|
1
|
Zeng J, Yuan L, Chen G, Qi Y, Qie X, Jin Y, Chen Y, Li H. The ferroptosis of sertoli cells inducing blood-testis barrier damage is produced by oxidative stress in cryptorchidism. Free Radic Biol Med 2025; 232:97-106. [PMID: 40032029 DOI: 10.1016/j.freeradbiomed.2025.02.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/17/2025] [Accepted: 02/26/2025] [Indexed: 03/05/2025]
Abstract
Oxidative Stress (OS) is the main cause of damage to the Blood-Testis Barrier (BTB) in cryptorchidism, which seriously endangers male reproductive health. It is well known that the OS induced ferroptosis is an important cause of dysfunction in the body. However, it is still unknown whether BTB damage in cryptorchidism leads to ferroptosis of Sertoli cells. We establishing the cryptorchidism model through surgery to avoid the complex effects of drugs on the model animals, combined with in vitro culture of the primary Sertoli cells for validation, and the methods of immunofluorescence staining, Western blotting and Prussian blue staining were used to study the oxidative stress in cryptorchidism. The effects of ferroptosis of Sertoli cells inducing BTB damage caused by OS in cryptorchidism were analyzed. We found that the inhibition of Nrf-2/keap-1/HO-1 pathway resulted in decreased expression levels of Glutathione Peroxidase 4 (GPX4), Ferroportin 1 (FPN1), and increased expression of Ferritin light chain (FTL) protein. Our research further confirms that inhibiting ferroptosis reduced BTB damage by reflecting a decrease expression of Zonula Occludens protein 1 (ZO-1), Occludin and Claudin-11 protein caused by OS. In addition, we found that the testosterone (T) secretion disorders and the supplementation of T can alleviate the damage of the BTB in cryptorchidism, and this effect is achieved through the Androgen Receptor (AR). In conclusion, our study found that the inhibition of Nrf-2/keap-1/HO-1 pathway in testis and the reduction of Tight junction proteins (TJs) ZO-1, Occludin and Claudin-11 protein expression levels in cryptorchidic mice, indicated that the cryptorchidism triggering a serious reproductive disorder, and one of the important reasons is the OS induced ferroptosis of Sertoli cells, which ultimately leads to the damage of the BTB. This findings may have important implications in the field of male reproductive disorders.
Collapse
Affiliation(s)
- Jianlin Zeng
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, China
| | - Ligang Yuan
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, China.
| | - Guojuan Chen
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Huangzhong District Animal Disease Prevention and Control Center, Xining, 811600, China
| | - Yumei Qi
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, China
| | - Xiaolong Qie
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, China
| | - Yajuan Jin
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, China
| | - Yulu Chen
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, China
| | - Haijun Li
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, China
| |
Collapse
|
|
2
|
Luo J, Lu W, Chen Y, Li G, Feng J, Huang Y, Yu Y, Cai S, Jian J, Yang S. SQSTM1/p62 from Litopenaeus vannamei is involved in the immune response to Vibrio infection. FISH & SHELLFISH IMMUNOLOGY 2025; 158:110161. [PMID: 39890038 DOI: 10.1016/j.fsi.2025.110161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/24/2025] [Accepted: 01/26/2025] [Indexed: 02/03/2025]
Abstract
Sequestosome 1 (SQSTM1 or p62) has multiple functional domains, and it can not only be involved in autophagy process, but also defend against oxidative stress by invoking the Keap1/Nrf2 signaling pathway. However, the role of p62 in the response of Pacific whiteleg shrimp Litopenaeus vannamei to bacterial infection is still unclear. This study successfully identified p62 from L. vannamei (Lv-p62). The length of the open reading frame (ORF) of Lv-p62 is 1908 bp, which encoded 635 amino acids, and had Phox and Bem1p domain (PB1), Zinc-binding and ubiquitin-associated (UBA) domains. The expression level of Lv-p62 in the hepatopancreas of healthy L. vannamei is the highest, and it could be significantly induced under the stimulation of Vibrio harveyi. Besides, knocking down Lv-p62 by using RNA interference technology could reduce the expression levels of Nrf2 (nuclear factor erythroid 2-related factor 2), LC3 (microtubule-associated protein 1 light chain 3) and autophagy-related gene (ATG3, ATG5 and ATG12). Compared with the stimulation with V. harveyi alone, stimulation with V. harveyi after knocking down Lv-p62 could reduce the expression of antioxidant-, autophagy- and apoptosis-related genes in L. vannamei. Moreover, knocking down Lv-p62 could reduce the apoptosis signal of hepatopancreas and the abnormal tissue structure caused by V. harveyi. These results indicated that Lv-p62 is involved in the immune response to Vibrio infection in L. vannamei, which further enriched the regulatory function of p62 and its role in the innate immunity of shrimp.
Collapse
Affiliation(s)
- Junliang Luo
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Wei Lu
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Yanghui Chen
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Guojian Li
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Jinyuan Feng
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Yanru Huang
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Yu Yu
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Shuanghu Cai
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Jichang Jian
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China
| | - Shiping Yang
- Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture & Key Laboratory of Control for Disease of Aquatic Animals of Guangdong Higher Education Institutes, Zhanjiang, China.
| |
Collapse
|
|
3
|
Hong SW, Page R, Truman P. Smoking, coffee intake, and Parkinson's disease: Potential protective mechanisms and components. Neurotoxicology 2025; 106:48-63. [PMID: 39701424 DOI: 10.1016/j.neuro.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 12/05/2024] [Accepted: 12/14/2024] [Indexed: 12/21/2024]
Abstract
Parkinson's disease (PD) is a common progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Environmental and lifestyle factors, such as smoking and coffee drinking, have been associated with a decreased risk for PD. However, the biological mechanisms underlying protective effects on PD are still not fully understood. It has been suggested that non-nicotine components in cigarette smoke and non-caffeine components in coffee may contribute to this protective effect. The aim of this review was to explore candidate molecules and mechanisms behind the effects of smoking and coffee drinking on PD by integrating findings from previous studies. By cross-referencing an index of tobacco constituents and a list of coffee constituents with existing literature on natural compounds and their structural analogs that show inhibitory activities against monoamine oxidase B, catechol O-methyltransferase, and α-synuclein fibrillation, we have identified tobacco and coffee components that inhibit these targets. Furthermore, tobacco and coffee components potentially play roles in suppressing neuroinflammation, activating the Nrf2 pathway as natural activators, and altering the gut microbiome. This review suggests that the phenolic compounds from tobacco and coffee investigated may contribute to the low incidence of PD in smokers and coffee drinkers, showing moderate to strong potential as therapeutic interventions. The current review suggests that multifunctional molecules found in coffee and cigarette smoke may have potential neuroprotective effects, but none of the data indicates that multifunctionality is required for these effects. This review will deepen our understanding of how smoking and coffee drinking are linked to a reduced risk of PD and will also be important in elucidating the mechanisms underlying the protective effects of smoking and coffee drinking on PD.
Collapse
Affiliation(s)
- Sa Weon Hong
- School of Health Sciences, Massey University, Wellington 6021, New Zealand.
| | - Rachel Page
- School of Health Sciences, Massey University, Wellington 6021, New Zealand
| | - Penelope Truman
- School of Health Sciences, Massey University, Wellington 6021, New Zealand
| |
Collapse
|
|
4
|
Xu S, Gao Z, Jiang L, Li J, Qin Y, Zhang D, Tian P, Wang W, Zhang N, Zhang R, Xu S. High glucose- or AGE-induced oxidative stress inhibits hippocampal neuronal mitophagy through the Keap1-Nrf2-PHB2 pathway in diabetic encephalopathy. Sci Rep 2024; 14:24044. [PMID: 39402106 PMCID: PMC11473637 DOI: 10.1038/s41598-024-70584-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 08/19/2024] [Indexed: 10/17/2024] Open
Abstract
Diabetic encephalopathy (DE) is a severe complication of diabetes, but its pathogenesis remains unclear. This study aimed to investigate the roles and underlying mechanisms of high glucose (HG)- and advanced glycosylation end product (AGE)-induced oxidative stress (OS) in the cognitive decline in DE. The DE mouse model was established using a high-fat diet and streptozotocin, and its cognitive functions were evaluated using the Morris Water Maze, novel object recognition, and Y-maze test. The results revealed increased reactive oxygen species (ROS) generation, mitophagy inhibition, and decreased prohibitin 2 (PHB2) expression in the hippocampal neurons of DE mice and HG- or AGE-treated HT-22 cells. However, overexpression of PHB2 reduced ROS generation, reversed mitophagy inhibition, and improved mitochondrial function in the HG- or AGE-treated HT-22 cells and ameliorated cognitive decline, improved mitochondrial structural damage, and reversed mitophagy inhibition of hippocampal neurons in DE mice. Further analysis revealed that the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was involved in the HG- or AGE-mediated downregulation of PHB2 in HT-22 cells. These results demonstrate that HG- or AGE-induced OS inhibits the mitophagy of hippocampal neurons via the Keap1-Nrf2-PHB2 pathway, thereby contributing to the cognitive decline in DE.
Collapse
Affiliation(s)
- Shan Xu
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
- Central Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China
| | - Zhaoyu Gao
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
- Hebei International Joint Research Center for Brain Science, Shijiazhuang, 050031, People's Republic of China
- Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, 050031, People's Republic of China
| | - Lei Jiang
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
- Hebei International Joint Research Center for Brain Science, Shijiazhuang, 050031, People's Republic of China
- Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, 050031, People's Republic of China
| | - Jiazheng Li
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
| | - Yushi Qin
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
| | - Di Zhang
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
| | - Pei Tian
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
| | - Wanchang Wang
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
| | - Nan Zhang
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China
- Hebei International Joint Research Center for Brain Science, Shijiazhuang, 050031, People's Republic of China
- Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, 050031, People's Republic of China
| | - Rui Zhang
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China.
- Hebei International Joint Research Center for Brain Science, Shijiazhuang, 050031, People's Republic of China.
- Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, 050031, People's Republic of China.
| | - Shunjiang Xu
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People's Republic of China.
- Hebei International Joint Research Center for Brain Science, Shijiazhuang, 050031, People's Republic of China.
- Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, 050031, People's Republic of China.
| |
Collapse
|
|
5
|
Chang S, Lv J, Wang X, Su J, Bian C, Zheng Z, Yu H, Bao J, Xin Y, Jiang X. Pathogenic mechanisms and latest therapeutic approaches for radiation-induced lung injury: A narrative review. Crit Rev Oncol Hematol 2024; 202:104461. [PMID: 39103129 DOI: 10.1016/j.critrevonc.2024.104461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 07/26/2024] [Accepted: 07/28/2024] [Indexed: 08/07/2024] Open
Abstract
The treatment of thoracic tumors with ionizing radiation can cause radiation-induced lung injury (RILI), which includes radiation pneumonitis and radiation-induced pulmonary fibrosis. Preventing RILI is crucial for controlling tumor growth and improving quality of life. However, the serious adverse effects of traditional RILI treatment methods remain a major obstacle, necessitating the development of novel treatment options that are both safe and effective. This review summarizes the molecular mechanisms of RILI and explores novel treatment options, including natural compounds, gene therapy, nanomaterials, and mesenchymal stem cells. These recent experimental approaches show potential as effective prevention and treatment options for RILI in clinical practice.
Collapse
Affiliation(s)
- Sitong Chang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiation Oncology, the First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun 130021, China.
| | - Jincai Lv
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
| | - Xuanzhong Wang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiation Oncology, the First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun 130021, China.
| | - Jing Su
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiation Oncology, the First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun 130021, China.
| | - Chenbin Bian
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiation Oncology, the First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun 130021, China.
| | - Zhuangzhuang Zheng
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiation Oncology, the First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun 130021, China.
| | - Huiyuan Yu
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiation Oncology, the First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun 130021, China.
| | - Jindian Bao
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiation Oncology, the First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun 130021, China.
| | - Ying Xin
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
| | - Xin Jiang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiation Oncology, the First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun 130021, China.
| |
Collapse
|
|
6
|
Szaefer H, Licznerska B, Baer-Dubowska W. The Aryl Hydrocarbon Receptor and Its Crosstalk: A Chemopreventive Target of Naturally Occurring and Modified Phytochemicals. Molecules 2024; 29:4283. [PMID: 39339278 PMCID: PMC11433792 DOI: 10.3390/molecules29184283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/30/2024] [Accepted: 09/07/2024] [Indexed: 09/30/2024] Open
Abstract
The aryl hydrocarbon receptor (AhR) is an environmentally sensitive transcription factor (TF) historically associated with carcinogenesis initiation via the activation of numerous carcinogens. Nowadays, the AhR has been attributed to multiple endogenous functions to maintain cellular homeostasis. Moreover, crosstalk, often reciprocal, has been found between the AhR and several other TFs, particularly estrogen receptors (ERs) and nuclear factor erythroid 2-related factor-2 (Nrf2). Adequate modulation of these signaling pathways seems to be an attractive strategy for cancer chemoprevention. Several naturally occurring and synthetically modified AhR or ER ligands and Nrf2 modulators have been described. Sulfur-containing derivatives of glucosinolates, such as indole-3-carbinol (I3C), and stilbene derivatives are particularly interesting in this context. I3C and its condensation product, 3,3'-diindolylmethane (DIM), are classic examples of blocking agents that increase drug-metabolizing enzyme activity through activation of the AhR. Still, they also affect multiple essential signaling pathways in preventing hormone-dependent cancer. Resveratrol is a competitive antagonist of several classic AhR ligands. Its analogs, with ortho-methoxy substituents, exert stronger antiproliferative and proapoptotic activity. In addition, they modulate AhR activity and estrogen metabolism. Their activity seems related to a number of methoxy groups introduced into the stilbene structure. This review summarizes the data on the chemopreventive potential of these classes of phytochemicals, in the context of AhR and its crosstalk modulation.
Collapse
Affiliation(s)
- Hanna Szaefer
- Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznań, Poland; (B.L.); (W.B.-D.)
| | | | | |
Collapse
|
|
7
|
Armeli F, Mengoni B, Laskin DL, Businaro R. Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation. Curr Issues Mol Biol 2024; 46:6868-6884. [PMID: 39057052 PMCID: PMC11276139 DOI: 10.3390/cimb46070410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/27/2024] [Accepted: 06/29/2024] [Indexed: 07/28/2024] Open
Abstract
The onset of neurodegenerative diseases involves a complex interplay of pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disorders, highlighting autophagy as pivotal in disease pathogenesis. Reactive oxygen species (ROS) play dual roles in cellular homeostasis and autophagy regulation, with disruptions of redox signaling contributing to neurodegeneration. The activation of the Nrf2 pathway represents a critical antioxidant mechanism, while autophagy maintains cellular homeostasis by degrading altered cell components. The interaction among p62/SQSTM1, Nrf2, and Keap1 forms a regulatory pathway essential for cellular stress response, whose dysregulation leads to impaired autophagy and aggregate accumulation. Targeting the Nrf2-p62/SQSTM1 pathway holds promise for therapeutic intervention, mitigating oxidative stress and preserving cellular functions. Additionally, this review explores the potential synergy between the endocannabinoid system and Nrf2 signaling for neuroprotection. Further research is needed to elucidate the involved molecular mechanisms and develop effective therapeutic strategies against neurodegeneration.
Collapse
Affiliation(s)
- Federica Armeli
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica, 79, 04100 Latina, Italy; (F.A.); (B.M.)
| | - Beatrice Mengoni
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica, 79, 04100 Latina, Italy; (F.A.); (B.M.)
| | - Debra L. Laskin
- Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA;
| | - Rita Businaro
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica, 79, 04100 Latina, Italy; (F.A.); (B.M.)
| |
Collapse
|
|
8
|
Panditrao Lahane G, Dhar A. Renoprotective effect of Nesfatin-1 in Adenine-Induced Chronic kidney Disease: An in vitro and in vivo study. Biochem Pharmacol 2024; 225:116284. [PMID: 38750903 DOI: 10.1016/j.bcp.2024.116284] [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: 01/19/2024] [Revised: 05/10/2024] [Accepted: 05/11/2024] [Indexed: 05/19/2024]
Abstract
Chronic Kidney Disease (CKD) presents a significant global health challenge with limited treatment options. Nesfatin-1, an anorexigenic peptide, has demonstrated antioxidant, anti-inflammatory, and anti-apoptotic properties in various diseases. However, the role of nesfatin-1 in CKD remains unclear. This study investigates the potential renoprotective effects of nesfatin-1 in adenine-induced CKD mice and in NRK-52E renal epithelial cells. Male C57BL/6J mice and NRK-52E renal epithelial cells were administered adenine to induce CKD. Various aspects of renal function, histopathology, oxidative stress, inflammation, apoptosis, and renal interstitial fibrosis were assessed and downstream pathways were investigated. Adenine-fed mice exhibited reduced nesfatin-1 expression and increased markers of kidney damage, including elevated blood urea nitrogen (BUN), serum creatinine, and histological abnormalities, reactive oxygen species (ROS), inflammation, apoptosis, and fibrosis. Treatment with nesfatin-1 in adenine induced mice significantly reversed these changes. Nesfatin-1 also lowered calcium levels and the expression of inflammatory markers, including IL-1β, IL-6, TNF-α, and Nf-kB. Furthermore, nesfatin-1 reduced the expression of apoptotic markers (Caspase-3, Caspase-1, Bax/Bcl2 ratio) and restored the balance of Bcl2 and MMP. Lastly, nesfatin-1 attenuated fibrotic markers (Tgf-β, Smad2/3,4, type IV collagen, α-SMA) in both adenine-induced CKD mice and NRK-52E cells. In conclusion, our results suggest that nesfatin-1 may enhance kidney function in adenine-induced CKD mice and NRK-52E cells. The renoprotective effects of nesfatin-1 are likely associated with its antioxidant, anti-inflammatory, anti-apoptotic, and anti-fibrotic properties.
Collapse
Affiliation(s)
- Ganesh Panditrao Lahane
- Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana 500078, India
| | - Arti Dhar
- Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana 500078, India.
| |
Collapse
|
|
9
|
Liu S, Zhang R, Zhang L, Yang A, Guo Y, Jiang L, Wang H, Xu S, Zhou H. Oxidative stress suppresses PHB2-mediated mitophagy in β-cells via the Nrf2/PHB2 pathway. J Diabetes Investig 2024; 15:559-571. [PMID: 38260951 PMCID: PMC11060161 DOI: 10.1111/jdi.14147] [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: 05/05/2023] [Revised: 12/20/2023] [Accepted: 12/27/2023] [Indexed: 01/24/2024] Open
Abstract
AIMS/INTRODUCTION Mitochondrial damage caused by oxidative stress is a main driver of pancreatic β-cell dysfunction in the pathogenesis of type 2 diabetes mellitus. Prohibitin2 (PHB2) is a vital inner mitochondrial membrane protein that participates in mitophagy to remove the damaged mitochondria. This study aimed to investigate the role and mechanisms of PHB2-mediated mitophagy in oxidative stress-induced pancreatic β-cell dysfunction. MATERIALS AND METHODS PHB2 and mitophagy-related protein expression were analyzed by real-time polymerase chain reaction and western blotting in RINm5F cells treated with H2O2 and islets of diabetic rats. Mitophagy was observed by mitochondrial and lysosome colocalization. RINm5F cells were transfected by phb2 siRNA or overexpression plasmid to explore the role of PHB2 in mitophagy of RINm5F cells. The mechanism of Nrf2 regulating PHB2 was explored by Nrf2 inhibitor and agonist. RESULTS The expression of PHB2, mitophagy related protein PINK1, and Parkin were decreased in RINm5F cells incubated with H2O2 and in islets of diabetic rats. Overexpression of PHB2 protected β-cells from oxidative stress by promoting mitophagy and inhibiting cell apoptosis, whereas transfection with PHB2 siRNA suppressed mitophagy. Furthermore, PHB2-mediated mitophagy induced by oxidative stress was through the Nrf2/PHB2 pathway in β-cells. Antioxidant NAC alleviated oxidative stress injury by promoting PHB2-mediated mitophagy. CONCLUSION Our study suggested that PHB2-mediated mitophagy can protect β-cells from apoptosis via the Nrf2/PHB2 pathway under oxidative stress. Antioxidants may protect β-cell from oxidative stress by prompting PHB2-mediated mitophagy. PHB2-mediated mitophagy as a potential mechanism takes part in the oxidative stress induced β-cell injury.
Collapse
Affiliation(s)
- Shan Liu
- Department of EndocrinologyThe First Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
- Hebei Key Laboratory of Brain Science and Psychiatric‐Psychologic DiseaseShijiazhuangHebeiChina
- Department of EndocrinologyThe Second Hospital of ShijiazhuangShijiazhuangHebeiChina
- Central LaboratoryThe First Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
| | - Rui Zhang
- Hebei Key Laboratory of Brain Science and Psychiatric‐Psychologic DiseaseShijiazhuangHebeiChina
- Central LaboratoryThe First Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
- Hebei International Joint Research Center for Brain ScienceShijiazhuangHebeiChina
| | - Lan Zhang
- Department of RadiologyThe Fourth Affiliated Hospital Zhejiang University School of MedicineYiwuZhejiangChina
| | - Aige Yang
- Department of EndocrinologyThe First Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
| | - Yuqing Guo
- Department of EndocrinologyThe First Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
| | - Lei Jiang
- Hebei Key Laboratory of Brain Science and Psychiatric‐Psychologic DiseaseShijiazhuangHebeiChina
- Central LaboratoryThe First Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
- Hebei International Joint Research Center for Brain ScienceShijiazhuangHebeiChina
| | - Huijuan Wang
- Department of EndocrinologyThe Second Hospital of ShijiazhuangShijiazhuangHebeiChina
| | - Shunjiang Xu
- Hebei Key Laboratory of Brain Science and Psychiatric‐Psychologic DiseaseShijiazhuangHebeiChina
- Central LaboratoryThe First Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
- Hebei International Joint Research Center for Brain ScienceShijiazhuangHebeiChina
| | - Huimin Zhou
- Department of EndocrinologyThe First Hospital of Hebei Medical UniversityShijiazhuangHebeiChina
| |
Collapse
|
|
10
|
Zhou J, Yun X, Wang J, Li Q, Wang Y, Zhang W, Fan Z. Biological toxicity of sulfamethoxazole in aquatic ecosystem on adult zebrafish (Danio rerio). Sci Rep 2024; 14:9401. [PMID: 38658643 PMCID: PMC11043448 DOI: 10.1038/s41598-024-59971-y] [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: 12/16/2023] [Accepted: 04/17/2024] [Indexed: 04/26/2024] Open
Abstract
This study evaluated the impacts of sulfamethoxazole (SMX) on antioxidant, immune, histopathological dynamic changes, and gut microbiota of zebrafish. SMX was carried out five groups: 0 (C), 3 mg/L (T3), 6 mg/L (T6), 12 mg/L (T12), and 24 mg/L (T24), with 5 replicates per group for an 8-weeks chronic toxicity test. It was found that SMX is considered to have low toxicity to adult zebrafish. SMX with the concentration not higher than 24 mg/L has no obvious inhibitory effect on the growth of fish. Under different concentrations of SMX stress, oxidative damage and immune system disorder were caused to the liver and gill, with the 12 and 24 mg/L concentration being the most significant. At the same time, it also causes varying degrees of pathological changes in both intestinal and liver tissues. As the concentration of SMX increases, the composition and abundance of the gut microbiota in zebrafish significantly decrease.
Collapse
Affiliation(s)
- Jie Zhou
- Lab of Aquatic Animal Nutrition & Environmental Health, Shandong Agricultural University, 61 Dazing Street, Tai'an, 271018, Shandong, China
| | - Xiao Yun
- Lab of Aquatic Animal Nutrition & Environmental Health, Shandong Agricultural University, 61 Dazing Street, Tai'an, 271018, Shandong, China
| | - Jiting Wang
- Lab of Aquatic Animal Nutrition & Environmental Health, Shandong Agricultural University, 61 Dazing Street, Tai'an, 271018, Shandong, China.
| | - Qi Li
- Lab of Aquatic Animal Nutrition & Environmental Health, Shandong Agricultural University, 61 Dazing Street, Tai'an, 271018, Shandong, China
| | - Yanli Wang
- Lab of Aquatic Animal Nutrition & Environmental Health, Shandong Agricultural University, 61 Dazing Street, Tai'an, 271018, Shandong, China
| | - Wenjing Zhang
- Lab of Aquatic Animal Nutrition & Environmental Health, Shandong Agricultural University, 61 Dazing Street, Tai'an, 271018, Shandong, China
| | - Zhicheng Fan
- Lab of Aquatic Animal Nutrition & Environmental Health, Shandong Agricultural University, 61 Dazing Street, Tai'an, 271018, Shandong, China
| |
Collapse
|
|
11
|
Cecerska-Heryć E, Wiśniewska Z, Serwin N, Polikowska A, Goszka M, Engwert W, Michałów J, Pękała M, Budkowska M, Michalczyk A, Dołęgowska B. Can Compounds of Natural Origin Be Important in Chemoprevention? Anticancer Properties of Quercetin, Resveratrol, and Curcumin-A Comprehensive Review. Int J Mol Sci 2024; 25:4505. [PMID: 38674092 PMCID: PMC11050349 DOI: 10.3390/ijms25084505] [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: 02/15/2024] [Revised: 04/17/2024] [Accepted: 04/18/2024] [Indexed: 04/28/2024] Open
Abstract
Malignant tumors are the second most common cause of death worldwide. More attention is being paid to the link between the body's impaired oxidoreductive balance and cancer incidence. Much attention is being paid to polyphenols derived from plants, as one of their properties is an antioxidant character: the ability to eliminate reactive oxygen and nitrogen species, chelate specific metal ions, modulate signaling pathways affecting inflammation, and raise the level and activity of antioxidant enzymes while lowering those with oxidative effects. The following three compounds, resveratrol, quercetin, and curcumin, are polyphenols modulating multiple molecular targets, or increasing pro-apoptotic protein expression levels and decreasing anti-apoptotic protein expression levels. Experiments conducted in vitro and in vivo on animals and humans suggest using them as chemopreventive agents based on antioxidant properties. The advantage of these natural polyphenols is low toxicity and weak adverse effects at higher doses. However, the compounds discussed are characterized by low bioavailability and solubility, which may make achieving the blood concentrations needed for the desired effect challenging. The solution may lie in derivatives of naturally occurring polyphenols subjected to structural modifications that enhance their beneficial effects or work on implementing new ways of delivering antioxidants that improve their solubility and bioavailability.
Collapse
Affiliation(s)
- Elżbieta Cecerska-Heryć
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Zofia Wiśniewska
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Natalia Serwin
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Aleksandra Polikowska
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Małgorzata Goszka
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Weronika Engwert
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Jaśmina Michałów
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Maja Pękała
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Marta Budkowska
- Department of Medical Analytics, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland;
| | - Anna Michalczyk
- Department of Psychiatry, Pomeranian Medical University of Szczecin, Broniewskiego 26, 71-460 Szczecin, Poland;
| | - Barbara Dołęgowska
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| |
Collapse
|
|
12
|
Kari ZA, Téllez-Isaías G, Khoo MI, Wee W, Kabir MA, Cheadoloh R, Wei LS. Resveratrol impacts on aquatic animals: a review. FISH PHYSIOLOGY AND BIOCHEMISTRY 2024; 50:307-318. [PMID: 38376668 DOI: 10.1007/s10695-024-01319-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 02/10/2024] [Indexed: 02/21/2024]
Abstract
Aquaculture has intensified tremendously with the increasing demand for protein sources as the global population grows. However, this industry is plagued with major challenges such as poor growth performance, the lack of a proper environment, and immune system impairment, thus creating stress for the aquaculture species and risking disease outbreaks. Currently, prophylactics such as antibiotics, vaccines, prebiotics, probiotics, and phytobiotics are utilized to minimize the negative impacts of high-density farming. One of the promising prophylactic agents incorporated in fish feed is resveratrol, a commercial phytophenol derived via the methanol extraction method. Recent studies have revealed many beneficial effects of resveratrol in aquatic animals. Therefore, this review discusses and summarizes the roles of resveratrol in improving growth performance, flesh quality, immune system, antioxidant capacity, disease resistance, stress mitigation, and potential combination with other prophylactic agents for aquatic animals.
Collapse
Affiliation(s)
- Zulhisyam Abdul Kari
- Department of Agricultural Sciences, Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Jeli Campus, 17600, Jeli, Kelantan, Malaysia.
- Advanced Livestock and Aquaculture Research Group, Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Jeli Campus, 17600, Jeli, Kelantan, Malaysia.
| | | | - Martina Irwan Khoo
- Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Malaysia
| | - Wendy Wee
- Center of Fundamental and Continuing Education, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia
| | | | - Romalee Cheadoloh
- Faculty of Science Technology and Agriculture, Yala Rajabhat University, 133 Thetsaban 3 Rd, Sateng, Mueang, 95000, Yala Province, Thailand
| | - Lee Seong Wei
- Department of Agricultural Sciences, Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Jeli Campus, 17600, Jeli, Kelantan, Malaysia.
- Advanced Livestock and Aquaculture Research Group, Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Jeli Campus, 17600, Jeli, Kelantan, Malaysia.
| |
Collapse
|
|
13
|
Salama MA, Alabiad MA, Saleh AA. Impact of resveratrol and zinc on biomarkers of oxidative stress induced by Trichinella spiralis infection. J Helminthol 2023; 97:e100. [PMID: 38099459 DOI: 10.1017/s0022149x23000810] [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: 12/18/2023]
Abstract
Trichinellosis is a re-emerging worldwide foodborne zoonosis. Oxidative stress is one of the most common detrimental effects caused by trichinellosis. In addition, Trichinella infection poses an infinite and major challenge to the host's immune system. Resistance and side effects limit the efficiency of the existing anti-trichinella medication. Given that concern, this work aimed to investigate the anti-helminthic, antioxidant, anti-inflammatory and immunomodulatory effects of resveratrol and zinc during both phases of Trichinella spiralis infection. Sixty-four Swiss albino mice were divided into four equal groups: non-infected control, infected control, infected and treated with resveratrol, and infected and treated with zinc. Animals were sacrificed on the 7th and 35th days post-infection for intestinal and muscular phase assessments. Drug efficacy was assessed by biochemical, parasitological, histopathological, immunological, and immunohistochemical assays. Resveratrol and zinc can be promising antiparasitic, antioxidant, anti-inflammatory, and immunomodulatory agents, as evidenced by the significant decrease in parasite burden, the significant improvement of liver and kidney function parameters, the increase in total antioxidant capacity (TAC), the reduction of malondialdehyde (MDA) level, the increase in nuclear factor (erythroid-derived 2)-like-2 factor expression, and the improvement in histopathological findings. Moreover, both drugs enhanced the immune system and restored the disturbed immune balance by increasing the interleukin 12 (IL-12) level. In conclusion, resveratrol and zinc provide protection for the host against oxidative harm and the detrimental effects produced by the host's defense response during Trichinella spiralis infection, making them promising natural alternatives for the treatment of trichinellosis.
Collapse
Affiliation(s)
- M A Salama
- Department of Medical Parasitology, Faculty of Medicine, Zagazig University, Egypt
| | - M A Alabiad
- Pathology Department, Faculty of Medicine, Zagazig University, Egypt
| | - A A Saleh
- Department of Medical Parasitology, Faculty of Medicine, Zagazig University, Egypt
| |
Collapse
|
|
14
|
Koc S, Aktas A, Sahin B, Ozer H, Zararsiz GE. Protective effect of ursodeoxycholic acid and resveratrol against tacrolimus induced hepatotoxicity. Biotech Histochem 2023; 98:471-478. [PMID: 37381715 DOI: 10.1080/10520295.2023.2228697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023] Open
Abstract
Tacrolimus (TAC) is a potent and well-tolerated immunosuppressive drug, but serious side effects including nephrotoxicity and hepatotoxicity have been reported. Ursodeoxycholic acid (UDCA) and resveratrol (RSV) exhibit hepatoprotective effects in liver diseases. We investigated the hepatoprotective effect of UDCA and RSV against TAC induced hepatotoxicity. We divided 40 male rats into five equal groups: A) control group, B) TAC group, C) TAC + UDCA group, D) TAC + RSV group, E) TAC + UDCA + RSV group. We administered 0.5 mg/kg TAC once daily, 25 mg/kg UDCA twice daily and 10 mg/kg RSV once daily. The drugs in the experimental groups were given by gavage from the first day of the study and continued for 21 days. Histopathologic and biochemical analyses were performed on day 22. In group B, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), total oxidative status (TOS) and malondialdehyde (MDA) levels were higher compared to group A, and catalase (CAT), superoxide dismutase (SOD) levels and total antioxidant status (TAS) were lower compared to group A. Severe cellular swelling, degeneration and focal necrosis were more evident in group B than in groups C-E. Histopathological improvement was observed in groups C-E, where UDCA and RSV were combined, compared to group B. We found that UDCA and RSV, together or separately, protected the liver against oxidative stress damage caused by TAC.
Collapse
Affiliation(s)
- Suleyman Koc
- Department of General Surgery, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
| | - Ahmet Aktas
- Department of İnternal Medicine, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
| | - Bilal Sahin
- Department of Physiology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
| | - Hatice Ozer
- Department of Pathology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
| | - Gozde Erturk Zararsiz
- Department of Biostatistics, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| |
Collapse
|
|
15
|
Zhigacheva IV, Rusina IF, Krikunova NI, Goloschapov AN, Veprintsev TL, Yablonskaya OI, Trofimov AV. Resveratrol and 2-Ethyl-6-Methyl-3-Hydroxypiridine N-Acetyl Cysteinate as Protecting Agents upon the Stress Exposure. Int J Mol Sci 2023; 24:13172. [PMID: 37685984 PMCID: PMC10487494 DOI: 10.3390/ijms241713172] [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: 07/02/2023] [Revised: 08/11/2023] [Accepted: 08/18/2023] [Indexed: 09/10/2023] Open
Abstract
The increased generation of reactive oxygen species (ROS) by mitochondria under stress conditions leads to lipid peroxidation (LPO) as a consequence of the ROS interactions with polyunsaturated fatty acids in the lipid bilayer of cell membranes, causing their damage. It was assumed that chemical preparations that reduce the excessive ROS generation by mitochondria should exhibit protecting properties under oxidative-stress conditions. In this context, the antioxidants resveratrol (RSV) and 2-ethyl-6-methyl-3-hydroxypyridine N-acetylcysteinate (NAC-3-HP) were examined as potential chemical protectors upon the exposure to stress, able to maintain the functional state of mitochondria.
Collapse
Affiliation(s)
- Irina V. Zhigacheva
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Ul. Kosygina 4, Moscow 119334, Russia
| | - Irina F. Rusina
- N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Ul. Kosygina 4, Moscow 119334, Russia
| | - Natalia I. Krikunova
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Ul. Kosygina 4, Moscow 119334, Russia
| | - Aleksandr N. Goloschapov
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Ul. Kosygina 4, Moscow 119334, Russia
| | - Timur L. Veprintsev
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Ul. Kosygina 4, Moscow 119334, Russia
| | - Olga I. Yablonskaya
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Ul. Kosygina 4, Moscow 119334, Russia
| | - Aleksei V. Trofimov
- Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Ul. Kosygina 4, Moscow 119334, Russia
- Moscow Institute of Physics and Technology (National Research University), Institutskii per. 9, Dolgoprudny 141701, Russia
| |
Collapse
|
|
16
|
Jiang Y, Zhang J, Shi C, Li X, Jiang Y, Mao R. NF- κB: a mediator that promotes or inhibits angiogenesis in human diseases? Expert Rev Mol Med 2023; 25:e25. [PMID: 37503730 DOI: 10.1017/erm.2023.20] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]
Abstract
The nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB) signaling pathway, which is conserved in invertebrates, plays a significant role in human diseases such as inflammation-related diseases and carcinogenesis. Angiogenesis refers to the growth of new capillary vessels derived from already existing capillaries and postcapillary venules. Maintaining normal angiogenesis and effective vascular function is a prerequisite for the stability of organ tissue function, and abnormal angiogenesis often leads to a variety of diseases. It has been suggested that NK-κB signalling molecules under pathological conditions play an important role in vascular differentiation, proliferation, apoptosis and tumourigenesis by regulating the transcription of multiple target genes. Many NF-κB inhibitors are being tested in clinical trials for cancer treatment and their effect on angiogenesis is summarised. In this review, we will summarise the role of NF-κB signalling in various neovascular diseases, especially in tumours, and explore whether NF-κB can be used as an attack target or activation medium to inhibit tumour angiogenesis.
Collapse
Affiliation(s)
- Yijing Jiang
- Department of Pathophysiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
| | - Jie Zhang
- Department of Oncology, Affiliated Tumor Hospital of Nantong University, 30Tongyang North Road, Pingchao Town, Nantong 226361, Jiangsu, People's Republic of China
| | - Conglin Shi
- Department of Pathogenic Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
| | - Xingjuan Li
- Department of Pathophysiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
| | - Yongying Jiang
- Department of Pathophysiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
| | - Renfang Mao
- Department of Pathophysiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
| |
Collapse
|
|
17
|
Shafik MS, El-Tanbouly DM, Bishr A, Attia AS. Insights into the role of PHLPP2/Akt/GSK3β/Fyn kinase/Nrf2 trajectory in the reno-protective effect of rosuvastatin against colistin-induced acute kidney injury in rats. J Pharm Pharmacol 2023:7140447. [PMID: 37095069 DOI: 10.1093/jpp/rgad019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 02/22/2023] [Indexed: 04/26/2023]
Abstract
OBJECTIVES Oxidative stress-mediated colistin's nephrotoxicity is associated with the diminished activity of nuclear factor erythroid 2-related factor 2 (Nrf2) that is primarily correlated with cellular PH domain and leucine-rich repeat protein phosphatase (PHLPP2) levels. This study investigated the possible modulation of PHLPP2/protein kinase B (Akt) trajectory as a critical regulator of Nrf2 stability by rosuvastatin (RST) to guard against colistin-induced oxidative renal damage in rats. METHODS Colistin (300,000 IU/kg/day; i.p.) was injected for 6 consecutive days, and rats were treated simultaneously with RST orally at 10 or 20 mg/kg. KEY FINDINGS RST enhanced renal nuclear Nrf2 translocation as revealed by immunohistochemical staining to boost the renal antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH) along with a marked reduction in caspase-3. Accordingly, rats treated with RST showed significant restoration of normal renal function and histological features. On the molecular level, RST effectively decreased the mRNA expression of PHLPP2 to promote Akt phosphorylation. Consequently, it deactivated GSK-3β and reduced the gene expression of Fyn kinase in renal tissues. CONCLUSIONS RST could attenuate colistin-induced oxidative acute kidney injury via its suppressive effect on PHLPP2 to endorse Nrf2 activity through modulating Akt/GSK3 β/Fyn kinase trajectory.
Collapse
Affiliation(s)
- Marihan S Shafik
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Egypt
| | - Dalia M El-Tanbouly
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Abeer Bishr
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Egypt
| | - Amina S Attia
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| |
Collapse
|
|
18
|
Liao J, Lu Q, Li Z, Li J, Zhao Q, Li J. Acetaminophen-induced liver injury: Molecular mechanism and treatments from natural products. Front Pharmacol 2023; 14:1122632. [PMID: 37050900 PMCID: PMC10083499 DOI: 10.3389/fphar.2023.1122632] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 03/13/2023] [Indexed: 03/29/2023] Open
Abstract
Acetaminophen (APAP) is a widely used analgesic and antipyretic over-the-counter medicine worldwide. Hepatotoxicity caused by APAP overdose is one of the leading causes of acute liver failure (ALF) in the US and in some parts of Europe, limiting its clinical application. Excessive APAP metabolism depletes glutathione and increases N-acetyl-p-benzoquinoneimide (NAPQI) levels, leading to oxidative stress, DNA damage, and cell necrosis in the liver, which in turn leads to liver damage. Studies have shown that natural products such as polyphenols, terpenes, anthraquinones, and sulforaphane can activate the hepatocyte antioxidant defense system with Nrf2 as the core player, reduce oxidative stress damage, and protect the liver. As the key enzyme metabolizing APAP into NAPQI, cytochrome P450 enzymes are also considered to be intriguing target for the treatment of APAP-induced liver injury. Here, we systematically review the hepatoprotective activity and molecular mechanisms of the natural products that are found to counteract the hepatotoxicity caused by APAP, providing reference information for future preclinical and clinical trials of such natural products.
Collapse
Affiliation(s)
- Jiaqing Liao
- Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, China
- School of Pharmacy, Chengdu University, Chengdu, China
| | - Qiuxia Lu
- Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, China
- School of Food and Biological Engineering, Chengdu University, Chengdu, China
| | - Zhiqi Li
- Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, China
- School of Food and Biological Engineering, Chengdu University, Chengdu, China
| | - Jintao Li
- Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, China
- School of Pharmacy, Chengdu University, Chengdu, China
| | - Qi Zhao
- Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, China
- School of Food and Biological Engineering, Chengdu University, Chengdu, China
- *Correspondence: Qi Zhao, ; Jian Li,
| | - Jian Li
- Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, China
- School of Basic Medical Sciences, Chengdu University, Chengdu, China
- *Correspondence: Qi Zhao, ; Jian Li,
| |
Collapse
|
|
19
|
Cracco P, Montalesi E, Parente M, Cipolletti M, Iucci G, Battocchio C, Venditti I, Fiocchetti M, Marino M. A Novel Resveratrol-Induced Pathway Increases Neuron-Derived Cell Resilience against Oxidative Stress. Int J Mol Sci 2023; 24:ijms24065903. [PMID: 36982977 PMCID: PMC10058936 DOI: 10.3390/ijms24065903] [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: 01/27/2023] [Revised: 03/16/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
A promising therapeutic strategy to delay and/or prevent the onset of neurodegenerative diseases (NDs) could be to restore neuroprotective pathways physiologically triggered by neurons against stress injury. Recently, we identified the accumulation of neuroglobin (NGB) in neuronal cells, induced by the 17β-estradiol (E2)/estrogen receptor β (ERβ) axis, as a protective response that increases mitochondria functionality and prevents the activation of apoptosis, increasing neuron resilience against oxidative stress. Here, we would verify if resveratrol (Res), an ERβ ligand, could reactivate NGB accumulation and its protective effects against oxidative stress in neuronal-derived cells (i.e., SH-SY5Y cells). Our results demonstrate that ERβ/NGB is a novel pathway triggered by low Res concentrations that lead to rapid and persistent NGB accumulation in the cytosol and in mitochondria, where the protein contributes to reducing the apoptotic death induced by hydrogen peroxide (H2O2). Intriguingly, Res conjugation with gold nanoparticles increases the stilbene efficacy in enhancing neuron resilience against oxidative stress. As a whole, ERβ/NGB axis regulation is a novel mechanism triggered by low concentration of Res to regulate, specifically, the neuronal cell resilience against oxidative stress reducing the triggering of the apoptotic cascade.
Collapse
Affiliation(s)
- Patrizio Cracco
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
| | - Emiliano Montalesi
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
| | - Martina Parente
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
| | - Manuela Cipolletti
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
| | - Giovanna Iucci
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
| | - Chiara Battocchio
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
| | - Iole Venditti
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
- IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, 00179 Rome, Italy
| | - Marco Fiocchetti
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
- IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, 00179 Rome, Italy
| | - Maria Marino
- Department of Science, University Roma Tre, V.le G. Marconi, 446, 00146 Rome, Italy
- IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, 00179 Rome, Italy
| |
Collapse
|
|
20
|
Butterfield DA, Boyd-Kimball D, Reed TT. Cellular Stress Response (Hormesis) in Response to Bioactive Nutraceuticals with Relevance to Alzheimer Disease. Antioxid Redox Signal 2023; 38:643-669. [PMID: 36656673 PMCID: PMC10025851 DOI: 10.1089/ars.2022.0214] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 01/08/2023] [Indexed: 01/20/2023]
Abstract
Significance: Alzheimer's disease (AD) is the most common form of dementia associated with aging. As the large Baby Boomer population ages, risk of developing AD increases significantly, and this portion of the population will increase significantly over the next several decades. Recent Advances: Research suggests that a delay in the age of onset by 5 years can dramatically decrease both the incidence and cost of AD. In this review, the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in AD is examined in the context of heme oxygenase-1 (HO-1) and biliverdin reductase-A (BVR-A) and the beneficial potential of selected bioactive nutraceuticals. Critical Issues: Nrf2, a transcription factor that binds to enhancer sequences in antioxidant response elements (ARE) of DNA, is significantly decreased in AD brain. Downstream targets of Nrf2 include, among other proteins, HO-1. BVR-A is activated when biliverdin is produced. Both HO-1 and BVR-A also are oxidatively or nitrosatively modified in AD brain and in its earlier stage, amnestic mild cognitive impairment (MCI), contributing to the oxidative stress, altered insulin signaling, and cellular damage observed in the pathogenesis and progression of AD. Bioactive nutraceuticals exhibit anti-inflammatory, antioxidant, and neuroprotective properties and are potential topics of future clinical research. Specifically, ferulic acid ethyl ester, sulforaphane, epigallocatechin-3-gallate, and resveratrol target Nrf2 and have shown potential to delay the progression of AD in animal models and in some studies involving MCI patients. Future Directions: Understanding the regulation of Nrf2 and its downstream targets can potentially elucidate therapeutic options for delaying the progression of AD. Antioxid. Redox Signal. 38, 643-669.
Collapse
Affiliation(s)
- D. Allan Butterfield
- Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA
- Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA
| | - Debra Boyd-Kimball
- Department of Biochemistry, Chemistry, and Physics, University of Mount Union, Alliance, Ohio, USA
| | - Tanea T. Reed
- Department of Chemistry, Eastern Kentucky University, Richmond, Kentucky, USA
| |
Collapse
|
|
21
|
Wang YX, Dai W, Li YZ, Wu ZY, Kan YQ, Zeng HC, He QZ. Bisphenol S induces oxidative stress-mediated impairment of testosterone synthesis by inhibiting the Nrf2/HO-1 signaling pathway. J Biochem Mol Toxicol 2023; 37:e23273. [PMID: 36541330 DOI: 10.1002/jbt.23273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 09/01/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022]
Abstract
Bisphenol S (BPS) is an environmental endocrine disruptor widely used in industrial production. BPS induces oxidative stress and exhibits male reproductive toxicity in mice, but the mechanisms by which BPS impairs steroid hormone synthesis are not fully understood. Nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 signaling is a key pathway in improving cellular antioxidant defense capacities. Therefore, this study explored the effects of exposure to BPS on testosterone synthesis in adult male mice and its mechanisms with regard to the Nrf2/HO-1 signaling pathway. Adult male C57BL/6 mice were orally exposed to BPS (2, 20, and 200 mg/kg BW) with sesame oil as a vehicle (0.1 ml/10 g BW) per day for 28 consecutive days. The results showed that compared with the control group, serum testosterone levels were substantially reduced in the 20 and 200 mg/kg BPS treatment groups, and testicular testosterone levels were reduced in all BPS treatment groups. These changes were accompanied by a prominent decrease in the expression levels of testosterone synthesis-related enzymes (STAR, CYP11A1, CYP17A1, HSD3B1, and HSD17B3) in the mouse testis. In addition, BPS induced oxidative stress in the testis by upregulating the messenger RNA and protein levels of Keap1 and downregulating the levels of Nrf2, HO-1, and downstream antioxidant enzymes (CAT, SOD1, and Gpx4). In summary, our results indicate that exposure of adult male mice to BPS can inhibit Nrf2/HO-1 signaling and antioxidant enzyme activity, which induces oxidative stress and thereby may impair testosterone synthesis in testicular tissues, leading to reproductive damage.
Collapse
Affiliation(s)
- Yu-Xiao Wang
- Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, People's Republic of China
| | - Wei Dai
- Yuecheng District Centers for Disease Control and Prevention, Shaoxing, Zhejiang, People's Republic of China
| | - Yi-Zhou Li
- Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, People's Republic of China
| | - Zi-Yao Wu
- Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, People's Republic of China
| | - Ya-Qi Kan
- Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, People's Republic of China
| | - Huai-Cai Zeng
- Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, People's Republic of China.,Department of Occupational and Environmental Health, Guilin Medical University, Guilin, People's Republic of China
| | - Qing-Zhi He
- School of Biotechnology, Guilin Medical University, Guilin, People's Republic of China
| |
Collapse
|
|
22
|
Protective effects of lignin fractions obtained from grape seeds against bisphenol AF neurotoxicity via antioxidative effects mediated by the Nrf2 pathway. Front Chem Sci Eng 2023. [DOI: 10.1007/s11705-022-2237-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
|
|
23
|
Quercetin and resveratrol inhibit ferroptosis independently of Nrf2-ARE activation in mouse hippocampal HT22 cells. Food Chem Toxicol 2023; 172:113586. [PMID: 36584933 DOI: 10.1016/j.fct.2022.113586] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/10/2022] [Accepted: 12/22/2022] [Indexed: 12/29/2022]
Abstract
Oxidative stress is the central pathomechanism in multiple cell death pathways, including ferroptosis, a form of iron-dependent programmed cell death. Various phytochemicals, which include the inducers of the nuclear factor erythroid-2-related factor 2-antioxidant response element (Nrf2-ARE) transcription pathway, prevent ferroptosis. We recently reported that several compounds, such as the potent Nrf2-ARE inducer curcumin, protect mouse hippocampus-derived HT22 cells against ferroptosis independently of Nrf2-ARE activity. The present study characterized the anti-ferroptotic mechanisms of two additional Nrf2-ARE inducers, quercetin and resveratrol. Both compounds prevented erastin- and RSL3-induced ferroptosis of wild-type HT22 cells, and also blocked the exacerbated erastin- and RSL3-induced ferroptosis of Nrf2-knockdown HT22 cells. In both HT22 cells, quercetin and resveratrol blocked erastin- and RSL3-induced elevation in reactive oxygen species. These results suggest that the Nrf2-ARE pathway does protect against ferroptosis, but quercetin and resveratrol act by reducing oxidative stress independently of Nrf2-ARE induction. Quercetin and resveratrol also reduced Fe2+ concentrations in HT22 cells and in cell-free reactions. Thus, quercetin and resveratrol likely protect against erastin- and RSL3-induced ferroptosis by inhibiting the iron-catalyzed generation of hydroxyl radicals. Unlike quercetin, resveratrol cannot form a chelate structure with Fe2+ but the density functional theory computation demonstrates that resveratrol can form stable monodentate complexes with the alkene moiety and the electron-rich A ring.
Collapse
|
|
24
|
Moghadam D, Zarei R, Vakili S, Ghojoghi R, Zarezade V, Veisi A, Sabaghan M, Azadbakht O, Behrouj H. The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress. Mol Biol Rep 2023; 50:77-84. [PMID: 36307623 DOI: 10.1007/s11033-022-08031-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 10/12/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND There is evidence that low doses or physiological concentrations of certain natural polyphenols enhance the activity of telomerase. However, the precise mechanism by which natural polyphenols regulate telomerase activity remains unclear. Recent research indicates that NF-E2 related factor 2 (Nrf2) and silent information regulator 1 (SIRT1) are involved in human telomerase reverse transcriptase (hTERT) regulation. Thus, in order to better comprehend the mechanism by which polyphenols regulate hTERT, the present study investigated the effects of the natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on hTERT, Nrf2, and SIRT1 expression as well as oxidative stress in HepG2 hepatocellular carcinoma. METHODS The trypan blue dye exclusion assay was used to assess cell viability. The level of mRNA for hTERT, Nrf2, and SIRT1 was then determined using real-time PCR. A spectrophotometric analysis was conducted to quantify oxidative stress markers. RESULTS The results demonstrated that Resveratrol induces the expression of hTERT and the SIRT1/Nrf2 pathway in a dose-dependent manner. Gallic acid at concentrations of 10 and 20 μM also increased the expression of the hTERT and SIRT1/Nrf2 pathway. Furthermore, dose-dependent overexpression of hTERT and Nrf2 was induced by Kuromanin chloride at 10 and 20 µM. Moreover, we found that Resveratrol and Kuromanin chloride ameliorated oxidative stress, whereas Gallic acid exacerbated it. CONCLUSIONS This study demonstrates that low doses of polyphenols (Resveratrol, Gallic acid, and Kuromanin chloride) upregulate the expression of the hTERT gene in the HepG2 hepatocellular carcinoma cell line, possibly via induction of the SIRT1/Nrf2 signaling pathway. Therefore, by targeting this pathway or hTERT, the anti-cancer effect of polyphenols can be enhanced.
Collapse
Affiliation(s)
- Delaram Moghadam
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Zarei
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sina Vakili
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Rozita Ghojoghi
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Vahid Zarezade
- Behbahan Faculty of Medical Sciences, Behbahan, Iran.,Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Veisi
- Behbahan Faculty of Medical Sciences, Behbahan, Iran
| | | | | | - Hamid Behrouj
- Behbahan Faculty of Medical Sciences, Behbahan, Iran.
| |
Collapse
|
|
25
|
Poudel S, Martins G, Cancela ML, Gavaia PJ. Resveratrol-Mediated Reversal of Doxorubicin-Induced Osteoclast Differentiation. Int J Mol Sci 2022; 23:ijms232315160. [PMID: 36499492 PMCID: PMC9738652 DOI: 10.3390/ijms232315160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/16/2022] [Accepted: 11/29/2022] [Indexed: 12/05/2022] Open
Abstract
Secondary osteoporosis has been associated with cancer patients undertaking Doxorubicin (DOX) chemotherapy. However, the molecular mechanisms behind DOX-induced bone loss have not been elucidated. Molecules that can protect against the adverse effects of DOX are still a challenge in chemotherapeutic treatments. We investigated the effect and mechanism of DOX in osteoclast differentiation and used the Sirt 1 activator resveratrol (RES) to counteract DOX-induced effects. RAW 264.7 cells were differentiated into osteoclasts under cotreatment with DOX and RES, alone or combined. RES treatment inhibited DOX-induced osteoclast differentiation, reduced the expression of osteoclast fusion marker Oc-stamp and osteoclast differentiation markers Rank, Trap, Ctsk and Nfatc1. Conversely, RES induced the upregulation of antioxidant genes Sod 1 and Nrf 2 while DOX significantly reduced the FoxM1 expression, resulting in oxidative stress. Treatment with the antioxidant MitoTEMPO did not influence DOX-induced osteoclast differentiation. DOX-induced osteoclastogenesis was studied using the cathepsin-K zebrafish reporter line (Tg[ctsk:DsRed]). DOX significantly increased ctsk signal, while RES cotreatment resulted in a significant reduction in ctsk positive cells. RES significantly rescued DOX-induced mucositis in this model. Additionally, DOX-exposed zebrafish displayed altered locomotor behavior and locomotory patterns, while RES significantly reversed these effects. Our research shows that RES prevents DOX-induced osteoclast fusion and activation in vitro and in vivo and reduces DOX-induced mucositis, while improving locomotion parameters.
Collapse
Affiliation(s)
- Sunil Poudel
- Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal
- Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139 Faro, Portugal
- PhD Program in Biomedical Sciences, FMCB, University of Algarve, 8005-139 Faro, Portugal
| | - Gil Martins
- Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal
- Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139 Faro, Portugal
- PhD Program in Biomedical Sciences, FMCB, University of Algarve, 8005-139 Faro, Portugal
| | - M. Leonor Cancela
- Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal
- Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139 Faro, Portugal
- Algarve Biomedical Center, University of Algarve, 8005-139 Faro, Portugal
| | - Paulo J. Gavaia
- Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal
- Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139 Faro, Portugal
- Correspondence: ; Tel.: +351-289-800057 or +351-289-800900 (ext. 7057)
| |
Collapse
|
|
26
|
Ávila C, Vinay JI, Arese M, Saso L, Rodrigo R. Antioxidant Intervention against Male Infertility: Time to Design Novel Strategies. Biomedicines 2022; 10:biomedicines10123058. [PMID: 36551814 PMCID: PMC9775742 DOI: 10.3390/biomedicines10123058] [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: 09/30/2022] [Revised: 11/21/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Infertility is a highly prevalent condition, affecting 9-20% of couples worldwide. Among the identifiable causes, the male factor stands out in about half of infertile couples, representing a growing problem. Accordingly, there has been a decline in both global fertility rates and sperm counts in recent years. Remarkably, nearly 80% of cases of male infertility (MI) have no clinically identifiable aetiology. Among the mechanisms likely plausible to account for idiopathic cases, oxidative stress (OS) has currently been increasingly recognized as a key factor in MI, through phenomena such as mitochondrial dysfunction, lipid peroxidation, DNA damage and fragmentation and finally, sperm apoptosis. In addition, elevated reactive oxygen species (ROS) levels in semen are associated with worse reproductive outcomes. However, despite an increasing understanding on the role of OS in the pathophysiology of MI, therapeutic interventions based on antioxidants have not yet provided a consistent benefit for MI, and there is currently no clear consensus on the optimal antioxidant constituents or regimen. Therefore, there is currently no applicable antioxidant treatment against this problem. This review presents an approach aimed at designing an antioxidant strategy based on the particular biological properties of sperm and their relationships with OS.
Collapse
Affiliation(s)
- Cristóbal Ávila
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380000, Chile
| | - José Ignacio Vinay
- Urology Department, University of Chile Clinical Hospital, Santiago 8380000, Chile
- Andrology Unit, Shady Grove Fertility, Santiago 7650672, Chile
| | - Marzia Arese
- Department of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, 00185 Rome, Italy
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer”, Faculty of Pharmacy and Medicine, Sapienza University, 00185 Rome, Italy
| | - Ramón Rodrigo
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380000, Chile
- Correspondence: ; Tel.: +56-229-786-126
| |
Collapse
|
|
27
|
Tang J, Zhang Z, Miao J, Tian Y, Pan L. Effects of benzo[a]pyrene exposure on oxidative stress and apoptosis of gill cells of Chlamys farreri in vitro. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2022; 93:103867. [PMID: 35483583 DOI: 10.1016/j.etap.2022.103867] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 03/30/2022] [Accepted: 04/21/2022] [Indexed: 06/14/2023]
Abstract
As a common pollutant in marine environment, benzo[a]pyrene (B[a]P) has high toxicity to economic shellfish. In order to explore the mechanism of oxidative stress and apoptosis, the effects of 0, 2, 4, 8 μg/mL B[a]P on gill cells of C. farreri at 12 and 24 h were studied. The results showed that B[a]P decreased the activity of gill cells, increased the content of reactive oxygen species (ROS) and the expression of antioxidant defense genes. Besides, B[a]P could induce oxidative damage to nucleus and mitochondria. The gene expression and enzyme activity of apoptosis pathway related factors were changed. In conclusion, these results showed that B[a]P could cause oxidative stress and oxidative damage in gill cells of C. farreri, and mediate gill cell apoptosis through mitochondrial pathway and death receptor pathway. This article provides a theoretical basis for clarifying the molecular mechanism of PAHs-included oxidative stress and apoptosis in bivalves.
Collapse
Affiliation(s)
- Jian Tang
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China
| | - Zixian Zhang
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China
| | - Jingjing Miao
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China
| | - Yimeng Tian
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China
| | - Luqing Pan
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China.
| |
Collapse
|
|
28
|
Shamarao N, Chethankumar M. Antiobesity drug-likeness properties and pancreatic lipase inhibition of a novel low molecular weight lutein oxidized product, LOP6. Food Funct 2022; 13:6036-6055. [PMID: 35615990 DOI: 10.1039/d1fo04064b] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Elevated expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), a key regulator of adipogenesis, leads to lipid accumulation and obesity. Although orlistat is effective for obesity, flatus with discharge, faecal urgency, oily evacuation and other allied side effects limit its usage. Thus, natural product-based drug intervention is the future of research and development of novel treatment. We synthesized and characterized total lutein oxidized products (LOPs) by exposing lutein to direct sunlight with a solar intensity of 5.89 kW h m-2 day-1 and at 31 ± 2 °C for 1-10 days. Total LOPs were analyzed on C18 and structural elucidation was carried on LCMS/MS-TOF. The pancreatic lipase inhibition kinetics was estimated. The binding effects of LOP6 (fragmented peak 6) on PPAR-γ, pancreatic lipase, pharmacokinetic properties and inhibition studies were analysed. Histological evaluation of liver and adipose tissues was performed to confirm the antiobesity effect of total LOPs. The yield of extracted lutein purified from shade-dried marigold flower petals was 6%. Total LOPs were formed on the 10th day upon exposure of lutein to direct sunlight. Total LOPs on the C18 column fragmented into eight oxidized products (LOP1 to LOP8). The total LOPs showed significant inhibition of pancreatic lipase activity with an IC50 of 1.6953 μg ml-1, and Km and Vmax of 3.05 μg and 1.19 μg s-1 respectively following mixed type of inhibition. The LOP6 [4-((1E,3E,5E)-3,7-dimethylocta-1,3,5,7-tetraen-1-yl)-3,5,5-trimethylcyclohex-3-enol] with an approximate molecular mass of 274.25 showed a binding energy of -5.40 kcal mol-1 with a Ki of 109.43 μM for PPAR-γ and a docking score of -5.35 kcal mol-1 with a Ki of 119.4 μM for pancreatic lipase. The IC50 of LOP6 was 11.8420 μg ml-1, and Km and Vmax were 2.519 μg and 1.294 μg s-1. The pharmacokinetic properties such as solubility, permeability, bioavailability, and topological polar surface area when tested with LOP6 were significantly better than those of lutein alone. The histological examination of the liver and adipose tissue revealed that all three doses of total LOPs were effective in alleviating the ballooning and vesicular degeneration of hepatocytes and invasion of inflammatory cells in the adipose tissue. Total LOPs and LOP6 inhibited pancreatic lipase activity in vitro. LOP6 showed a better docking score for PPAR-γ and pancreatic lipase in comparison to orlistat. Histological data showed that the total LOPs exerted antiobesity activity. Thus, LOPs might provide a novel treatment approach for obesity.
Collapse
Affiliation(s)
- Nagashree Shamarao
- Research Scholar, JSS Research Foundation, SJCE Technical Institutions Campus, Mysuru-570006, Karnataka, India
| | - Mukunda Chethankumar
- Postgraduate Department of Biochemistry, JSS College of Arts Commerce and Science (Autonomous), Ooty Road, Mysuru-570025, Karnataka, India.
| |
Collapse
|
|
29
|
Vejarano R, Luján-Corro M. Red Wine and Health: Approaches to Improve the Phenolic Content During Winemaking. Front Nutr 2022; 9:890066. [PMID: 35694174 PMCID: PMC9174943 DOI: 10.3389/fnut.2022.890066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 05/05/2022] [Indexed: 12/25/2022] Open
Abstract
There is ample evidence regarding the health benefits of red wine consumption due to its content of phenolic compounds, as an alternative to improve the state of health and prevent various diseases, being the implementation of procedures that allow a greater extraction and stability of phenolic compounds during the elaboration a key aspect. The first part of this review summarizes some studies, mostly at the preclinical level, on the mechanisms by which phenolic compounds act in the human organism, taking advantage of their antioxidant, anti-inflammatory, antitumor, antithrombotic, antiatherogenic, antimicrobial, antiviral, and other activities. Although the migration of grape components into the must/wine occurs during the winemaking process, the application of new technologies may contribute to increasing the content of phenolic compounds in the finished wine. Some of these technologies have been evaluated on an industrial scale, and in some cases, they have been included in the International Code of Oenological Practice by the International Organization of Vine and Wine (OIV). In this sense, the second part of this review deals with the use of these novel technologies that can increase, or at least maintain, the polyphenol content. For example, in the pre-fermentative stage, phenolic extraction can be increased by treating the berries or must with high pressures, pulsed electric fields (PEF), ultrasound (US), e-beam radiation or ozone. At fermentative level, yeasts with high production of pyranoanthocyanins and/or their precursor molecules, low polyphenol absorption, and low anthocyanin-β-glucosidase activity can be used. Whereas, at the post-fermentative level, aging-on-lees (AOL) can contribute to maintaining polyphenol levels, and therefore transmitting health benefits to the consumer.
Collapse
Affiliation(s)
- Ricardo Vejarano
- Department of Research, Innovation and Social Responsibility, Universidad Privada del Norte (UPN), Trujillo, Peru
| | - Mariano Luján-Corro
- School of Agroindustrial Engineering, Universidad Nacional de Trujillo (UNT), Trujillo, Peru
| |
Collapse
|
|
30
|
Zhou Q, Zhang N, Hu T, Xu H, Duan X, Liu B, Chen F, Wang M. Dietary phenolic-type Nrf2-activators: implications in the control of toxin-induced hepatic disorders. Food Funct 2022; 13:5480-5497. [PMID: 35411358 DOI: 10.1039/d1fo04237h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Numerous studies have exemplified the importance of nuclear factor erythroid 2-related factor 2 (Nrf2) activation in the alleviation of toxin-induced hepatic disorders primarily through eliminating oxidative stress. Whereafter, increasingly more efforts have been contributed to finding Nrf2-activators, especially from dietary polyphenols. The present review summarized the phenolic-type Nrf2-activators published in the past few decades, analyzed their effectiveness based on their structural characteristics and outlined their related mechanisms. It turns out that flavonoids are the largest group of phenolic-type Nrf2-activators, followed by nonflavonoids and phenolic acids. When counting on subgroups, the top three types are flavonols, flavones, and hydroxycinnamic acids, with curcuminoids having the highest effective doses. Moreover, most polyphenols work through the phosphorylation of Nrf2. Besides, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) are the frequent targets of these Nrf2-activators, which indirectly mediate the behavior of Nrf2. However, current data are not sufficient to conclude any structure-activity relationship.
Collapse
Affiliation(s)
- Qian Zhou
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Nana Zhang
- School of Biological Sciences, The University of Hong Kong, Hong Kong, China
| | - Tingyan Hu
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Hui Xu
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Xinxing Duan
- Schlegel Research Institute for Aging & Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, Canada
| | - Bin Liu
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Feng Chen
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| | - Mingfu Wang
- Institute for Advanced Study, Shenzhen University, Shenzhen, China. .,Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
| |
Collapse
|
|
31
|
Greifová H, Jambor T, Tokárová K, Knížatová N, Lukáč N. In Vitro Effect of Resveratrol Supplementation on Oxidative Balance and Intercellular Communication of Leydig Cells Subjected to Induced Oxidative Stress. Folia Biol (Praha) 2022. [DOI: 10.3409/fb_70-1.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Many studies have revealed that oxidative stress is a primary factor in the pathogenesis of male reproductive system dysfunctions. The strong antioxidant and cytoprotective effects of resveratrol have previously been demonstrated, but its effect in the context of the male reproduction
remains unconvincing. To observe the biological activity of resveratrol in protecting the male reproductive function, hydrogen peroxide-induced oxidative stress in Leydig cells was used as a cell model. The aim of the present study was to examine if resveratrol could induce changes in the
gap junction intercellular communication (GJIC), nitric oxide production, total oxidant status (TOS) and total antioxidant capacity (TAC) in TM3 Leydig cells subjected to H2O2. The Leydig cells were exposed to a resveratrol treatment (5, 10, 20, 50 and 100 μM) in the
presence or absence of H2O2 (300/600 μM) during a 24 h in vitro culture. The cell lysates to assess TOS and TAC, NO production were quantified in a culture medium using the Griess method, and the Scrape Loading/Dye Transfer (SL/DT) technique was used for the
determination of GJIC in the exposed TM3 Leydig cells. Treatment with higher doses of resveratrol alone led to a significantly increased TOS (p<0.05 with 100 μM) and NO production (p<0.05 with 50 μM and 100 μM), but significantly reduced TAC (p<0.01 with 100 μM) and GJIC
(p<0.05 with 100 μM), while the SL/DT evaluation in the cells exposed to resveratrol at concentrations 5 μM (p<0.05) and 10 μM (p<0.01) revealed a significant stimulation of GJIC. The most potent cytoprotective or stimulatory effect of resveratrol in the cells co-exposed
to oxidative stress (300 μM H2O2) was observed at a concentration of 10 μM in the case of GJIC, which was manifested by a significant increase in the values (p<0.05) compared to the control group treated with H2O2 alone.
Collapse
Affiliation(s)
- Hana Greifová
- Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
| | - Tomáš Jambor
- BioFood Centre, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
| | - Katarína Tokárová
- Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
| | - Nikola Knížatová
- Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
| | - Norbert Lukáč
- Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
| |
Collapse
|
|
32
|
Wang S, Wu H, Zhu Y, Cui H, Yang J, Lu M, Cheng H, Gu L, Xu T, Xu L. Effect of Lycopene on the Growth Performance, Antioxidant Enzyme Activity, and Expression of Gene in the Keap1-Nrf2 Signaling Pathway of Arbor Acres Broilers. Front Vet Sci 2022; 9:833346. [PMID: 35359683 PMCID: PMC8964064 DOI: 10.3389/fvets.2022.833346] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 01/31/2022] [Indexed: 12/12/2022] Open
Abstract
The objective of this study was to determine the effect of dietary lycopene supplementation on the growth performance, antioxidant enzyme activity of serum and liver, and gene expressions associated with Kelch-like ech-associated protein-1 (Keap1)/Nuclear Factor E2-related factor 2 (Nrf2) pathway in liver of Arbor Acres broilers. A total of 288 1-day-old male broilers were randomly divided into 4 treatments with 6 replicates and 12 chickens for each replicate. The control group was fed with the basal diet, while the treated groups were fed with the basal diet with 10, 20, and 30 mg/kg lycopene in powder. Feed and water were provided ad libitum for 42 days. Compared with the control group, (a) the average daily gain increased (p = 0.002 vs. p = 0.001) and the feed conversion ratio decreased (p = 0.017 vs. p = 0.023) in groups treated with lycopene in the grower and whole phases, and the average daily feed intake was quadratically affected (p = 0.043) by lycopene in the grower phase; (b) the serum superoxide dismutase content was linearly affected (p = 0.035) by lycopene at 21 days; (c) the serum glutathione peroxidase content, superoxide dismutase content, and total antioxidant capability were higher (p = 0.014, p = 0.003, and p = 0.016, respectively) in the 30 mg/kg lycopene group at 42 days; (d) the liver glutathione peroxidase and superoxide dismutase contents in groups treated with lycopene were higher (p ≤ 0.001 vs. p ≤ 0.001) at 21 days; (e) the liver glutathione peroxidase content was higher (p ≤ 0.001) in the 20 and 30 mg/kg lycopene groups, at 42 days; (f) the mRNA expression levels of Nrf2, superoxide dismutase 2, NAD(P)H quinone dehydrogenase 1, and heme oxygenase 1 genes were higher (21 days: p = 0.042, p = 0.021, p = 0.035, and p = 0.043, respectively; 42 days: p = 0.038, p = 0.025, p = 0.034, and p = 0.043, respectively) in the 20 and 30 mg/kg lycopene groups at 21 and 42 days. The 30 mg/kg lycopene concentration improved the growth performance, antioxidant enzyme activity in serum and liver, and gene expression in the Keap1-Nrf2 signaling pathway of Arbor Acres broilers.
Collapse
Affiliation(s)
- Sibo Wang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Hongzhi Wu
- Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou, China
| | - Yunhui Zhu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Hongxia Cui
- Inner Mongolia Ordos City Agricultural and Forestry Technology Extension Center, Ordos, China
| | - Ji Yang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Mingyuan Lu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Huangzuo Cheng
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Lihong Gu
- Institute of Animal Science & Veterinary, Hainan Academy of Agricultural Science, Haikou, China
| | - Tieshan Xu
- Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou, China
| | - Li Xu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
- *Correspondence: Li Xu
| |
Collapse
|
|
33
|
Chakkittukandiyil A, Sajini DV, Karuppaiah A, Selvaraj D. The principal molecular mechanisms behind the activation of Keap1/Nrf2/ARE pathway leading to neuroprotective action in Parkinson's disease. Neurochem Int 2022; 156:105325. [PMID: 35278519 DOI: 10.1016/j.neuint.2022.105325] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 03/03/2022] [Accepted: 03/06/2022] [Indexed: 02/07/2023]
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder. PD is associated with the loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. Present therapies for PD provide only symptomatic relief by restoring the dopamine (DA) level. However, they are not disease modifying agents and so they do not delay the disease progression. Alpha-synuclein aggregation, oxidative stress, mitochondrial dysfunction and chronic inflammation are considered to be the major pathological mechanisms mediating neurodegeneration in PD. To resist oxidative stress, the human body has an antioxidant defence mechanism consisting of many antioxidants and cytoprotective genes. The expression of those genes are largely controlled by the Kelch-like ECH-associated protein 1/Nuclear factor - erythroid - 2 - related factor 2/Antioxidant response element (Keap1/Nrf2/ARE) signalling pathway. The transcription factor Nrf2 is activated in response to oxidative or electrophilic stress and protects the cells from oxidative stress and inflammation. Nrf2 has been widely considered as a therapeutic target for neurodegeneration and several drugs are now being tested in clinical trials. Regulation of the Keap1/Nrf2/ARE pathway by small molecules which can act as Nrf2 activators could be effective for treating oxidative stress and neuroinflammation in PD. In this review, we had discussed the principal molecular mechanisms behind the neuroprotective effects of Keap1/Nrf2/ARE pathway in PD. Additionally, we also discussed the small molecules and phytochemicals that could activate the Nrf2 mediated anti-oxidant pathway for neuroprotection in PD.
Collapse
Affiliation(s)
- Amritha Chakkittukandiyil
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
| | - Deepak Vasudevan Sajini
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
| | - Arjunan Karuppaiah
- Department of Pharmaceutics, PSG College of Pharmacy, Peelamedu, Coimbatore, Tamil Nadu, India
| | - Divakar Selvaraj
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.
| |
Collapse
|
|
34
|
Zhang X, Wang S, Wu Y, Liu X, Wang J, Han D. Ellagic Acid Alleviates Diquat-Induced Jejunum Oxidative Stress in C57BL/6 Mice through Activating Nrf2 Mediated Signaling Pathway. Nutrients 2022; 14:1103. [PMID: 35268077 PMCID: PMC8912502 DOI: 10.3390/nu14051103] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/25/2022] [Accepted: 03/03/2022] [Indexed: 02/04/2023] Open
Abstract
Ellagic acid (EA) is the main constituent found in pomegranate rind, which has anti-inflammatory and antioxidant effects. However, whether EA can alleviate diquat-induced oxidative stress is still unknown. Here, the effects and mechanisms of EA on jejunum oxidative stress induced by diquat was investigated. Oxidative stress was induced in mice by administrating diquat (25 mg/kg body weight) followed by treatment with 100 mg/kg body weight EA for 5 days. Results showed that oral administration of EA significantly ameliorated diquat-induced weight loss and oxidative stress (p < 0.05) evidenced by reduced ROS production in the jejunum. Furthermore, EA up-regulated the mRNA expression of the antioxidant enzymes (Nrf2, GPX1 and HO-1) when mice were challenged with diquat, compared with the diquat group (p < 0.05). Importantly, pharmacological inhibition of Nrf2 by ML385 counteracted the EA-mediated alleviation of jejunum oxidative stress, as evidence by body weight and ROS production. Also, immunohistochemistry staining confirmed the markedly decreased jejunal Nrf2 expression. The up-regulated effect on NQO1 and HO-1 mRNA expression induced by EA was diminished in mice treated with ML385 (p < 0.05). Together, our results demonstrated that therapeutic and preventative EA treatment was effective in reducing weight loss and oxidative stress induced by diquat through the Nrf2 mediated signaling pathway.
Collapse
Affiliation(s)
| | | | | | | | | | - Dandan Han
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (X.Z.); (S.W.); (Y.W.); (X.L.); (J.W.)
| |
Collapse
|
|
35
|
Navarro-Orcajada S, Conesa I, Vidal-Sánchez FJ, Matencio A, Albaladejo-Maricó L, García-Carmona F, López-Nicolás JM. Stilbenes: Characterization, bioactivity, encapsulation and structural modifications. A review of their current limitations and promising approaches. Crit Rev Food Sci Nutr 2022; 63:7269-7287. [PMID: 35234546 DOI: 10.1080/10408398.2022.2045558] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Stilbenes are phenolic compounds naturally synthesized as secondary metabolites by the shikimate pathway in plants. Research on them has increased in recent years due to their therapeutic potential as antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective and anti-obesity agents. Amongst them, resveratrol has attracted the most attention, although there are other natural and synthesized stilbenes with enhanced properties. However, stilbenes have some physicochemical and pharmacokinetic problems that need to be overcome before considering their applications. Human clinical evidence of their bioactivity is still controversial due to this fact and hence, exhaustive basis science on stilbenes is needed before applied science. This review gathers the main physicochemical and biological properties of natural stilbenes, establishes structure-activity relationships among them, emphasizing the current problems that limit their applications and presenting some promising approaches to overcome these issues: the encapsulation in different agents and the structural modification to obtain novel stilbenes with better features. The bioactivity of stilbenes should move from promising to evident.
Collapse
Affiliation(s)
- Silvia Navarro-Orcajada
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | - Irene Conesa
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | - Francisco José Vidal-Sánchez
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | | | - Lorena Albaladejo-Maricó
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | - Francisco García-Carmona
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | - José Manuel López-Nicolás
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| |
Collapse
|
|
36
|
Abu Zeid IM, Al-Asmari KM, Altayb HN, Al-Attar AM, Qahl SH, Alomar MY. Predominance of Antioxidants in Some Edible Plant Oils in Ameliorating Oxidative Stress and Testicular Toxicity Induced by Malathion. Life (Basel) 2022; 12:life12030350. [PMID: 35330101 PMCID: PMC8948629 DOI: 10.3390/life12030350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 02/21/2022] [Accepted: 02/25/2022] [Indexed: 11/16/2022] Open
Abstract
Malathion (MAL) is an insecticide that has been linked to reproductive system damage in both humans and animals. In the present investigation, the antitoxic effects of coffee and olive oils on MAL-induced testicular dysfunctions were evaluated. MAL-intoxicated rats were supplemented with coffee and olive oils (400 mg/kg) for 7 weeks. Exposure to MAL resulted in statistically altered antioxidant enzymes and histopathological findings of necrotic seminiferous tubules and spermatogenetic arrest in rats after seven weeks of treatment. The effects of MAL intoxication on physiological and histopathological changes were improved by the use of these oils. Murine double minute 2 (MDM2) was found to interact well with chlorogenic acid and oleuropein, two compounds from coffee and olive oils, respectively. Coffee oil and olive oil were found to be promising therapeutic agents for MAL-induced testicular toxicity and oxidative damage.
Collapse
Affiliation(s)
- Isam M. Abu Zeid
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; (I.M.A.Z.); (A.M.A.-A.); (M.Y.A.)
- Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in Biotechnology, King Abdulaziz University, P.O. Box 80200, Jeddah 21589, Saudi Arabia
| | - Khalid M. Al-Asmari
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; (I.M.A.Z.); (A.M.A.-A.); (M.Y.A.)
- Correspondence:
| | - Hisham N. Altayb
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Building A 90, Jeddah 21589, Saudi Arabia;
| | - Atef M. Al-Attar
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; (I.M.A.Z.); (A.M.A.-A.); (M.Y.A.)
- Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in Biotechnology, King Abdulaziz University, P.O. Box 80200, Jeddah 21589, Saudi Arabia
| | - Safa H. Qahl
- Department of Biology, College of Sciences, University of Jeddah, Jeddah 21959, Saudi Arabia;
| | - Mohammed Y. Alomar
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; (I.M.A.Z.); (A.M.A.-A.); (M.Y.A.)
| |
Collapse
|
|
37
|
Bakry OA, Sobhy S, Essam El Deen M, Seleit I. Serum Nuclear Factor E-2 Related Factor 2 in Female Pattern Hair Loss. J Cosmet Dermatol 2022; 21:4882-4887. [PMID: 35201659 DOI: 10.1111/jocd.14878] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 02/10/2022] [Accepted: 02/21/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Female pattern hair loss (FPHL) is a common dermatological complaint with multifactorial etiology. Nuclear factor erythroid-2-related factor 2 (NRF2) is a transcription factor that has a major role in protection from ROS-induced apoptosis. AIM to investigate the relationship between Nrf2 and systemic oxidative stress in FPHL patients. PATIENTS AND METHODS This case-control study included 30 patients with FPHL and 30 age- and sex-matched healthy volunteers as a control group. Serum NRF2, total antioxidant capacity (TAC), and total oxidant capacity (TOC) were measured by ELISA and oxidative stress index (OSI) was calculated. RESULTS The serum level of TOC and OSI were found to be significantly higher (P ≤ 0.001 for both) while serum level of NRF2 and TAC were found to be significantly lower in cases than controls (P <0.001 for both). There was a significant negative correlation between TAC and BMI (P = 0.03, r= -0.391 ) and a significant positive correlation between OSI and BMI (P= 0.04, r= 0.365). There was a significant positive correlation between serum level of NRF2 and TAC (P = 0.003, r= 0.532) and a significant negative correlation between serum the level of NRF2 and TOC (P= 0.02, r= -0.418) and OSI (P= 0.003, r= -0.395). CONCLUSION Systemic oxidative stress in FPHL may be, at least in part, due to NRF2 deficiency. NRF2 activators may help in treatment of this disease. NRF2 deficiency has no role in disease severity. Healthy diet and body weight reduction may help in improving oxidative stress and subsequently improving FPHL.
Collapse
Affiliation(s)
- O A Bakry
- Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufiya University, Egypt
| | - S Sobhy
- Department of Biochemistry and Molecular Biology, Menoufiya University, Egypt
| | - M Essam El Deen
- Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufiya University, Egypt
| | - I Seleit
- Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufiya University, Egypt
| |
Collapse
|
|
38
|
Jiang Z, Zhang M, Liu K, Xue Y, Li X, Dong C. Phylogeny of the HO family in cyprinus carpio and the response of the HO-1 gene to adding Bacillus coagulans in feed under Cd 2+ stress. FISH PHYSIOLOGY AND BIOCHEMISTRY 2022; 48:117-131. [PMID: 35006528 DOI: 10.1007/s10695-021-01041-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 12/10/2021] [Indexed: 06/14/2023]
Abstract
The heavy metal cadmium (Cd2+) is an environmental pollutant that poses serious health hazards. Due to the increasing contamination of aquatic systems with Cd2+, the increased accumulation of Cd2+ in fish has become a food safety and public health concern. Heme oxygenase (HO) is an important antioxidant enzyme that plays a key role in defending the body against oxidative damage, but little research has been done in common carp. In this study, 6 HO genes were identified in the common carp genome database. Comparative genomics analysis showed considerable expansion of the HO genes and verified the four-round whole genome duplication (WGD) event in common carp. Phylogenetic analysis revealed that all HO genes of common carp were clustered into orthologous groups, indicating high conservation during evolution. In addition, the tissue distribution results showed that most HO genes had extensive tissue distribution and showed tissue-specific expression patterns. Exposure to 0.5 mg/L Cd2+ significantly reduced the expression of TGF-β and IL-10 in common carp, which may indicate that Cd2+ exposure can destroy the physical barrier function of the intestine, inhibit intestinal immune defense and induce intestinal inflammation. To find a suitable concentration of Bacillus coagulans that could activate HO-1 genes and the immunity of the organism, we investigated the changes in HO-1 gene expression levels in the intestinal tract of common carp under Cd2+ stress at 30 days and 60 days by adding different concentrations of B. coagulans to the feed. Compared with the Cd2+ stress group without supplementation, the expression levels of the HO-1 gene in the gut of three different concentrations of B. coagulans were almost increased. And B. coagulans with L2 concentrations had better activation effect on the HO-1 gene. Similarly, compared to the Cd2+ stressed group, adding B. coagulans to the diet can almost cause the early upregulation of IL-10 and TGF-β genes. Therefore, the addition of appropriate concentrations of B. coagulans may be a good way to activate HO-1, IL-10, and TGF-β genes, reduce oxidative damage, and encourage the immune.
Collapse
Affiliation(s)
- Zhou Jiang
- School of law / College of Fishery, Henan Normal University, Xinxiang, Henan, 453007, China
| | - Meng Zhang
- School of law / College of Fishery, Henan Normal University, Xinxiang, Henan, 453007, China
| | - Kaiyue Liu
- School of law / College of Fishery, Henan Normal University, Xinxiang, Henan, 453007, China
| | - Yaguo Xue
- School of law / College of Fishery, Henan Normal University, Xinxiang, Henan, 453007, China
- State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, 361005, China
| | - Xuejun Li
- School of law / College of Fishery, Henan Normal University, Xinxiang, Henan, 453007, China.
| | - Chuanju Dong
- School of law / College of Fishery, Henan Normal University, Xinxiang, Henan, 453007, China.
- State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, 361005, China.
| |
Collapse
|
|
39
|
Zhang Z, Yang K, Mao R, Zhong D, Xu Z, Xu J, Xiong M. Ginsenoside Rg1 inhibits oxidative stress and inflammation in rats with spinal cord injury via Nrf2/HO-1 signaling pathway. Neuroreport 2022; 33:81-89. [PMID: 34954769 DOI: 10.1097/wnr.0000000000001757] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES In this study, our objective was to investigate the underlying mechanism of the neuroprotective role of ginsenoside Rg1 in attenuating spinal cord injury (SCI). METHODS A rat SCI model was established and treated with ginsenoside Rg1 and nuclear factor erythroid 2-related factor2(Nrf2) inhibitor all-trans retinoic acid (ATRA). The protective effects of ginsenoside Rg1 were evaluated by Basso, Beattie and Bresnahan (BBB) scale, hematoxylin/eosin staining, ELISA assay, western blotting and quantitative reverse transcription PCR (RT-qPCR). RESULTS Ginsenoside Rg1 alleviated neuronal edema and bleeding in the injured spinal cord, reduced inflammatory cell infiltration and cell necrosis, further repaired the injured spinal cord structure, improved BBB motor score in the SCI rat model and improved hind limb motor function. Meanwhile, ginsenoside Rg1 significantly increased the content of antioxidant enzymes superoxide dismutase and glutathione, and inhibited the production of oxidative marker malondialdehyde. In addition, ginsenoside Rg1also significantly inhibits the activities of the inflammatory factors tumor necrosis factor-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) to reduce the inflammatory response after trauma. Furthermore, western blot and RT-qPCR also suggested that ginsenoside Rg1 could activate the protein expression of Nrf2 and heme oxygenase-1 (HO-1) after SCI, and the inhibition of ATRA on these improvements further verified the neuroprotective effect of Nrf2 and HO-1 in ginsenoside Rg1 on SCI. CONCLUSION Ginsenoside Rg1 has a neuroprotective effect on SCI and can improve motor dysfunction caused by injury. The underlying mechanism may play antioxidative stress and anti-inflammatory effect by regulating the Nrf2/HO-1 signaling pathway.
Collapse
Affiliation(s)
| | | | - Rui Mao
- Neurology, Sinopharm Dongfeng General Hospital
| | | | | | - Jie Xu
- Department of Institute of Clinical Medcine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | | |
Collapse
|
|
40
|
Das R, Mitra S, Tareq AM, Emran TB, Hossain MJ, Alqahtani AM, Alghazwani Y, Dhama K, Simal-Gandara J. Medicinal plants used against hepatic disorders in Bangladesh: A comprehensive review. JOURNAL OF ETHNOPHARMACOLOGY 2022; 282:114588. [PMID: 34480997 DOI: 10.1016/j.jep.2021.114588] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 08/19/2021] [Accepted: 08/29/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Liver disease is a major cause of illness and death worldwide which accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma. That's why it is seeking the researchers' attention to find out the effective treatment strategies. Phytochemicals from natural resources are the main leads for the development of noble hepatoprotective drugs. The majority of the natural sources whose active compounds are currently employed actually have an ethnomedical use. Ethnopharmacological research is essential for the development of these bioactive compounds. These studies not only provide scientific evidence on medicinal plants utilized for particular therapeutic purposes, but they also ensure cultural heritage preservation. Plenty of experimental studies have been well-documented that the ethnomedicinal plants are of therapeutics' interest for the advanced pharmacological intervention in terms of hepatic disorders. AIM OF THE STUDY This study summarizes the processes of hepatotoxicity induced by various toxins and explores identified hepatoprotective plants and their phytoconstituents, which can guide the extraction of novel phytochemical constituents from plants to treat liver injury. This review aimed to summarize the hepatoprotective activity of Bangladeshi medicinal plants where the bioactive compounds may be leads for the drug discovery in future. MATERIALS AND METHODS Literature searches in electronic databases, such as Web of Science, Science Direct, SpringerLink, PubMed, Google Scholar, Semantic Scholar, Scopus, BanglaJOL, and so on, were performed using the keywords 'Bangladesh', 'ethnomedicinal plants', 'Hepatoprotective agents' as for primary searches, and secondary search terms were used as follows, either alone or in combination: traditional medicine, medicinal plants, folk medicine, liver, hepatitis, therapeutic uses, and anti-inflammatory. Besides, several books, including the book entitled "Medicinal plants of Bangladesh: chemical constituents and uses" authored by Abdul Ghani, were carefully considered, which contained pharmacological properties and phytoconstituents of many medicinal plants growing and traditionally available in Bangladesh. Among them, the most promising plant species with their latest therapeutic effects against hepatic disorders were deeply considered in this review. RESULTS The results of this study revealed that in most cases, therapy using plant extracts stabilized altered hepatic biochemical markers induced by hepatotoxins. Initially, we investigated 32 plant species for hepatoprotective activity, however after extensive literature searching; we observed that 20 plants offer good pharmacological evidence of hepatoprotective function. Consequently, most bioactive compounds derived from the herbs including berberine, thymoquinone, andrographolide, ursolic acid, luteolin, naringenin, genistein, quercetin, troxerutin, morin, epigallocatechin-3-gallate, chlorogenic acid, emodin, curcumin, resveratrol, capsaicin, ellagic acid, etc. are appeared to be effective against hepatic disorders. CONCLUSIONS Flavonoids, phenolic acids, monoterpenoids, diterpenoids, triterpenoids, alkaloids, chromenes, capsaicinoids, curcuminoids, and anthraquinones are among the phytoconstituents were appraised to have hepatoprotective activities. All the actions displayed by these ethnomedicinal plants could make them serve as leads in the formulation of drugs with higher efficacy to treat hepatic disorders.
Collapse
Affiliation(s)
- Rajib Das
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Abu Montakim Tareq
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4381, Bangladesh.
| | - Md Jamal Hossain
- Department of Pharmacy, State University of Bangladesh, 77 Satmasjid Road, Dhanmondi, Dhaka, 1205, Bangladesh
| | - Ali M Alqahtani
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia
| | - Yahia Alghazwani
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareil-ly, 243122, Uttar Pradesh, India
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E32004, Ourense, Spain.
| |
Collapse
|
|
41
|
Khaled S, Makled MN, Nader MA. Protective effects of propolis extract against nicotine-evoked pulmonary and hepatic damage. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:5812-5826. [PMID: 34431048 DOI: 10.1007/s11356-021-16093-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 08/18/2021] [Indexed: 06/13/2023]
Abstract
There is increasing interest in the use of natural products to treat many diseases, considering the minimal toxicity, availability, and low cost. Propolis, a natural resinous product produced by honeybees, has been proven for its antioxidant and anti-inflammatory properties. Therefore, this study was designed to investigate the protective potential of propolis extract against nicotine-induced pulmonary and hepatic damage in rats. Sprague Dawley rats were divided into six groups: control, propolis (200 and 300 mg/kg, p.o.), nicotine (10 mg/kg, i.p), and nicotine plus propolis-treated groups. Nicotine and propolis were given every day for 8 weeks. Then, blood and bronchoalveolar lavage fluid (BALF) were collected for assessing liver and lung functions. Liver and lung tissues were also harvested to assess oxidative stress and inflammatory biomarkers in addition to histopathological and immunohistochemical analysis. Both doses of propolis significantly decreased AST, ALT, ALP, and total and differential cell counts in a dose-dependent manner. Propolis extract significantly attenuated oxidative stress in both lung and liver tissues. The restoration of antioxidant status (GSH level, SOD activities) and reduction of nitric oxide and MDA content was more so in propolis 300-treated than propolis 200-treated group. This was parallel to the improvement seen in histopathological examination. Propolis 200 and 300 significantly decreased Nrf2 expression and increased HO-1 expression in a dose-dependent manner. Moreover, immunohistochemical examination revealed that propolis 200 and 300 decreased the expression of iNOS in lung and liver tissues while decreased TNF-α expression in lung tissues only. Propolis extract could have a protective potential against nicotine-induced pulmonary and hepatic damage via activating Nrf2/HO-1 signaling.
Collapse
Affiliation(s)
- Shimaa Khaled
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Horus University, New Damietta, 34518, Egypt.
| | - Mirhan N Makled
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
| | - Manar A Nader
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
| |
Collapse
|
|
42
|
LONG L, MENG X, SUN J, JING L, CHEN D, YU R. Ameliorated effect of Lactobacillus plantarum SCS2 on the oxidative stress in HepG2 cells induced by AFB1. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.16522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Lan LONG
- Chengdu University of Traditional Chinese Medicine, China
| | - Xiao MENG
- Chengdu University of Traditional Chinese Medicine, China
| | - Jiayi SUN
- Chengdu University of Traditional Chinese Medicine, China
| | - Lin JING
- Chengdu University of Traditional Chinese Medicine, China
| | - Dayi CHEN
- Chengdu University of Traditional Chinese Medicine, China
| | - Rong YU
- Chengdu University of Traditional Chinese Medicine, China
| |
Collapse
|
|
43
|
Therapeutic Effects of Resveratrol on Nonalcoholic Fatty Liver Disease Through Inflammatory, Oxidative Stress, Metabolic, and Epigenetic Modifications. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2021; 2343:19-35. [PMID: 34473313 DOI: 10.1007/978-1-0716-1558-4_2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing around the world, in association with the progressive elevation in overweight and obesity. The accumulation of lipids in NAFLD patients contributes to the development of insulin resistance, inflammation and oxidative stress in hepatocytes, and alteration of blood lipids and glycaemia. There are currently no effective pharmacological therapies for NAFLD, although lifestyle and dietary modifications targeting weight reduction are among the prevailing alternative approaches. For this reason, new approaches should be investigated. The natural polyphenol resveratrol represents a potential new treatment for management of NAFLD due to anti-inflammatory and antioxidant properties. Although preclinical trials have demonstrated promising results of resveratrol against NALFD, the lack of conclusive results creates the need for more trials with larger numbers of patients, longer time courses, and standardized protocols.
Collapse
|
|
44
|
Yang H, Wang Y, Liu M, Liu X, Jiao Y, Jin S, Shan A, Feng X. Effects of Dietary Resveratrol Supplementation on Growth Performance and Anti-Inflammatory Ability in Ducks ( Anas platyrhynchos) through the Nrf2/HO-1 and TLR4/NF-κB Signaling Pathways. Animals (Basel) 2021; 11:3588. [PMID: 34944363 PMCID: PMC8698092 DOI: 10.3390/ani11123588] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 12/08/2021] [Accepted: 12/15/2021] [Indexed: 12/17/2022] Open
Abstract
The aim of this study was to explore the effect of dietary resveratrol on the growth performance and anti-inflammatory mechanism in ducks. A total of 280 one-day-old specific pathogen-free male ducklings (Anas platyrhynchos) with an average body weight of 35 ± 1 g were randomly divided into two dietary treatment groups with different supplementation levels of resveratrol for growth performance experiments: R0 and R400 (0 and, 400 mg kg-1 resveratrol, respectively). At the age of 28 days, 16 ducks were selected from each treatment group and divided into four subgroups for a 2 × 2 factorial pathological experiment: R0; R400; R0 + LPS; R400 + LPS, (0 mg kg-1 resveratrol, 400 mg kg-1 resveratrol, 0 mg kg-1 resveratrol, 400 mg kg-1 resveratrol + 5 mg lipopolysaccharide/kg body weight). The results showed that resveratrol significantly improved final body weight and average daily gain (p < 0.01) and alleviated the lipopolysaccharide-induced inflammatory response with a reduction in IL-1β and IL-6 in the plasma and the liver (p < 0.05). Resveratrol improved mRNA levels of Nrf2 and HO-1 and decreased the mRNA levels of TLR4 and NF-κB in duck liver (p < 0.05). Dietary resveratrol can improve growth performance and reduce inflammation through the Nrf2/HO-1 and TLR4/NF-κB signaling pathways in duck.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Xingjun Feng
- Laboratory of Molecular Nutrition, Institute of Animal Nutrition, Northeast Agricultural University, Changjiang Street 600#, Xiangfang District, Harbin 150030, China; (H.Y.); (Y.W.); (M.L.); (X.L.); (Y.J.); (S.J.); (A.S.)
| |
Collapse
|
|
45
|
Zhang X, Liu X, Wan F, You W, Tan X, Sheng Q, Li C, Hu Z, Liu G, Zhao H. Protective effect of resveratrol against hydrogen peroxide-induced oxidative stress in bovine skeletal muscle cells. Meat Sci 2021; 185:108724. [PMID: 34952489 DOI: 10.1016/j.meatsci.2021.108724] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 10/04/2021] [Accepted: 12/13/2021] [Indexed: 11/16/2022]
Abstract
The objective of this study was to investigate the protective effects and the underlying mechanisms of resveratrol (RES) against hydrogen peroxide (H2O2)-induced oxidative stress in bovine skeletal muscle cells (BMCs). Pretreatment of BMCs with RES prior to H2O2 exposure increased cell viability, attenuated reactive oxygen species, and stabilized the redox state. H2O2 exposure activated sirtuin type 1 (SIRT1) and nuclear factor E2-related factor 2 (NRF2)-mediated signaling pathways. Pretreatment with RES did not alter SIRT1-regulated genes but inhibited the upregulation of NRF2, whereas enhanced heme oxygenase 1 (HO-1) expression. Pretreatment with RES prior to H2O2 exposure failed to suppress NRF2 expression when NRF2 was knocked down by RNA interference. However, HO-1 expression still could be induced by RES. These results suggest that RES has benifical effects against oxidative stress. NRF2-mediated pathway play an important role, and HO-1 upregulation is the key process in RES regulation. RES may be used as a therapeutic agent for meat quality improvement in beef cattle.
Collapse
Affiliation(s)
- Xianglun Zhang
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China
| | - Xiaomu Liu
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China
| | - Fachun Wan
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, China
| | - Wei You
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China
| | - Xiuwen Tan
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China
| | - Qingkai Sheng
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China
| | - Chuanhao Li
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China
| | - Zhuran Hu
- Shandong Green and Blue Bio-technology Co. Ltd, Taian, China
| | - Guifen Liu
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China.
| | - Hongbo Zhao
- Shandong Academy of Agricultural Sciences Animal Science and Veterinary Medicine Institute, Shandong Key Lab of Animal Disease Control and Breeding, Jinan, China.
| |
Collapse
|
|
46
|
Liu F, Wang Y, Zhou X, Liu M, Jin S, Shan A, Feng X. Resveratrol Relieved Acute Liver Damage in Ducks ( Anas platyrhynchos) Induced by AFB1 via Modulation of Apoptosis and Nrf2 Signaling Pathways. Animals (Basel) 2021; 11:ani11123516. [PMID: 34944291 PMCID: PMC8698071 DOI: 10.3390/ani11123516] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 11/19/2021] [Accepted: 12/07/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Aflatoxin B1 is ubiquitous in food and feed, which not only poses a great threat to animals, but also affects human health. It is unclear whether resveratrol can resist aflatoxin B1 damage in ducks’ livers. Therefore, the effect of resveratrol supplementation in the diets on liver injury aflatoxin B1was investigated through the gavage of aflatoxin B1. It was found that a diet that includes resveratrol can effectively protect ducks’ livers from acute injury caused by aflatoxin B1. Our study suggests that resveratrol serves as a potential phytochemical feed additive for the treatment of acute aflatoxin B1 poisoning in ducks Abstract The presence of aflatoxin B1 (AFB1) in feed is a serious threat to livestock and poultry health and to human food safety. Resveratrol (Res) is a polyphenolic compound with antioxidant, anti-apoptotic and other biological activities; however, it is not clear whether it can improve AFB1 induced hepatotoxicity. Therefore, this study was conducted to investigate the effects of dietary Res on liver injury induced by AFB1 and its mechanisms. A total of 270 one-day-old male specific pathogen free (SPF) ducks, with no significant difference in weight, were randomly assigned to three groups: the control group, the AFB1 group and the AFB1 + Res group, which were fed a basic diet, a basic diet and a basic diet containing 500 mg/kg Res, respectively. On the 70th day, the ducks in theAFB1 group and the AFB1+ 500 mg/kg Res group were given 60 μg/kg AFB1 via gavage. When comparing the AFB1 group and the AFB1 + Res group and also with the control group, AFB1 significantly increased liver damage, cytochrome P450 (CYP450) and AFB1-DNA adduct content, increased oxidative stress levels and induced liver apoptosis, which was improved by Res supplementation. In sum, the addition of Res to feed can increase the activity of the II-phase enzyme, activate the nuclear factor E2-related factor 2 (Nrf2) signal pathway, and protect ducks’ livers from the toxicity, oxidative stress and inflammatory reaction induced by AFB1.
Collapse
|
|
47
|
de Rus Jacquet A, Ambaw A, Tambe MA, Ma SY, Timmers M, Grace MH, Wu QL, Simon JE, McCabe GP, Lila MA, Shi R, Rochet JC. Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models. Food Funct 2021; 12:11987-12007. [PMID: 34751296 PMCID: PMC10822195 DOI: 10.1039/d1fo00007a] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease's motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression. In this study, we characterized the neuroprotective effects of isoflavones, a class of dietary polyphenols found in soy products and in the medicinal plant red clover (Trifolium pratense). We found that isoflavone-rich extracts and individual isoflavones rescued the loss of dopaminergic neurons and the shortening of neurites in primary mesencephalic cultures exposed to two PD-related insults, the environmental toxin rotenone and an adenovirus encoding the A53T aSyn mutant. The extracts and individual isoflavones also activated the Nrf2-mediated antioxidant response in astrocytes via a mechanism involving inhibition of the ubiquitin-proteasome system, and they alleviated deficits in mitochondrial respiration. Furthermore, an isoflavone-enriched soy extract reduced motor dysfunction exhibited by rats lesioned with the PD-related neurotoxin 6-OHDA. These findings suggest that plant-derived isoflavones could serve as dietary supplements to delay PD onset in at-risk individuals and mitigate neurodegeneration in the brains of patients.
Collapse
Affiliation(s)
- Aurélie de Rus Jacquet
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
| | - Abeje Ambaw
- Department of Basic Medical Sciences, Purdue University, West Lafayette, IN, 47907, USA
| | - Mitali Arun Tambe
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
| | - Sin Ying Ma
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
| | - Michael Timmers
- Plants for Human Health Institute, Department of Food Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC, 28081, USA
| | - Mary H Grace
- Plants for Human Health Institute, Department of Food Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC, 28081, USA
| | - Qing-Li Wu
- Department of Plant Biology, Rutgers University, New Brunswick, NJ, 08901, USA
| | - James E Simon
- Department of Plant Biology, Rutgers University, New Brunswick, NJ, 08901, USA
| | - George P McCabe
- Department of Statistics, Purdue University, West Lafayette, IN 47907, USA
| | - Mary Ann Lila
- Plants for Human Health Institute, Department of Food Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC, 28081, USA
| | - Riyi Shi
- Department of Basic Medical Sciences, Purdue University, West Lafayette, IN, 47907, USA
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47907, USA
- Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, 47907, USA
| | - Jean-Christophe Rochet
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
- Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, 47907, USA
| |
Collapse
|
|
48
|
Morales-Rubio R, Amador-Muñoz O, Rosas-Pérez I, Sánchez-Pérez Y, García-Cuéllar C, Segura-Medina P, Osornio-Vargas Á, De Vizcaya-Ruiz A. PM 2.5 induces airway hyperresponsiveness and inflammation via the AhR pathway in a sensitized Guinea pig asthma-like model. Toxicology 2021; 465:153026. [PMID: 34774659 DOI: 10.1016/j.tox.2021.153026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 10/28/2021] [Accepted: 11/02/2021] [Indexed: 01/09/2023]
Abstract
Exposure to fine particulate matter (PM2.5) induces airway inflammation and hyperreactivity that lead to asthma. The mechanisms involved are still under investigation. We investigated the effect of resveratrol (3,4',5-trihydroxystilbene) (RES) on airway hyperresponsiveness, inflammation and CYP1A1 protein expression (an aryl hydrocarbon receptor (AhR) target) induced by PM2.5 exposure in an allergic asthma experimental guinea pig model. The polyphenolic compound RES was used due to its antioxidant and anti-inflammatory properties and as an antagonist of the AhR; thus, providing mechanistic insights. Animals were sensitized with aluminum hydroxide and ovalbumin and exposed to filtered air or PM2.5. Exposure to PM2.5 was conducted using a whole-body chamber particle concentrator (5 h/day) for 15 days. Animals received saline solution or RES (10 mg/kg per day) orally for 21 days simultaneously to the OVA challenge or PM2.5 exposure. PM2.5 exposure (mean 433 ± 111 μg/m3 in the exposure chamber) in OVA challenged animals induced an asthma-like phenotype characterized by increased baseline lung resistance (Rrs) and central airway resistance (Rn) in response to acetylcholine (ACh) evaluated using a flexiVent system®. A parallel increase of pro-inflammatory cytokines (IL-6, IL-17, TNF-α and IFN-γ), inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid (BALF) and lung CYP1A1 increase also occurred. RES significantly inhibited airway hyperresponsiveness, inflammation, and CYP1A1 protein expression in the OVA-challenged PM2.5 exposed animals. In summary, with the use of RES we demonstrate that PM-induced airway hyperreactivity is modulated by the inflammatory response via the AhR pathway in an allergic asthma guinea pig model.
Collapse
|
|
49
|
Yang H, Wang Y, Jin S, Pang Q, Shan A, Feng X. Dietary resveratrol alleviated lipopolysaccharide-induced ileitis through Nrf2 and NF-κB signalling pathways in ducks (Anas platyrhynchos). J Anim Physiol Anim Nutr (Berl) 2021; 106:1306-1320. [PMID: 34729831 DOI: 10.1111/jpn.13657] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/12/2021] [Accepted: 10/20/2021] [Indexed: 02/06/2023]
Abstract
Gram-negative bacteria contamination of feed can occur at all the stage of feed production, storage, transportation and utilization. Lipopolysaccharide (LPS) is a major toxic metabolite of Gram-negative bacteria. The aim of this study was to explore the effect of dietary resveratrol on the duck ileitis caused by LPS and its optimum addition level in diet. The results showed that LPS-induced duck ileitis with the destruction of intestinal structure, oxidative stress, mitochondrial dysfunction, inflammatory response and permeability alteration. Dietary resveratrol alleviated LPS-induced intestinal dysfunction and the increase of intestinal permeability by linearly increasing mRNA levels of tight junction protein genes (Claudin-1, Occludin-1, ZO-1) (p < 0.05) and protein expression of Claudin-1 (p < 0.01). In addition, dietary resveratrol improved the antioxidant capacity of duck ileum by reducing the production of MDA and increasing the activity of T-SOD (p < 0.01) and CAT. Lipopolysaccharide increased Keap1 at mRNA and protein level (p < 0.01) and decreased the protein level of Nrf2 (p < 0.05). Dietary resveratrol significantly downregulated expression of Keap1 and upregulated expression of Nrf2 in duck (p < 0.05). Dietary resveratrol suppressed the TLR4/NF-κB signalling pathway and the expression of its downstream genes including IKK, TXNIP, NLRP3, Caspase-1, IL-6 and IL-18. Meanwhile, the levels of inflammatory cytokines (IL-6, IL-18 and TNF-α) showed a linearly decrease (p < 0.01) with increasing dietary resveratrol level. These results demonstrated that resveratrol alleviated the LPS-induced acute ileitis of duck through Nrf2 and NF-κB signalling pathways, and the dietary resveratrol of 500 mg/kg is more efficiently.
Collapse
Affiliation(s)
- Hao Yang
- Institute of Animal Nutrition, Northeast Agricultural University, Xiangfang District, Harbin, China
| | - Yingjie Wang
- Institute of Animal Nutrition, Northeast Agricultural University, Xiangfang District, Harbin, China
| | - Sanjun Jin
- Institute of Animal Nutrition, Northeast Agricultural University, Xiangfang District, Harbin, China
| | - Qian Pang
- Institute of Animal Nutrition, Northeast Agricultural University, Xiangfang District, Harbin, China
| | - Anshan Shan
- Institute of Animal Nutrition, Northeast Agricultural University, Xiangfang District, Harbin, China
| | - Xingjun Feng
- Institute of Animal Nutrition, Northeast Agricultural University, Xiangfang District, Harbin, China
| |
Collapse
|
|
50
|
Antiaging Potential of Peptides from Underused Marine Bioresources. Mar Drugs 2021; 19:md19090513. [PMID: 34564175 PMCID: PMC8466736 DOI: 10.3390/md19090513] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 08/26/2021] [Accepted: 09/07/2021] [Indexed: 12/28/2022] Open
Abstract
Aging is a biological process that occurs under normal conditions and in several chronic degenerative diseases. Bioactive natural peptides have been shown to improve the effects of aging in cell and animal models and in clinical trials. However, few reports delve into the enormous diversity of peptides from marine organisms. This review provides recent information on the antiaging potential of bioactive peptides from underused marine resources, including examples that scavenge free radicals in vitro, inhibit cell apoptosis, prolong the lifespan of fruit flies and Caenorhabditis elegans, suppress aging in mice, and exert protective roles in aging humans. The underlying molecular mechanisms involved, such as upregulation of oxidase activity, inhibition of cell apoptosis and MMP-1 expression, restoring mitochondrial function, and regulating intestinal homeostasis, are also summarized. This work will help highlight the antiaging potential of peptides from underused marine organisms which could be used as antiaging foods and cosmetic ingredients in the near future.
Collapse
|