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Lei J, Shu Z, Zhu H, Zhao L. AMPK Regulates M1 Macrophage Polarization through the JAK2/STAT3 Signaling Pathway to Attenuate Airway Inflammation in Obesity-Related Asthma. Inflammation 2025; 48:372-392. [PMID: 38886294 DOI: 10.1007/s10753-024-02070-x] [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: 04/07/2024] [Revised: 05/09/2024] [Accepted: 05/30/2024] [Indexed: 06/20/2024]
Abstract
Abstract-Obesity-related asthma is primarily characterized by nonallergic inflammation, with pathogenesis involving oxidative stress, metabolic imbalance, and immunoinflammatory mechanisms. M1 macrophages, which predominantly secrete pro-inflammatory factors, mediate insulin resistance and systemic metabolic inflammation in obese individuals. Concurrently, adenosine monophosphate-activated protein kinase (AMPK) serves as a critical regulator of intracellular energy metabolism and is closely associated with macrophage activation. However, their specific roles and associated mechanisms in obesity-related asthma remain to be explored. In this study, we investigated the macrophage polarization status and potential interventional mechanisms through obesity-related asthmatic models and lipopolysaccharide (LPS) -treated RAW264.7 cell with a comprehensive series of evaluations, including HE, PAS and Masson staining of lung histopathology, immunohistochemical staining, immunofluorescence technology, qRT-PCR, Western Blot, and ELISA inflammatory factor analysis. The results revealed M1 macrophage polarization in obesity-related asthmatic lung tissue alongside downregulation of AMPK expression. Under LPS stimulation, exogenous AMPK activation attenuated M1 macrophage polarization via the Janus kinase 2/ signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Additionally, in obesity-related asthmatic mice, AMPK activation was found to alleviate airway inflammation by regulating M1 macrophage polarization, the mechanism closely associated with the JAK2/STAT3 pathway. These findings not only advance our understanding of macrophage polarization in obesity-related asthma, but also provide new therapeutic targets for its treatment.
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Affiliation(s)
- Jiahui Lei
- Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Zhengzhou, 450003, China
| | - Zhenhui Shu
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, 450003, China
| | - He Zhu
- Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Zhengzhou, 450003, China
| | - Limin Zhao
- Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, China.
- To whom correspondence should be addressed at Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, No.7 Weiwu Road, Jinshui District, Zhengzhou, 450003, Henan Province, China.
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2
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Chen D, Wu W, Li J, Huang X, Chen S, Zheng T, Huang G, Ouyang S. Targeting mitochondrial function as a potential therapeutic approach for allergic asthma. Inflamm Res 2025; 74:1. [PMID: 39762562 DOI: 10.1007/s00011-024-01972-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 11/14/2024] [Accepted: 11/27/2024] [Indexed: 01/11/2025] Open
Abstract
Allergic asthma is a chronic complex airway disease characterized by airway hyperresponsiveness, eosinophilic inflammation, excessive mucus secretion, and airway remodeling, with increasing mortality and incidence globally. The pathogenesis of allergic asthma is influenced by various factors including genetics, environment, and immune responses, making it complex and diverse. Recent studies have found that various cellular functions of mitochondria such as calcium regulation, adenosine triphosphate production, changes in redox potential, and free radical scavenging, are involved in regulating the pathogenesis of asthma. This review explores the involvement of mitochondrial functional changes in the pathogenesis of asthma, and investigate the potential of targeting cellular mitochondria as a therapeutic approach for asthma. Those insights can provide a novel theoretical foundations and treatment strategies for understanding and preventing asthma.
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Affiliation(s)
- Daichi Chen
- Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Wanhua Wu
- Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Jianing Li
- Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Xueqin Huang
- Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Su Chen
- Liaobu Hospital of Dongguan City, Dongguan, 523430, China
| | - TingTing Zheng
- Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Gonghua Huang
- Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Suidong Ouyang
- Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, College of Medical Technology, Guangdong Medical University, Dongguan, 523808, China.
- Liaobu Hospital of Dongguan City, Dongguan, 523430, China.
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3
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Liao W, Tran QTN, Peh HY, Chan CCMY, Fred Wong WS. Natural Products for the Management of Asthma and COPD. Handb Exp Pharmacol 2025; 287:175-205. [PMID: 38418669 DOI: 10.1007/164_2024_709] [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] [Indexed: 03/02/2024]
Abstract
Chronic airway inflammatory diseases like asthma, chronic obstructive pulmonary disease (COPD), and their associated exacerbations cause significant socioeconomic burden. There are still major obstacles to effective therapy for controlling severe asthma and COPD progression. Advances in understanding the pathogenesis of the two diseases at the cellular and molecular levels are essential for the development of novel therapies. In recent years, significant efforts have been made to identify natural products as potential drug leads for treatment of human diseases and to investigate their efficacy, safety, and underlying mechanisms of action. Many major active components from various natural products have been extracted, isolated, and evaluated for their pharmacological efficacy and safety. For the treatment of asthma and COPD, many promising natural products have been discovered and extensively investigated. In this chapter, we will review a range of natural compounds from different chemical classes, including terpenes, polyphenols, alkaloids, fatty acids, polyketides, and vitamin E, that have been demonstrated effective against asthma and/or COPD and their exacerbations in preclinical models and clinical trials. We will also elaborate in detail their underlying mechanisms of action unraveled by these studies and discuss new opportunities and potential challenges for these natural products in managing asthma and COPD.
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Affiliation(s)
- Wupeng Liao
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore
- Singapore-HUJ Alliance for Research and Enterprise (SHARE), National University of Singapore, Singapore, Singapore
| | - Quy T N Tran
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore
- Singapore-HUJ Alliance for Research and Enterprise (SHARE), National University of Singapore, Singapore, Singapore
- Drug Discovery and Optimization Platform (DDOP), Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore
| | - Hong Yong Peh
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore
- Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Christabel Clare M Y Chan
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore
- Drug Discovery and Optimization Platform (DDOP), Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore
| | - W S Fred Wong
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore.
- Singapore-HUJ Alliance for Research and Enterprise (SHARE), National University of Singapore, Singapore, Singapore.
- Drug Discovery and Optimization Platform (DDOP), Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore.
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4
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Lu K, Li C, Men J, Xu B, Chen Y, Yan P, Gai Z, Zhang Q, Zhang L. Traditional Chinese medicine to improve immune imbalance of asthma: focus on the adjustment of gut microbiota. Front Microbiol 2024; 15:1409128. [PMID: 39411430 PMCID: PMC11473343 DOI: 10.3389/fmicb.2024.1409128] [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: 03/29/2024] [Accepted: 09/10/2024] [Indexed: 10/19/2024] Open
Abstract
Asthma, being the prevailing respiratory ailment globally, remains enigmatic in terms of its pathogenesis. In recent times, the advancement of traditional Chinese medicine pertaining to the intestinal microbiota has yielded a plethora of investigations, which have substantiated the potential of traditional Chinese medicine in disease prevention and treatment through modulation of the intestinal microbiota. Both animal models and clinical trials have unequivocally demonstrated the indispensable role of the intestinal microbiota in the pathogenesis of asthma. This article presents a summary of the therapeutic effects of traditional Chinese medicine in the context of regulating gut microbiota and its metabolites, thereby achieving immune regulation and inhibiting airway inflammation associated with asthma. It elucidates the mechanism by which traditional Chinese medicine modulates the gut microbiota to enhance asthma management, offering a scientific foundation for the utilization of traditional Chinese medicine in the treatment of asthma.
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Affiliation(s)
- Ke Lu
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Chen Li
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jingwen Men
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Bin Xu
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yang Chen
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Peizheng Yan
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zhibo Gai
- Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Qingxiang Zhang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Lu Zhang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
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Mohamed MME, Amrani Y. Obesity Enhances Non-Th2 Airway Inflammation in a Murine Model of Allergic Asthma. Int J Mol Sci 2024; 25:6170. [PMID: 38892358 PMCID: PMC11172812 DOI: 10.3390/ijms25116170] [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: 04/19/2024] [Revised: 05/25/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Obese patients with asthma present with aggravated symptoms that are also harder to treat. Here, we used a mouse model of allergic asthma sensitised and challenged to house dust mite (HDM) extracts to determine whether high-fat-diet consumption would exacerbate the key features of allergic airway inflammation. C57BL/6 mice were intranasally sensitised and challenged with HDM extracts over a duration of 3 weeks. The impact of high-fat-diet (HFD) vs. normal diet (ND) chow was studied on HDM-induced lung inflammation and inflammatory cell infiltration as well as cytokine production. HFD-fed mice had greater inflammatory cell infiltration around airways and blood vessels, and an overall more severe degree of inflammation than in the ND-fed mice (semiquantitative blinded evaluation). Quantitative assessment of HDM-associated Th2 responses (numbers of lung CD4+ T cells, eosinophils, serum levels of allergen-specific IgE as well as the expression of Th2 cytokines (Il5 and Il13)) did not show significant changes between the HFD and ND groups. Interestingly, the HFD group exhibited a more pronounced neutrophilic infiltration within their lung tissues and an increase in non-Th2 cytokines (Il17, Tnfa, Tgf-b, Il-1b). These findings provide additional evidence that obesity triggered by a high-fat-diet regimen may exacerbate asthma by involving non-Th2 and neutrophilic pathways.
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Affiliation(s)
| | - Yassine Amrani
- Department of Respiratory Sciences, Clinical Sciences, Glenfield Hospital, University of Leicester, Leicester LE3 9QP, UK;
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Farhan M, Rizvi A, Aatif M, Muteeb G, Khan K, Siddiqui FA. Dietary Polyphenols, Plant Metabolites, and Allergic Disorders: A Comprehensive Review. Pharmaceuticals (Basel) 2024; 17:670. [PMID: 38931338 PMCID: PMC11207098 DOI: 10.3390/ph17060670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/15/2024] [Accepted: 05/19/2024] [Indexed: 06/28/2024] Open
Abstract
Given the ongoing rise in the occurrence of allergic disorders, alterations in dietary patterns have been proposed as a possible factor contributing to the emergence and progression of these conditions. Currently, there is a significant focus on the development of dietary therapies that utilize natural compounds possessing anti-allergy properties. Dietary polyphenols and plant metabolites have been intensively researched due to their well-documented anti-inflammatory, antioxidant, and immunomodulatory characteristics, making them one of the most prominent natural bioactive chemicals. This study seeks to discuss the in-depth mechanisms by which these molecules may exert anti-allergic effects, namely through their capacity to diminish the allergenicity of proteins, modulate immune responses, and modify the composition of the gut microbiota. However, further investigation is required to fully understand these effects. This paper examines the existing evidence from experimental and clinical studies that supports the idea that different polyphenols, such as catechins, resveratrol, curcumin, quercetin, and others, can reduce allergic inflammation, relieve symptoms of food allergy, asthma, atopic dermatitis, and allergic rhinitis, and prevent the progression of the allergic immune response. In summary, dietary polyphenols and plant metabolites possess significant anti-allergic properties and can be utilized for developing both preventative and therapeutic strategies for targeting allergic conditions. The paper also discusses the constraints in investigating and broad usage of polyphenols, as well as potential avenues for future research.
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Affiliation(s)
- Mohd Farhan
- Department of Chemistry, College of Science, King Faisal University, Al Ahsa 31982, Saudi Arabia
- Department of Basic Sciences, Preparatory Year, King Faisal University, Al Ahsa 31982, Saudi Arabia
| | - Asim Rizvi
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India;
| | - Mohammad Aatif
- Department of Public Health, College of Applied Medical Sciences, King Faisal University, Al Ahsa 31982, Saudi Arabia;
| | - Ghazala Muteeb
- Department of Nursing, College of Applied Medical Sciences, King Faisal University, Al Ahsa 31982, Saudi Arabia;
| | - Kimy Khan
- Department of Dermatology, Almoosa Specialist Hospital, Dhahran Road, Al Mubarraz 36342, Al Ahsa, Saudi Arabia;
| | - Farhan Asif Siddiqui
- Department of Laboratory and Blood Bank, King Fahad Hospital, Prince Salman Street, Hofuf 36441, Saudi Arabia;
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Zhou Y, Zeng Y, Wang R, Pang J, Wang X, Pan Z, Jin Y, Chen Y, Yang Y, Ling W. Resveratrol Improves Hyperuricemia and Ameliorates Renal Injury by Modulating the Gut Microbiota. Nutrients 2024; 16:1086. [PMID: 38613119 PMCID: PMC11013445 DOI: 10.3390/nu16071086] [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: 03/11/2024] [Revised: 03/25/2024] [Accepted: 04/05/2024] [Indexed: 04/14/2024] Open
Abstract
Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.
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Affiliation(s)
- Yuqing Zhou
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (Y.Z.); (J.P.); (X.W.); (Z.P.); (Y.J.); (Y.C.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
| | - Yupeng Zeng
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (Y.Z.); (J.P.); (X.W.); (Z.P.); (Y.J.); (Y.C.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
| | - Ruijie Wang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China
- Department of Nutrition, School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China
| | - Juan Pang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (Y.Z.); (J.P.); (X.W.); (Z.P.); (Y.J.); (Y.C.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
| | - Xin Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (Y.Z.); (J.P.); (X.W.); (Z.P.); (Y.J.); (Y.C.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
| | - Zhijun Pan
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (Y.Z.); (J.P.); (X.W.); (Z.P.); (Y.J.); (Y.C.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
| | - Yufeng Jin
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (Y.Z.); (J.P.); (X.W.); (Z.P.); (Y.J.); (Y.C.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
| | - Yu Chen
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (Y.Z.); (J.P.); (X.W.); (Z.P.); (Y.J.); (Y.C.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
| | - Yan Yang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China
- Department of Nutrition, School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China
| | - Wenhua Ling
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (Y.Z.); (J.P.); (X.W.); (Z.P.); (Y.J.); (Y.C.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China;
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou 510080, China
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Pathak MP, Patowary P, Chattopadhyay P, Barbhuiyan PA, Islam J, Gogoi J, Wankhar W. Obesity-associated Airway Hyperresponsiveness: Mechanisms Underlying Inflammatory Markers and Possible Pharmacological Interventions. Endocr Metab Immune Disord Drug Targets 2024; 24:1053-1068. [PMID: 37957906 DOI: 10.2174/0118715303256440231028072049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 08/14/2023] [Accepted: 09/15/2023] [Indexed: 11/15/2023]
Abstract
Obesity is rapidly becoming a global health problem affecting about 13% of the world's population affecting women and children the most. Recent studies have stated that obese asthmatic subjects suffer from an increased risk of asthma, encounter severe symptoms, respond poorly to anti-asthmatic drugs, and ultimately their quality-of-life decreases. Although, the association between airway hyperresponsiveness (AHR) and obesity is a growing concern among the public due to lifestyle and environmental etiologies, however, the precise mechanism underlying this association is yet to establish. Apart from aiming at the conventional antiasthmatic targets, treatment should be directed towards ameliorating obesity pathogenesis too. Understanding the pathogenesis underlying the association between obesity and AHR is limited, however, a plethora of obesity pathologies have been reported viz., increased pro-inflammatory and decreased anti-inflammatory adipokines, depletion of ROS controller Nrf2/HO-1 axis, NLRP3 associated macrophage polarization, hypertrophy of WAT, and down-regulation of UCP1 in BAT following down-regulated AMPKα and melanocortin pathway that may be correlated with AHR. Increased waist circumference (WC) or central obesity was thought to be related to severe AHR, however, some recent reports suggest body mass index (BMI), not WC tends to exaggerate airway closure in AHR due to some unknown mechanisms. This review aims to co-relate the above-mentioned mechanisms that may explain the copious relation underlying obesity and AHR with the help of published reports. A proper understanding of these mechanisms discussed in this review will ensure an appropriate treatment plan for patients through advanced pharmacological interventions.
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Affiliation(s)
| | - Pompy Patowary
- Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur, India
| | | | | | - Johirul Islam
- Department of Pharmaceutical Sciences, School of Health Sciences, Assam Kaziranga University, Jorhat, India
| | - Jyotchna Gogoi
- Department of Biochemistry, Faculty of Science, Assam Down Town University, Guwahati, India
| | - Wankupar Wankhar
- Department of Dialysis, Faculty of Paramedical Science, Assam Down Town University, Guwahati, India
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Dębińska A, Sozańska B. Dietary Polyphenols-Natural Bioactive Compounds with Potential for Preventing and Treating Some Allergic Conditions. Nutrients 2023; 15:4823. [PMID: 38004216 PMCID: PMC10674996 DOI: 10.3390/nu15224823] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/14/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023] Open
Abstract
In light of the constantly increasing prevalence of allergic diseases, changes in dietary patterns have been suggested as a plausible environmental explanation for the development and progression of these diseases. Nowadays, much attention has been paid to the development of dietary interventions using natural substances with anti-allergy activities. In this respect, dietary polyphenols have been studied extensively as one of the most prominent natural bioactive compounds with well-documented anti-inflammatory, antioxidant, and immunomodulatory properties. This review aims to discuss the mechanisms underlying the potential anti-allergic actions of polyphenols related to their ability to reduce protein allergenicity, regulate immune response, and gut microbiome modification; however, these issues need to be elucidated in detail. This paper reviews the current evidence from experimental and clinical studies confirming that various polyphenols such as quercetin, curcumin, resveratrol, catechins, and many others could attenuate allergic inflammation, alleviate the symptoms of food allergy, asthma, and allergic rhinitis, and prevent the development of allergic immune response. Conclusively, dietary polyphenols are endowed with great anti-allergic potential and therefore could be used either for preventive approaches or therapeutic interventions in relation to allergic diseases. Limitations in studying and widespread use of polyphenols as well as future research directions are also discussed.
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Affiliation(s)
- Anna Dębińska
- Department and Clinic of Paediatrics, Allergology and Cardiology, Wrocław Medical University, ul. Chałubińskiego 2a, 50-368 Wrocław, Poland;
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Alharris E, Mohammed A, Alghetaa H, Zhou J, Nagarkatti M, Nagarkatti P. The Ability of Resveratrol to Attenuate Ovalbumin-Mediated Allergic Asthma Is Associated With Changes in Microbiota Involving the Gut-Lung Axis, Enhanced Barrier Function and Decreased Inflammation in the Lungs. Front Immunol 2022; 13:805770. [PMID: 35265071 PMCID: PMC8898895 DOI: 10.3389/fimmu.2022.805770] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 01/26/2022] [Indexed: 12/18/2022] Open
Abstract
Asthma is a chronic respiratory disease highly prevalent worldwide. Recent studies have suggested a role for microbiome-associated gut-lung axis in asthma development. In the current study, we investigated if Resveratrol (RES), a plant-based polyphenol, can attenuate ovalbumin (OVA)-induced murine allergic asthma, and if so, the role of microbiome in the gut-lung axis in this process. We found that RES attenuated allergic asthma with significant improvements in pulmonary functions in OVA-exposed mice when tested using plethysmography for frequency (F), mean volume (MV), specific airway resistance (sRaw), and delay time(dT). RES treatment also suppressed inflammatory cytokines in the lungs. RES modulated lung microbiota and caused an abundance of Akkermansia muciniphila accompanied by a reduction of LPS biosynthesis in OVA-treated mice. Furthermore, RES also altered gut microbiota and induced enrichment of Bacteroides acidifaciens significantly in the colon accompanied by an increase in butyric acid concentration in the colonic contents from OVA-treated mice. Additionally, RES caused significant increases in tight junction proteins and decreased mucin (Muc5ac) in the pulmonary epithelium of OVA-treated mice. Our results demonstrated that RES may attenuate asthma by inducing beneficial microbiota in the gut-lung axis and through the promotion of normal barrier functions of the lung.
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Affiliation(s)
| | | | | | | | | | - Prakash Nagarkatti
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States
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11
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Allam VSRR, Paudel KR, Gupta G, Singh SK, Vishwas S, Gulati M, Gupta S, Chaitanya MVNL, Jha NK, Gupta PK, Patel VK, Liu G, Kamal MA, Hansbro PM, Oliver BGG, Chellappan DK, Dua K. Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:62733-62754. [PMID: 35796922 PMCID: PMC9477936 DOI: 10.1007/s11356-022-21454-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 06/10/2022] [Indexed: 02/05/2023]
Abstract
Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.
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Affiliation(s)
| | - Keshav Raj Paudel
- Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, 2007, Australia
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, P.O. Box: 123 Broadway, Ultimo, NSW, 2007, Australia
| | - Sukriti Vishwas
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, P.O. Box: 123 Broadway, Ultimo, NSW, 2007, Australia
| | - Saurabh Gupta
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | | | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, Uttar Pradesh, India
- Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, 248007, India
| | - Piyush Kumar Gupta
- Department of Life Sciences, School of Basic Sciences and Research (SBSR), Sharda University, Greater Noida, Uttar Pradesh, Australia
| | - Vyoma K Patel
- School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, 2052, Australia
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Gang Liu
- Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, 2007, Australia
| | - Mohammad Amjad Kamal
- King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah, 21589, Saudi Arabia
- Institutes for Systems Genetics, Frontiers Science Center for Disease related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- Enzymoics, Novel Global Community Educational Foundation, 7 Peterlee Place, Hebersham, NSW, 2770, Australia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Philip M Hansbro
- Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW, 2007, Australia
| | - Brian Gregory George Oliver
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia
- Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, Malaysia
| | - Kamal Dua
- Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, P.O. Box: 123 Broadway, Ultimo, NSW, 2007, Australia.
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia.
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12
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Zhang LX, Li CX, Kakar MU, Khan MS, Wu PF, Amir RM, Dai DF, Naveed M, Li QY, Saeed M, Shen JQ, Rajput SA, Li JH. Resveratrol (RV): A pharmacological review and call for further research. Biomed Pharmacother 2021; 143:112164. [PMID: 34649335 DOI: 10.1016/j.biopha.2021.112164] [Citation(s) in RCA: 189] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/27/2021] [Accepted: 09/03/2021] [Indexed: 12/27/2022] Open
Abstract
Resveratrol (RV) is a well-known polyphenolic compound in various plants, including grape, peanut, and berry fruits, which is quite famous for its association with several health benefits such as anti-obesity, cardioprotective neuroprotective, antitumor, antidiabetic, antioxidants, anti-age effects, and glucose metabolism. Significantly, promising therapeutic properties have been reported in various cancer, neurodegeneration, and atherosclerosis and are regulated by several synergistic pathways that control oxidative stress, cell death, and inflammation. Similarly, RV possesses a strong anti-adipogenic effect by inhibiting fat accumulation processes and activating oxidative and lipolytic pathways, exhibiting their cardioprotective effects by inhibiting platelet aggregation. The RV also shows significant antibacterial effects against various food-borne pathogens (Listeria, Campylobacter, Staphylococcus aureus, and E. coli) by inhibiting an electron transport chain (ETC) and F0F1-ATPase, which decreases the production of cellular energy that leads to the spread of pathogens. After collecting and analyzing scientific literature, it may be concluded that RV is well tolerated and favorably affects cardiovascular, neurological, and diabetic disorders. As such, it is possible that RV can be considered the best nutritional additive and a complementary drug, especially a therapeutic candidate. Therefore, this review would increase knowledge about the blend of RV as well as inspire researchers around the world to consider RV as a pharmaceutical drug to combat future health crises against various inhumane diseases. In the future, this article will be aware of discoveries about the potential of this promising natural compound as the best nutraceuticals and therapeutic drugs in medicine.
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Affiliation(s)
- Li-Xue Zhang
- School of Medicine, Northwest Minzu University, Lanzhou 730030, China
| | - Chang-Xing Li
- Department of Human Anatomy, Medical College of Qinghai University, 810000 Xining, China
| | - Mohib Ullah Kakar
- Faculty of Marine Sciences, Lasbela University of Agriculture Water and Marine Sciences, Uthal 90150, Balochistan, Pakistan
| | - Muhammad Sajjad Khan
- The Cholistan University of Veterinary and Animal Sciences, Bahawalpur 6300, Pakistan.
| | - Pei-Feng Wu
- Department of Human Anatomy, Medical College of Qinghai University, 810000 Xining, China
| | - Rai Muhammad Amir
- Institute of Food and Nutritional Sciences, PMAS-Arid Agriculture University, Rawalpindi, Pakistan
| | - Dong-Fang Dai
- Department of Human Anatomy, Medical College of Qinghai University, 810000 Xining, China
| | - Muhammad Naveed
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Qin-Yuan Li
- Department of Human Anatomy, Medical College of Qinghai University, 810000 Xining, China
| | - Muhammad Saeed
- The Cholistan University of Veterinary and Animal Sciences, Bahawalpur 6300, Pakistan
| | - Ji-Qiang Shen
- Department of Human Anatomy, Medical College of Qinghai University, 810000 Xining, China
| | - Shahid Ali Rajput
- College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Jian-Hua Li
- Department of Human Anatomy, Medical College of Qinghai University, 810000 Xining, China.
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13
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Liu JX, Zhang Y, Yuan HY, Liang J. The treatment of asthma using the Chinese Materia Medica. JOURNAL OF ETHNOPHARMACOLOGY 2021; 269:113558. [PMID: 33186702 DOI: 10.1016/j.jep.2020.113558] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 10/12/2020] [Accepted: 11/02/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Asthma is a costly global health problem that negatively influences the quality of life of patients. The Chinese Materia Medica (CMM) contains remedies that have been used for the treatment of asthma for millennia. This article strives to systematically summarize the current research progress so that more comprehensive examinations of various databases related to CMM anti-asthma drugs, can be performed, so as to sequentially provide effective basic data for development and application of anti-asthma drugs based on the CMM. MATERIALS AND METHODS The research data published over the past 20 years for asthma treatment based on traditional CMM remedies were retrieved and collected from libraries and online databases (PubMed, ScienceDirect, Elsevier, Spring Link, Web of Science, PubChem Compound, Wan Fang, CNKI, Baidu, and Google Scholar). Information was also added from classic CMM, literature, conference papers on classic herbal formulae, and dissertations (PhD or Masters) based on traditional Chinese medicine. RESULTS This review systematically summarizes the experimental studies on the treatment of asthma with CMM, covering the effective chemical components, typical asthma models, important mechanisms and traditional anti-asthma CMM formulae. The therapy value of the CMM for anti-asthma is clarified, and the original data and theoretical research foundation are provided for the development of new anti-asthmatic data and research for the CMM. CONCLUSIONS Substantial progress against asthma has been made through relevant experimental research based on the CMM. These advances improved the theoretical basis of anti-asthma drugs for CMM and provided a theoretical basis for the application of a asthma treatment that is unique. By compiling these data, it is expected that the CMM will now contain a clearer mechanism of action and a greater amount of practical data that can be used for future anti-asthma drug research.
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Affiliation(s)
- Jun-Xi Liu
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin, 150040, PR China; Department of Pharmacy, Heilongjiang Nursing College, 209 Academy Road, Harbin, 150086, PR China
| | - Yang Zhang
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin, 150040, PR China
| | - Hong-Yu Yuan
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin, 150040, PR China
| | - Jun Liang
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin, 150040, PR China.
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14
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Active ingredients from Chinese medicine plants as therapeutic strategies for asthma: Overview and challenges. Biomed Pharmacother 2021; 137:111383. [PMID: 33761604 DOI: 10.1016/j.biopha.2021.111383] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 02/02/2021] [Accepted: 02/08/2021] [Indexed: 12/11/2022] Open
Abstract
Although considerable advance has been made in diagnosing and treating, asthma is still a serious public health challenge. Traditional Chinese medicine (TCM) is an effective therapy of complementary and alternative medicine. More and more scientific evidences support the use of TCM for asthma treatment, and active ingredients from Chinese medicine plants are becoming a hot issue. PURPOSE OF REVIEW To summarize the frontier knowledge on the function and underlying mechanisms of the active ingredients in asthma treatments and provide a fully integrated, reliable reference for exploring innovative treatments for asthma. METHODS The cited literature was obtained from the PubMed and CNIK databases (up to September 2020). Experimental studies on the active ingredients of Chinese medicine and their therapeutic mechanisms were identified. The key words used in the literature retrieval were "asthma" and "traditional Chinese medicine" or "Chinese herbal medicine". The literature on the active ingredients was then screened manually. RESULTS We summarized the effect of these active ingredients on asthma, primarily including the effect through which these ingredients can regulate the immunologic equilibrium mechanism by acting on a number of signalling pathways, such as Notch, JAK-STAT-MAPK, adiponectin-iNOS-NF-κB, PGD2-CRTH2, PI3K/AKT, Keap1-Nrf2/HO-1, T-bet/Gata-3 and Foxp3-RORγt, thereby regulating the progression of asthma. CONCLUSION The active ingredients from Chinese medicine have multilevel effects on asthma by regulating the immunologic equilibrium mechanism or signalling pathways, giving them great clinical value. However, the safety and functional mechanism of these ingredients still must be further determined.
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15
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Checa J, Aran JM. Airway Redox Homeostasis and Inflammation Gone Awry: From Molecular Pathogenesis to Emerging Therapeutics in Respiratory Pathology. Int J Mol Sci 2020; 21:E9317. [PMID: 33297418 PMCID: PMC7731288 DOI: 10.3390/ijms21239317] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/05/2020] [Indexed: 02/06/2023] Open
Abstract
As aerobic organisms, we are continuously and throughout our lifetime subjected to an oxidizing atmosphere and, most often, to environmental threats. The lung is the internal organ most highly exposed to this milieu. Therefore, it has evolved to confront both oxidative stress induced by reactive oxygen species (ROS) and a variety of pollutants, pathogens, and allergens that promote inflammation and can harm the airways to different degrees. Indeed, an excess of ROS, generated intrinsically or from external sources, can imprint direct damage to key structural cell components (nucleic acids, sugars, lipids, and proteins) and indirectly perturb ROS-mediated signaling in lung epithelia, impairing its homeostasis. These early events complemented with efficient recognition of pathogen- or damage-associated recognition patterns by the airway resident cells alert the immune system, which mounts an inflammatory response to remove the hazards, including collateral dead cells and cellular debris, in an attempt to return to homeostatic conditions. Thus, any major or chronic dysregulation of the redox balance, the air-liquid interface, or defects in epithelial proteins impairing mucociliary clearance or other defense systems may lead to airway damage. Here, we review our understanding of the key role of oxidative stress and inflammation in respiratory pathology, and extensively report current and future trends in antioxidant and anti-inflammatory treatments focusing on the following major acute and chronic lung diseases: acute lung injury/respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and cystic fibrosis.
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Affiliation(s)
| | - Josep M. Aran
- Immune-Inflammatory Processes and Gene Therapeutics Group, IDIBELL, L’Hospitalet de Llobregat, 08908 Barcelona, Spain;
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16
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Anti-allergic and anti-inflammatory effects of resveratrol via inhibiting TXNIP-oxidative stress pathway in a mouse model of allergic rhinitis. World Allergy Organ J 2020; 13:100473. [PMID: 33133334 PMCID: PMC7586246 DOI: 10.1016/j.waojou.2020.100473] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 09/15/2020] [Accepted: 09/17/2020] [Indexed: 01/03/2023] Open
Abstract
Background Allergic rhinitis (AR) is a type I hypersensitivity mediated by IgE in the nose. Thioredoxin-interacting protein (TXNIP) plays a pivotal role in the process of producing reactive oxygen species (ROS). Resveratrol is a TXNIP inhibitor. Nonetheless, its role and mechanism in AR are still undetermined. The present study aimed to explore the effect and mechanism of resveratrol on an ovalbumin (OVA) induced mouse model of AR. Methods AR murine model was established using OVA and administrated intranasally with resveratrol or N-acetylcysteine (NAC). Hematoxylin and eosin (HE) stain was used for evaluating eosinophils. Immunohistochemistry (IHC) staining and real-time PCR were employed to evaluate immunolabeling and mRNA expression of TXNIP in nasal mucosas of mice. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in nasal tissue homogenates were measured using MDA and SOD Assay Kit. Concentrations of OVA-specific IgE and histamines in serum, and OVA-specific IgE, PGD2, LTC4, ECP, IL-4, IL-5, IL-6, IL-33 and TNF-α in nasal lavage fluid (NLF) were assayed by ELISA. In vitro studies, western blotting, real-time PCR, ELISA, ROS detecting dye DCFH-DA, MDA, and SOD Assay Kit were performed to evaluate the effects and mechanisms of OVA, resveratrol or NAC on spleen mononuclear cells. Results We found significant alternations of sneezing, nasal rubbing, inflammatory cytokines, eosinophil numbers, TXNIP, MDA, and SOD levels in resveratrol or NAC treated mice compared with untreated AR mice. In cultured spleen mononuclear cells, TXNIP, MDA, SOD, ROS and inflammatory cytokines levels were altered by OVA but reversed by resveratrol or NAC. Conclusions Resveratrol could effectively alleviate murine AR by inhibiting TXNIP-oxidative stress pathway.
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Key Words
- AR, Allergic rhinitis
- Allergic rhinitis
- ELISA, Enzyme-linked immunosorbent assay
- IHC, Immunohistochemistry
- MDA, Malondialdehyde
- NAC, N-acetylcysteine
- NLF, Nasal lavage fluid
- OVA, Ovalbumin
- Ovalbumin
- Oxidative stress
- ROS, Reactive oxygen species
- Reactive oxygen species
- Resveratrol
- SOD, Superoxide dismutase
- TXNIP
- TXNIP, Thioredoxin-interacting protein
- Th2, Type 2T helper
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17
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Ma BN, Li XJ. Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases. CHINESE HERBAL MEDICINES 2020; 12:349-358. [PMID: 32963508 PMCID: PMC7498443 DOI: 10.1016/j.chmed.2020.07.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/09/2020] [Accepted: 07/30/2020] [Indexed: 12/19/2022] Open
Abstract
Lung diseases and their related complications represent a critical source of morbidity and mortality globally and have become a research focus in recent years. There are plenty of hazards that threaten the health of lung by exposure to external environmental stimuli, such as dust, cigarette smoke, PM2.5, air pollution and pathogen infection. These risks lead to the impairment of lung function and subsequent lung diseases including pneumonia, chronic obstructive pulmonary disease (COPD), asthma and idiopathic pulmonary fibrosis (IPF). Compared with antibiotics and corticosteroids therapies, traditional Chinese medicine prescriptions are more effective with fewer side effects. A considerable variety of bioactive ingredients have been extracted and identified from Chinese herbal medicines and are used for the treatment of different lung diseases, including resveratrol. Increasing studies have reported promising therapeutic effects of resveratrol against lung diseases by inhibiting oxidative stress, inflammation, aging, fibrosis and cancer both in vitro and in vivo. In this review, the recent progress in the studies of lung-protective effects and underlying mechanisms of resveratrol and also highlight the potency of resveratrol and traditional Chinese prescriptions containing resveratrol as promising therapeutic options were summarized for the treatment of lung and respiratory diseases.
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Affiliation(s)
- Bo-Ning Ma
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xiao-Jiaoyang Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China
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18
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Arteaga-Badillo DA, Portillo-Reyes J, Vargas-Mendoza N, Morales-González JA, Izquierdo-Vega JA, Sánchez-Gutiérrez M, Álvarez-González I, Morales-González Á, Madrigal-Bujaidar E, Madrigal-Santillán E. Asthma: New Integrative Treatment Strategies for the Next Decades. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E438. [PMID: 32872366 PMCID: PMC7558718 DOI: 10.3390/medicina56090438] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/20/2020] [Accepted: 08/24/2020] [Indexed: 02/07/2023]
Abstract
Asthma is a chronic disease whose main anatomical-functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.
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Affiliation(s)
- Diego A. Arteaga-Badillo
- Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla, Pachuca de Soto 42080, Mexico; (D.A.A.-B.); (J.P.-R.); (J.A.I.-V.); (M.S.-G.)
| | - Jacqueline Portillo-Reyes
- Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla, Pachuca de Soto 42080, Mexico; (D.A.A.-B.); (J.P.-R.); (J.A.I.-V.); (M.S.-G.)
| | - Nancy Vargas-Mendoza
- Escuela Superior de Medicina, Instituto Politécnico Nacional, “Unidad Casco de Santo Tomas”, Ciudad de México 11340, Mexico; (N.V.-M.); (J.A.M.-G.)
| | - José A. Morales-González
- Escuela Superior de Medicina, Instituto Politécnico Nacional, “Unidad Casco de Santo Tomas”, Ciudad de México 11340, Mexico; (N.V.-M.); (J.A.M.-G.)
| | - Jeannett A. Izquierdo-Vega
- Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla, Pachuca de Soto 42080, Mexico; (D.A.A.-B.); (J.P.-R.); (J.A.I.-V.); (M.S.-G.)
| | - Manuel Sánchez-Gutiérrez
- Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla, Pachuca de Soto 42080, Mexico; (D.A.A.-B.); (J.P.-R.); (J.A.I.-V.); (M.S.-G.)
| | - Isela Álvarez-González
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, “Unidad Profesional A. López Mateos”, Ciudad de México 07738, Mexico; (I.Á.-G.); (E.M.-B.)
| | - Ángel Morales-González
- Escuela Superior de Cómputo, Instituto Politécnico Nacional, “Unidad Profesional A. López Mateos”, Ciudad de México 07738, Mexico;
| | - Eduardo Madrigal-Bujaidar
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, “Unidad Profesional A. López Mateos”, Ciudad de México 07738, Mexico; (I.Á.-G.); (E.M.-B.)
| | - Eduardo Madrigal-Santillán
- Escuela Superior de Medicina, Instituto Politécnico Nacional, “Unidad Casco de Santo Tomas”, Ciudad de México 11340, Mexico; (N.V.-M.); (J.A.M.-G.)
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19
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Wu YF, Chen YQ, Li Q, Ye XY, Zuo X, Shi YL, Guo XY, Xu L, Sun L, Li CW, Yang Y. Supplementation with Tetrahydrocurcumin Enhances the Therapeutic Effects of Dexamethasone in a Murine Model of Allergic Asthma. Int Arch Allergy Immunol 2020; 181:822-830. [PMID: 32784298 DOI: 10.1159/000509367] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 06/10/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Tetrahydrocurcumin (THC) is the major active metabolite of curcumin, which is a dietary factor derived from Curcuma species. Our previous study demonstrated a significant beneficial effect of THC in mice with allergic asthma. Glucocorticosteroids (GCs) are commonly used drugs in asthma. Whether THC supplementation could promote the beneficial effects of GC therapy on asthma has not yet been reported. The current study aimed to investigate the combined efficacy of GC and THC treatment in a mouse model of allergic asthma. METHODS BALB/c mice were randomly divided into 5 groups: the control group, ovalbumin (OVA)-induced group, and OVA-induced mice treated with dietary THC only, intraperitoneal injection of dexamethasone (DEX) only, or THC combined with DEX. The nasal symptoms, histopathological alterations of lung tissues, lung cytokine production, and Th cell subsets were assessed. RESULTS THC or DEX had beneficial effects on nasal symptoms and pathological lung changes, and the therapeutic effects between THC and DEX treatment were comparable. Importantly, compared to the monotherapy groups (THC or DEX only), the combination of THC and DEX showed a significantly reduced nasal rubbing frequency, lower mucus hyperproduction, lower Th2 and Th17 cell numbers as well as lower related cytokine levels (IL-4, IL-5, and IL-17A). CONCLUSIONS Supplementation with THC can enhance the therapeutic effects of DEX to alleviate airway symptoms, lung inflammation, and the Th2 response. Our findings suggest that dietary administration of THC could act as an add-on therapy for asthma treated with GCs.
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Affiliation(s)
- Yin Fan Wu
- School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Guangzhou Campus), Guangzhou, China.,Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, China
| | - Yan Qiu Chen
- Department of Otolaryngology, Guangzhou Women and Children Medical Centre, Guangzhou, China
| | - Qin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Guangzhou Campus), Guangzhou, China.,Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, China.,School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - Xiao Yan Ye
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiao Zuo
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Guangzhou Campus), Guangzhou, China.,Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, China.,School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - Yi Lin Shi
- School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Guangzhou Campus), Guangzhou, China.,Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, China
| | - Xing Yue Guo
- School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Guangzhou Campus), Guangzhou, China.,Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, China
| | - Lin Xu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Guangzhou Campus), Guangzhou, China.,Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, China.,School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - Lin Sun
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chun Wei Li
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,
| | - Yan Yang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Guangzhou Campus), Guangzhou, China.,Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, China.,School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
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20
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Chen Y, Zhang H, Chen Y, Zhang Y, Shen M, Jia P, Ji S, Wang T. Resveratrol Alleviates Endoplasmic Reticulum Stress-Associated Hepatic Steatosis and Injury in Mice Challenged with Tunicamycin. Mol Nutr Food Res 2020; 64:e2000105. [PMID: 32529694 DOI: 10.1002/mnfr.202000105] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 05/12/2020] [Indexed: 12/24/2022]
Abstract
SCOPE Endoplasmic reticulum (ER) stress is widely recognized as a critical factor linked to lipid metabolic disorders in nonalcoholic fatty liver disease. However, its pathogenesis remains elusive, and therapeutic options are limited. This study investigates the potential of resveratrol (RSV) to alleviate hepatic steatosis and injury in a tunicamycin (TM)-induced murine ER stress model and provides detailed evidence. METHODS AND RESULTS Male C57BL/6J mice were orally administered either RSV or vehicle for 2 weeks before the TM challenge. Results indicated that TM induced ER morphological damage and severe unfolded protein reaction (UPR), accompanied by increases in lipid accumulation, oxidative damage, and inflammatory response. Administering RSV decreased the expression of ER stress markers, partially normalized the active levels of UPR sensors, and facilitated sirtuin 1 activity in the liver under ER stress. Notably, the TM-induced hepatic steatosis was also alleviated by RSV, possibly by regulating the expression pattern of genes involving lipid oxidation and delivery. Consistently, RSV attenuated the TM-induced increases in lipid peroxidation, hepatocyte apoptosis, and the overactivation of inflammatory signals. CONCLUSION RSV may have an auxiliary therapeutic potential to prevent the development of steatosis and its progression to steatohepatitis in the liver by alleviating severe ER stress.
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Affiliation(s)
- Yanan Chen
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China
| | - Hao Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China
| | - Yueping Chen
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China
| | - Yuying Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China
| | - Mingming Shen
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China
| | - Peilu Jia
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China
| | - Shuli Ji
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China
| | - Tian Wang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China
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21
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Zhang Y, Guo L, Law BYK, Liang X, Ma N, Xu G, Wang X, Yuan X, Tang H, Chen Q, Wong VKW, Wang X. Resveratrol decreases cell apoptosis through inhibiting DNA damage in bronchial epithelial cells. Int J Mol Med 2020; 45:1673-1684. [PMID: 32186748 PMCID: PMC7169938 DOI: 10.3892/ijmm.2020.4539] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 01/28/2020] [Indexed: 12/11/2022] Open
Abstract
One of the major risk factors for asthma development is exposure to environmental allergens. House dust mites (HDM) can induce DNA damage, resulting in asthma. Resveratrol (RES) produced by several plants, has anti‑apoptotic properties and may affect a variety of biological processes. The aim of the present study was to investigate the protective role of RES against apoptosis in bronchial epithelial cells. C57BL/6J mice treated with HDM exhibited high levels of cell apoptosis, while RES significantly reversed this process. Induced DNA damage was more severe in the HDM group vs. the HDM combined with RES group. This result was confirmed by immunostaining and western blot analysis of the protein expression of the DNA damage‑related gene γH2AX, which was highly induced by HDM. In addition, treatment with RES protected bronchial epithelial cells exposed to HDM from DNA damage. RES decreases reactive oxygen species levels to inhibit oxidative DNA damage in bronchial epithelial cells. Furthermore, compared with the HDM group, induced cell apoptosis could be attenuated by RES in the group of combined treatment with RES and HDM. A DNA repair inhibitor augmented DNA damage and apoptosis in bronchial epithelial cells, whereas RES significantly attenuated cell apoptosis through inhibiting DNA damage.
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Affiliation(s)
- Yun Zhang
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau 999078, P.R. China
| | - Linlin Guo
- Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Betty Yuen-Kwan Law
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau 999078, P.R. China
| | - Xiaobo Liang
- Laboratory of Inflammation and Allergy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Ning Ma
- Laboratory of Inflammation and Allergy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Guofeng Xu
- Laboratory of Inflammation and Allergy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Xiaoyun Wang
- Laboratory of Inflammation and Allergy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Xiefang Yuan
- Laboratory of Inflammation and Allergy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Hongmei Tang
- Laboratory of Inflammation and Allergy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Qi Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau 999078, P.R. China
| | - Vincent Kam-Wai Wong
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau 999078, P.R. China
| | - Xing Wang
- Laboratory of Inflammation and Allergy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
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22
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Zhu FF, Wang YM, He GZ, Chen YF, Gao YD. Different effects of acetyl-CoA carboxylase inhibitor TOFA on airway inflammation and airway resistance in a mice model of asthma. Pharmacol Rep 2020; 72:1011-1020. [PMID: 32048254 PMCID: PMC7223088 DOI: 10.1007/s43440-019-00027-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 10/14/2019] [Accepted: 11/20/2019] [Indexed: 12/20/2022]
Abstract
Background and objective Acetyl CoA carboxylase (ACC) regulates the differentiation of Th1, Th2, Th17 cells and Treg cells, which play a critical role in airway inflammation of asthma. Here we investigated the role of ACC in the pathogenesis of asthma. Methods Chicken Ovalbumin-sensitized and -challenged mice were divided into three groups, PBS group, DMSO (solvent of TOFA) group and ACC inhibitor 5-tetradecyloxy-2-furoic acid (TOFA) + DMSO group. Airway inflammation was assessed with histology, percentages of CD4+T cell subsets in lung and spleen was assessed with flow cytometry, and airway responsiveness was assessed with FinePointe RC system. The expression of characteristic transcription factors of CD4+T cell subsets was evaluated with real-time PCR. Cytokine levels in bronchoalveolar lavage fluid (BALF) and serum was determined with ELISA. Results In asthma mice, the expression of ACC increased, while the expression of phosphorylated ACC (pACC) decreased. TOFA had no significant effect on pACC expression. TOFA reduced serum IgE, airway inflammatory cells infiltration and goblet cell hyperplasia, but dramatically increased airway responsiveness. TOFA significantly reduced the percentages of Th1, Th2, Th17 cells in lung and spleen, the expression of GATA3 and RORγt in lung, and IFN-γ, IL-4, IL-17A levels in BALF and serum. TOFA had no significant effect on the percentage of Treg cells, IL-10 level and the expression of T-bet and Foxp3. Conclusion Acetyl-CoA carboxylase inhibitor TOFA might have a distinct effect on asthmatic airway inflammation and airway hyperresponsiveness.
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Affiliation(s)
- Fang-Fang Zhu
- Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yi-Min Wang
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, People's Republic of China
| | - Guang-Zhen He
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, People's Republic of China
| | - Yi-Fei Chen
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, People's Republic of China
| | - Ya-Dong Gao
- Department of Allergology, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, People's Republic of China.
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23
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Athari SS. Targeting cell signaling in allergic asthma. Signal Transduct Target Ther 2019; 4:45. [PMID: 31637021 PMCID: PMC6799822 DOI: 10.1038/s41392-019-0079-0] [Citation(s) in RCA: 180] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 09/03/2019] [Accepted: 09/15/2019] [Indexed: 02/08/2023] Open
Abstract
Asthma is chronic inflammation of the airways characterized by airway hyper-responsiveness, wheezing, cough, and dyspnea. Asthma affects >350 million people worldwide. The Th2 immune response is a major contributor to the pathophysiology of asthma. Targeted therapy modulating cell signaling pathways can be a powerful strategy to design new drugs to treat asthma. The potential molecular pathways that can be targeted include IL-4-IL-13-JAK-STAT-MAP kinases, adiponectin-iNOS-NF-κB, PGD2-CRTH2, IFNs-RIG, Wnt/β-catenin-FAM13A, FOXC1-miR-PI3K/AKT, JNK-Gal-7, Nrf2-ROS, Foxp3-RORγt, CysLTR, AMP, Fas-FasL, PTHrP/PPARγ, PAI-1, FcɛRI-LAT-SLP-76, Tim-3-Gal-9, TLRs-MyD88, PAR2, and Keap1/Nrf2/ARE. Therapeutic drugs can be designed to target one or more of these pathways to treat asthma.
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Affiliation(s)
- Seyyed Shamsadin Athari
- Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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24
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Zhu L, Chen X, Chong L, Kong L, Wen S, Zhang H, Zhang W, Li C. Adiponectin alleviates exacerbation of airway inflammation and oxidative stress in obesity-related asthma mice partly through AMPK signaling pathway. Int Immunopharmacol 2018; 67:396-407. [PMID: 30584969 DOI: 10.1016/j.intimp.2018.12.030] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 12/07/2018] [Accepted: 12/13/2018] [Indexed: 12/15/2022]
Abstract
Adiponectin plays a role in asthma and obesity, but its effects and mechanism in obesity-related asthma remain elusive. This study aimed to evaluate the effects of adiponectin on airway inflammation and oxidative stress and to determine its mechanism in obesity-related asthma. Male C57BL6/J mice fed with a high-fat diet to induce obesity were sensitized and challenged with ovalbumin to induce asthma, and treated with adiponectin (1 mg/kg) and AMP-activated protein kinase (AMPK) inhibitor compound C (20 mg/kg) twice before the first ovalbumin challenge. We found exogenous adiponectin significantly reduced airway resistance, inflammatory infiltration in lung tissue, and cell counts in bronchoalveolar lavage fluid. Adiponectin inhibited great levels of eotaxin, myeloperoxidase, tumor necrosis factor-α, 8‑hydroxy‑2'‑deoxyguanosine, and nitric oxide in obesity-related asthma mice. Moreover, we found increased nuclear factor kappa B p65, inducible nitric oxide synthase and B-cell lymphoma 2 protein expression were down-regulated with adiponectin administration. Additionally, adiponectin elevated the lower levels of pAMPK and AMPK activity in lung tissue. These protective effects of adiponectin were reversed after treatment with the AMPK inhibitor compound C. Thus, we conclude that adiponectin alleviates exacerbation of airway inflammation and oxidative stress in a murine model of obesity-related asthma partly through AMPK signaling pathway.
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Affiliation(s)
- Lili Zhu
- Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, No.109 Xueyuanxi Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China
| | - Xiuzhen Chen
- Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, No.109 Xueyuanxi Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China; Department of Pediatrics, Hubei Maternal and Child Health Hospital, No.745 Wuluo Road, Hongshan District, Wuhan 430070, Hubei Province, China
| | - Lei Chong
- Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, No.109 Xueyuanxi Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China
| | - Ludan Kong
- Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, No.109 Xueyuanxi Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China
| | - Shunhang Wen
- Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, No.109 Xueyuanxi Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China
| | - Hailin Zhang
- Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, No.109 Xueyuanxi Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China
| | - Weixi Zhang
- Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, No.109 Xueyuanxi Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China
| | - Changchong Li
- Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, No.109 Xueyuanxi Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China.
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25
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Li XN, Ma LY, Ji H, Qin YH, Jin SS, Xu LX. Resveratrol protects against oxidative stress by activating the Keap-1/Nrf2 antioxidant defense system in obese-asthmatic rats. Exp Ther Med 2018; 16:4339-4348. [PMID: 30542383 PMCID: PMC6257826 DOI: 10.3892/etm.2018.6747] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 02/02/2018] [Indexed: 02/06/2023] Open
Abstract
The aim of the present study was to investigate the potential mechanism underlying the anti-obesity-asthmatic effects of resveratrol (RSV) in a rat model of obese-asthma. Rat models of obesity and asthma were established using a high-fat diet and the administration of ovalbumin, respectively. Rats were divided into 7 different groups: A normal control, a normal obese, a normal asthma, a normal obese + asthma, a RSV obese, a RSV asthma and a RSV obese + asthma group. Body weight, Lee index, body fat and lung histopathological changes were evaluated. Serum lipid levels were evaluated using calorimetric methods. Levels of reactive oxygen species (ROS) were examined using enzyme-linked immunosorbent assays. Cellular antioxidant enzyme activities were measured using commercial kits. Levels of kelch-like ECH associated protein 1 (Keap-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) was examined using western blot analysis. The results indicated that obese and asthma rat models were successfully established. It was also demonstrated that RSV decreased fasting blood glucose in obese, asthmatic and obese-asthmatic rats. RSV altered serum lipid levels; it significantly increased high density lipoprotein cholesterol levels and significantly decreased serum triglyceride, serum total cholesterol and very low density lipoprotein levels, compared with untreated obese, asthmatic and obese-asthmatic rats (P<0.05). ROS levels were significantly decreased in the RSV treatment group compared with obese, asthmatic and obese-asthmatic rats (P<0.05). RSV treatment significantly increased catalase, glutathione, glutathione peroxidase and total superoxide dismutase levels compared with untreated obese, asthmatic and obese-asthmatic rats (P<0.05). Furthermore, RSV treatment significantly downregulated Keap-1 and upregulated Nrf2 levels in the heart, lung and kidney tissues of rats compared with untreated controls. Therefore, the results demonstrate that RSV protects against oxidative stress by activating the Keap-1/Nrf2 antioxidant defense system in obese-asthmatic rat models.
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Affiliation(s)
- Xiao-Nan Li
- Department of Pediatrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Lu-Yi Ma
- Department of Pediatrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Hong Ji
- Department of Pediatrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Yuan-Hua Qin
- Department of Parasitology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Shan-Shan Jin
- Department of Pediatrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Li-Xin Xu
- Department of Pediatrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
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26
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Alexandre EC, Calmasini FB, Sponton ACDS, de Oliveira MG, André DM, Silva FH, Delbin MA, Mónica FZ, Antunes E. Influence of the periprostatic adipose tissue in obesity-associated mouse urethral dysfunction and oxidative stress: Effect of resveratrol treatment. Eur J Pharmacol 2018; 836:25-33. [PMID: 30102890 DOI: 10.1016/j.ejphar.2018.08.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 08/07/2018] [Accepted: 08/10/2018] [Indexed: 11/15/2022]
Abstract
Obese mice display overactive bladder (OAB) associated with impaired urethra smooth muscle (USM) function. In this study, we evaluated the role of the adipose tissue surrounding the urethra and prostate in obese mice (here referred as periprostatic adipose tissue; PPAT) to the USM dysfunction. Male C57BL6/JUnib mice fed with either a standard-chow or high-fat diet to induce obesity were used. In PPAT, histological analysis, and qPCR analysis for gp91phox, tumor necrosis factor-α (TNF-α) and superoxide dismutase (SOD) were conducted. In USM, concentration-response curves to contractile and relaxing agents, as well as measurements of reactive-oxygen species and nitric oxide (NO) levels were performed. The higher PPAT area in obese mice was accompanied by augmented gp91phox (NOX2) and TNF-α expressions, together with decreased SOD1 expression. In USM of obese group, the contractile responses to phenylephrine and vasopressin were increased, whereas the relaxations induced with glyceryl trinitrate were reduced. The reactive-oxygen species and NO levels in USM of obese mice were increased and decreased, respectively. A higher SOD expression was also detected in obese group whilst no changes in the gp91phox levels were observed. We next evaluated the effects of the antioxidant resveratrol (100 mg/kg/day, two-weeks, PO) in the functional alterations and NO levels of obese mice. Resveratrol treatment in obese mice reversed both the functional USM dysfunction and the reduced NO production. Our data show that PPAT exerts a local inflammatory response and increases oxidative stress that lead to urethral dysfunction. Resveratrol could be an auxiliary option to prevent obesity-associated urethral dysfunction.
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Affiliation(s)
- Eduardo C Alexandre
- Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil.
| | - Fabiano B Calmasini
- Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil
| | - Amanda C da S Sponton
- Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-862, Brazil
| | - Mariana G de Oliveira
- Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil
| | - Diana M André
- Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil
| | - Fábio H Silva
- Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas 13083-878, Brazil
| | - Maria Andréia Delbin
- Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil
| | - Fabíola Z Mónica
- Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil
| | - Edson Antunes
- Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil
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27
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Resveratrol Modulates and Reverses the Age-Related Effect on Adenosine-Mediated Signalling in SAMP8 Mice. Mol Neurobiol 2018; 56:2881-2895. [DOI: 10.1007/s12035-018-1281-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 07/23/2018] [Indexed: 12/20/2022]
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André DM, Horimoto CM, Calixto MC, Alexandre EC, Antunes E. Epigallocatechin-3-gallate protects against the exacerbation of allergic eosinophilic inflammation associated with obesity in mice. Int Immunopharmacol 2018; 62:212-219. [PMID: 30015241 DOI: 10.1016/j.intimp.2018.06.028] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 05/23/2018] [Accepted: 06/18/2018] [Indexed: 12/25/2022]
Abstract
Obesity is linked to worse asthma symptoms. Epigallocatechin-3-gallate (EGCG) reduces airway inflammation, but no study investigated the effects of EGCG on obesity-associated asthma. We aimed here to evaluate the effects of EGCG on allergen-induced airway inflammation in high-fat diet-fed mice. Male C57Bl/6 mice maintained on either standard-chow or high-fat diet for 12 weeks were treated or not with EGCG (10 mg/kg/day, gavage, two weeks). Animals were intranasally challenged with ovalbumin (OVA). In lung tissue and bronchoalveolar lavage fluid (BALF), cell counting and markers of inflammation and oxidative stress were evaluated. High-fat diet-fed mice exhibited significantly higher body weight and epididymal fat mass compared with lean group. EGCG treatment reduced by 20% the epididymal fat mass in obese mice (P < 0.05). The OVA-induced increases of total cells and eosinophils in lung tissue of obese mice were significantly reduced EGCG treatment. The increased levels of TNF-α, IL-4, IL-5 and eotaxin in BALF of obese mice were normalized by EGCG. Likewise, the enhanced expression of inducible nitric oxide synthase (iNOS) and nitric oxide metabolite (NOx) levels in obese mice were normalized by EGCG. Reactive‑oxygen species (ROS) and superoxide dismutase (SOD) levels were elevated and reduced, respectively, in lung tissue of obese mice, both of which were restored by EGCG. In lean mice, EGCG had no significant effect in evaluated parameter (body measures, and inflammatory and oxidative markers). EGCG turns to normal the levels of inflammatory and oxidative stress markers in lungs of obese mice, suggesting it could be an option to attenuate obesity-related asthma.
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Affiliation(s)
- Diana Majolli André
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Cristina Maki Horimoto
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Marina Ciarallo Calixto
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Eduardo Costa Alexandre
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Edson Antunes
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
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Anti-Inflammatory Effects of Resveratrol: Mechanistic Insights. Int J Mol Sci 2018; 19:ijms19061812. [PMID: 29925765 PMCID: PMC6032205 DOI: 10.3390/ijms19061812] [Citation(s) in RCA: 174] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 06/10/2018] [Accepted: 06/12/2018] [Indexed: 12/14/2022] Open
Abstract
Inflammation is the principal response invoked by the body to address injuries. Despite inflammation constituting a crucial component of tissue repair, it is well known that unchecked or chronic inflammation becomes deleterious, leading to progressive tissue damage. Studies over the past years focused on foods rich in polyphenols with anti-inflammatory and immunomodulatory properties, since inflammation was recognized to play a central role in several diseases. In this review, we discuss the beneficial effects of resveratrol, the most widely investigated polyphenol, on cancer and neurodegenerative, respiratory, metabolic, and cardiovascular diseases. We highlight how resveratrol, despite its unfavorable pharmacokinetics, can modulate the inflammatory pathways underlying those diseases, and we identify future opportunities for the evaluation of its clinical feasibility.
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30
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Mendes-Braz M, Martins JO. Diabetes Mellitus and Liver Surgery: The Effect of Diabetes on Oxidative Stress and Inflammation. Mediators Inflamm 2018; 2018:2456579. [PMID: 29853784 PMCID: PMC5964489 DOI: 10.1155/2018/2456579] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Revised: 04/02/2018] [Accepted: 04/11/2018] [Indexed: 12/11/2022] Open
Abstract
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycaemia and high morbidity worldwide. The detrimental effects of hyperglycaemia include an increase in the oxidative stress (OS) response and an enhanced inflammatory response. DM compromises the ability of the liver to regenerate and is particularly associated with poor prognosis after ischaemia-reperfusion (I/R) injury. Considering the growing need for knowledge of the impact of DM on the liver following a surgical procedure, this review aims to present recent publications addressing the effects of DM (hyperglycaemia) on OS and the inflammatory process, which play an essential role in I/R injury and impaired hepatic regeneration after liver surgery.
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Affiliation(s)
- Mariana Mendes-Braz
- Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences of University Sao Paulo (FCF/USP), São Paulo, SP, Brazil
| | - Joilson O. Martins
- Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences of University Sao Paulo (FCF/USP), São Paulo, SP, Brazil
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31
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Rauf A, Imran M, Suleria HAR, Ahmad B, Peters DG, Mubarak MS. A comprehensive review of the health perspectives of resveratrol. Food Funct 2018; 8:4284-4305. [PMID: 29044265 DOI: 10.1039/c7fo01300k] [Citation(s) in RCA: 203] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Many natural products present in our diet, including flavonoids, can prevent the progression of cancer and other diseases. Resveratrol, a natural polyphenol present in various fruits and vegetables, plays an important role as a therapeutic and chemopreventive agent used in the treatment of various illnesses. It exhibits effects against different types of cancer through different pathways. It additionally exerts antidiabetic, anti-inflammatory, and anti-oxidant effects in a variety of cell types. Furthermore, the cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. Accordingly, this article presents an overview of recent developments in the use of resveratrol for the prevention and treatment of different diseases along with various mechanisms. In addition, the present review summarizes the most recent literature pertaining to resveratrol as a chemotherapeutic agent against multiple diseases and provides an assessment of the potential of this natural compound as a complementary or alternative medicine.
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Affiliation(s)
- Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar-23561, Khyber Pakhtunkhwa, Pakistan.
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Obesity-induced mouse benign prostatic hyperplasia (BPH) is improved by treatment with resveratrol: implication of oxidative stress, insulin sensitivity and neuronal growth factor. J Nutr Biochem 2018; 55:53-58. [DOI: 10.1016/j.jnutbio.2017.12.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Revised: 11/01/2017] [Accepted: 12/21/2017] [Indexed: 12/15/2022]
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Zhu XD, Lei XP, Dong WB. Resveratrol as a potential therapeutic drug for respiratory system diseases. DRUG DESIGN DEVELOPMENT AND THERAPY 2017; 11:3591-3598. [PMID: 29290681 PMCID: PMC5736354 DOI: 10.2147/dddt.s148868] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Respiratory system diseases are common and major ailments that seriously endanger human health. Resveratrol, a polyphenolic phytoalexin, is considered an anti-inflammatory, antioxidant, and anticancer agent. Thanks to its wide range of biological activities, resveratrol has become a hotspot in many fields, including respiratory system diseases. Indeed, research has demonstrated that resveratrol is helpful to relieve pulmonary function in the general population. Meanwhile, growing evidence indicates that resveratrol plays a protective role in respiratory system diseases. This review aimed to summarize the main protective effects of resveratrol in respiratory system diseases, including its anti-inflammatory, antiapoptotic, antioxidant, antifibrotic, antihypertensive, and anticancer activities. We found that resveratrol plays a protective role in the respiratory system through a variety of mechanisms, and so it may become a new drug for the treatment of respiratory system diseases.
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Affiliation(s)
- Xiao-Dan Zhu
- Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China
| | - Xiao-Ping Lei
- Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China
| | - Wen-Bin Dong
- Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China
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High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol. Sci Rep 2017; 7:17296. [PMID: 29229986 PMCID: PMC5725490 DOI: 10.1038/s41598-017-17558-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 11/28/2017] [Indexed: 12/14/2022] Open
Abstract
Insulin resistance plays an important role in obesity-associated asthma exacerbations. Using a murine model of allergic airway inflammation, we evaluated the insulin signaling transmission in lungs of obese compared with lean mice. We further evaluated the effects of the polyphenol resveratrol in the pulmonary insulin signaling. In lean mice, insulin stimulation significantly increased phosphorylations of AKT, insulin receptor substrate 1 (IRS-1) and insulin receptor β (IRβ) in lung tissue and isolated bronchi (p < 0.05), which were impaired in obese group. Instead, obese mice displayed increased tyrosine nitrations of AKT, IRβ and IRS-1 (p < 0.05). Two-week therapy of obese mice with resveratrol (100 mg/kg/day) restored insulin-stimulated AKT, IRS-1 and IRβ phosphorylations, and simultaneously blunted the tyrosine nitration of these proteins. Additionally, the c-Jun N-terminal kinase (JNK) and inhibitor of NF-κB Kinase (IκK) phosphorylations were significantly increased in obese group, an effect normalized by resveratrol. In separate experiments, the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (20 mg/kg/day, three weeks) mimicked the protective effects exerted by resveratrol in lungs of obese mice. Lungs of obese mice display nitrosative-associated impairment of insulin signaling, which is reversed by resveratrol. Polyphenols may be putative drugs to attenuate asthma exacerbations in obese individuals.
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Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes. Sci Rep 2017; 7:6444. [PMID: 28744004 PMCID: PMC5527079 DOI: 10.1038/s41598-017-06835-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 06/19/2017] [Indexed: 12/21/2022] Open
Abstract
Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo. Sirt1 inhibition of FcεRI signaling also involved an alternative component, PTP1B, which attenuated the inhibitory AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol stimulated the inhibitory AMPK axis, with reciprocal suppression of the stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our results provide a molecular explanation for the beneficial role of Sirt1 in allergy and underscore a potential application of Sirt1 activators as a new class of anti-allergic agents.
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Rui Y, Cheng J, Qin L, Shan C, Chang J, Wang G, Wan Z. Effects of vitamin D and resveratrol on metabolic associated markers in liver and adipose tissue from SAMP8 mice. Exp Gerontol 2017; 93:16-28. [PMID: 28411010 DOI: 10.1016/j.exger.2017.03.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 03/17/2017] [Accepted: 03/19/2017] [Indexed: 12/31/2022]
Abstract
SAMP8 mice exhibit multiple metabolic characteristics associated with age, and it is a suitable candidate for researching aging associated metabolic dysfunction. OBJECTIVES We aimed to 1) explore how key metabolic markers will be altered in both liver and adipose tissue with aging in SAMP8 mice; and 2) how the combination of vitamin D (VD) with resveratrol (RSV) will affect aging associated metabolic impairment in liver and adipose tissue from SAMP8 mice. METHODS SAMP8 mice and their control SAMR1 mice were divided into 5 groups, i.e. SAMR1, SAMP8, SAMP8 mice supplemented with VD, RSV and VD combined with RSV group, respectively. At the end of the intervention, glucose and insulin tolerance, p-AMP-activated protein kinase (AMPK) and amyloid precursor protein (APP), and endoplasmic reticulum (ER) stress markers in liver and adipose tissue, adiponectin secretion, p-NF-κBp65 and TNF-α protein expression in adipose tissue were determined. RESULTS Compared to SAMR1 control, SAMP8 mice demonstrate impaired glucose tolerance and reduction in circulating adiponectin level; in the liver, SAMP8 mice have reduction in p-Aktser473, elevation in PTP1B and APP, p-eIF2α, GRP78 and p-JNK protein expression. In epididymal (EPI) fat, SAMP8 mice also have elevated p-Aktser473 and PTP1B compared to SAMR1 mice. In both epididymal (EPI) and subcutaneous (SC) fat, there were elevated ER stress markers, reduced p-AMPK and elevated APP, as well as elevated p-NF-κBp65 and TNF-α protein expression from SAMP8 compared to SAMR1 mice. In liver, the combined intervention significantly restored p-Aktser473, p-eIF2α and p-JNK protein expression. In both EPI and SC fat, the combined intervention is effective for reducing p-NF-κB p65 and TNF-α in both fat depot, while only partially reduced ER stress markers in SC fat. As for adiponectin, their combination is unable to reverse reduction in adiponectin level. Adiponectin secretion in SC fat from VD, RSV and VDRSV group were also significantly reduced compared to SAMR1. CONCLUSION The combined intervention might exert greater beneficial effects for reversing aging associated metabolic dysfunction in liver and adipose tissue from SAMP8 mice.
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Affiliation(s)
- Yehua Rui
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, PR China
| | - Jinbo Cheng
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, PR China
| | - Liqiang Qin
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, PR China
| | - Cheng Shan
- University of Waterloo, Waterloo, Ontario, Canada
| | - Jie Chang
- Department of Occupational and Environmental Health, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou 215123, PR China
| | - Guiping Wang
- Laboratory Animal Center, Soochow University, 199 Ren'ai Road, Suzhou 215123, PR China
| | - Zhongxiao Wan
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, Soochow University, 199 Ren'ai Road, Suzhou 215123, PR China.
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Zhu LY, Ni ZH, Luo XM, Wang XB. Advance of antioxidants in asthma treatment. World J Respirol 2017; 7:17-28. [DOI: 10.5320/wjr.v7.i1.17] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 11/23/2016] [Accepted: 01/14/2017] [Indexed: 02/07/2023] Open
Abstract
Asthma is an allergic disease, characterized as a recurrent airflow limitation, airway hyperreactivity, and chronic inflammation, involving a variety of cells and cytokines. Reactive oxygen species have been proven to play an important role in asthma. The pathogenesis of oxidative stress in asthma involves an imbalance between oxidant and antioxidant systems that is caused by environment pollutants or endogenous reactive oxygen species from inflammation cells. There is growing evidence that antioxidant treatments that include vitamins and food supplements have been shown to ameliorate this oxidative stress while improving the symptoms and decreasing the severity of asthma. In this review, we summarize recent studies that are related to the mechanisms and biomarkers of oxidative stress, antioxidant treatments in asthma.
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Liu CW, Sung HC, Lin SR, Wu CW, Lee CW, Lee IT, Yang YF, Yu IS, Lin SW, Chiang MH, Liang CJ, Chen YL. Resveratrol attenuates ICAM-1 expression and monocyte adhesiveness to TNF-α-treated endothelial cells: evidence for an anti-inflammatory cascade mediated by the miR-221/222/AMPK/p38/NF-κB pathway. Sci Rep 2017; 7:44689. [PMID: 28338009 PMCID: PMC5364502 DOI: 10.1038/srep44689] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Accepted: 02/13/2017] [Indexed: 01/12/2023] Open
Abstract
Resveratrol, an edible polyphenolic phytoalexin, improves endothelial dysfunction and attenuates inflammation. However, the mechanisms have not been thoroughly elucidated. Therefore, we investigated the molecular basis of the effects of resveratrol on TNF-α-induced ICAM-1 expression in HUVECs. The resveratrol treatment significantly attenuated the TNF-α-induced ICAM-1 expression. The inhibition of p38 phosphorylation mediated the reduction in ICAM-1 expression caused by resveratrol. Resveratrol also decreased TNF-α-induced IκB phosphorylation and the phosphorylation, acetylation, and translocation of NF-κB p65. Moreover, resveratrol induced the AMPK phosphorylation and the SIRT1 expression in TNF-α-treated HUVECs. Furthermore, TNF-α significantly suppressed miR-221/-222 expression, which was reversed by resveratrol. miR-221/-222 overexpression decreased p38/NF-κB and ICAM-1 expression, which resulted in reduced monocyte adhesion to TNF-α-treated ECs. In a mouse model of acute TNF-α-induced inflammation, resveratrol effectively attenuated ICAM-1 expression in the aortic ECs of TNF-α-treated wild-type mice. These beneficial effects of resveratrol were lost in miR-221/222 knockout mice. Our data showed that resveratrol counteracted the TNF-α-mediated reduction in miR-221/222 expression and decreased the TNF-α-induced activation of p38 MAPK and NF-κB, thereby suppressing ICAM-1 expression and monocyte adhesion. Collectively, our results show that resveratrol attenuates endothelial inflammation by reducing ICAM-1 expression and that the protective effect was mediated partly through the miR-221/222/AMPK/p38/NF-κB pathway.
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Affiliation(s)
- Chen-Wei Liu
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hsin-Ching Sung
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shu-Rung Lin
- Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Taoyuan, Taiwan.,Center for Nanotechnology and Center for Biomedical Technology, Chung-Yuan Christian University, Taoyuan, Taiwan
| | - Chun-Wei Wu
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chiang-Wen Lee
- Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan
| | - I-Ta Lee
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Yi-Fan Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - I-Shing Yu
- Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Shu-Wha Lin
- Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Hsien Chiang
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chan-Jung Liang
- Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.,Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Taiwan
| | - Yuh-Lien Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
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姚 笑, 夏 凡, 唐 外, 周 本. [Effect of Hugan Qingzhi tablets on AMPK pathway activation and NF-κB-p65 protein expression in the liver of rats with nonalcoholic fatty liver disease]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2017; 37:56-62. [PMID: 28109099 PMCID: PMC6765763 DOI: 10.3969/j.issn.1673-4254.2017.01.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVE To investigate the effect of Hugan Qingzhi tablets on lipid metabolism and inflammation in rats fed on high-fat diet and explore the underlying mechanisms. METHODS Sixty male Sprague-Dawley rats were randomly divided into 6 groups, namely HFD group (with high-fat diet and distilled water), control group (with normal diet and distilled water), fenofibrate group (with high-fat diet and treatment with 0.1 g<kg fenofibrate suspension), and low-, moderate- and high-dose Hugan Qingzhi tablet groups (with high-fat diet and treatment with 0.54, 1.08, and 2.16 g<kg Hugan Qingzhi suspension). After daily corresponding treatments for 12 weeks, the histological changes in the liver were observed with HE staining. The serum levels of triglyceride (TG), cholesterol (CHOL), alanine transaminase (ALT), and aspartate aminotransferase (AST), and the levels of TG and CHOL in the hepatic tissue were assayed. The proinflammatory cytokines TNF-α, IL-6 and CRP were detected with enzyme-linked immunoassay, and p-AMPK, SREBP-1c, FASN and NF-αB-p65 expression levels in the liver were determined with qRT-PCR or Western blotting. RESULTS At high and moderate doses, Hugan Qingzhi effectively decreased the levels of ALT, AST, TG and CHOL levels in the serum, lowered the hepatic levels of TNF-α, IL-6 and CRP, enhanced p-AMPK, and reduced the expression of SREBP-1c, FASN and Ac-NF-αB-p65 in the liver of rats fed on high-fat diet. CONCLUSION Hugan Qingzhi tablets alleviates hyperlipidemia and inflammation in rats fed with high-fat diet possibly by activating AMPK pathway and suppress NF-αB activity to arrest the progression of nonalcoholic fatty liver disease.
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Affiliation(s)
- 笑睿 姚
- />南方医科大学珠江医院药学部，广东 广州 510282Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - 凡 夏
- />南方医科大学珠江医院药学部，广东 广州 510282Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - 外姣 唐
- />南方医科大学珠江医院药学部，广东 广州 510282Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - 本杰 周
- />南方医科大学珠江医院药学部，广东 广州 510282Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
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Kim HY. Resveratrol in Asthma: A French Paradox? ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2017; 9:1-2. [PMID: 27826956 PMCID: PMC5102830 DOI: 10.4168/aair.2017.9.1.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 09/01/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Hye Young Kim
- Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Korea.,Department of Medical Science, Seoul National University College of Medicine, Seoul, Korea.
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