxious agents as well as lung cancer, lung infection, and allergic and immunologic disorders were also indicated in the experimental and clinical studies. Therefore, this review may be considered a scientific basis for development of therapies using this plant, to improve respiratory, allergic, and immunologic disorders.
Collapse
Affiliation(s)
- Sima Beigoli
- Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sepideh Behrouz
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arghavan Memarzia
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyyedeh Zahra Ghasemi
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Marzie Boskabady
- Dental Materials Research Center and Department of Pediatric Dentistry, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pediatric Dentistry, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Narges Marefati
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farzaneh Kianian
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Khazdair
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Hesham El-Seedi
- Department of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23, Uppsala, Sweden
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
- Al-Rayan Research and Innovation Center, Al-Rayan Colleges, Medina 42541, Saudi Arabia
| | - Mohammad Hosein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
27
|
Frank J, Kisters K, Stirban OA, Obeid R, Lorkowski S, Wallert M, Egert S, Podszun MC, Eckert GP, Pettersen JA, Venturelli S, Classen HG, Golombek J. The role of biofactors in the prevention and treatment of age-related diseases. Biofactors 2021; 47:522-550. [PMID: 33772908 DOI: 10.1002/biof.1728] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 03/03/2021] [Accepted: 03/11/2021] [Indexed: 02/07/2023]
Abstract
The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.
Collapse
Affiliation(s)
- Jan Frank
- University of Hohenheim, Institute of Nutritional Sciences, Stuttgart, Germany
| | - Klaus Kisters
- Medical Clinic I, St. Anna-Hospital & ESH Excellence Centre, Herne, Germany
| | | | - Rima Obeid
- Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Homburg/Saar, Germany
| | - Stefan Lorkowski
- Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
| | - Maria Wallert
- Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
| | - Sarah Egert
- University of Hohenheim, Institute of Nutritional Medicine, Stuttgart, Germany
| | - Maren C Podszun
- University of Hohenheim, Institute of Nutritional Sciences, Stuttgart, Germany
| | - Gunter P Eckert
- Department of Nutritional Sciences, Laboratory for Nutrition in Prevention and Therapy, Justus-Liebig-University of Giessen, Giessen, Germany
| | - Jacqueline A Pettersen
- Northern Medical Program, University of Northern British Columbia, Prince George, Canada
- Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, Canada
| | - Sascha Venturelli
- University of Hohenheim, Institute of Nutritional Sciences, Stuttgart, Germany
| | - Hans-Georg Classen
- University of Hohenheim, Institute of Nutritional Sciences, Stuttgart, Germany
| | | |
Collapse
|
28
|
Quercetin and non-alcoholic fatty liver disease: A review based on experimental data and bioinformatic analysis. Food Chem Toxicol 2021; 154:112314. [PMID: 34087406 DOI: 10.1016/j.fct.2021.112314] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 05/18/2021] [Accepted: 05/29/2021] [Indexed: 02/08/2023]
Abstract
Quercetin, a polyphenol widely present in the plant kingdom, has received great interest due to pleiotropic effects. As evidenced by animal and cellular studies, quercetin exerts hepatoprotection against non-alcoholic fatty liver disease (NAFLD), particularly in hepatic steatosis and hepatitis. Mechanically, various hypotheses of such protective effects have been actively proposed, including improving fatty acid metabolism, anti-inflammation, anti-oxidant, modulating gut microbiota and bile acid, etc. Here, the role of quercetin in NAFLD was summarized. With a particular focus on molecular mechanism, we comprehensively discussed the pathways of quercetin on NAFLD based on the analysis from Gene Expression Omnibus (GEO) database and experimental evidence.
Collapse
|
29
|
Shokri-Mashhadi N, Kazemi M, Saadat S, Moradi S. Effects of select dietary supplements on the prevention and treatment of viral respiratory tract infections: a systematic review of randomized controlled trials. Expert Rev Respir Med 2021; 15:805-821. [PMID: 33858268 DOI: 10.1080/17476348.2021.1918546] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Introduction: Viral respiratory tract infections (RTIs) have been recognized as a global public health burden. Despite current theories about their effectiveness, the true benefits of dietary supplements on the prevention and treatment of viral RTIs remain elusive, due to contradictory reports. Hence, we aimed to evaluate the effectiveness of dietary supplements on the prevention and treatment of viral RTIs.Areas covered: We systematically searched databases of PubMed, Web of Science, Scopus, and Google Scholar through 4 March 2020, to identify randomized controlled trials that evaluated the effects of consuming selected dietary supplements on the prevention or treatment of viral RTIs.Expert opinion: Thirty-nine randomized controlled trials (n = 16,797 participants) were eligible and included. Namely, vitamin D supplementation appeared to improve viral RTIs across cohorts particulate in those with vitamin D deficiency. Among the evaluated dietary supplements, specific lactobacillus strains were used most commonly with selected prebiotics that showed potentially positive effects on the prevention and treatment of viral RTIs. Further, ginseng extract supplementation may effectively prevent viral RTIs as adjuvant therapy. However, longitudinal research is required to confirm these observations and address the optimal dose, duration, and safety of dietary supplements being publicly recommended.
Collapse
Affiliation(s)
- Nafiseh Shokri-Mashhadi
- Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Kazemi
- Division of Nutritional Sciences, Human Metabolic Research Unit, Cornell University, Ithaca, NewYork, USA
| | - Saeed Saadat
- Department of Computer Sciences, Faculty of Mathematics and Natural Sciences, Heinrich Heine Universität, Düsseldorf, Germany
| | - Sajjad Moradi
- Halal Research Center of IRI, FDA, Tehran, Iran.,Nutritional Sciences Department, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| |
Collapse
|
30
|
Benameur T, Soleti R, Porro C. The Potential Neuroprotective Role of Free and Encapsulated Quercetin Mediated by miRNA against Neurological Diseases. Nutrients 2021; 13:1318. [PMID: 33923599 PMCID: PMC8073422 DOI: 10.3390/nu13041318] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/11/2021] [Accepted: 04/12/2021] [Indexed: 12/13/2022] Open
Abstract
Chronic neuroinflammation is a pathological condition of numerous central nervous system (CNS) diseases such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis and many others. Neuroinflammation is characterized by the microglia activation and concomitant production of pro-inflammatory cytokines leading to an increasing neuronal cell death. The decreased neuroinflammation could be obtained by using natural compounds, including flavonoids known to modulate the inflammatory responses. Among flavonoids, quercetin possess multiple pharmacological applications including anti-inflammatory, antitumoral, antiapoptotic and anti-thrombotic activities, widely demonstrated in both in vitro and in vivo studies. In this review, we describe the recent findings about the neuroprotective action of quercetin by acting with different mechanisms on the microglial cells of CNS. The ability of quercetin to influence microRNA expression represents an interesting skill in the regulation of inflammation, differentiation, proliferation, apoptosis and immune responses. Moreover, in order to enhance quercetin bioavailability and capacity to target the brain, we discuss an innovative drug delivery system. In summary, this review highlighted an important application of quercetin in the modulation of neuroinflammation and prevention of neurological disorders.
Collapse
Affiliation(s)
- Tarek Benameur
- College of Medicine, Department of Biomedical Sciences, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
| | - Raffaella Soleti
- Univ Angers, Université de Nantes, Inserm, CRCINA, SFR ICAT, F-49800 Angers, France;
| | - Chiara Porro
- Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy
| |
Collapse
|
31
|
Dietary Anti-Aging Polyphenols and Potential Mechanisms. Antioxidants (Basel) 2021; 10:antiox10020283. [PMID: 33668479 PMCID: PMC7918214 DOI: 10.3390/antiox10020283] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 02/08/2021] [Accepted: 02/09/2021] [Indexed: 12/15/2022] Open
Abstract
For years, the consumption of a diet rich in fruits and vegetables has been considered healthy, increasing longevity, and decreasing morbidities. With the assistance of basic research investigating the potential mechanisms, it has become clear that the beneficial effects of plant-based foods are mainly due to the large amount of bioactive phenolic compounds contained. Indeed, substantial dietary intervention studies in humans have supported that the supplementation of polyphenols have various health-promoting effects, especially in the elderly population. In vitro examinations on the anti-aging mechanisms of polyphenols have been widely performed, using different types of natural and synthetic phenolic compounds. The aim of this review is to critically evaluate the experimental evidence demonstrating the beneficial effects of polyphenols on aging-related diseases. We highlight the potential anti-aging mechanisms of polyphenols, including antioxidant signaling, preventing cellular senescence, targeting microRNA, influencing NO bioavailability, and promoting mitochondrial function. While the trends on utilizing polyphenols in preventing aging-related disorders are getting growing attention, we suggest the exploration of the beneficial effects of the combination of multiple polyphenols or polyphenol-rich foods, as this would be more physiologically relevant to daily life.
Collapse
|
32
|
Desjarlais M, Wirth M, Lahaie I, Ruknudin P, Hardy P, Rivard A, Chemtob S. Nutraceutical Targeting of Inflammation-Modulating microRNAs in Severe Forms of COVID-19: A Novel Approach to Prevent the Cytokine Storm. Front Pharmacol 2020; 11:602999. [PMID: 33362557 PMCID: PMC7759543 DOI: 10.3389/fphar.2020.602999] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 11/17/2020] [Indexed: 12/13/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has become the number one health problem worldwide. As of August 2020, it has affected more than 18 million humans and caused over 700,000 deaths worldwide. COVID-19 is an infectious disease that can lead to severe acute respiratory syndrome. Under certain circumstances, the viral infection leads to excessive and uncontrolled inflammatory response, which is associated with the massive release of inflammatory cytokines in pulmonary alveolar structures. This phenomenon has been referred to as the “cytokine storm,” and it is closely linked to lung injury, acute respiratory syndrome and mortality. Unfortunately, there is currently no vaccine available to prevent the infection, and no effective treatment is available to reduce the mortality associated with the severe form of the disease. The cytokine storm associate with COVID-19 shows similarities with those observed in other pathologies such as sepsis, acute respiratory distress syndrome, acute lung injury and other viral infection including severe cases of influenza. However, the specific mechanisms that cause and modulate the cytokine storm in the different conditions remain to be determined. micro-RNAs are important regulators of gene expression, including key inflammatory cytokines involved in the massive recruitment of immune cells to the lungs such as IL1β, IL6, and TNFα. In recent years, it has been shown that nutraceutical agents can modulate the expression of miRs involved in the regulation of cytokines in various inflammatory diseases. Here we review the potential role of inflammatory-regulating-miRs in the cytokine storm associated with COVID-19, and propose that nutraceutical agents may represent a supportive therapeutic approach to modulate dysregulated miRs in this condition, providing benefits in severe respiratory diseases.
Collapse
Affiliation(s)
- Michel Desjarlais
- Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, Université de Montréal, Montréal, QC, Canada.,Departments of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC, Canada
| | - Maëlle Wirth
- Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, Université de Montréal, Montréal, QC, Canada.,Departments of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC, Canada
| | - Isabelle Lahaie
- Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, Université de Montréal, Montréal, QC, Canada
| | - Pakiza Ruknudin
- Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, Université de Montréal, Montréal, QC, Canada
| | - Pierre Hardy
- Departments of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC, Canada
| | - Alain Rivard
- Department of Medicine, Centre Hospitalier de l'Université de Montréal (CHUM) Research Center, Montréal, QC, Canada
| | - Sylvain Chemtob
- Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, Université de Montréal, Montréal, QC, Canada.,Departments of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC, Canada
| |
Collapse
|
33
|
Koudoufio M, Desjardins Y, Feldman F, Spahis S, Delvin E, Levy E. Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders? Antioxidants (Basel) 2020; 9:E982. [PMID: 33066106 PMCID: PMC7601951 DOI: 10.3390/antiox9100982] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 09/30/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Lifestyle factors, especially diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given their anti-oxidant and anti-inflammatory actions. In fact, polyphenols can prevent or reverse the progression of disease processes through many distinct mechanisms. In particular, the crosstalk between polyphenols and gut microbiota, recently unveiled thanks to DNA-based tools and next generation sequencing, unravelled the central regulatory role of dietary polyphenols and their intestinal micro-ecology metabolites on the host energy metabolism and related illnesses. The objectives of this review are to: (1) provide an understanding of classification, structure, and bioavailability of dietary polyphenols; (2) underline their metabolism by gut microbiota; (3) highlight their prebiotic effects on microflora; (4) discuss the multifaceted roles of their metabolites in CMD while shedding light on the mechanisms of action; and (5) underscore their ability to initiate host epigenetic regulation. In sum, the review clearly documents whether dietary polyphenols and micro-ecology favorably interact to promote multiple physiological functions on human organism.
Collapse
Affiliation(s)
- Mireille Koudoufio
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Nutrition, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Yves Desjardins
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Francis Feldman
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Nutrition, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Schohraya Spahis
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Nutrition, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Edgard Delvin
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Biochemistry, Université de Montréal, Montreal, QC H3T 1J4, Canada
| | - Emile Levy
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Nutrition, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
- Department of Pediatrics, Université de Montréal, Montreal, QC H3T 1J4, Canada
| |
Collapse
|
34
|
Owczarczyk-Saczonek A, Purzycka-Bohdan D, Nedoszytko B, Reich A, Szczerkowska-Dobosz A, Bartosiñska J, Batycka-Baran A, Czajkowski R, Dobrucki IT, Dobrucki LW, Górecka-Sokołowska M, Janaszak-Jasiecka A, Kalinowski L, Krasowska D, Radulska A, Reszka E, Samotij D, Słominski A, Słominski R, Sobalska-Kwapis M, Stawczyk-Macieja M, Strapagiel D, Szczêch J, Żmijewski M, Nowicki RJ. Pathogenesis of psoriasis in the "omic" era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis. Postepy Dermatol Alergol 2020; 37:452-467. [PMID: 32994764 PMCID: PMC7507147 DOI: 10.5114/ada.2020.98284] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 05/28/2020] [Indexed: 12/15/2022] Open
Abstract
Psoriasis is a systemic disease that is strictly connected with metabolic disorders (insulin resistance, atherogenic dyslipidemia, arterial hypertension, and cardiovascular diseases). It occurs more often in patients with a more severe course of the disease. Obesity is specially an independent risk factor and it is associated with a worse treatment outcome because of the high inflammatory activity of visceral fatty tissue and the production of inflammatory mediators involved in the development of both psoriasis and metabolic disorders. However, in psoriasis the activation of the Th17/IL-17 and the abnormalities in the Th17/Treg balance axis are observed, but this pathomechanism does not fully explain the frequent occurrence of metabolic disorders. Therefore, there is a need to look for better biomarkers in the diagnosis, prognosis and monitoring of concomitant disorders and therapeutic effects in psoriasis. In addition, the education on the use of a proper diet as a prophylaxis for the development of the above disorders is an important element of holistic care for a patient with psoriasis. Diet may affect gene expression due to epigenetic modification which encompasses interactions of environment, nutrition and diseases. Patients with psoriasis should be advised to adopt proper diet and dietician support.
Collapse
Affiliation(s)
- Agnieszka Owczarczyk-Saczonek
- Chair and Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
| | - Dorota Purzycka-Bohdan
- Chair and Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland
| | - Bogusław Nedoszytko
- Chair and Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland
| | - Adam Reich
- Department of Dermatology, University of Rzeszow, Rzeszow, Poland
| | - Aneta Szczerkowska-Dobosz
- Chair and Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland
| | - Joanna Bartosiñska
- Chair and Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
| | - Aleksandra Batycka-Baran
- Chair and Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland
| | - Rafał Czajkowski
- Chair and Department of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Iwona T. Dobrucki
- Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
| | - Lawrence W. Dobrucki
- Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA
- Department of Medical Laboratory Diagnostics, Medical University of Gdansk, Gdansk, Poland
- Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.PL), Gdansk, Poland
| | | | - Anna Janaszak-Jasiecka
- Department of Medical Laboratory Diagnostics, Medical University of Gdansk, Gdansk, Poland
| | - Leszek Kalinowski
- Department of Medical Laboratory Diagnostics, Medical University of Gdansk, Gdansk, Poland
- Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland
- Gdansk University of Technology, Gdansk, Poland
| | - Dorota Krasowska
- Chair and Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
| | - Adrianna Radulska
- Department of Pharmaceutical Biochemistry, Medical University of Gdansk, Gdansk, Poland
| | - Edyta Reszka
- Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland
| | - Dominik Samotij
- Department of Dermatology, University of Rzeszow, Rzeszow, Poland
| | - Andrzej Słominski
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, USA
| | - Radomir Słominski
- Department of Medicine and Microbiology, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, USA
| | | | - Marta Stawczyk-Macieja
- Chair and Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland
| | | | - Justyna Szczêch
- Department of Dermatology, University of Rzeszow, Rzeszow, Poland
| | - Michał Żmijewski
- Department of Histology, Medical University of Gdansk, Gdansk, Poland
| | - Roman J. Nowicki
- Chair and Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland
| |
Collapse
|
35
|
Liu L, Wang Q, Qiu Z, Kang Y, Liu J, Ning S, Yin Y, Pang D, Xu S. Noncoding RNAs: the shot callers in tumor immune escape. Signal Transduct Target Ther 2020; 5:102. [PMID: 32561709 PMCID: PMC7305134 DOI: 10.1038/s41392-020-0194-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 05/05/2020] [Accepted: 05/06/2020] [Indexed: 01/17/2023] Open
Abstract
Immunotherapy, designed to exploit the functions of the host immune system against tumors, has shown considerable potential against several malignancies. However, the utility of immunotherapy is heavily limited due to the low response rate and various side effects in the clinical setting. Immune escape of tumor cells may be a critical reason for such low response rates. Noncoding RNAs (ncRNAs) have been identified as key regulatory factors in tumors and the immune system. Consequently, ncRNAs show promise as targets to improve the efficacy of immunotherapy in tumors. However, the relationship between ncRNAs and tumor immune escape (TIE) has not yet been comprehensively summarized. In this review, we provide a detailed account of the current knowledge on ncRNAs associated with TIE and their potential roles in tumor growth and survival mechanisms. This review bridges the gap between ncRNAs and TIE and broadens our understanding of their relationship, providing new insights and strategies to improve immunotherapy response rates by specifically targeting the ncRNAs involved in TIE.
Collapse
Affiliation(s)
- Lei Liu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Qin Wang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Zhilin Qiu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Yujuan Kang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Jiena Liu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Shipeng Ning
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Yanling Yin
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Da Pang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China. .,Heilongjiang Academy of Medical Sciences, Harbin, 150086, China.
| | - Shouping Xu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
| |
Collapse
|
36
|
Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases. Biomolecules 2020; 10:biom10040641. [PMID: 32326376 PMCID: PMC7226566 DOI: 10.3390/biom10040641] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 04/16/2020] [Accepted: 04/17/2020] [Indexed: 12/14/2022] Open
Abstract
Atherosclerosis is the main process behind cardiovascular diseases (CVD), maladies which continue to be responsible for up to 70% of death worldwide. Despite the ongoing development of new and potent drugs, their incomplete efficacy, partial intolerance and numerous side effects make the search for new alternatives worthwhile. The focus of the scientific world turned to the potential of natural active compounds to prevent and treat CVD. Essential for effective prevention or treatment based on phytochemicals is to know their mechanisms of action according to their bioavailability and dosage. The present review is focused on the latest data about phenolic compounds and aims to collect and correlate the reliable existing knowledge concerning their molecular mechanisms of action to counteract important risk factors that contribute to the initiation and development of atherosclerosis: dyslipidemia, and oxidative and inflammatory-stress. The selection of phenolic compounds was made to prove their multiple benefic effects and endorse them as CVD remedies, complementary to allopathic drugs. The review also highlights some aspects that still need clear scientific explanations and draws up some new molecular approaches to validate phenolic compounds for CVD complementary therapy in the near future.
Collapse
|
37
|
Propolis Affects Pseudomonas aeruginosa Growth, Biofilm Formation, eDNA Release and Phenazine Production: Potential Involvement of Polyphenols. Microorganisms 2020; 8:microorganisms8020243. [PMID: 32059431 PMCID: PMC7074903 DOI: 10.3390/microorganisms8020243] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 02/07/2020] [Accepted: 02/10/2020] [Indexed: 01/18/2023] Open
Abstract
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen responsible for a wide range of clinical conditions, from mild infections to life-threatening nosocomial biofilm-associated diseases, which are particularly severe in susceptible individuals. The aim of this in vitro study was to assess the effects of an Albanian propolis on several virulence-related factors of P. aeruginosa, such as growth ability, biofilm formation, extracellular DNA (eDNA) release and phenazine production. To this end, propolis was processed using three different solvents and the extracted polyphenolic compounds were identified by means of high performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) analysis. As assessed by a bioluminescence-based assay, among the three propolis extracts, the ethanol (EtOH) extract was the most effective in inhibiting both microbial growth and biofilm formation, followed by propylene glycol (PG) and polyethylene glycol 400 (PEG 400) propolis extracts. Furthermore, Pseudomonas exposure to propolis EtOH extract caused a decrease in eDNA release and phenazine production. Finally, caffeic acid phenethyl ester (CAPE) and quercetin decreased upon propolis EtOH extract exposure to bacteria. Overall, our data add new insights on the anti-microbial properties of a natural compound, such as propolis against P. aeruginosa. The potential implications of these findings will be discussed.
Collapse
|
38
|
Guo S, Zhou W, Wu J, Liu X, Meng Z, Tian J, Liu S, Ni M, Zhang J, Jia S, Li Y, Zhang X. Network pharmacology-based study on the mechanism of “Jiu Wei Zhu Huang San” in respiratory tract infections treatment. Eur J Integr Med 2019. [DOI: 10.1016/j.eujim.2019.101013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
|
39
|
Lorente-Cebrián S, Herrera K, I. Milagro F, Sánchez J, de la Garza AL, Castro H. miRNAs and Novel Food Compounds Related to the Browning Process. Int J Mol Sci 2019; 20:E5998. [PMID: 31795191 PMCID: PMC6928892 DOI: 10.3390/ijms20235998] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 10/26/2019] [Accepted: 10/28/2019] [Indexed: 02/08/2023] Open
Abstract
Obesity prevalence is rapidly increasing worldwide. With the discovery of brown adipose tissue (BAT) in adult humans, BAT activation has emerged as a potential strategy for increasing energy expenditure. Recently, the presence of a third type of fat, referred to as beige or brite (brown in white), has been recognized to be present in certain kinds of white adipose tissue (WAT) depots. It has been suggested that WAT can undergo the process of browning in response to stimuli that induce and enhance the expression of thermogenesis: a metabolic feature typically associated with BAT. MicroRNAs (miRNAs) are small transcriptional regulators that control gene expression in a variety of tissues, including WAT and BAT. Likewise, it was shown that several food compounds could influence miRNAs associated with browning, thus, potentially contributing to the management of excessive adipose tissue accumulation (obesity) through specific nutritional and dietetic approaches. Therefore, this has created significant excitement towards the development of a promising dietary strategy to promote browning/beiging in WAT to potentially contribute to combat the growing epidemic of obesity. For this reason, we summarize the current knowledge about miRNAs and food compounds that could be applied in promoting adipose browning, as well as the cellular mechanisms involved.
Collapse
Affiliation(s)
- Silvia Lorente-Cebrián
- Department of Nutrition, Food Science and Physiology/Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain; (S.L.-C.)
- Navarra Institute for Health Research, Navarra Institute for Health Research, 31008 Pamplona, Spain
| | - Katya Herrera
- Centro de Investigación en Nutrición y Salud Pública, Facultad de Salud Pública y Nutrición, Universidad Autonoma de Nuevo Leon, 64460 Monterrey, Mexico; (K.H.)
- Nutrition Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, 64460 Monterrey, Mexico
| | - Fermín I. Milagro
- Department of Nutrition, Food Science and Physiology/Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain; (S.L.-C.)
- Navarra Institute for Health Research, Navarra Institute for Health Research, 31008 Pamplona, Spain
- CIBERobn, Fisiopatología de la Obesidad y la Nutrición, Carlos III Health Institute, 28029 Madrid, Spain
| | - Juana Sánchez
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics and Obesity), University of the Balearic Islands, 07122 Palma, Spain;
- Instituto de Investigación Sanitaria Illes Balears, 07020 Palma, Spain
| | - Ana Laura de la Garza
- Centro de Investigación en Nutrición y Salud Pública, Facultad de Salud Pública y Nutrición, Universidad Autonoma de Nuevo Leon, 64460 Monterrey, Mexico; (K.H.)
- Nutrition Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, 64460 Monterrey, Mexico
| | - Heriberto Castro
- Centro de Investigación en Nutrición y Salud Pública, Facultad de Salud Pública y Nutrición, Universidad Autonoma de Nuevo Leon, 64460 Monterrey, Mexico; (K.H.)
- Nutrition Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, 64460 Monterrey, Mexico
| |
Collapse
|
40
|
Kim DH, Khan H, Ullah H, Hassan STS, Šmejkal K, Efferth T, Mahomoodally MF, Xu S, Habtemariam S, Filosa R, Lagoa R, Rengasamy KR. MicroRNA targeting by quercetin in cancer treatment and chemoprotection. Pharmacol Res 2019; 147:104346. [PMID: 31295570 DOI: 10.1016/j.phrs.2019.104346] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 07/05/2019] [Accepted: 07/05/2019] [Indexed: 02/08/2023]
Abstract
A growing number of evidences from clinical and preclinical studies have shown that dysregulation of microRNA (miRNA) function contributes to the progression of cancer and thus miRNA can be an effective target in therapy. Dietary phytochemicals, such as quercetin, are natural products that have potential anti-cancer properties due to their proven antioxidant, anti-inflammatory, and anti-proliferative effects. Available experimental studies indicate that quercetin could modulate multiple cancer-relevant miRNAs including let-7, miR-21, miR-146a and miR-155, thereby inhibiting cancer initiation and development. This paper reviews the data supporting the use of quercetin for miRNA-mediated chemopreventive and therapeutic strategies in various cancers, with the aim to comprehensively understand its health-promoting benefits and pharmacological potential. Integration of technology platforms for miRNAs biomarker and drug discovery is also presented.
Collapse
Affiliation(s)
- Doo Hwan Kim
- Department of Bioresources and Food Science, Konkuk University, Seoul, 05029, South Korea
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan.
| | - Hammad Ullah
- Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan
| | - Sherif T S Hassan
- Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 612 42, Brno, Czech Republic
| | - Karel Šmejkal
- Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 612 42, Brno, Czech Republic
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany
| | | | - Suowen Xu
- University of Rochester, Aab Cardiovascular Research Institute, Rochester, NY, 14623, USA
| | - Solomon Habtemariam
- Pharmacognosy Research Laboratories and Herbal Analysis Services UK, University of Greenwich, UK
| | - Rosanna Filosa
- Institute of Food Sciences, National Research Council, Roma str. 64, Avellino, 83100, Italy; Consorzio Sannio Tech, AMP Biotec, Appia Str, Apollosa, Benevento, 82030, Italy
| | - Ricardo Lagoa
- School of Technology and Management, Polytechnic Institute of Leiria, Portugal; UCIBIO-Faculty of Science and Technology, University NOVA of Lisbon, Portugal.
| | - Kannan Rr Rengasamy
- Department of Bioresources and Food Science, Konkuk University, Seoul, 05029, South Korea.
| |
Collapse
|
41
|
Kocic H, Damiani G, Stamenkovic B, Tirant M, Jovic A, Tiodorovic D, Peris K. Dietary compounds as potential modulators of microRNA expression in psoriasis. Ther Adv Chronic Dis 2019; 10:2040622319864805. [PMID: 31431821 PMCID: PMC6686315 DOI: 10.1177/2040622319864805] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 06/28/2019] [Indexed: 12/11/2022] Open
Abstract
Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between 'good and bad' miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other 'omics', may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.
Collapse
Affiliation(s)
- Hristina Kocic
- Clinic for Dermatology Clinical Center University Nis, Klinicki Centar Nis, Bul Dr Zorana Djindjica 48, Nis, 18000, Serbia
| | - Giovanni Damiani
- Unita Operativa di Dermatologia, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universita degli Studi di Milano, Milano, Italy
| | - Bojana Stamenkovic
- Department of Rheumatology, Institut za Kardiovaskularne Bolesti Niska Banja University Nis, Nis, Serbia
| | | | - Andrija Jovic
- Dermatology, Clinic for Dermatology University Clinical Center Nis, Nis, Serbia
| | - Danica Tiodorovic
- Dermatology, Clinic for Dermatology, Medical Faculty University Nis, Nis, Serbia
| | - Ketty Peris
- Dermatology, Institute of Dermatology, Catholic University, Roma, Italy
| |
Collapse
|
42
|
Heenatigala Palliyage G, Singh S, Ashby CR, Tiwari AK, Chauhan H. Pharmaceutical Topical Delivery of Poorly Soluble Polyphenols: Potential Role in Prevention and Treatment of Melanoma. AAPS PharmSciTech 2019; 20:250. [PMID: 31297635 DOI: 10.1208/s12249-019-1457-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 06/06/2019] [Indexed: 01/10/2023] Open
Abstract
Melanoma is regarded as the fifth and sixth most common cancer in men and women, respectively, and it is estimated that one person dies from melanoma every hour in the USA. Unfortunately, the treatment of melanoma is difficult because of its aggressive metastasis and resistance to treatment. The treatment of melanoma continues to be a challenging issue due to the limitations of available treatments such as a low response rate, severe adverse reactions, and significant toxicity. Natural polyphenols have attracted considerable attention from the scientific community due to their chemopreventive and chemotherapeutic efficacy. It has been suggested that poorly soluble polyphenols such as curcumin, resveratrol, quercetin, coumarin, and epigallocatechin-3-gallate may have significant benefits in the treatment of melanoma due to their antioxidant, anti-inflammatory, antiproliferative, and chemoprotective efficacies. The major obstacles for the use of polyphenolic compounds are low stability and poor bioavailability. Numerous nanoformulations, including solid lipid nanoparticles, polymeric nanoparticles, micelles, and liposomes, have been formulated to enhance the bioavailability and stability, as well as the therapeutic efficacy of polyphenols. This review will provide an overview of poorly soluble polyphenols that have been reported to have antimetastatic efficacy in melanomas.
Collapse
|
43
|
Dostal Z, Modriansky M. The effect of quercetin on microRNA expression: A critical review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2019; 163:95-106. [PMID: 31263290 DOI: 10.5507/bp.2019.030] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 06/11/2019] [Indexed: 02/06/2023] Open
Abstract
Quercetin, a flavonoid with multiple proven health benefits to both man and animals, displays a plethora of biological activities, collectively referred to as pleiotropic. The most studied of these are antioxidant and anti-inflammatory but modulation of signalling pathways is important as well. One of the lesser-known and recently discovered roles of quercetin, is modulation of microRNA (miRNA) expression. miRNAs are important posttranscriptional modulators that play a critical role in health and disease and many of these non-coding oligonucleotides are recognized as oncogenic or tumor suppressor miRNAs. This review is an evaluation of the recent relevant literature on the subject, with focus on the ability of quercetin to modulate miRNA expression. It includes a summary of recent knowledge on miRNAs deregulated by quercetin, an overview of quercetin pharmacokinetics and miRNA biogenesis, for the interested reader.
Collapse
Affiliation(s)
- Zdenek Dostal
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.,Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic Corresponding author: Martin Modriansky, e-mail
| | - Martin Modriansky
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.,Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic Corresponding author: Martin Modriansky, e-mail
| |
Collapse
|
44
|
Gadecka A, Bielak-Zmijewska A. Slowing Down Ageing: The Role of Nutrients and Microbiota in Modulation of the Epigenome. Nutrients 2019; 11:nu11061251. [PMID: 31159371 PMCID: PMC6628342 DOI: 10.3390/nu11061251] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/27/2019] [Accepted: 05/28/2019] [Indexed: 12/13/2022] Open
Abstract
The human population is getting ageing. Both ageing and age-related diseases are correlated with an increased number of senescent cells in the organism. Senescent cells do not divide but are metabolically active and influence their environment by secreting many proteins due to a phenomenon known as senescence associated secretory phenotype (SASP). Senescent cells differ from young cells by several features. They possess more damaged DNA, more impaired mitochondria and an increased level of free radicals that cause the oxidation of macromolecules. However, not only biochemical and structural changes are related to senescence. Senescent cells have an altered chromatin structure, and in consequence, altered gene expression. With age, the level of heterochromatin decreases, and less condensed chromatin is more prone to DNA damage. On the one hand, some gene promoters are easily available for the transcriptional machinery; on the other hand, some genes are more protected (locally increased level of heterochromatin). The structure of chromatin is precisely regulated by the epigenetic modification of DNA and posttranslational modification of histones. The methylation of DNA inhibits transcription, histone methylation mostly leads to a more condensed chromatin structure (with some exceptions) and acetylation plays an opposing role. The modification of both DNA and histones is regulated by factors present in the diet. This means that compounds contained in daily food can alter gene expression and protect cells from senescence, and therefore protect the organism from ageing. An opinion prevailed for some time that compounds from the diet do not act through direct regulation of the processes in the organism but through modification of the physiology of the microbiome. In this review we try to explain the role of some food compounds, which by acting on the epigenetic level might protect the organism from age-related diseases and slow down ageing. We also try to shed some light on the role of microbiome in this process.
Collapse
Affiliation(s)
- Agnieszka Gadecka
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
| | - Anna Bielak-Zmijewska
- Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
| |
Collapse
|
45
|
Yu H, Guo Z, Wang S, Fernando GSN, Channa S, Kazlauciunas A, Martin DP, Krasnikov SA, Kulak A, Boesch C, Sergeeva NN. Fabrication of Hybrid Materials from Titanium Dioxide and Natural Phenols for Efficient Radical Scavenging against Oxidative Stress. ACS Biomater Sci Eng 2019; 5:2778-2785. [PMID: 33405610 DOI: 10.1021/acsbiomaterials.9b00535] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Oxidative stress caused by free radicals is one of the great threats to inflict intracellular damage. Here, we report a convenient approach to the synthesis, characterization, and evaluation of the radical activity of titanium-based composites. We have investigated the potential of natural antioxidants (curcumin, quercetin, catechin, and vitamin E) as radical scavengers and stabilizers. The titanium oxide composites were prepared via three steps including sol-gel synthesis, carboxylation, and esterification. The characterization of the titanium-phenol composites was carried out by FTIR, PXRD, UV-vis and SEM methods. The radical scavenging ability of the novel materials was evaluated using DPPH and an in vitro LPO assay using isolated rat liver mitochondria. The novel materials exhibit both a higher stability and an antioxidant activity in comparison to bare TiO2. It was found that curcumin and quercetin based composites show the highest antioxidant efficiency among the composites under study followed by catechin and vitamin E based materials. The results from an MTT assay carried out on the Caco-2 cell line indicate that the composites do not contribute to the cytotoxicity in vitro. This study demonstrates that a combination of powerful antioxidants with titanium dioxide can change its functional properties and provide a convenient strategy against oxidative stress.
Collapse
Affiliation(s)
- Huayang Yu
- Department of Colour Science, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | - Zhili Guo
- School of Food Science and Nutrition, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | - Shuqi Wang
- Department of Colour Science, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | | | - Simran Channa
- Department of Colour Science, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | - Algy Kazlauciunas
- Department of Colour Science, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | - David P Martin
- Department of Colour Science, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | - Sergey A Krasnikov
- Department of Colour Science, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | - Alexander Kulak
- Department of Colour Science, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | - Christine Boesch
- School of Food Science and Nutrition, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| | - Natalia N Sergeeva
- Department of Colour Science, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K
| |
Collapse
|
46
|
Baenas N, Wagner AE. Drosophila melanogaster as an alternative model organism in nutrigenomics. GENES AND NUTRITION 2019; 14:14. [PMID: 31080523 PMCID: PMC6501408 DOI: 10.1186/s12263-019-0641-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 04/17/2019] [Indexed: 12/12/2022]
Abstract
Nutrigenomics explains the interaction between the genome, the proteome, the epigenome, the metabolome, and the microbiome with the nutritional environment of an organism. It is therefore situated at the interface between an organism's health, its diet, and the genome. The diet and/or specific dietary compounds are able to affect not only the gene expression patterns, but also the epigenetic mechanisms as well as the production of metabolites and the bacterial composition of the microbiota. Drosophila melanogaster provides a well-suited model organism to unravel these interactions in the context of nutrigenomics as it combines several advantages including an affordable maintenance, a short generation time, a high fecundity, a relatively short life expectancy, a well-characterized genome, and the availability of several mutant fly lines. Furthermore, it hosts a mammalian-like intestinal system with a clear microbiota and a fat body resembling the adipose tissue with liver-equivalent oenocytes, supporting the fly as an excellent model organism not only in nutrigenomics but also in nutritional research. Experimental approaches that are essentially needed in nutrigenomic research, including several sequencing technologies, have already been established in the fruit fly. However, studies investigating the interaction of a specific diet and/or dietary compounds in the fly are currently very limited. The present review provides an overview of the fly's morphology including the intestinal microbiome and antimicrobial peptides as modulators of the immune system. Additionally, it summarizes nutrigenomic approaches in the fruit fly helping to elucidate host-genome interactions with the nutritional environment in the model organism Drosophila melanogaster.
Collapse
Affiliation(s)
- Nieves Baenas
- 1Institute of Nutritional Medicine, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
| | - Anika E Wagner
- 2Institute of Nutritional Sciences, Justus-Liebig-University, Wilhelmstrasse 20, 35392 Giessen, Germany
| |
Collapse
|
47
|
Orang AV, Petersen J, McKinnon RA, Michael MZ. Micromanaging aerobic respiration and glycolysis in cancer cells. Mol Metab 2019; 23:98-126. [PMID: 30837197 PMCID: PMC6479761 DOI: 10.1016/j.molmet.2019.01.014] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/22/2019] [Accepted: 01/30/2019] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Cancer cells possess a common metabolic phenotype, rewiring their metabolic pathways from mitochondrial oxidative phosphorylation to aerobic glycolysis and anabolic circuits, to support the energetic and biosynthetic requirements of continuous proliferation and migration. While, over the past decade, molecular and cellular studies have clearly highlighted the association of oncogenes and tumor suppressors with cancer-associated glycolysis, more recent attention has focused on the role of microRNAs (miRNAs) in mediating this metabolic shift. Accumulating studies have connected aberrant expression of miRNAs with direct and indirect regulation of aerobic glycolysis and associated pathways. SCOPE OF REVIEW This review discusses the underlying mechanisms of metabolic reprogramming in cancer cells and provides arguments that the earlier paradigm of cancer glycolysis needs to be updated to a broader concept, which involves interconnecting biological pathways that include miRNA-mediated regulation of metabolism. For these reasons and in light of recent knowledge, we illustrate the relationships between metabolic pathways in cancer cells. We further summarize our current understanding of the interplay between miRNAs and these metabolic pathways. This review aims to highlight important metabolism-associated molecular components in the hunt for selective preventive and therapeutic treatments. MAJOR CONCLUSIONS Metabolism in cancer cells is influenced by driver mutations but is also regulated by posttranscriptional gene silencing. Understanding the nuanced regulation of gene expression in these cells and distinguishing rapid cellular responses from chronic adaptive mechanisms provides a basis for rational drug design and novel therapeutic strategies.
Collapse
Affiliation(s)
- Ayla V Orang
- Flinders Centre for Innovation in Cancer, Flinders University, Flinders Medical Centre, Adelaide, South Australia 5042, Australia.
| | - Janni Petersen
- Flinders Centre for Innovation in Cancer, Flinders University, Flinders Medical Centre, Adelaide, South Australia 5042, Australia.
| | - Ross A McKinnon
- Flinders Centre for Innovation in Cancer, Flinders University, Flinders Medical Centre, Adelaide, South Australia 5042, Australia.
| | - Michael Z Michael
- Flinders Centre for Innovation in Cancer, Flinders University, Flinders Medical Centre, Adelaide, South Australia 5042, Australia.
| |
Collapse
|
48
|
Akbari Kordkheyli V, Khonakdar Tarsi A, Mishan MA, Tafazoli A, Bardania H, Zarpou S, Bagheri A. Effects of quercetin on microRNAs: A mechanistic review. J Cell Biochem 2019; 120:12141-12155. [PMID: 30957271 DOI: 10.1002/jcb.28663] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 02/10/2019] [Accepted: 02/14/2019] [Indexed: 12/21/2022]
Abstract
MicroRNA (miRNA)-dependent pathways are one of the newest gene regulation mechanisms in various diseases, particularly in cancers. miRNAs are endogenous noncoding RNAs with about 18 to 25 nucleotide length, which can regulate the expression of at least 60% of human total genome posttranscriptionally. Quercetin is the most abundant flavonoid in a variety of fruits, flowers, and medical herbs, known as a strong free radical scavenger that could show antioxidant, anti-inflammatory, and antitumor activities. Recent studies also reported its strong impact on various miRNA expressions in different abnormalities. In this review, we aimed to summarize the studies focused on the effects of quercetin on different miRNA expressions to more clear the main possible mechanisms of quercetin influences and introduce it as a beneficial agent for regulation of miRNAs in various biological directions.
Collapse
Affiliation(s)
- Vahid Akbari Kordkheyli
- Department of Clinical Biochemistry-Biophysics and Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Abbas Khonakdar Tarsi
- Department of Clinical Biochemistry-Biophysics and Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohammad A Mishan
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Tafazoli
- Department of Analysis and Bioanalysis of Medicines, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, 15-089 Bialystok, Poland.,Department of Endocrinology, Diabetology and Internal Medicine, Clinical Research Center, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Hassan Bardania
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Setareh Zarpou
- Department of Clinical Biochemistry-Biophysics and Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Abouzar Bagheri
- Department of Clinical Biochemistry-Biophysics and Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| |
Collapse
|
49
|
Khadrawy O, Gebremedhn S, Salilew-Wondim D, Taqi MO, Neuhoff C, Tholen E, Hoelker M, Schellander K, Tesfaye D. Endogenous and Exogenous Modulation of Nrf2 Mediated Oxidative Stress Response in Bovine Granulosa Cells: Potential Implication for Ovarian Function. Int J Mol Sci 2019; 20:E1635. [PMID: 30986945 PMCID: PMC6480527 DOI: 10.3390/ijms20071635] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 03/26/2019] [Accepted: 03/29/2019] [Indexed: 02/06/2023] Open
Abstract
Nrf2 is a redox sensitive transcription factor regulating the expression of antioxidant genes as defense mechanism against various stressors. The aim of this study is to investigate the potential role of noncoding miRNAs as endogenous and quercetin as exogenous regulators of Nrf2 pathway in bovine granulosa cells. For this cultured granulosa cells were used for modulation of miRNAs (miR-28, 153 and miR-708) targeting the bovine Nrf2 and supplementation of quercentin to investigate the regulatory mechanisms of the Nrf2 antioxidant system. Moreover, cultured cells were treated with hydrogen peroxide to induce oxidative stress in those cells. Our results showed that, oxidative stress activated the expression of Nrf2 as a defense mechanism, while suppressing the expression of those miRNAs. Overexpression of those miRNAs resulted in downregulation of Nrf2 expression resulted in higher ROS accumulation, reduced mitochondrial activity and cellular proliferation. Quercetin supplementation showed its protective role against oxidative stress induced by H₂O₂ by inducing the expression of antioxidant enzymes. In conclusion, this study highlighted the involvement of miR-153, miR-28 and miR-708 in regulatory network of Nrf2 mediated antioxidant system in bovine granulosa cells function. Furthermore, quercetin at a low dose played a protective role in bovine granulosa cells against oxidative stress damage.
Collapse
Affiliation(s)
- Omar Khadrawy
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
| | - Samuel Gebremedhn
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
| | - Dessie Salilew-Wondim
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
| | - Mohamed Omar Taqi
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
| | - Christiane Neuhoff
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
| | - Ernst Tholen
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
| | - Michael Hoelker
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
- Teaching and Research Station Frankenforst, Faculty of Agriculture, University of Bonn, 53639 Königswinter, Germany.
- Center of Integrated Dairy Research, University of Bonn, 53175 Bonn, Germany.
| | - Karl Schellander
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
- Center of Integrated Dairy Research, University of Bonn, 53175 Bonn, Germany.
| | - Dawit Tesfaye
- Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, 53175 Bonn, Germany.
- Center of Integrated Dairy Research, University of Bonn, 53175 Bonn, Germany.
| |
Collapse
|
50
|
Cheng B, Zhu Q, Lin W, Wang L. MicroRNA-122 inhibits epithelial-mesenchymal transition of hepatic stellate cells induced by the TGF-β1/Smad signaling pathway. Exp Ther Med 2018; 17:284-290. [PMID: 30651793 PMCID: PMC6307443 DOI: 10.3892/etm.2018.6962] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 09/06/2018] [Indexed: 12/12/2022] Open
Abstract
Transforming growth factor (TGF)-β1 may stimulate the activation of hepatic stellate cells (HSCs), resulting in the development of liver fibrosis. As micro RNA (miRNA)-122 is known to be associated with liver inflammation, its effects on the epithelial-mesenchymal transition (EMT) of HSCs through the inhibition of the TGF-β1/drosophila mothers against decapentaplegic protein 4 (Smad4) signaling pathway were investigated. The MTT assay was performed to explore the optimum TGF-β1 concentration suitable for HSC stimulation. Fluorescence microscopy was used to observe the transfection efficiency and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to observe gene and protein expression levels of α-smooth muscle actin (α-SMA), E-cadherin, N-cadherin and Smad4, respectively, in HSCs treated with TGF-β1 or TGF-β1 and miRNA-122. MTT assay results indicated that the concentration of 10 µg/l TGF-β1 was suitable for maximum growth and survival of HSCs. Notably, the mRNA expression levels of N-cadherin and α-SMA were significantly increased (each, P<0.05), but the expression levels of E-cadherin were decreased following 10 µg/l TGF-β1 treatment. Similar results were observed regarding the protein expression levels of N-cadherin, α-SMA and E-cadherin. Furthermore, the expression of F-actin was increased in the 10 µg/l TGF-β1 treated group compared with the 0 µg/l TGF-β1 treaded group and stretching of the muscle fiber filament was observed. miRNA-122 lentiviral vector transfection significantly decreased the mRNA expression of N-cadherin and increased the mRNA expression of E-cadherin in HSCs stimulated with TGF-β1, as evident from RT-qPCR results. Similar results were also observed regarding the protein expression levels of N-cadherin and E-cadherin. The expression levels of Smad4, the primary component of the TGF-β1 signaling pathway, were significantly lower in cells treated with TGF-β1 and miRNA-122 (P<0.01) compared those treated with TGF-β1. Thus, miRNA-122 may inhibit the activation and EMT of HSCs stimulated by TGF-β1.
Collapse
Affiliation(s)
- Bianqiao Cheng
- Department of Hepatology, The Second Hospital of Fuzhou Affiliated Xiamen University, Fuzhou, Fujian 350007, P.R. China
| | - Qi Zhu
- Department of Hepatology, The Second Hospital of Fuzhou Affiliated Xiamen University, Fuzhou, Fujian 350007, P.R. China
| | - Weiguo Lin
- Department of Hepatology, The Second Hospital of Fuzhou Affiliated Xiamen University, Fuzhou, Fujian 350007, P.R. China
| | - Lihui Wang
- Department of Hepatology, The Second Hospital of Fuzhou Affiliated Xiamen University, Fuzhou, Fujian 350007, P.R. China
| |
Collapse
|