|
1
|
Hendawy AS, Sabra ANA, George MY, Rashad E, El-Demerdash E, Botros SS. The antifibrotic effect of Vildagliptin and Diaminodiphenyl Sulfone in murine schistosomiasis mansoni. Sci Rep 2025; 15:10084. [PMID: 40128243 PMCID: PMC11933376 DOI: 10.1038/s41598-025-91955-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 02/24/2025] [Indexed: 03/26/2025] Open
Abstract
Schistosomiasis drastically affects human health, where S. mansoni-induced hepatic fibrosis remains a serious problem with no available drug yet. The current study aimed to evaluate the hepatoprotective effects of Vildagliptin (Vilda), Diaminodiphenyl Sulfone (DDS), and their combination (Vilda/DDS) against S. mansoni-induced hepatic fibrosis and elucidate their underlying molecular mechanisms. S.mansoni-infected mice were administered praziquantel (PZQ) for two consecutive days, or Vilda, DDS, and Vilda/DDS for 14 consecutive days. Schistosomiasis-induced hepatic fibrosis was assessed parasitologically, biochemically, and pathologically. Results revealed that Vilda, DDS, and Vida/DDS treatments significantly reduced worm count, oogram stages, ova count, and ameliorated the granulomatous inflammatory reactions and hepatotoxicity indices. Moreover, they enhanced hepatic Nrf2/HO-1 pathway with significant increasing SOD and reducing MDA levels. Furthermore, they significantly downregulated the hepatic TLR4/NF-κB and NLRP3 inflammasome pathways leading to a significant reduction in TNF-α and caspase-1 levels which is important in the activation of IL-1β and caspase-3. Notably, significant downregulation in hepatic TGF-β1, α-SMA, and MMP-9 expressions were also recorded. In conclusion, Vilda/DDS showed antioxidant, anti-inflammatory and antifibrotic activities in comparison to either Vilda or DDS alone against S. mansoni-induced hepatic fibrosis. Therefore, Vilda/DDS is a promising approach for managing S. mansoni infection, liver fibrosis, and associated disease morbidity.
Collapse
Affiliation(s)
- Amira S Hendawy
- Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, P.O. Box 30, Imbaba, Giza, 12411, Egypt
| | - Abdel-Nasser A Sabra
- Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, P.O. Box 30, Imbaba, Giza, 12411, Egypt
| | - Mina Y George
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, 11566, Egypt
| | - Eman Rashad
- Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Ebtehal El-Demerdash
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, 11566, Egypt.
| | - Sanaa S Botros
- Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, P.O. Box 30, Imbaba, Giza, 12411, Egypt
| |
Collapse
|
|
2
|
Tang W, Huang X, Yi YD, Cao F, Deng M, Fan J, Jiang ZX, Tao LM, Wang X, Shi L. Hyaluronic acid-curcumin nanoparticles for preventing the progression of experimental autoimmune uveitis through the Keap1/Nrf2/HO-1 signaling pathway. J Nanobiotechnology 2025; 23:89. [PMID: 39915858 PMCID: PMC11804030 DOI: 10.1186/s12951-024-03082-3] [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: 08/21/2024] [Accepted: 12/25/2024] [Indexed: 02/09/2025] Open
Abstract
Globally, uveitis is a collection of intraocular inflammatory disorders that affect mainly the uvea, resulting in irreversible blindness and a heavy socioeconomic burden. Excessive autoimmune inflammation and oxidative stress are major drivers that contribute to the initiation and progression of uveitis. Nevertheless, current therapeutic methods for uveitis are limited and are accompanied by several serious adverse effects. Recently, nanotechnology-based antioxidant strategies have provided novel options for the treatment of ocular diseases. Although curcumin (CUR) has prominent antioxidant capacity and reactive oxygen species (ROS) scavenging ability, its low bioavailability and undetermined mechanisms limit its extensive application. This investigation demonstrated that esterified hyaluronic acid-curcumin nanoparticles (HA-CUR NPs) with superior aqueous dispersion exhibited exceptional antioxidant enzyme mimetic activity, incorporating superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and free radical scavenging ability. Further in vitro and in vivo experimental results validated the protective function of HA-CUR NPs against oxidative stress-induced damage and inflammatory responses, attenuated pathological progression, relieved microvascular damage, and regulated fundus blood flow in retinal vascular networks. This may be attributable to the specific ability of HA-CUR NPs to target the CD44 receptor and activate the Keap1/Nrf2/HO-1 signaling pathway, suggesting a potential mechanism. In summary, this study revealed that HA-CUR NPs, which are composed of a natural product and biomacromolecules with outstanding artificial antioxidant enzyme activities, may be novel agents for effectively and safely treating uveitis and other ROS-related diseases.
Collapse
Affiliation(s)
- Weiwei Tang
- Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - Xiaomin Huang
- Eye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan University, NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, P. R. China
| | - Yun-Di Yi
- Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - Fan Cao
- Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - Manli Deng
- Eye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan University, NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, P. R. China
| | - Jiawei Fan
- Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - Zheng-Xuan Jiang
- Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China.
| | - Li-Ming Tao
- Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China.
| | - Xianwen Wang
- School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei, 230032, P. R. China.
| | - Lei Shi
- Department of Ophthalmology, Anhui No. 2 Provincial People's Hospital, Hefei, 230041, P. R. China.
- Anhui Province Key Laboratory of Occupational Health, Anhui No. 2 Provincial People's Hospital, Hefei, 230041, P. R. China.
| |
Collapse
|
|
3
|
Saleh NEH, Ibrahim MY, Saad AH, Abdel-Hakeem EA, Saleh RK, Habeeb WN. The impact of consuming different types of high-caloric fat diet on the metabolic status, liver, and aortic integrity in rats. Sci Rep 2024; 14:18602. [PMID: 39127712 PMCID: PMC11316824 DOI: 10.1038/s41598-024-68299-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 07/22/2024] [Indexed: 08/12/2024] Open
Abstract
Consumption of high-caloric diets contributes to the alarming number of overweight and obese individuals worldwide, which in turn leads to several diseases and multiple organ dysfunction. Not only has the number of calories taken per day but also the type of fat in the diet has an important impact on health. Accordingly, the purpose of the current study was to examine the impact of different types of high-caloric fat diets on the metabolic status and the integrity of the liver and aorta in albino rats. Adult male albino rats were divided into 6 groups: Control group, long chain-saturated fat group (SFD), long chain-monounsaturated fat (MUFAs) group, long chain-polyunsaturated fat (PUFAs) group, medium-chain fat (MCFAs) group, and short-chain fat (SCFAs) group. Body mass index (BMI), Lee index, and visceral fat amount were reported. Serum levels of insulin, liver transaminases, lipid profile, and different oxidative stress and inflammatory markers were evaluated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and adiponectin/leptin ratio were also calculated. Histopathological examinations of liver and aorta with Masson's trichrome stain, and immune-staining for Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) were also done. SFD group showed significantly elevated liver transaminases, inflammatory markers, HOMA-IR, dyslipidemia, reduced adiponectin, and deficient anti-oxidative response compared to other groups together with disturbed hepatic and aortic architecture. Other treated groups showed an improvement. PUFAs group showed the highest level of improvement. Not all high-fat diets are hazardous. Diets rich in PUFAs, MUFAs, MCFAs, or SCFAs may protect against the hazards of high caloric diet.
Collapse
Affiliation(s)
| | - Mariam Yahia Ibrahim
- Department of Medical Physiology, Faculty of Medicine, Minia University, El-Minia, 61511, Egypt
| | - Adel Hussein Saad
- Department of Medical Physiology, Faculty of Medicine, Minia University, El-Minia, 61511, Egypt
| | - Elshymaa A Abdel-Hakeem
- Department of Medical Physiology, Faculty of Medicine, Minia University, El-Minia, 61511, Egypt
| | - Rabeh Khairy Saleh
- Department of Pathology, Faculty of Medicine, Minia University, El-Minia, 61511, Egypt
| | - Wagdy N Habeeb
- Department of Medical Physiology, Faculty of Medicine, Minia University, El-Minia, 61511, Egypt
| |
Collapse
|
|
4
|
Xie N, Ma R, Wang L, Shu Y, He P, Zhou Y, Xiang Y, Wang Y. Cannabidiol regulates the activation of hepatic stellate cells by modulating the NOX4 and NF-κB pathways. Food Chem Toxicol 2024; 186:114517. [PMID: 38382869 DOI: 10.1016/j.fct.2024.114517] [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: 12/20/2023] [Revised: 02/12/2024] [Accepted: 02/12/2024] [Indexed: 02/23/2024]
Abstract
Cannabidiol (CBD) is an extract of natural cannabinoids that has therapeutic implications for a variety of ailments, such as neurological diseases, cardiomyopathy, and diabetes, due to its strong anti-inflammatory and oxidative stress properties. Our purpose was to reveal the possible underlying mechanisms and effect of CBD on the glucose oxidase (GO)-induced activation of HSC-T6 and LX-2 cells. The results showed that CBD effectively inhibited the proliferation and activation of HSC-T6 and LX-2 cells, and reduced the production of profibrotic factors to different degrees. CBD disrupted the NOX4 signalling pathway in activated HSC-T6 and LX-2 cells, reduced ROS and MDA levels, and increased SOD and GSH levels, thereby stabilizing the oxidative imbalance. CBD significantly inhibited the phosphorylation and degradation of NF-κB and IκBα, and decreased the release of TNF-α, IL-1β and IL-6. Moreover, CBD and an NF-κB-specific inhibitor (CAPE) effectively inhibited the expression of α-SMA, COL I, TNF-α and IL-1β to promote collagen metabolism and inhibit the inflammatory response. Overall, CBD inhibited HSCs activation through a and the mechanism involving the inhibition of NOX4 and NF-κB-dependent ROS regulation, thereby reducing inflammation and ameliorating oxidative imbalances.
Collapse
Affiliation(s)
- Na Xie
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China; Xindu District People's Hospital, Department of Medical Laboratory, Chengdu, Sichuan, China
| | - Run Ma
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Lian Wang
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Yuanhui Shu
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China; School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Ping He
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China; School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Yan Zhou
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China; School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Yining Xiang
- Department of Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Yuping Wang
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China; School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, 550004, China.
| |
Collapse
|
|
5
|
Kerch G. Nanocomposite Hydrogels and Extracellular Matrix-Advantages and Associated Risks. Gels 2023; 9:754. [PMID: 37754435 PMCID: PMC10530377 DOI: 10.3390/gels9090754] [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: 08/14/2023] [Revised: 09/08/2023] [Accepted: 09/09/2023] [Indexed: 09/28/2023] Open
Abstract
Hydrogels can be considered as mimics of the extracellular matrix (ECM). Through integrins, the cytoskeleton is connected to the ECM, and cytoskeleton tension depends on ECM stiffness. A number of age-related diseases depend on cellular processes related to cytoskeleton function. Some examples of cancer initiation and progression and heart disease in relation to ECM stiffness have been analyzed. The incorporation of rigid particles into the ECM can increase ECM stiffness and promote the formation of internal residual stresses. Water migration, changes in water binding energy to biomactomolecules, and changes in the state of water from tightly bound water to free and loosely bound water lead to changes in the stiffness of the ECM. Cardiac tissue engineering, ECM stiffness and cancer, the equivalence of ECM stiffness, oxidative stress, inflammation, multi-layer polyelectrolyte complex hydrogels and bioprinting, residual internal stresses, viscoelastic hydrogels, hydrogel nanocomposites, and the effect of water have been reported. Special attention has been paid to the role of bound water and internal stresses in ECM stiffness. The risks related to rigid particle incorporation into the ECM have been discussed. The potential effect of polyphenols, chitosan, and chitosan oligosaccharide on ECM stiffness and the potential for anti-TNF-α and anti-NF-κB therapies have been discussed.
Collapse
Affiliation(s)
- Garry Kerch
- Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, 1048 Riga, Latvia
| |
Collapse
|
|
6
|
Gianì F, Allia F, Trovato MA, Masto R, Pellegriti G, Vigneri R. Antioxidant Defense Capacity Is Reduced in Thyroid Stem/Precursor Cells Compared to Differentiated Thyrocytes. Int J Mol Sci 2023; 24:11509. [PMID: 37511265 PMCID: PMC10380350 DOI: 10.3390/ijms241411509] [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: 05/05/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
There is much evidence linking oxidative stress to thyroid cancer, and stem cells are thought to play a key role in the tumor-initiating mechanism. Their vulnerability to oxidative stress is unexplored. This study aimed to comparatively evaluate the antioxidant capacity of stem/precursor thyroid cells and mature thyrocytes. Human stem/precursor cells and mature thyrocytes were exposed to increasing concentrations of menadione, an oxidative-stress-producing agent, and reactive oxygen species (ROS) production and cell viability were measured. The expression of antioxidant and detoxification genes was measured via qPCR as well as the total antioxidant capacity and the content of glutathione. Menadione elevated ROS generation in stem/precursor thyroid cells more than in mature thyrocytes. The ROS increase was inversely correlated (p = 0.005) with cell viability, an effect that was partially prevented by the antioxidant curcumin. Most thyroid antioxidant defense genes, notably those encoding for the glutathione-generating system and phase I detoxification enzymes, were significantly less expressed in stem/precursor thyroid cells. As a result, the glutathione level and the total antioxidant capacity in stem/precursor thyroid cells were significantly decreased. This reduced antioxidant defense may have clinical implications, making stem/precursor thyroid cells critical targets for environmental conditions that are not detrimental for differentiated thyrocytes.
Collapse
Affiliation(s)
- Fiorenza Gianì
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, 95122 Catania, Italy
| | - Fabio Allia
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, 95122 Catania, Italy
| | | | - Roberta Masto
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, 95122 Catania, Italy
| | - Gabriella Pellegriti
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, 95122 Catania, Italy
- Oncology, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Riccardo Vigneri
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, 95122 Catania, Italy
| |
Collapse
|
|
7
|
Ghorbanpour A, Salari S, Baluchnejadmojarad T, Roghani M. Capsaicin protects against septic acute liver injury by attenuation of apoptosis and mitochondrial dysfunction. Heliyon 2023; 9:e14205. [PMID: 36938442 PMCID: PMC10018474 DOI: 10.1016/j.heliyon.2023.e14205] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 02/20/2023] [Accepted: 02/23/2023] [Indexed: 03/05/2023] Open
Abstract
Capsaicin is the main pungent bioactive constituent in red chili with promising therapeutic properties due to its anti-oxidative and anti-inflammatory effects. No evidence exists on the beneficial effect of capsaicin on apoptosis and mitochondrial function in acute liver injury (ALI) under septic conditions. For inducing septic ALI, lipopolysaccharide (LPS, 50 μg/kg) and d-galactose (D-Gal, 400 mg/kg) was intraperitoneally injected and capsaicin was given orally at 5 or 20 mg/kg. Functional markers of liver function and mitochondrial dysfunction were determined as well as hepatic assessment of apoptotic, oxidative, and inflammatory factors. Capsaicin at the higher dose appropriately decreased serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in addition to reducing hepatic level of malondialdehyde (MDA), reactive oxygen species (ROS), nitrite, NF-kB, TLR4, IL-1β, TNF-α, caspase 3, DNA fragmentation and boosting sirtuin 1, Nrf2, superoxide dismutase (SOD) activity, and heme oxygenase (HO-1). These beneficial effects of capsaicin were associated with reversal and/or improvement of gene expression for pro-apoptotic Bax, anti-apoptotic Bcl2, mitochondrial and metabolic regulators PGC-1α, sirtuin 1, and AMPK, and inflammation-associated factors. Additionally, capsaicin exerted a hepatoprotective effect, as revealed by its reduction of liver histopathological changes. These findings evidently indicate hepatoprotective property of capsaicin under septic conditions that can be attributed to its down-regulation of oxidative and inflammatory processes besides its potential to attenuate mitochondrial dysfunction and apoptosis.
Collapse
Affiliation(s)
| | | | | | - Mehrdad Roghani
- Neurophysiology Research Center, Shahed University, Tehran, Iran
- Corresponding author.
| |
Collapse
|
|
8
|
Nithyashree N, Prakash N, Waghe P, Santhosh CR, Pavithra BH, Rajashekaraiah R, Sathyanarayana ML, Sunilchandra U, Anjan Kumar KR, Manjunatha SS, Muralidhar Y, Shivaprasad GR. Nanocurcumin Restores Arsenic-Induced Disturbances in Neuropharmacological Activities in Wistar Rats. Toxicol Int 2022. [DOI: 10.18311/ti/2022/v29i3/30342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The present study was carried out to examine the ameliorative potential of nanocurcumin against arsenic induced (sub-chronic) alterations in central nervous system in male Wistar rats. Nanocurcumin was synthesised and the hydrodynamic diameter, zeta potential and particle size were~76.60 nm, (-) 30 mV and 95nm, respectively. Experimental rats sub-chronically exposed to sodium (meta) arsenite (As; 10 mg.kg-1; 70 days; p.o) induced significant (p<0.05) reduction in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione and favoured free radical generation and induced lipid peroxidation in brain tissue. The exposure resulted in significant (p<0.05) decrease in voluntary- and involuntary motor activities and enhanced anxiety levels. However, experimental rats receiving nanocurcumin (15 mg.kg-1; p.o) showed significant (p<0.05) recovery in enzymatic - and non-enzymatic antioxidant defence system and restoration of redox balance and overcome arsenic induced depression in motor activities and elevated anxiety levels. Further, Arsenic induced elevation in pro-inflammatory cytokines, cyclooxygenase-2 activity and prostaglandin-E2 in brain and angiotensin-II levels (plasma) was significantly (p<0.05) ameliorated by nanocurcumin. Additionally, quantitative real -time polymerase chain reaction revealed a fivefold decrease in Nox2 expression in brain following nanocurcumin administration. Thus, the study concludes that nanocurcumin can serve as a potential therapeutic candidate to counter arsenic induced redox imbalance and neuropharmacological disturbances and there exists a vast scope to exploit its utility after appropriate clinical modelling.
Collapse
|
|
9
|
Irfan Z, Khanam S, Karmakar V, Firdous SM, El Khier BSIA, Khan I, Rehman MU, Khan A. Pathogenesis of Huntington's Disease: An Emphasis on Molecular Pathways and Prevention by Natural Remedies. Brain Sci 2022; 12:1389. [PMID: 36291322 PMCID: PMC9599635 DOI: 10.3390/brainsci12101389] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/25/2022] [Accepted: 10/03/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Huntington's disease is an inherited autosomal dominant trait neuro-degenerative disorder caused by changes (mutations) of a gene called huntingtin (htt) that is located on the short arm (p) of chromosome 4, CAG expansion mutation. It is characterized by unusual movements, cognitive and psychiatric disorders. OBJECTIVE This review was undertaken to apprehend biological pathways of Huntington's disease (HD) pathogenesis and its management by nature-derived products. Natural products can be lucrative for the management of HD as it shows protection against HD in pre-clinical trials. Advanced research is still required to assess the therapeutic effectiveness of the known organic products and their isolated compounds in HD experimental models. SUMMARY Degeneration of neurons in Huntington's disease is distinguished by progressive loss of motor coordination and muscle function. This is due to the expansion of CAG trinucleotide in the first exon of the htt gene responsible for neuronal death and neuronal network degeneration in the brain. It is believed that the factors such as molecular genetics, oxidative stress, excitotoxicity, mitochondrial dysfunction, neuroglia dysfunction, protein aggregation, and altered UPS leads to HD. The defensive effect of the natural product provides therapeutic efficacy against HD. Recent reports on natural drugs have enlightened the protective role against HD via antioxidant, anti-inflammatory, antiapoptotic, and neurofunctional regulation.
Collapse
Affiliation(s)
- Zainab Irfan
- Department of Pharmaceutical Technology, Brainware University, Kolkata 700125, West Bengal, India
| | - Sofia Khanam
- Department of Pharmacology, Calcutta Institute of Pharmaceutical Technology & AHS, Howrah 711316, West Bengal, India
| | - Varnita Karmakar
- Department of Pharmacology, Eminent College of Pharmaceutical Technology, Barasat 700126, West Bengal, India
| | - Sayeed Mohammed Firdous
- Department of Pharmacology, Calcutta Institute of Pharmaceutical Technology & AHS, Howrah 711316, West Bengal, India
| | | | - Ilyas Khan
- Department of Mathematics, College of Science Al-Zulfi, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Muneeb U. Rehman
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Andleeb Khan
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
| |
Collapse
|
|
10
|
Curcumin attenuates LPS-induced sickness behavior and fever in rats by modulating Nrf2 activity. Neurosci Lett 2022; 781:136680. [PMID: 35568344 DOI: 10.1016/j.neulet.2022.136680] [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: 01/26/2022] [Revised: 04/26/2022] [Accepted: 05/09/2022] [Indexed: 11/21/2022]
Abstract
Lipopolysaccharide (LPS) is a potent inducer of inflammation, triggering behavioral changes and fever. The present study aimed to evaluate whether pretreatment with curcumin prevents the behavioral changes and fever induced by LPS through the modulation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Male Wistar rats received either vehicle or LPS and after 2 h, the behavioral responses were assessed through open field test (OFT), social interaction test, forced swim test (FST), and food intake assessment. The febrile response was assessed by telemetry after vehicle or LPS injection to evaluate the effect of curcumin on the thermoregulatory response during the immunological challenge. The pretreatment with curcumin at doses of 50 and 100 mg/kg prevented the reduction of distance traveled on OFT, increased the immobility time of FST, impaired social withdrawal, decreased food intake, and induced fever. In addition, at these doses, it was possible to observe a significant decrease in the plasma levels of cytokines and an increase in Nrf2 translocation to the cell nucleus during the immunological challenge. Our data provide further evidence of curcumin's ability to prevent LPS-induced sickness behavior and fever possibly by a mechanism related to the modulation of Nrf2 translocation.
Collapse
|
|
11
|
Guo M, Gu L, Hui H, Li X, Jin L. Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice. Front Pharmacol 2022; 13:830532. [PMID: 35370722 PMCID: PMC8966672 DOI: 10.3389/fphar.2022.830532] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 02/02/2022] [Indexed: 12/12/2022] Open
Abstract
Alcoholic liver disease (ALD) caused by excessive drinking is a health and economic concern worldwide. Given the high morbidity, mortality, and the progressive nature of ALD, finding effective interventions is essential. Previous studies have confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. Dracocephalum tanguticum Maxim (DTM) is one of the important traditional Tibetan medicines in China with the effect of clearing away liver heat, used for the treatment of hepatitis. In this study, the DTM chloroform extract (DtM-C), ethyl acetate extract (DtM-E), and n-butanol extract (DtM-B) were obtained by ethanol extraction combined with fractional extraction. Acute ALD was induced in mice given intragastric ethanol. Serum and liver biochemical markers were detected by ELISA. Liver histological observation, Oil Red O, and Masson's trichrome staining were performed. Liver injury cells were induced by ethanol. The cell vitality was detected by using MTT colorimetry. The expressions of Nrf2, NF-κB, STAT3, AP-1, CREB, HIF-1α, HO-1, NQO-1, GSTA1, IKB2, and Keap1 were detected by real-time polymerase chain reaction (PCR) to elucidate the mechanism of hepatoprotective effect, and the results were verified by using Western blot. The results of serum liver function indicators (ALT, AST, and ADH), serum hepatic lipid indicators (TC, TG, HDL-C, and LDL-C), and lipid peroxidation indicators (ADH, MDA, SOD, CAT, and GSH-Px) in liver tissue and liver histological observation showed that DtM-E could improve liver function, alleviate fatty degeneration, edema, cell necrosis, and liver fibrosis caused by alcohol. DtM-E also increased the vitality of EtOH-induced liver injury cells, upregulated the mRNA expression of Nrf2, HO-1, NQO-1, and GSTA1, while downregulated the expression of Keap-1, p65, and NF-κB. Western blot results were consistent with PCR. The results suggest that DtM-E has a protective effect against ALD in vitro and in vivo, and its mechanism of action may be related to the activation of Nrf2/Keap-1 and inhibition of the P65/NF-κB signaling pathways.
Collapse
Affiliation(s)
- Min Guo
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China.,Institute of Chinese Materia Medica, Gansu Academy of Traditional Chinese Medicine, Lanzhou, China.,Laboratory of Chinese Medicine, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, China
| | - Liwei Gu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Heping Hui
- Gansu Agriculture Technology College, Lanzhou, China
| | - Xiaodong Li
- Institute of Chinese Materia Medica, Gansu Academy of Traditional Chinese Medicine, Lanzhou, China.,Laboratory of Chinese Medicine, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, China
| | - Ling Jin
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
| |
Collapse
|
|
12
|
Ghafouri-Fard S, Shoorei H, Bahroudi Z, Hussen BM, Talebi SF, Taheri M, Ayatollahi SA. Nrf2-Related Therapeutic Effects of Curcumin in Different Disorders. Biomolecules 2022; 12:82. [PMID: 35053230 PMCID: PMC8773597 DOI: 10.3390/biom12010082] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 12/18/2021] [Accepted: 12/25/2021] [Indexed: 12/12/2022] Open
Abstract
Curcumin is a natural polyphenol with antioxidant, antibacterial, anti-cancer, and anti-inflammation effects. This substance has been shown to affect the activity of Nrf2 signaling, a pathway that is activated in response to stress and decreases levels of reactive oxygen species and electrophilic substances. Nrf2-related effects of curcumin have been investigated in different contexts, including gastrointestinal disorders, ischemia-reperfusion injury, diabetes mellitus, nervous system diseases, renal diseases, pulmonary diseases, cardiovascular diseases as well as cancers. In the current review, we discuss the Nrf2-mediated therapeutic effects of curcumin in these conditions. The data reviewed in the current manuscript indicates curcumin as a potential activator of Nrf2 and a therapeutic substance for the protection of cells in several pathological conditions.
Collapse
Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 16666-63111, Iran;
| | - Hamed Shoorei
- Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand 9717853577, Iran;
| | - Zahra Bahroudi
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166-15731, Iran;
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil 44001, Kurdistan Region, Iraq;
| | - Seyedeh Fahimeh Talebi
- Department of Pharmacology, College of Pharmacy, Birjand University of Medical Sciences, Birjand 9717853577, Iran;
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, 07743 Jena, Germany
| | | |
Collapse
|
|
13
|
Shahcheraghi SH, Salemi F, Peirovi N, Ayatollahi J, Alam W, Khan H, Saso L. Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects. Molecules 2021; 27:167. [PMID: 35011412 PMCID: PMC8746993 DOI: 10.3390/molecules27010167] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 12/10/2021] [Accepted: 12/14/2021] [Indexed: 12/12/2022] Open
Abstract
Nuclear factor erythroid 2 p45-related factor (2Nrf2) is an essential leucine zipper protein (bZIP) that is primarily located in the cytoplasm under physiological conditions. Nrf2 principally modulates endogenous defense in response to oxidative stress in the brain.In this regard, Nrf2 translocates into the nucleus and heterodimerizes with the tiny Maf or Jun proteins. It then attaches to certain DNA locations in the nucleus, such as electrophile response elements (EpRE) or antioxidant response elements (ARE), to start the transcription of cytoprotective genes. Many neoplasms have been shown to have over activated Nrf2, strongly suggesting that it is responsible for tumors with a poor prognosis. Exactly like curcumin, Zinc-curcumin Zn (II)-curc compound has been shown to induce Nrf2 activation. In the cancer cell lines analyzed, Zinc-curcumin Zn (II)-curc compound can also display anticancer effects via diverse molecular mechanisms, including markedly increasing heme oxygenase-1 (HO-1) p62/SQSTM1 and the Nrf2 protein levels along with its targets. It also strikingly decreases the levels of Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1) protein.As a result, the crosstalk between p62/SQSTM1 and Nrf2 could be used to improve cancer patient response to treatments. The interconnected anti-inflammatory and antioxidative properties of curcumin resulted from its modulatory effects on Nrf2 signaling pathway have been shown to improve insulin resistance. Curcumin exerts its anti-inflammatory impact through suppressing metabolic reactions and proteins such as Keap1 that provoke inflammation and oxidation. A rational amount of curcumin-activated antioxidant Nrf2 HO-1 and Nrf2-Keap1 pathways and upregulated the modifier subunit of glutamate-cysteine ligase involved in the production of the intracellular antioxidant glutathione. Enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). A variety of in vivo, in vitro and clinical studies has been done so far to confirm the protective role of curcumin via Nrf2 regulation. This manuscript is designed to provide a comprehensive review on the molecular aspects of curcumin and its derivatives/analogs via regulation of Nrf2 regulation.
Collapse
Affiliation(s)
- Seyed Hossein Shahcheraghi
- Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd 8916978477, Iran; (S.H.S.); (J.A.)
| | - Fateme Salemi
- School of Medicine, Islamic Azad University of Medical Sciences, Yazd 19395/1495, Iran;
| | - Niloufar Peirovi
- School of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran;
| | - Jamshid Ayatollahi
- Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd 8916978477, Iran; (S.H.S.); (J.A.)
| | - Waqas Alam
- Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan;
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan;
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, 00185 Rome, Italy;
| |
Collapse
|
|
14
|
Xiao S, Deng Y, Shen N, Sun Y, Tang H, Hu P, Ren H, Peng M. Curc-mPEG454, a PEGylated curcumin derivative, as a multi-target anti-fibrotic prodrug. Int Immunopharmacol 2021; 101:108166. [PMID: 34628270 DOI: 10.1016/j.intimp.2021.108166] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/06/2021] [Accepted: 09/14/2021] [Indexed: 10/20/2022]
Abstract
Our previous studies demonstrated that Curc-mPEG454, a curcumin derivative modified with short-chain polyethylene glycol (PEG), not only increased the blood concentration of curcumin, but also retained its anti-inflammatory activity. Here, we aimed to evaluate the anti-fibrotic effect of Curc-mPEG454 on a rat liver fibrosis model induced by carbon tetrachloride (CCl4), and to explore the underlying mechanisms by integrating our total liver RNA sequencing (RNA-seq) data with recent liver single-cell sequencing (scRNA-seq) studies. 50 mg/kg and 100 mg/kg Curc-mPEG454 treatment significantly reduced the elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) induced by CCl4, and the incidence of liver cirrhosis decreased from 75% to 37% and 35%, respectively. RNA-seq analysis revealed that Curc-mPEG454 significantly upregulated aldehyde oxidase 1 (AOX1) while downregulated cytochrome p450 26A1 (CYP26A1) and cytochrome p450 26B1 (CYP26B1) resulting in restoring liver retinoic acid (RA) level, increased glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) expression to synthesize hepatic glutathione (GSH), and inhibited liver inflammation via down-regulating the Prostaglandin E Synthase 2 (PTGES2)/prostacyclin E2 (PGE2) signaling. Integrating scRNA-seq data revealed that Curc-mPEG454 effectively inhibited the expansion of scar-associated macrophage subpopulation and scar-producing myofibroblasts in the damaged liver, and remodeled the fibrotic niche via regulation of ligand-receptor interactions including platelet-derived growth factor-B (PDGF-B)/platelet-derived growth factor receptor-α (PDGFR-α) signaling. As a multi-target prodrug, PEGylated curcumin deserves further attention and research.
Collapse
Affiliation(s)
- Shuang Xiao
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
| | - Yanhong Deng
- People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750004, China
| | - Neng Shen
- Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Yong Sun
- Department of Endocrinology and Metabolism, Dazhou Central Hospital, Dazhou 635000, Sichuan, China
| | - Huadong Tang
- Zhejiang University of Technology, Hangzhou 310014, China
| | - Peng Hu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
| | - Hong Ren
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
| | - Mingli Peng
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
| |
Collapse
|
|
15
|
Haryuna TSH, Amellya D, Munir D, Zubaidah TSH. The Benefits of Curcuminoid to Expression Nuclear Factor Erythroid 2 Related Factor 2 (NRF2) and Signal to Noise Ratio (SNR) Value in the Noise Exposed Organ of Corti of Rattus Norvegicus. Rep Biochem Mol Biol 2021; 10:373-379. [PMID: 34981013 PMCID: PMC8718775 DOI: 10.52547/rbmb.10.3.373] [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: 02/17/2021] [Accepted: 04/06/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Noise-induced hearing loss (NIHL) can cause damage to the cochlea. Curcumin and nuclear factor erythroid 2-related factor 2 (NRF2) are transcription activators that play a crucial role in defence mechanisms against oxidative stress. The aim of this study was to determine the effect of curcuminoid administration on NRF2 expression, in the organ of Corti of cochlea of Rattus norvegicus that were exposed to noise, from the results of the distortion product otoacoustic emission (DPOAE) examination. METHODS We divided 36 rats into six groups including Group 1 (control); Group 2 (noise exposure without curcuminoid administration); Group 3 (noise exposure+curcuminoid dose 100 mg/day for four days); Group 4 (noise exposure+curcuminoid dose 200 mg/day for four days); Group 5 (curcuminoid dose of 100 mg/day for 14 days followed by two days of noise exposure); Group 6 (curcuminoid dose 200 mg/day for 14 days followed by two days of noise exposure). RESULTS Following noise exposure in rats, there was an effect/correlation between NRF2 expression, the SNR values obtained from DPOAE and curcuminoid administration. CONCLUSION There was a correlation between curcuminoid administration, NRF2 expression and DPOAE treatment. Following noise exposure in rats (Rattus norvegicus), SNR values obtained from DPOAE showed improved cochlear function.
Collapse
Affiliation(s)
- Tengku Siti Hajar Haryuna
- Department of Otorhinolaryngology, Faculty of medicine, Universitas Sumatera Utara, Medan, Sumatera Utara, 20155, Indonesia.
| | - Diana Amellya
- Department of Otorhinolaryngology, Faculty of medicine, Universitas Sumatera Utara, Medan, Sumatera Utara, 20155, Indonesia.
| | - Delfitri Munir
- Department of Otorhinolaryngology, Faculty of medicine, Universitas Sumatera Utara, Medan, Sumatera Utara, 20155, Indonesia.
| | - Tengku Siti Harilza Zubaidah
- Department of Ophtalmology, Faculty of medicine, Universitas Sumatera Utara, Medan, Sumatera Utara, 20155, Indonesia.
| |
Collapse
|
|
16
|
Vargas-Mendoza N, García-Machorro J, Angeles-Valencia M, Martínez-Archundia M, Madrigal-Santillán EO, Morales-González Á, Anguiano-Robledo L, Morales-González JA. Liver disorders in COVID-19, nutritional approaches and the use of phytochemicals. World J Gastroenterol 2021; 27:5630-5665. [PMID: 34629792 PMCID: PMC8473593 DOI: 10.3748/wjg.v27.i34.5630] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/19/2021] [Accepted: 07/19/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a "cytokine storm" and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate aminotransferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.
Collapse
Affiliation(s)
- Nancy Vargas-Mendoza
- Laboratorio de Medicina de Conservacion, Instituto Politécnico Nacional, México 11340, Mexico
| | - Jazmín García-Machorro
- Laboratorio de Medicina de Conservacion, Instituto Politécnico Nacional, México 11340, Mexico
| | | | - Marlet Martínez-Archundia
- Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotécnológica, Instituto Politécnico Nacional, México 11340, Mexico
| | | | | | | | - José A Morales-González
- Laboratorio Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México 11340, Mexico
| |
Collapse
|
|
17
|
Guo SP, Chang HC, Lu LS, Liu DZ, Wang TJ. Activation of kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/antioxidant response element pathway by curcumin enhances the anti-oxidative capacity of corneal endothelial cells. Biomed Pharmacother 2021; 141:111834. [PMID: 34153850 DOI: 10.1016/j.biopha.2021.111834] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/04/2021] [Accepted: 06/14/2021] [Indexed: 01/24/2023] Open
Abstract
Fuchs endothelial corneal dystrophy is one of the most common indications for corneal transplantation, and impaired anti-oxidative function is observed in corneal endothelial cells (CECs). Curcumin is well-known for its anti-oxidative property; but, no study has examined the effect of curcumin on anti-oxidative therapeutic roles in corneal endothelial disease. In our experiments, oxidative stress 0.25 mM tert-butyl hydroperoxide for 2 h was induced in immortalized human CECs pretreated with curcumin. Cell behavior and viability, reactive oxygen species production, and the protein expression of the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element (ARE) pathway were examined; the Keap1/Nrf2/ARE pathway is crucial anti-oxidative pathway of curcumin. The results showed that pretreatment with 12.5 μM curcumin significantly reduced the ROS production and improved the survival of CECs under oxidative stress. In addition, curcumin pretreatment significantly increased the expression of nuclear Nrf2, and the productions of superoxide dismutase 1 and heme oxygenase-1, which were the target anti-oxidative enzymes of the Keap1/Nrf2/ARE pathway. Our findings showed that curcumin enhanced the growth and differentiation of CECs under oxidative stress. The activation of Keap1/Nrf2/ARE pathway by curcumin was crucial for CECs to improve their anti-oxidative capacity.
Collapse
Affiliation(s)
- Siao-Pei Guo
- Department of Ophthalmology, Taipei Medical University Hospital, Taipei 110301, Taiwan; Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110301, Taiwan
| | - Hua-Ching Chang
- Department of Dermatology, Taipei Medical University Hospital, Taipei 110301, Taiwan
| | - Long-Sheng Lu
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan; Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110301, Taiwan
| | - Der-Zen Liu
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110301, Taiwan; Medical and Pharmaceutical Industry Technology and Development Center, New Taipei City 248, Taiwan
| | - Tsung-Jen Wang
- Department of Ophthalmology, Taipei Medical University Hospital, Taipei 110301, Taiwan; Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wuxing Street, Xinyi District, Taipei 110301, Taiwan.
| |
Collapse
|
|
18
|
Ashrafizadeh M, Ahmadi Z, Mohammadinejad R, Farkhondeh T, Samarghandian S. Curcumin Activates the Nrf2 Pathway and Induces Cellular Protection Against Oxidative Injury. Curr Mol Med 2021; 20:116-133. [PMID: 31622191 DOI: 10.2174/1566524019666191016150757] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 09/11/2019] [Accepted: 09/18/2019] [Indexed: 12/15/2022]
Abstract
Curcumin is a naturally occurring polyphenol that is isolated from the rhizome of Curcuma longa (turmeric). This medicinal compound has different biological activities, including antioxidant, antibacterial, antineoplastic, and anti-inflammatory. It also has therapeutic effects on neurodegenerative disorders, renal disorders, and diabetes mellitus. Curcumin is safe and well-tolerated at high concentrations without inducing toxicity. It seems that curcumin is capable of targeting the Nrf2 signaling pathway in protecting the cells against oxidative damage. Besides, this strategy is advantageous in cancer therapy. Accumulating data demonstrates that curcumin applies four distinct ways to stimulate the Nrf2 signaling pathway, including inhibition of Keap1, affecting the upstream mediators of Nrf2, influencing the expression of Nrf2 and target genes, and finally, improving the nuclear translocation of Nrf2. In the present review, the effects of curcumin on the Nrf2 signaling pathway to exert its therapeutic and biological activities has been discussed.
Collapse
Affiliation(s)
- Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Zahra Ahmadi
- Department of Basic Science, Veterinary Medicine Faculty, Shushtar University, Khuzestan, Iran
| | - Reza Mohammadinejad
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Tahereh Farkhondeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Saeed Samarghandian
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
| |
Collapse
|
|
19
|
Yousef MI, Abd HH, Helmy YM, Kamel MAN. Synergistic effect of curcumin and chitosan nanoparticles on nano-hydroxyapatite-induced reproductive toxicity in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:9362-9376. [PMID: 33141380 DOI: 10.1007/s11356-020-11395-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 10/22/2020] [Indexed: 06/11/2023]
Abstract
Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (HAPNPs), a prospective nano-biomaterial, is extensively studied, its interaction on the reproductive system following exposure is less exploited. In the present study, male rats were exposed to HAPNPs (300 mg/kg BW) to determine its possible reproductive toxicity. Also, the protective effects of chitosan (CSNPs, 280 mg/kg BW) and/or curcumin (CurNPs, 15 mg/kg BW) nanoparticles against HAPNPs-induced reproductive toxicity were studied. Animals were orally gavage daily with respective doses for 45 consecutive days. The obtained results indicated that HAPNPs caused a significant decrease in sperm count, sperm motility, testosterone hormone, steroidogenic enzymes (17-ketosteroid reductase and 17β-hydroxysteroid dehydrogenase), and antioxidant enzymes (glutathione peroxidase, glutathione S-transferase, catalase, and superoxide dismutase) in addition to total antioxidant capacity and reduced glutathione. LH and FSH, abnormal sperm, oxidative stress parameters (thiobarbituric acid-reactive substances (TBARS), nitric oxide (NO), and 8-hydroxy-deoxyguanosine (8-OHdG)), p53, TNFα, and interleukin-6 were significantly increased. The DNA damage was also analyzed by assaying 8-OHdG level which is considered as an indicator of genotoxicity and also suppression of the gene expression of mtTFA, induction of UCP2. Similarly, the histopathological evaluation was also changed following exposure to HAPNPs. The antioxidant activity of CSNPs and CurNPs showed mitigating effect against reproductive deterioration induced by HAPNPs throughout improvements in semen characteristics, sex hormones, inflammatory factors, and antioxidant status. The present study concluded that HAPNPs induced reproductive toxicity and it is important to use nano-antioxidants CSNPs and CurNPs as protective agents.
Collapse
Affiliation(s)
- Mokhtar Ibrahim Yousef
- Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, 163 Horreya Avenue, Chatby, PO Box 832, Alexandria, 21526, Egypt.
| | - Haitham Hassan Abd
- Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, 163 Horreya Avenue, Chatby, PO Box 832, Alexandria, 21526, Egypt
| | - Yasser Mohamed Helmy
- Scientific Consultant at Pharco Company for Pharmaceutical Products, Alexandria, Egypt
| | - Maher Abdel-Nabi Kamel
- Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt
| |
Collapse
|
|
20
|
Rahban M, Habibi-Rezaei M, Mazaheri M, Saso L, Moosavi-Movahedi AA. Anti-Viral Potential and Modulation of Nrf2 by Curcumin: Pharmacological Implications. Antioxidants (Basel) 2020; 9:E1228. [PMID: 33291560 PMCID: PMC7761780 DOI: 10.3390/antiox9121228] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 11/29/2020] [Accepted: 12/01/2020] [Indexed: 12/13/2022] Open
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor that maintains the cell's redox balance state and reduces inflammation in different adverse stresses. Under the oxidative stress, Nrf2 is separated from Kelch-like ECH-associated protein 1 (Keap1), which is a key sensor of oxidative stress, translocated to the nucleus, interacts with the antioxidant response element (ARE) in the target gene, and then activates the transcriptional pathway to ameliorate the cellular redox condition. Curcumin is a yellow polyphenolic curcuminoid from Curcuma longa (turmeric) that has revealed a broad spectrum of bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Curcumin significantly increases the nuclear expression levels and promotes the biological effects of Nrf2 via the interaction with Cys151 in Keap1, which makes it a marvelous therapeutic candidate against a broad range of oxidative stress-related diseases, including type 2 diabetes (T2D), neurodegenerative diseases (NDs), cardiovascular diseases (CVDs), cancers, viral infections, and more recently SARS-CoV-2. Currently, the multifactorial property of the diseases and lack of adequate medical treatment, especially in viral diseases, result in developing new strategies to finding potential drugs. Curcumin potentially opens up new views as possible Nrf2 activator. However, its low bioavailability that is due to low solubility and low stability in the physiological conditions is a significant challenge in the field of its efficient and effective utilization in medicinal purposes. In this review, we summarized recent studies on the potential effect of curcumin to activate Nrf2 as the design of potential drugs for a viral infection like SARS-Cov2 and acute and chronic inflammation diseases in order to improve the cells' protection.
Collapse
Affiliation(s)
- Mahdie Rahban
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran 1417614335, Iran;
| | - Mehran Habibi-Rezaei
- School of Biology, College of Science, University of Tehran, Tehran 1417614335, Iran
- Center of Excellence in NanoBiomedicine, University of Tehran, Tehran 1417614335, Iran
| | - Mansoureh Mazaheri
- Research Center of Food Technology and Agricultural Products, Department of Food Toxicology, Standard Research Institute, Karaj 3158777871, Iran;
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy;
| | - Ali A. Moosavi-Movahedi
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran 1417614335, Iran;
- UNESCO Chair on Interdisciplinary Research in Diabetes, University of Tehran, Tehran 1417614335, Iran
| |
Collapse
|
|
21
|
Roife D, Sarcar B, Fleming JB. Stellate Cells in the Tumor Microenvironment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1263:67-84. [PMID: 32588324 DOI: 10.1007/978-3-030-44518-8_6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
As tumor microenvironments share many of the same qualities as chronic wounds, attention is turning to the wound-repair cells that support the growth of cancerous cells. Stellate cells are star-shaped cells that were first discovered in the perisinusoidal spaces in the liver and have been found to support wound healing by the secretion of growth factors and extracellular matrix. They have since been also found to serve a similar function in the pancreas. In both organs, the wound-healing process may become dysregulated and lead to pathological fibrosis (also known as cirrhosis in the liver). In recent years there has been increasing attention paid to the role of these cells in tumor formation and progression. They may be a factor in initiating the first steps of carcinogenesis such as with liver cirrhosis and hepatocellular carcinoma and also contribute to continued tumor growth, invasion, metastasis, evasion of the immune system, and resistance to chemotherapy, in cancers of both the liver and pancreas. In this chapter we aim to review the structure and function of hepatic and pancreatic stellate cells and their contributions to the tumor microenvironment in their respective cancers and also discuss potential new targets for cancer therapy based on our new understanding of these vital components of the tumor stroma.
Collapse
Affiliation(s)
- David Roife
- Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL, USA.,Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Bhaswati Sarcar
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Jason B Fleming
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
| |
Collapse
|
|
22
|
Ceccherini E, Cecchettini A, Morales MA, Rocchiccioli S. The Potentiality of Herbal Remedies in Primary Sclerosing Cholangitis: From In Vitro to Clinical Studies. Front Pharmacol 2020; 11:813. [PMID: 32587513 PMCID: PMC7298067 DOI: 10.3389/fphar.2020.00813] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 05/19/2020] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis is a complex pathological condition, characterized by chronic inflammation and fibrosis of the biliary epithelium. Without proper clinical management, progressive bile ducts and liver damage lead to cirrhosis and, ultimately, to liver failure. The known limited role of current drugs for treating this cholangiopathy has driven researchers to assess alternative therapeutic options. Some herbal remedies and their phytochemicals have shown anti-fibrotic properties in different experimental models of hepatic diseases and, occasionally, in clinical trials in primary sclerosing cholangitis patients; however their mechanism of action is not completely understood. This review briefly examines relevant studies focusing on the potential anti-fibrotic properties of Silybum marianum, Curcuma longa, Salvia miltiorrhiza, and quercetin. Each natural product is individually reviewed and the possible mechanisms of action discussed.
Collapse
Affiliation(s)
- Elisa Ceccherini
- Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy
| | - Antonella Cecchettini
- Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Silvia Rocchiccioli
- Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy
| |
Collapse
|
|
23
|
Huang H, Zhong L, Zhou J, Hou Y, Zhang Z, Xing X, Sun J. Leydig-like cells derived from reprogrammed human foreskin fibroblasts by CRISPR/dCas9 increase the level of serum testosterone in castrated male rats. J Cell Mol Med 2020; 24:3971-3981. [PMID: 32160419 PMCID: PMC7171312 DOI: 10.1111/jcmm.15018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 12/28/2019] [Accepted: 01/06/2020] [Indexed: 12/13/2022] Open
Abstract
In the past few years, Leydig cell (LC) transplantation has been regarded as an effective strategy for providing physiological patterns of testosterone in vivo. Recently, we have successfully converted human foreskin fibroblasts (HFFs) into functional Leydig‐like cells (iLCs) in vitro by using the CRISPR/dCas9 system, which shows promising potential for seed cells. However, it is not known whether the reprogrammed iLCs can survive or restore serum testosterone levels in vivo. Therefore, in this study, we evaluate whether reprogrammed iLCs can restore the serum testosterone levels of castrated rats when they are transplanted into the fibrous capsule. We first developed the castrated Sprague Dawley rat model through bilateral orchiectomy and subsequently injected extracellular matrix gel containing transplanted cells into the fibrous capsule of castrated rats. Finally, we evaluated dynamic serum levels of testosterone and luteinizing hormone (LH) in castrated rats, the survival of implanted iLCs, and the expression levels of Leydig steroidogenic enzymes by immunofluorescence staining and Western blotting. Our results demonstrated that implanted iLCs could partially restore the serum testosterone level of castrated rats, weakly mimic the role of adult Leydig cells in the hypothalamic‐pituitary‐gonadal axis for a short period, and survive and secrete testosterone, through 6 weeks after transplantation. Therefore, this study may be valuable for treating male hypogonadism in the future.
Collapse
Affiliation(s)
- Hua Huang
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liang Zhong
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jin Zhou
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanping Hou
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhiyuan Zhang
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyu Xing
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Sun
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
|
24
|
Wang K, Xu J, Liu Y, Cui Z, He Z, Zheng Z, Huang X, Zhang Y. Self-assembled Angelica sinensis polysaccharide nanoparticles with an instinctive liver-targeting ability as a drug carrier for acute alcoholic liver damage protection. Int J Pharm 2020; 577:118996. [DOI: 10.1016/j.ijpharm.2019.118996] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 12/07/2019] [Accepted: 12/23/2019] [Indexed: 12/11/2022]
|
|
25
|
Bosello Travain V, Miotto G, Vučković AM, Cozza G, Roveri A, Toppo S, Ursini F, Venerando R, Zaccarin M, Maiorino M. Lack of glutathione peroxidase-8 in the ER impacts on lipid composition of HeLa cells microsomal membranes. Free Radic Biol Med 2020; 147:80-89. [PMID: 31857233 DOI: 10.1016/j.freeradbiomed.2019.12.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 12/09/2019] [Indexed: 01/04/2023]
Abstract
GPx8 is a glutathione peroxidase homolog inserted in the membranes of endoplasmic reticulum (ER), where it seemingly plays a role in controlling redox status by preventing the spill of H2O2. We addressed the impact of GPx8 silencing on the lipidome of microsomal membranes, using stably GPx8-silenced HeLa cells. The two cell lines were clearly separated by Principal Component Analysis (PCA) and Partial Least Square Discriminant analysis (PLS-DA) of lipidome. Considering in detail the individual lipid classes, we observed that unsaturated glycerophospholipids (GPL) decreased, while only in phosphatidylinositols (PI) a substitution of monounsaturated fatty acids (MUFA) for polyunsaturated fatty acids (PUFA) was observed. Among sphingolipids (SL), ceramides (CER) decreased while sphingomyelins (SM) and neutral glycophingolipids (nGSL) increased. Here, in addition, longer chains than in controls in the amide fatty acid were present. The increase up to four folds of the CER (d18:1; c24:0) containing three hexose units, was the most remarkable species increasing in the differential lipidome of siGPx8 cells. Quantitative RT-PCR complied with lipidomic analysis specifically showing an increased expression of: i) acyl-CoA synthetase 5 (ACSL5); ii) CER synthase 2 and 4; iii) CER transporter (CERT); iv) UDP-glucosyl transferase (UDP-GlcT), associated to a decreased expression of UDP-galactosyl transferase (UDP-GalT). A role of the unfolded protein response (UPR) and the spliced form of the transcription factor XBP1 on the transcriptional changes of GPx8 silenced cells was ruled-out. Similarly, also the involvement of Nrf2 and NF-κB. Altogether our results indicate that GPx8-silencing of HeLa yields a membrane depleted by about 24% of polyunsaturated GPL and a corresponding increase of saturated or monounsaturated SM and specific nGSL. This is tentatively interpreted as an adaptive mechanism leading to an increased resistance to radical oxidations. Moreover, the marked shift of fatty acid composition of PI emerges as a possibly relevant issue in respect to the impact of GPx8 on signaling pathways.
Collapse
Affiliation(s)
- Valentina Bosello Travain
- Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Giovanni Miotto
- CRIBI Biotechnology Center, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Ana-Marija Vučković
- Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Giorgio Cozza
- Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Antonella Roveri
- Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Stefano Toppo
- CRIBI Biotechnology Center, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Fulvio Ursini
- Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Rina Venerando
- Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Mattia Zaccarin
- Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| | - Matilde Maiorino
- Department of Molecular Medicine, University of Padova, Viale G. Colombo, 3, I-35131, Padova, Italy.
| |
Collapse
|
|
26
|
Roudsari NM, Lashgari NA, Momtaz S, Farzaei MH, Marques AM, Abdolghaffari AH. Natural polyphenols for the prevention of irritable bowel syndrome: molecular mechanisms and targets; a comprehensive review. Daru 2019; 27:755-780. [PMID: 31273572 PMCID: PMC6895345 DOI: 10.1007/s40199-019-00284-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Accepted: 06/14/2019] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a well diagnosed disease, thoroughly attributed to series of symptoms criteria that embrace a broad range of abdominal complainers. Such criteria help to diagnosis the disease and can guide controlled clinical trials to seek new therapeutic agents. Accordingly, a verity of mechanisms and pathophysiological conditions including inflammation, oxidative stress, lipid peroxidation and different life styles are involved in IBS. Predictably, diverse therapeutic approaches are available and prescribed by clinicians due to major manifestations (i.e., diarrhea-predominance, constipation-predominance, abdominal pain and visceral hypersensitivity), psychological disturbances, and patient preferences between herbal treatments versus pharmacological therapies, dietary or microbiological approaches. Herein, we gathered the latest scientific data between 1973 and 2019 from databases such as PubMed, Google Scholar, Scopus and Cochrane library on relevant studies concerning beneficial effects of herbal treatments for IBS, in particular polyphenols. This is concluded that polyphenols might be applicable for preventing IBS and improving the IBS symptoms, mainly through suppressing the inflammatory signaling pathways, which nowadays are known as novel platform for the IBS management. Graphical abstract.
Collapse
Affiliation(s)
- Nazanin Momeni Roudsari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Naser-Aldin Lashgari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - André M Marques
- Oswaldo Cruz Foundation (FIOCRUZ), Institute of Technology in Pharmaceuticals (Farmanguinhos), Rio de Janeiro, RJ, Brazil
| | - Amir Hossein Abdolghaffari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
- Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
- Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| |
Collapse
|
|
27
|
Burge K, Gunasekaran A, Eckert J, Chaaban H. Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection. Int J Mol Sci 2019; 20:ijms20081912. [PMID: 31003422 PMCID: PMC6514688 DOI: 10.3390/ijms20081912] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 04/15/2019] [Accepted: 04/17/2019] [Indexed: 02/07/2023] Open
Abstract
Intestinal inflammatory diseases, such as Crohn’s disease, ulcerative colitis, and necrotizing enterocolitis, are becoming increasingly prevalent. While knowledge of the pathogenesis of these related diseases is currently incomplete, each of these conditions is thought to involve a dysfunctional, or overstated, host immunological response to both bacteria and dietary antigens, resulting in unchecked intestinal inflammation and, often, alterations in the intestinal microbiome. This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation, potentially resulting in systemic inflammation and, in severe cases, sepsis. Chronic inflammation of this nature, in the case of inflammatory bowel disease, can even spur cancer growth in the longer-term. Recent research has indicated certain natural products with anti-inflammatory properties, such as curcumin, can help tame the inflammation involved in intestinal inflammatory diseases, thus improving intestinal barrier function, and potentially, clinical outcomes. In this review, we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its antimicrobial and immunomodulatory properties, as well as its potential to alter the intestinal microbiome. Curcumin may play a significant role in intestinal inflammatory disease treatment in the future, particularly as an adjuvant therapy.
Collapse
Affiliation(s)
- Kathryn Burge
- Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, 1200 North Everett Drive, ETNP7504, Oklahoma City, OK 73104, USA.
| | - Aarthi Gunasekaran
- Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, 1200 North Everett Drive, ETNP7504, Oklahoma City, OK 73104, USA.
| | - Jeffrey Eckert
- Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, 1200 North Everett Drive, ETNP7504, Oklahoma City, OK 73104, USA.
| | - Hala Chaaban
- Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, 1200 North Everett Drive, ETNP7504, Oklahoma City, OK 73104, USA.
| |
Collapse
|
|
28
|
Xu J, Zhou L, Weng Q, Xiao L, Li Q. Curcumin analogues attenuate Aβ 25-35-induced oxidative stress in PC12 cells via Keap1/Nrf2/HO-1 signaling pathways. Chem Biol Interact 2019; 305:171-179. [PMID: 30946834 DOI: 10.1016/j.cbi.2019.01.010] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Revised: 12/21/2018] [Accepted: 01/06/2019] [Indexed: 12/24/2022]
Abstract
Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer's Disease (AD). In the present study, we adopted an vitro model that involved Aβ25-35-induced oxidative damage in PC12 cells. Aβ25-35 (10 μΜ) treatment for 24 h induced significant cell death and oxidative stress in PC12 cells, as evidenced by cell viability reduction, LDH release, ROS accumulation and increased production MDA. (1E,4E)-1, 5-bis(4-hydroxy-3-methoxyphenyl) penta-1, 4-dien-3-one (CB) and (1E, 4E)-1-(3, 4-dimethoxyphenyl)-5-(4-hydroxy-3, 5-dime-thoxyphenyl) Penta-1, 4-dien-3-one (FE), two Curcumin (Cur) analogues displayed neuroprotective effects against Aβ25-35-induced oxidative damage and cellular apoptosis in PC12 cells. Here, we investigated three different treatment ways of CB and FE. It was interesting that post-treatment of CB and FE (restoring way) showed similar effect to the preventive way, while attenuating way did not show any protective effect. We found that low dose CB and FE increased transcriptional factor NF-E2-related factor 2 (Nrf2)/hemo oxygenase 1 (HO-1) protein expression and decreased Kelch-like ECH-associated protein 1 (Keap1) in PC 12 cells. In addition, CB and FE promoted the translation of Nrf2 into nuclear and enhanced the activity of superoxide dismutase (SOD)/catalase, which confirmed cytoprotection against Aβ25-35-induced oxidative damage. Moreover, CB and FE could increase Bcl-2 expression level, decrease the level of Bax and Cyt-c in Aβ25-35-treated PC12 cells. Ultimately, the neuroprotective effect of CB and FE provides a pharmacological basis for its clinical use in prevention and treatment of AD.
Collapse
Affiliation(s)
- Jialin Xu
- College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Leilei Zhou
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Qi Weng
- College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Linxia Xiao
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, Zhejiang, 310014, PR China
| | - Qingyong Li
- College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, Zhejiang, 310014, PR China; Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, Zhejiang, 310014, PR China.
| |
Collapse
|
|
29
|
Xu MB, Rong PQ, Jin TY, Zhang PP, Liang HY, Zheng GQ. Chinese Herbal Medicine for Wilson's Disease: A Systematic Review and Meta-Analysis. Front Pharmacol 2019; 10:277. [PMID: 31001112 PMCID: PMC6455065 DOI: 10.3389/fphar.2019.00277] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 03/04/2019] [Indexed: 02/06/2023] Open
Abstract
Wilson's disease (WD) is a rare autosomal recessive inherited disorder of chronic copper toxicosis. Currently, Chinese herbal medicines (CHM) is widely used for WD. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for WD and its possible mechanisms. Randomized-controlled clinical trials (RCTs), which compared CHM with Western conventional medicine or placebo for WD, were searched in six databases from inception to July 2017. The methodological quality was assessed using 7-item criteria from the Cochrane's collaboration tool. All the data were analyzed using Rev-Man 5.3 software. Eighteen studies involving 1,220 patients were identified for the final analyses. A score of study quality ranged from 2/7 to 4/7 points. Meta-analyses showed that CHM could significantly increase 24-h urinary copper excretion and improve liver function and the total clinical efficacy rate for WD compared with control (p < 0.05). Additionally, CHM was well tolerated in patients with WD. The underlying mechanisms of CHM for WD are associated with reversing the ATP7B mutants, exerting anti-oxidation, anti-inflammation, and anti-hepatic fibrosis effects. In conclusion, despite the apparent positive results, the present evidence supports, to a limited extent because of the methodological flaws and CHM heterogeneity, that CHM paratherapy can be used for patients with WD but could not be recommended as monotherapy in WD. Further rigorous RCTs focusing on individual CHM formula for WD are warranted.
Collapse
Affiliation(s)
| | | | | | | | | | - Guo-Qing Zheng
- Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
|
30
|
El-Khadragy MF, Al-Olayan EM, Elmallah MIY, Alharbi AM, Yehia HM, Abdel Moneim AE. Probiotics and yogurt modulate oxidative stress and fibrosis in livers of Schistosoma mansoni-infected mice. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 19:3. [PMID: 30606163 PMCID: PMC6318950 DOI: 10.1186/s12906-018-2406-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Accepted: 12/07/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND Considerable morbidity, mortality, and economic loss result from schistosomiasis infection. Deposition of Schistosoma eggs in the hepatic portal vein is considered as the main causative agent for the development of liver fibrosis and subsequent liver cirrhosis. Probiotics are exogenous and beneficial microorganisms to living hosts against the harmful effect of many parasites. Strong evidence suggests the importance of probiotics in the control strategy of helminth. The ultimate goal of this study is to evaluate the protective effect of probiotics and yogurt on Schistosoma mansoni-induced oxidative stress and hepatic fibrosis in mice. METHODS Mice were infected by tail immersion of schistosomal cercariae followed by an oral treatment with either probiotics or yogurt for one week before infection and immediately post-infection. Mice were scarified on day 56 following infection with S. mansoni and liver sample were obtained. RESULTS We showed that oral administration of probiotics or yogurt revealed a significant reduction in worm number, egg load, and granuloma size in liver tissue, which is mainly assigned to the decreased expression level of matrix metalloproteinases 9 (MMP-9) in liver tissue. A significant reduction in the oxidative stress markers-induced by S. mansoni infection including lipid peroxidation and nitrite/nitrate was also detected. The level of some antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and reduced glutathione was greatly enhanced. Furthermore, treatment with probiotics or yogurt inhibited apoptosis in hepatic tissue, which is mainly assigned to the decreased expression level of caspases-3 in liver tissue. CONCLUSION Our findings represent the promising anti-schistosomal activities of probiotics and yogurt.
Collapse
Affiliation(s)
- Manal F. El-Khadragy
- Chair Vaccines Research of Infectious Diseases, Faculty of Science, King Saud University, Riyadh, Saudi Arabia
- Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
| | - Ebtesam M. Al-Olayan
- Chair Vaccines Research of Infectious Diseases, Faculty of Science, King Saud University, Riyadh, Saudi Arabia
- Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia
| | | | - Afra M. Alharbi
- Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia
| | - Hany M. Yehia
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
- Department of Food Science and Nutrition, Faculty of Home Economics, Helwan University, Cairo, Egypt
| | - Ahmed E. Abdel Moneim
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
| |
Collapse
|
|
31
|
Curcumin Exerted Neuroprotection against Ozone-Induced Oxidative Damage and Decreased NF- κB Activation in Rat Hippocampus and Serum Levels of Inflammatory Cytokines. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:9620684. [PMID: 30693069 PMCID: PMC6332875 DOI: 10.1155/2018/9620684] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 10/01/2018] [Accepted: 10/23/2018] [Indexed: 12/14/2022]
Abstract
Ozone is a harmful tropospheric pollutant, causing the formation of reactive oxygen and nitrogen species that lead to oxidative damage in living beings. NF-κB can be activated in response to oxidative damage, inducing an inflammatory response. Nowadays, there are no reliable results that consolidate the use of antioxidants to protect from damage caused by ozone, particularly in highly polluted cities. Curcumin has a strong antioxidant activity and is a potent inhibitor of NF-κB activation with no side effects. The aim of this study is to evaluate the effect of curcumin in preventive and therapeutic approaches against oxidative damage, NF-κB activation, and the rise in serum levels of IL-1β and TNF-α induced by acute and chronic exposure to ozone in rat hippocampus. One hundred male Wistar rats were distributed into five groups; the intact control, curcumin-fed control, the ozone-exposed group, and the preventive and therapeutic groups. These last two groups were exposed to ozone and received food supplemented with curcumin. Lipid peroxidation was determined by spectrophotometry, and protein oxidation was evaluated by immunodetection of carbonylated proteins and densitometry analysis. Activation of NF-κB was assessed by electrophoretic mobility shift assay (EMSA), and inflammatory cytokines (IL-1β and TNF-α) were determined by ELISA. Curcumin decreased NF-κB activation and serum levels of inflammatory cytokines as well as protein and lipid oxidation, in both therapeutic and preventive approaches. Curcumin has proven to be a phytodrug against the damage caused by the environmental exposure to ozone.
Collapse
|
|
32
|
Lin XP, Xue C, Zhang JM, Wu WJ, Chen XY, Zeng YM. Curcumin Inhibits Lipopolysaccharide-Induced Mucin 5AC Hypersecretion and Airway Inflammation via Nuclear Factor Erythroid 2-Related Factor 2. Chin Med J (Engl) 2018; 131:1686-1693. [PMID: 29998888 PMCID: PMC6048919 DOI: 10.4103/0366-6999.235863] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: Excess mucus production is an important pathophysiological feature of chronic inflammatory airway diseases. Effective therapies are currently lacking. The aim of the study was to evaluate the effects of curcumin (CUR) on lipopolysaccharide (LPS)-induced mucus secretion and inflammation, and explored the underlying mechanism in vivo and in vitro. Methods: For the in vitro study, human bronchial epithelial (NCI-H292) cells were pretreated with CUR or vehicle for 30 min, and then exposed to LPS for 24 h. Next, nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down with Nrf2 small interfering RNA (siRNA) to confirm the specific role of Nrf2 in mucin regulation of CUR in NCI-H292 cells. In vivo, C57BL/6 mice were randomly assigned to three groups (n = 7 for each group): control group, LPS group, and LPS + CUR group. Mice in LPS and LPS + CUR group were injected with saline or CUR (50 mg/kg) intraperitoneally 2 h before intratracheal instillation with LPS (100 μg/ml) for 7 days. Cell lysate and lung tissue were obtained to measured Mucin 5AC (MUC5AC) and Nrf2 mRNA and protein expression by a real-time polymerase chain reaction and Western blotting. Bronchoalveolar lavage fluid (BALF) was collected to enumerate total cells and neutrophils. Histopathological changes of the lung were observed. Data were analyzed by one-way analysis of variance. Student's t-test was used when two groups were compared. Results: CUR significantly decreased the expression of MUC5AC mRNA and protein in NCI-H292 cells exposed to LPS. This effect was dose dependent (2.424 ± 0.318 vs. 7.169 ± 1.785, t = 4.534, and 1.060 ± 0.197 vs. 2.340 ± 0.209, t = 7.716; both P < 0.05, respectively) and accompanied by increased mRNA and protein expression of Nrf2 (1.952 ± 0.340 vs. 1.142 ± 0.176, t = −3.661, and 2.010 ± 0.209 vs. 1.089 ± 0.132, t = −6.453; both P < 0.05, respectively). Furthermore, knockdown of Nrf2 with siRNA increased MUC5AC mRNA expression by 47.7%, compared with levels observed in the siRNA-negative group (6.845 ± 1.478 vs. 3.391 ± 0.517, t = −3.821, P < 0.05). Knockdown of Nrf2 with siRNA also markedly increased MUC5AC protein expression in NCI-H292 cells. CUR also significantly decreased LPS-induced mRNA and protein expression of MUC5AC in mouse lung (1.672 ± 0.721 vs. 5.961 ± 2.452, t = 2.906, and 0.480 ± 0.191 vs. 2.290 ± 0.834, t = 3.665, respectively; both P < 0.05). Alcian blue/periodic acid-Schiff staining also showed that CUR suppressed mucin production. Compared with the LPS group, the numbers of inflammatory cells (247 ± 30 vs. 334 ± 24, t = 3.901, P < 0.05) and neutrophils (185 ± 22 vs. 246 ± 20, t = 3.566, P < 0.05) in BALF decreased in the LPS + CUR group, as well as reduced inflammatory cell infiltration in lung tissue. Conclusion: CUR inhibits LPS-induced airway mucus hypersecretion and inflammation through activation of Nrf2 possibly.
Collapse
Affiliation(s)
- Xiao-Ping Lin
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University; Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian 362000, China
| | - Cheng Xue
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University; Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian 362000, China
| | - Jia-Min Zhang
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University; Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian 362000, China
| | - Wei-Jing Wu
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University; Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian 362000, China
| | - Xiao-Yang Chen
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University; Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian 362000, China
| | - Yi-Ming Zeng
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University; Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian 362000, China
| |
Collapse
|
|
33
|
Wang H, Sun Z, Liu D, Li X, Rehman RU, Wang H, Wu Z. Apple phlorizin attenuates oxidative stress in Drosophila melanogaster. J Food Biochem 2018; 43:e12744. [PMID: 31353567 DOI: 10.1111/jfbc.12744] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Revised: 10/17/2018] [Accepted: 10/30/2018] [Indexed: 12/17/2022]
Abstract
Apple phlorizin has a lot of applications owing to its antioxidant and hepatoprotective properties. This study explored the antioxidant effects and life span-prolonging activity of apple phlorizin in Drosophila melanogaster. Treatment with apple phlorizin was found to significantly extend the life span and ameliorate the age-related decline of locomotor function. This life span-extending activity was associated with the increased activity of superoxide dismutase, catalase, mRNA expression of glutamate-cysteine ligase catalytic subunit, cap-n-collar (cnc, homologue of mammalian Nrf2 gene), Keap1, and deacetylase sir2, as well as the downregulation of methuselah. Computational analysis suggested phlorizin could work as a Nrf2 activator and exert its biological activities by interfering with the Keap1 and Nrf2 binding. Therefore, it was concluded that the antioxidant and anti-aging effects of phlorizin might, at least in part, be mediated through the cooperation with the endogenous stress defense system. PRACTICAL APPLICATIONS: Phlorizin, from apple peel, has been used as a nutrient for over 100 years. To date, despite extensive research on phlorizin, a report on its effect on the antioxidant system in fruit flies is yet lacking. This report demonstrates that phlorizin can exert a protective effect on antioxidant issues and prolong life in fruit flies, which is valuable in the rational utilization of phlorizin in functional foods.
Collapse
Affiliation(s)
- Hao Wang
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin, China.,Key Laboratory of Food Nutrition and Safety, Ministry of Education, Tianjin University of Science & Technology, Tianjin, China
| | - Zhenou Sun
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin, China.,College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Dong Liu
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin, China
| | - Xiang Li
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin, China
| | - Rizwan-Ur Rehman
- Center for Food Safety Standards, The University of Lahore-Gujrat Campus, Pakistan
| | - Huali Wang
- China National Center for Food Safety Risk Assessment, Beijing, China
| | - Zijian Wu
- College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, China
| |
Collapse
|
|
34
|
Abou El-ezz D, Maher A, Sallam N, El-brairy A, Kenawy S. Trans-cinnamaldehyde Modulates Hippocampal Nrf2 Factor and Inhibits Amyloid Beta Aggregation in LPS-Induced Neuroinflammation Mouse Model. Neurochem Res 2018; 43:2333-2342. [DOI: 10.1007/s11064-018-2656-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 09/06/2018] [Accepted: 10/03/2018] [Indexed: 12/29/2022]
|
|
35
|
Curc-mPEG454, a PEGylated Curcumin Derivative, Improves Anti-inflammatory and Antioxidant Activities: a Comparative Study. Inflammation 2018; 41:579-594. [PMID: 29234949 DOI: 10.1007/s10753-017-0714-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
We previously demonstrated that a PEGylated curcumin (Curc-mPEG454) significantly inhibited cyclooxygenase 2 (COX-2) expression and improved the progression of liver fibrosis. The current study systematically evaluates its anti-inflammatory and antioxidant activities in vitro in a comparative study with curcumin, aspirin, NS-398, and vitamin C. RAW264.7 murine macrophages were pretreated with Curc-mPEG454, curcumin, aspirin, NS-398, or vitamin C at the indicated concentration for 2 h; then, the cells were stimulated with 1 μg/mL lipopolysaccharide (LPS) for 24 h. The levels of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, PGE2, NO, and GSH, and the activities of COX-2, SOD, and CAT, and the transcription factors involved in inflammation, such as NF-κB, c-Jun, and Nrf2, were measured. Curc-mPEG454 showed lower cytotoxicity (IC50 57.8 μM) when compared with that of curcumin (IC50 32.6 μM) and inhibited the release of the inflammatory cytokines IL-6, TNF-α, IL-1β, and MCP-1 in a concentration-dependent manner. At 16 μM, Curc-mPEG454 was most potent in the suppression of COX-2 expression at a transcriptional level rather than in the suppression of the catalytic activity of COX-2. Like curcumin, Curc-mPEG454 significantly reduced intracellular ROS production and enhanced the activities of SOD and CAT and the level of GSH to protect cells from LPS-induced oxidative injury. Further, its anti-inflammatory and antioxidation mechanisms are related to inhibition of NF-κB p65 nuclear translocation and c-Jun phosphorylation and to activation of Nrf2. Taken together, these findings indicate that PEGylation of curcumin not only improves its biological properties but also interferes with multiple targets involved in the inflammatory response. Curc-mPEG454 is a powerful and beneficial anti-inflammatory and antioxidant agent that merits further investigation. Graphical Abstract ᅟ.
Collapse
|
|
36
|
Chatterjee P, Yadav M, Chauhan N, Huang Y, Luo Y. Cancer Cell Metabolism Featuring Nrf2. Curr Drug Discov Technol 2018; 17:263-271. [PMID: 30207221 DOI: 10.2174/1570163815666180911092443] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 08/14/2018] [Accepted: 08/31/2018] [Indexed: 11/22/2022]
Abstract
Although the major role of Nrf2 has long been established as a transcription factor for providing cellular protection against oxidative stress, multiple pieces of research and reviews now claim exactly the opposite. The dilemma - "to activate or inhibit" the protein requires an immediate answer, which evidently links cellular metabolism to the causes and purpose of cancer. Profusely growing cancerous cells have prolific energy requirements, which can only be fulfilled by modulating cellular metabolism. This review highlights the cause and effect of Nrf2 modulation in cancer that in turn channelize cellular metabolism, thereby fulfilling the energy requirements of cancer cells. The present work also highlights the purpose of genetic mutations in Nrf2, in relation to cellular metabolism in cancer cells, thus pointing out a newer approach where parallel mutations may be the key factor to decide whether to activate or inhibit Nrf2.
Collapse
Affiliation(s)
- Payal Chatterjee
- Department of Pharmaceutical Sciences, Softvision College, Indore, MP 452010, India.,Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Mukesh Yadav
- Department of Pharmaceutical Sciences, Softvision College, Indore, MP 452010, India
| | - Namrata Chauhan
- Department of Pharmaceutical Sciences, Softvision College, Indore, MP 452010, India
| | - Ying Huang
- Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Yun Luo
- Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA 91766, United States
| |
Collapse
|
|
37
|
Farzaei MH, Zobeiri M, Parvizi F, El-Senduny FF, Marmouzi I, Coy-Barrera E, Naseri R, Nabavi SM, Rahimi R, Abdollahi M. Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective. Nutrients 2018; 10:855. [PMID: 29966389 PMCID: PMC6073929 DOI: 10.3390/nu10070855] [Citation(s) in RCA: 256] [Impact Index Per Article: 36.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 06/23/2018] [Accepted: 06/28/2018] [Indexed: 12/12/2022] Open
Abstract
Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental pollutants and dietary components, which in turn results in progression of liver injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver fibrosis and cirrhosis. During the past 30 years and even after the major progress in the liver disease management, millions of people worldwide still suffer from an acute or chronic liver condition. Curcumin is one of the most commonly used indigenous molecules endowed by various shielding functionalities that protects the liver. The aim of the present study is to comprehensively review pharmacological effects and molecular mechanisms, as well as clinical evidence, of curcumin as a lead compound in the prevention and treatment of oxidative associated liver diseases. For this purpose, electronic databases including “Scopus,” “PubMed,” “Science Direct” and “Cochrane library” were extensively searched with the keywords “curcumin or curcuminoids” and “hepatoprotective or hepatotoxicity or liver” along with “oxidative or oxidant.” Results showed that curcumin exerts remarkable protective and therapeutic effects of oxidative associated liver diseases through various cellular and molecular mechanisms. Those mechanisms include suppressing the proinflammatory cytokines, lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as well as ameliorating cellular responses to oxidative stress such as the expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself acts as a free radical scavenger over the activity of different kinds of ROS via its phenolic, β-diketone and methoxy group. Further clinical studies are still needed in order to recognize the structure-activity relationships and molecular mechanisms of curcumin in oxidative associated liver diseases.
Collapse
Affiliation(s)
- Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
| | - Mahdi Zobeiri
- Internal Medicine Department, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
| | - Fatemeh Parvizi
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
| | - Fardous F El-Senduny
- Biochemistry division, Chemistry Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt.
| | - Ilias Marmouzi
- Laboratory of Pharmacology and Toxicology Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10100, Morocco.
| | - Ericsson Coy-Barrera
- Bioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Campus Nueva Granada, Cajicá 250247, Colombia.
| | - Rozita Naseri
- Internal Medicine Department, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baghyatollah University of Medical Sciences, Tehran 1435916471, Iran.
| | - Roja Rahimi
- Department of Persian Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran 1416663361, Iran.
| | - Mohammad Abdollahi
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS) and Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
| |
Collapse
|
|
38
|
Maiti P, Dunbar GL. Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases. Int J Mol Sci 2018; 19:E1637. [PMID: 29857538 PMCID: PMC6032333 DOI: 10.3390/ijms19061637] [Citation(s) in RCA: 132] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 05/02/2018] [Accepted: 05/25/2018] [Indexed: 12/27/2022] Open
Abstract
Progressive accumulation of misfolded amyloid proteins in intracellular and extracellular spaces is one of the principal reasons for synaptic damage and impairment of neuronal communication in several neurodegenerative diseases. Effective treatments for these diseases are still lacking but remain the focus of much active investigation. Despite testing several synthesized compounds, small molecules, and drugs over the past few decades, very few of them can inhibit aggregation of amyloid proteins and lessen their neurotoxic effects. Recently, the natural polyphenol curcumin (Cur) has been shown to be a promising anti-amyloid, anti-inflammatory and neuroprotective agent for several neurodegenerative diseases. Because of its pleotropic actions on the central nervous system, including preferential binding to amyloid proteins, Cur is being touted as a promising treatment for age-related brain diseases. Here, we focus on molecular targeting of Cur to reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in different animal models of neurodegenerative diseases. We specifically highlight Cur as a potential treatment for Alzheimer's, Parkinson's, Huntington's, and prion diseases. In addition, we discuss the major issues and limitations of using Cur for treating these diseases, along with ways of circumventing those shortcomings. Finally, we provide specific recommendations for optimal dosing with Cur for treating neurological diseases.
Collapse
Affiliation(s)
- Panchanan Maiti
- Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
- Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA.
- Department of Psychology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
- Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI 48604, USA.
- Department of Biology, Saginaw Valley State University, Saginaw, MI 48610, USA.
- Brain Research Laboratory, Saginaw Valley State University, Saginaw, MI 48610, USA.
| | - Gary Leo Dunbar
- Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
- Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA.
- Department of Psychology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
- Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI 48604, USA.
| |
Collapse
|
|
39
|
PPAR γ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling. PPAR Res 2018; 2018:6970407. [PMID: 29686697 PMCID: PMC5852857 DOI: 10.1155/2018/6970407] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 12/20/2017] [Indexed: 12/12/2022] Open
Abstract
Background and Aims Accumulating evidence reveals that PPARγ plays a unique role in the regulation of hepatic fibrosis and hepatic stellate cells (HSCs) activation. This study was aimed at investigating the role of PPARγ in hypoxia-induced hepatic fibrogenesis and its possible mechanism. Methods Rats used for CCl4-induced hepatic fibrosis model were exposed to hypoxia for 8 hours each day. Rats exposed to hypoxia were treated with or without the PPARγ agonist rosiglitazone. Liver sections were stained with HE and Sirius red staining 8 weeks later. HSCs were exposed to hypoxic environment in the presence or absence of rosiglitazone, and expression of PPARγ and two fibrosis markers, α-SMA and desmin, were measured using western blot and immunofluorescence staining. Next, levels of PPARγ, α-SMA, and desmin as well as PKG and cGMP activity were detected using PI3K/AKT and a cGMP activator or inhibitor. Results Hypoxia promoted the induction and progress of hepatic fibrosis and HSCs activation. Meanwhile, rosiglitazone significantly antagonized the effects induced by hypoxia. Signaling by sGC/cGMP/PKG promoted the inhibitory effect of PPARγ on hypoxia-induced activation of HSCs. Moreover, PI3K/AKT signaling or PDE5 blocked the above response of PPARγ. Conclusion sGC/cGMP/PKG and PI3K/AKT signals act on PPARγ synergistically to attenuate hypoxia-induced HSC activation.
Collapse
|
|
40
|
Ortega-Domínguez B, Aparicio-Trejo OE, García-Arroyo FE, León-Contreras JC, Tapia E, Molina-Jijón E, Hernández-Pando R, Sánchez-Lozada LG, Barrera-Oviedo D, Pedraza-Chaverri J. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic. Food Chem Toxicol 2017; 107:373-385. [DOI: 10.1016/j.fct.2017.07.018] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2017] [Revised: 07/06/2017] [Accepted: 07/07/2017] [Indexed: 01/03/2023]
|
|
41
|
Nrf2 activation is required for curcumin to induce lipocyte phenotype in hepatic stellate cells. Biomed Pharmacother 2017; 95:1-10. [PMID: 28826090 DOI: 10.1016/j.biopha.2017.08.037] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 07/20/2017] [Accepted: 08/07/2017] [Indexed: 12/18/2022] Open
Abstract
Hepatic fibrosis is a reversible scarring response that commonly occurs with chronic liver injury. During hepatic fibrogenesis, the major effector hepatic stellate cells (HSCs) become activated, featured by disappeared intracellular lipid droplets, decreased retinoid storage, and dysregulated expression of genes associated with lipid and retinoid metabolism. Compelling evidence suggested that recovery of retinoid droplets could inhibit HSC activation, while the precise molecular basis underlying the phenotypical switch still remained unclear. In this study, curcumin increased the abundance of lipid droplets and content of triglyceride in activated HSCs. In addition, curcumin could concentration-dependently regulate genes associated with lipid and retinoid metabolism. Further, consistent results were obtained from in vivo experiments. Curcumin increased Nrf2 expression and nuclear translocation, and its binding activity to DNA, which might be associated with suppression of Kelch-like ECH-associated protein 1 in HSCs. Of interest was that Nrf2 overexpression plasmids, in contract to Nrf2 siRNA, strengthened the effect of curcumin on induction of lipocyte phenotype. In in vivo system, Nrf2 knockdown mediated by Nrf2 shRNA lentivirus not only accelerated the lipid degradation in HSCs but also promoted the progression of CCl4-induced hepatic fibrosis in mice. Noteworthily, Nrf2 knockdown abolished the protective effect of curcumin. In conclusion, curcumin could induce lipocyte phenotype of activated HSCs via activating Nrf2. Nrf2 could be a target molecule for antifibrotic strategy.
Collapse
|
|
42
|
Pandey MK, Gupta SC, Nabavizadeh A, Aggarwal BB. Regulation of cell signaling pathways by dietary agents for cancer prevention and treatment. Semin Cancer Biol 2017; 46:158-181. [PMID: 28823533 DOI: 10.1016/j.semcancer.2017.07.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 07/05/2017] [Accepted: 07/12/2017] [Indexed: 12/17/2022]
Abstract
Although it is widely accepted that better food habits do play important role in cancer prevention and treatment, how dietary agents mediate their effects remains poorly understood. More than thousand different polyphenols have been identified from dietary plants. In this review, we discuss the underlying mechanism by which dietary agents can modulate a variety of cell-signaling pathways linked to cancer, including transcription factors, nuclear factor κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), activator protein-1 (AP-1), β-catenin/Wnt, peroxisome proliferator activator receptor- gamma (PPAR-γ), Sonic Hedgehog, and nuclear factor erythroid 2 (Nrf2); growth factors receptors (EGFR, VEGFR, IGF1-R); protein Kinases (Ras/Raf, mTOR, PI3K, Bcr-abl and AMPK); and pro-inflammatory mediators (TNF-α, interleukins, COX-2, 5-LOX). In addition, modulation of proteasome and epigenetic changes by the dietary agents also play a major role in their ability to control cancer. Both in vitro and animal based studies support the role of dietary agents in cancer. The efficacy of dietary agents by clinical trials has also been reported. Importantly, natural agents are already in clinical trials against different kinds of cancer. Overall both in vitro and in vivo studies performed with dietary agents strongly support their role in cancer prevention. Thus, the famous quote "Let food be thy medicine and medicine be thy food" made by Hippocrates 25 centuries ago still holds good.
Collapse
Affiliation(s)
- Manoj K Pandey
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
| | - Subash C Gupta
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Ali Nabavizadeh
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
| | | |
Collapse
|
|
43
|
Kundu P, Das M, Tripathy K, Sahoo SK. Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson's Disease. ACS Chem Neurosci 2016; 7:1658-1670. [PMID: 27642670 DOI: 10.1021/acschemneuro.6b00207] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain. The present study involves formulation of curcumin and piperine coloaded glyceryl monooleate (GMO) nanoparticles coated with various surfactants with a view to enhance the bioavailability of curcumin and penetration of both drugs to the brain tissue crossing the BBB and to enhance the anti-parkinsonism effect of both drugs in a single platform. In vitro results demonstrated augmented inhibition of αS protein into oligomers and fibrils, reduced rotenone induced toxicity, oxidative stress, and apoptosis, and activation of autophagic pathway by dual drug loaded NPs compared to native counterpart. Further, in vivo studies revealed that our formulated dual drug loaded NPs were able to cross BBB, rescued the rotenone induced motor coordination impairment, and restrained dopaminergic neuronal degeneration in a PD mouse model.
Collapse
Affiliation(s)
- Paromita Kundu
- Institute of Life Sciences, Nalco Square, Bhubaneswar 751023, India
| | - Manasi Das
- Institute of Life Sciences, Nalco Square, Bhubaneswar 751023, India
| | - Kalpalata Tripathy
- Department
of Pathology, Shri Ramachandra Bhanj Medical College, Cuttack 753007, India
| | - Sanjeeb K Sahoo
- Institute of Life Sciences, Nalco Square, Bhubaneswar 751023, India
| |
Collapse
|