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Huang CY, Ng MY, Lin T, Liao YW, Huang WS, Hsieh CW, Yu CC, Chen CJ. Quercetin ameliorates advanced glycation end product-induced wound healing impairment and inflammaging in human gingival fibroblasts. J Dent Sci 2024; 19:268-275. [PMID: 38303825 PMCID: PMC10829550 DOI: 10.1016/j.jds.2023.04.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/15/2023] [Indexed: 02/03/2024] Open
Abstract
Background/purpose Diabetes mellitus (DM) and periodontal disease are both prevalent and chronic inflammatory disorders that have significant health impact. Many studies have pointed out that advanced glycation end-products (AGEs) in DM induces inflammaging, which is a pre-aging and hyperinflammatory condition, and it has been linked to a greater likelihood in developing periodontitis. Inflammaging in DM has been shown to be driven by AGEs-induced cell senescence, inflammatory cytokines, and oxidative stress, resulting in the degradation of periodontium. Quercetin has shown abilities to decrease inflammation and oxidative stress in a variety of tissues, however, the effect in diabetic periodontitis remains uncertain. Thus, the aim of this study was to investigate its impacts on inflammaging in diabetic periodontitis. Materials and methods We examined cell proliferation in human gingival fibroblasts (HGF), wound healing, IL-6 and IL-8 secretions, cellular senescence expression, and the formation of reactive oxygen species (ROS) in response to AGE stimulation with and without Quercetin intervention. Following that, we looked into NF-κβ activity to see if Quercetin mediate its effects via this pro-inflammatory signaling. Results Quercetin at 20 μM and below did not have any impact on HGFs' cell proliferation rate. Quercetin intervention improved the AGEs-impaired wound healing, in addition to the attenuation of AGEs-induced ROS in a dose-dependent pattern. Moreover, Quercetin therapy dose-dependently inhibited AGEs-induced cell senescence activity along with its senescence associated secretion phenotype (SASP) secretions such as IL-6 and IL-8. Western blot analysis indicated that Quercetin was able to reverse the phosphorylation of p65 and Iκβ in AGEs-stimulated HGFs, demonstrating it can modulate NF-κβ pathway. Conclusion Accumulation of AGEs can elicit inflammaging in HGFs, as seen by increased pro-inflammatory cytokines, cell senescence expression and oxidative stress. The results proposed that Quercetin is able to ameliorate inflammaging in diabetic periodontitis and improve wound healing via the suppression of NF-κβ pathway and hence, may be a promising approach for treatment of diabetes-associated periodontitis.
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Affiliation(s)
- Chao-Yen Huang
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Min Yee Ng
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
| | - Taichen Lin
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yi-Wen Liao
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Wei-Shiuan Huang
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
| | - Chang-Wei Hsieh
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan
| | - Cheng-Chia Yu
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chun-Jung Chen
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Division of Periodontics, Department of Dentistry, Chi Mei Medical Center, Tainan, Taiwan
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Pellegrino M, Bevacqua E, Frattaruolo L, Cappello AR, Aquaro S, Tucci P. Enhancing the Anticancer and Anti-Inflammatory Properties of Curcumin in Combination with Quercetin, for the Prevention and Treatment of Prostate Cancer. Biomedicines 2023; 11:2023. [PMID: 37509660 PMCID: PMC10377667 DOI: 10.3390/biomedicines11072023] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/11/2023] [Accepted: 07/15/2023] [Indexed: 07/30/2023] Open
Abstract
Prostate cancer is the second most common cancer in men. Although epidemiologic studies show that a higher intake of polyphenols, curcumin (CUR), and quercetin (QRT), in particular, result in lower prostate cancer risk, the chemopreventive mechanisms underlying the effects of CUR and QRT have not been fully understood yet, and most investigations were conducted with individual compounds. Here, we investigated the anticancer and anti-inflammatory effects of CUR in combination with QRT, respectively, in a human prostate cancer cell line, PC-3, and in LPS-stimulated RAW 264.7 cells, and found that their combination significantly inhibited proliferation and arrested the cell cycle, inducing apoptosis, so exhibiting synergic activities stronger than single drug use. Moreover, via their antioxidant effects, the combination of CUR and QRT modulated several inflammation-mediated signaling pathways (ROS, nitric oxide, and pro-inflammatory cytokines) thus helping protect cells from undergoing molecular changes that trigger carcinogenesis. Although additional studies, including in vivo experiments and translational studies, are required, this study raises the possibility of their use as a safe, effective, and affordable therapeutic approach to prostate cancer.
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Affiliation(s)
- Michele Pellegrino
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | - Emilia Bevacqua
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | - Luca Frattaruolo
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | - Anna Rita Cappello
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | - Stefano Aquaro
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | - Paola Tucci
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
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Zhang Y, Huang Y, Li Z, Wu H, Zou B, Xu Y. Exploring Natural Products as Radioprotective Agents for Cancer Therapy: Mechanisms, Challenges, and Opportunities. Cancers (Basel) 2023; 15:3585. [PMID: 37509245 PMCID: PMC10377328 DOI: 10.3390/cancers15143585] [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: 05/27/2023] [Revised: 07/04/2023] [Accepted: 07/09/2023] [Indexed: 07/30/2023] Open
Abstract
Radiotherapy is an important cancer treatment. However, in addition to killing tumor cells, radiotherapy causes damage to the surrounding cells and is toxic to normal tissues. Therefore, an effective radioprotective agent that prevents the deleterious effects of ionizing radiation is required. Numerous synthetic substances have been shown to have clear radioprotective effects. However, most of these have not been translated for use in clinical applications due to their high toxicity and side effects. Many medicinal plants have been shown to exhibit various biological activities, including antioxidant, anti-inflammatory, and anticancer activities. In recent years, new agents obtained from natural products have been investigated by radioprotection researchers, due to their abundance of sources, high efficiency, and low toxicity. In this review, we summarize the mechanisms underlying the radioprotective effects of natural products, including ROS scavenging, promotion of DNA damage repair, anti-inflammatory effects, and the inhibition of cell death signaling pathways. In addition, we systematically review natural products with radioprotective properties, including polyphenols, polysaccharides, alkaloids, and saponins. Specifically, we discuss the polyphenols apigenin, genistein, epigallocatechin gallate, quercetin, resveratrol, and curcumin; the polysaccharides astragalus, schisandra, and Hohenbuehelia serotina; the saponins ginsenosides and acanthopanax senticosus; and the alkaloids matrine, ligustrazine, and β-carboline. However, further optimization through structural modification, improved extraction and purification methods, and clinical trials are needed before clinical translation. With a deeper understanding of the radioprotective mechanisms involved and the development of high-throughput screening methods, natural products could become promising novel radioprotective agents.
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Affiliation(s)
- Yi Zhang
- Division of Thoracic Oncology, Cancer Center, Department of Radiation Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Ying Huang
- College of Management, Sichuan Agricultural University, Chengdu 611130, China
| | - Zheng Li
- Division of Thoracic Oncology, Cancer Center, Department of Radiation Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hanyou Wu
- Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, China
| | - Bingwen Zou
- Division of Thoracic Oncology, Cancer Center, Department of Radiation Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yong Xu
- Division of Thoracic Oncology, Cancer Center, Department of Radiation Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
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Fonseca M, Rehman M, Soares R, Fonte P. The Impact of Flavonoid-Loaded Nanoparticles in the UV Protection and Safety Profile of Topical Sunscreens. Biomolecules 2023; 13:biom13030493. [PMID: 36979428 PMCID: PMC10046639 DOI: 10.3390/biom13030493] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 02/14/2023] [Accepted: 02/17/2023] [Indexed: 03/10/2023] Open
Abstract
Excessive UV radiation exposure is harmful to skin cells since sunburn is accompanied by oxidative burst, leading to a rapid increase in skin cancer. However, the insufficient UV photoprotection of approved sunscreens and the negative impact of their compositions on ecosystems and human health makes the utility of sunscreen a questionable recommendation. Therefore, discovering UV filters with significant antioxidant activity and improved topical performance and photostability is an urgent need. Recently, the use of nanosized natural molecules incorporated in sunscreens has been a scientific hot topic, as it has been suggested that they provide a synergistic effect with synthetic UV filters, improving overall SPF and antioxidant activity, higher retention on the epidermis, and less toxicity. The aim of this review was to verify the usefulness of sunscreens incorporating flavonoid-loaded nanoparticles. A literature review was performed, where original and review articles published in the last 6 years were analyzed. Formulations containing nanosized flavonoids with improved UVA photoprotection and safer toxicological profiles, associated or not with synthetic filters, are promising sunscreens and more clinical investigation must be performed to validate these findings.
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Affiliation(s)
- Magda Fonseca
- EPI Unit, Department of Epidemiological Research, Institute of Public Health of University of Porto (ISPUP), Rua das Taipas 135, 4050-600 Porto, Portugal
| | - Mubashar Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Raquel Soares
- Department of Biomedicine, Faculty of Medicine, University of Porto, Al Prof Hernani Monteiro, 4200-319 Porto, Portugal
- I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Pedro Fonte
- Center for Marine Sciences (CCMAR), Gambelas Campus, University of Algarve, 8005-139 Faro, Portugal
- Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, Gambelas Campus, University of Algarve, 8005-139 Faro, Portugal
- IBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
- Associate Laboratory i4HB—Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
- Correspondence:
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Qureshi N, Desousa J, Siddiqui AZ, Drees BM, Morrison DC, Qureshi AA. Dysregulation of Gene Expression of Key Signaling Mediators in PBMCs from People with Type 2 Diabetes Mellitus. Int J Mol Sci 2023; 24:2732. [PMID: 36769056 PMCID: PMC9916932 DOI: 10.3390/ijms24032732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/17/2023] [Accepted: 01/19/2023] [Indexed: 02/04/2023] Open
Abstract
Diabetes is currently the fifth leading cause of death by disease in the USA. The underlying mechanisms for type 2 Diabetes Mellitus (DM2) and the enhanced susceptibility of such patients to inflammatory disorders and infections remain to be fully defined. We have recently shown that peripheral blood mononuclear cells (PBMCs) from non-diabetic people upregulate expression of inflammatory genes in response to proteasome modulators, such as bacterial lipopolysaccharide (LPS) and soybean lectin (LEC); in contrast, resveratrol (RES) downregulates this response. We hypothesized that LPS and LEC will also elicit a similar upregulation of gene expression of key signaling mediators in (PBMCs) from people with type 2 diabetes (PwD2, with chronic inflammation) ex vivo. Unexpectedly, using next generation sequencing (NGS), we show for the first time, that PBMCs from PwD2 failed to elicit a robust LPS- and LEC-induced gene expression of proteasome subunit LMP7 (PSMB8) and mediators of T cell signaling that were observed in non-diabetic controls. These repressed genes included: PSMB8, PSMB9, interferon-γ, interferon-λ, signal-transducer-and-activator-of-transcription-1 (STAT1), human leukocyte antigen (HLA DQB1, HLA DQA1) molecules, interleukin 12A, tumor necrosis factor-α, transporter associated with antigen processing 1 (TAP1), and several others, which showed a markedly weak upregulation with toxins in PBMCs from PwD2, as compared to those from non-diabetics. Resveratrol (proteasome inhibitor) further downregulated the gene expression of these inflammatory mediators in PBMCs from PwD2. These results might explain why PwD2 may be susceptible to infectious disease. LPS and toxins may be leading to inflammation, insulin resistance, and thus, metabolic changes in the host cells.
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Affiliation(s)
- Nilofer Qureshi
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
- Department of Pharmacology/Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA
| | - Julia Desousa
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
- Department of Pharmacology/Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA
| | - Adeela Z. Siddiqui
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
| | - Betty M. Drees
- Internal Medicine, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
| | - David C. Morrison
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
| | - Asaf A. Qureshi
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
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Qureshi N, Desousa J, Siddiqui AZ, Morrison DC, Qureshi AA. Reprograming of Gene Expression of Key Inflammatory Signaling Pathways in Human Peripheral Blood Mononuclear Cells by Soybean Lectin and Resveratrol. Int J Mol Sci 2022; 23:12946. [PMID: 36361735 PMCID: PMC9659230 DOI: 10.3390/ijms232112946] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/17/2022] [Accepted: 10/20/2022] [Indexed: 02/03/2025] Open
Abstract
Inflammation is linked to several human diseases like microbial infections, cancer, heart disease, asthma, diabetes, and neurological disorders. We have shown that the prototype inflammatory agonist LPS modulates the activity of Ubiquitin-Proteasome System (UPS) and regulates transcription factors such as NF-κB, leading to inflammation, tolerance, hypoxia, autophagy, and apoptosis of cells. We hypothesized that proteasome modulators resveratrol and soybean lectin would alter the gene expression of mediators involved in inflammation-induced signaling pathways, when administered ex vivo to human peripheral blood mononuclear blood cells (PBMCs) obtained from normal healthy controls. To test this hypothesis, analysis of RNA derived from LPS-treated human PBMCs, with or without resveratrol and soybean lectin, was carried out using Next Generation Sequencing (NGS). Collectively, the findings described herein suggest that proteasome modulators, resveratrol (proteasome inhibitor) and lectins (proteasome activator), have a profound capacity to modulate cytokine expression in response to proteasome modulators, as well as expression of mediators in multiple signaling pathways in PBMCs of control subjects. We show for the first-time that resveratrol downregulates expression of mediators involved in several key signaling pathways IFN-γ, IL-4, PSMB8 (LMP7), and a subset of LPS-induced genes, while lectins induced IFN-γ, IL-4, PSMB8, and many of the same genes as LPS that are important for innate and adaptive immunity. These findings suggest that inflammation may be influenced by common dietary components and this knowledge may be used to prevent or reverse inflammation-based diseases.
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Affiliation(s)
- Nilofer Qureshi
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri, 2411 Holmes Street, Kansas City, MO 64108, USA
- Pharmacology/Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA
| | - Julia Desousa
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri, 2411 Holmes Street, Kansas City, MO 64108, USA
- Pharmacology/Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA
| | - Adeela Z. Siddiqui
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri, 2411 Holmes Street, Kansas City, MO 64108, USA
| | - David C. Morrison
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri, 2411 Holmes Street, Kansas City, MO 64108, USA
| | - Asaf A. Qureshi
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri, 2411 Holmes Street, Kansas City, MO 64108, USA
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Seo J, Lee U, Seo S, Wibowo AE, Pongtuluran OB, Lee K, Han SB, Cho S. Anti-inflammatory and antioxidant activities of methanol extract of Piper betle Linn. (Piper betle L.) leaves and stems by inhibiting NF-κB/MAPK/Nrf2 signaling pathways in RAW 264.7 macrophages. Biomed Pharmacother 2022; 155:113734. [PMID: 36152408 DOI: 10.1016/j.biopha.2022.113734] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 09/15/2022] [Accepted: 09/19/2022] [Indexed: 11/18/2022] Open
Abstract
Oxidative stress and chronic inflammation are closely linked to various diseases. However, previous studies have demonstrated that plant extracts could prevent and alleviate these adverse outcomes. Piper betle Linn. (Piper betle L.) is a cosmopolitan plant that belongs to the Piperaceae family, whose leaves are edible and possess several health benefits. This study sought to characterize the anti-inflammatory and antioxidant effects of a methanol extract of Piper betle L. leaves and stems (MPBLLS). MPBLLS was found to have a dose-dependent radical scavenging effect, as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl assay. Additionally, MPBLLS inhibited the lipopolysaccharide (LPS)-stimulated production of nitric oxide and prostaglandin E2 by reducing the expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages without affecting cell viability. Furthermore, our findings suggested that the inhibitory effects of MPBLLS on pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 were due to the inhibition of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-treated RAW 264.7 macrophages. MPBLLS and hydroxychavicol, a major constituent of MPBLLS, suppressed LPS-induced translocation of NF-κB p65 from cytoplasm to nucleus. Interestingly, MPBLLS increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and transcription levels of Nrf2 target genes in a dose-dependent manner. Collectively, our findings suggest that MPBLLS could serve as a basis for the development of novel orally-administered therapies due to its inhibitory effects on oxidative and inflammatory stress. DATA AVAILABILITY: The data presented in this study are available on request from the corresponding author.
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Affiliation(s)
- Jihye Seo
- Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
| | - Unju Lee
- Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
| | - Sumin Seo
- Biomedical Mass Spectrometry Lab, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
| | - Agung Eru Wibowo
- Research Center for Pharmaceutical Ingredients and Traditional Medicine, Health Research Organization, National Research and Innovation Agency (BRIN), Cibinong, Bogor, Jawa Barat 16911, Indonesia.
| | - Olivia Bunga Pongtuluran
- Research Center for Agroindustry, Food and Agriculture Research Organization, National Research and Innovation Agency (BRIN), Cibinong, Bogor, Jawa Barat 16911, Indonesia.
| | - KyuJong Lee
- International Biological Material Research Center, Korea Research Institute of Bioscience & Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
| | - Sang Beom Han
- Biomedical Mass Spectrometry Lab, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
| | - Sayeon Cho
- Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
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Schwager J, Bompard A, Raederstorff D, Hug H, Bendik I. Resveratrol and ω-3 PUFAs Promote Human Macrophage Differentiation and Function. Biomedicines 2022; 10:biomedicines10071524. [PMID: 35884829 PMCID: PMC9313469 DOI: 10.3390/biomedicines10071524] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/21/2022] [Accepted: 06/23/2022] [Indexed: 12/15/2022] Open
Abstract
Monocytes differentiate into M1 and M2 macrophages, which are classically activated by microbial products such as LPS or IFN-γ and interleukins (e.g., the anti-inflammatory and Th2 promoting IL-4), respectively. The contribution of nutrients or nutrient-based substances such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and resveratrol (Res) on the differentiation and function of M1 and M2 macrophages was evaluated. THP-1 cells and peripheral blood mononuclear cells (PBMCs) were differentiated into M1 and M2 cells and activated with LPS/IFN-γ or IL-4/IL-13. Macrophage lineage specific surface determinants (e.g., CD11b, CD11c, CD14, CD206, CD209, CD274, HLA-DR, CCR7, CCR2) were analysed by cytofluorometry. Res and ω-3 PUFAs altered CD14, CD206, CD274 and HL-DR surface expression patterns in M1 and M2 macrophages differentiated from PBMC. LPS/IFN-γ or IL-14/IL-13 activated macrophages subpopulations, which secreted cytokines and chemokines as measured by multiplex ELISA. Res and ω-3 PUFA reduced IL-1β, IL-6, TNF-α, CXCL10/IP-10, CCL13/MCP-4 and CCL20/MIP-3α in LPS/IFN-γ activated human leukaemia THP-1 cells, which is indicative of a dampening effect on M1 macrophages. However, Res increased M1 prototypic cytokines such as IL-1β or IL-6 in macrophages derived from PBMCs and also modified the expression of IL-12p70. Collectively, Res and ω-3 PUFAs distinctly promoted the differentiation and function of M1 and M2 macrophages. We conclude that these substances strengthen the macrophage-mediated effects on the innate and adaptive immune response.
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Affiliation(s)
- Joseph Schwager
- DSM, HNC, Innovation, Global R&D Center, Wurmisweg 567, CH-4303 Kaiseraugst, Switzerland; (D.R.); (H.H.); (I.B.)
- Correspondence: ; Tel.: +41-79-488-0905
| | - Albine Bompard
- DSM, HNB, BDT, Toxicology & Kinetics, Wurmisweg 567, CH-4303 Kaiseraugst, Switzerland;
| | - Daniel Raederstorff
- DSM, HNC, Innovation, Global R&D Center, Wurmisweg 567, CH-4303 Kaiseraugst, Switzerland; (D.R.); (H.H.); (I.B.)
| | - Hubert Hug
- DSM, HNC, Innovation, Global R&D Center, Wurmisweg 567, CH-4303 Kaiseraugst, Switzerland; (D.R.); (H.H.); (I.B.)
| | - Igor Bendik
- DSM, HNC, Innovation, Global R&D Center, Wurmisweg 567, CH-4303 Kaiseraugst, Switzerland; (D.R.); (H.H.); (I.B.)
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Akhtar MA. Anti-Inflammatory Medicinal Plants of Bangladesh—A Pharmacological Evaluation. Front Pharmacol 2022; 13:809324. [PMID: 35401207 PMCID: PMC8987533 DOI: 10.3389/fphar.2022.809324] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 02/01/2022] [Indexed: 12/12/2022] Open
Abstract
Inflammatory diseases are considered major threats to human health worldwide. In Bangladesh, a number of medicinal plants have been used in traditional medicine from time immemorial in the treatment of diverse diseases, including inflammatory disorders. This assignment aims at providing the status of the medicinal plants of Bangladesh which are traditionally used in the management of inflammatory disorders and are investigated for their anti-inflammatory prospects using different preclinical studies and future research directions. The information of medicinal plants assembled in this review was obtained from a literature search of electronic databases such as Google Scholar, PubMed, Scopus, Web of Science and ScienceDirect up to December, 2020 from publications on plants investigated for their anti-inflammatory activities, in which the place of plant sample collection was identified as Bangladesh. Keywords for primary searches were “anti-inflammatory,” “Bangladeshi,” and “medicinal plants.” Criteria followed to include plant species were plants that showed significant anti-inflammatory activities in 1) two or more sets of experiments in a single report, 2) same or different sets of experiments in two or more reports, and, 3) plants which are traditionally used in the treatment of inflammation and inflammatory disorders. In this study, 48 species of medicinal plants have been reviewed which have been used in traditional healing practices to manage inflammatory disorders in Bangladesh. The mechanistic pathways of the in vivo and in vitro study models used for the evaluation of anti-inflammatory properties of plant samples have been discussed. Selected plants were described in further detail for their habitat, anti-inflammatory studies conducted in countries other than Bangladesh, and anti-inflammatory active constituents isolated from these plants if any. Medicinal plants of Bangladesh have immense significance for anti-inflammatory activity and have potential to contribute toward the discovery and development of novel therapeutic approaches to combat diseases associated with inflammation. However, the plants reviewed in this article had chiefly undergone preliminary screening and require substantial investigations including identification of active molecules, understanding the mechanism of action, and evaluation for safety and efficacy to be followed by the formulation of safe and effective drug products.
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Alam A, Al Arif Jahan A, Bari MS, Khandokar L, Mahmud MH, Junaid M, Chowdhury MS, Khan MF, Seidel V, Haque MA. Allium vegetables: Traditional uses, phytoconstituents, and beneficial effects in inflammation and cancer. Crit Rev Food Sci Nutr 2022; 63:6580-6614. [PMID: 35170391 DOI: 10.1080/10408398.2022.2036094] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The genus Allium comprises of at least 918 species; the majority grown for dietary and medicinal purposes. This review describes the traditional uses, phytoconstituents, anti-inflammatory and anticancer activity, and safety profile of six main species, namely Allium sativum L. (garlic), Allium cepa L. (onions), Allium ampeloprasum L. (leek), Allium fistulosum L. (scallion), Allium schoenoprasum L. (chives) and Allium tuberosum Rottler (garlic chives). These species contain at least 260 phytoconstituents; mainly volatile compounds-including 63 organosulfur molecules-, saponins, flavonoids, anthocyanins, phenolic compounds, amino acids, organic acids, fatty acids, steroids, vitamins and nucleosides. They have prominent in vitro anti-inflammatory activity, and in vivo replications of such results have been achieved for all except for A. schoenoprasum. They also exert cytotoxicity against different cancer cell lines. Several anticancer phytoconstituents have been characterized from all except for A. fistulosum. Organosulfur constituents, saponins and flavonoid glycosides have demonstrated anti-inflammatory and anticancer activity. Extensive work has been conducted mainly on the anti-inflammatory and anticancer activity of A. sativum and A. cepa. The presence of anti-inflammatory and anticancer constituents in these two species suggests that similar bioactive constituents could be found in other species. This provides future avenues for identifying new Allium-derived anti-inflammatory and anticancer agents.
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Affiliation(s)
- Ashraful Alam
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
| | - Abdullah Al Arif Jahan
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
| | - Md Sazzadul Bari
- Department of Chemistry, Purdue University, West Lafayette, Indiana, USA
| | | | - Md Hasan Mahmud
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
| | - Muhammed Junaid
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
| | | | - Mohammad Forhad Khan
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
- Department of Chemistry, Purdue University, West Lafayette, Indiana, USA
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Md Areeful Haque
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
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11
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Sekar P, Ravitchandirane R, Khanam S, Muniraj N, Cassinadane AV. Novel molecules as the emerging trends in cancer treatment: an update. Med Oncol 2022; 39:20. [PMID: 34982273 DOI: 10.1007/s12032-021-01615-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 11/19/2021] [Indexed: 12/15/2022]
Abstract
As per World Health Organization cancer remains as a leading killer disease causing nearly 10 million deaths in 2020. Since the burden of cancer increases worldwide, warranting an urgent search for anti-cancer compounds from natural sources. Secondary metabolites from plants, marine organisms exhibit a novel chemical and structural diversity holding a great promise as therapeutics in cancer treatment. These natural metabolites target only the cancer cells and the normal healthy cells are left unharmed. In the emerging trends of cancer treatment, the natural bioactive compounds have long become a part of cancer chemotherapy. In this review, we have tried to compile about eight bioactive compounds from plant origin viz. combretastatin, ginsenoside, lycopene, quercetin, resveratrol, silymarin, sulforaphane and withaferin A, four marine-derived compounds viz. bryostatins, dolastatins, eribulin, plitidepsin and three microorganisms viz. Clostridium, Mycobacterium bovis and Streptococcus pyogenes with their well-established anticancer potential, mechanism of action and clinical establishments are presented.
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Affiliation(s)
- Priyanka Sekar
- Sri Venkateshwaraa Medical College Hospital and Research Centre, Pondicherry, 605102, India
| | | | - Sofia Khanam
- Calcutta Institute of Pharmaceutical Technology and Allied Health Sciences, Howrah, WB, 711316, India
| | - Nethaji Muniraj
- Centre for Cancer Immunology Research, Children's National Hospital, Children's National Research Institute, 111 Michigan Ave NW, Washington, D.C, 20010, USA.
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12
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Ham JR, Yun KW, Lee MK. Anti-Inflammatory and Antioxidant in Vitro Activities of Magnoliae Flos Ethanol Extract. Prev Nutr Food Sci 2021; 26:485-491. [PMID: 35047446 PMCID: PMC8747962 DOI: 10.3746/pnf.2021.26.4.485] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/20/2021] [Accepted: 08/27/2021] [Indexed: 12/29/2022] Open
Abstract
This study evaluated Magnoliea Flos ethanol extract (MFE) as a potential natural anti-inflammatory and antioxidant in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in vitro antioxidant assays. MFE (10, 30, and 50 μg/mL) dose-dependently inhibited LSP-induced nitric oxide production, which is mediated by down-regulating gene and protein expression of inducible nitric oxide synthase and cyclooxygenase-2. MFE also down-regulated both gene and protein expression of nuclear factor-kappa B and its downstream genes, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), compared with vehicle-treated cells. As a result, MFE treatment of LPS-stimulated macrophages significantly suppressed release of pro-inflammatory cytokines, such as TNF-α and IL-6. The antioxidant in vitro test revealed 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities of MFE (0.25∼5 mg/mL) of 16.62% to 75.17% and 38.54% to 92.91%, respectively. The ferric reducing antioxidant ability of MFE was 0.54 mM to 2.14 mM. Overall, MFE exhibited antioxidant activity and an effective anti-inflammatory response in LPS-stimulated macrophages, which is potentially valuable for application as a natural functional material.
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Affiliation(s)
- Ju Ri Ham
- Mokpo Marine Food-Industry Research Center, Jeonnam 58621, Korea
| | - Kyeong Won Yun
- Department of Oriental Medicine Resources, Sunchon National University, Jeonnam 57922, Korea
| | - Mi-Kyung Lee
- Department of Food and Nutrition, Sunchon National University, Jeonnam 57922, Korea
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13
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Jo HM, Ahn C, Kim H, Kang BT, Jeung EB, Yang MP. Effect of quercetin on formation of porcine neutrophil extracellular trap. Vet Immunol Immunopathol 2021; 241:110335. [PMID: 34627080 DOI: 10.1016/j.vetimm.2021.110335] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 08/02/2021] [Accepted: 10/02/2021] [Indexed: 10/20/2022]
Abstract
Neutrophil extracellular trap (NET) formation is an immune response to the invasion of external microorganisms. Quercetin, a member of the flavonoid family found in fruits and vegetables, has been examined in multiple biological contexts. The objective of this study was to examine the effect of quercetin on porcine NET formation. We measured NET formation by peripheral blood polymorphonuclear cells (PMNs) using propidium iodide (PI) dye. The amount of tumor necrosis factor (TNF)-α in culture supernatants was quantified by ELISA, and TNF-α mRNA expression was measured by RT-PCR. Direct treatment of PMNs with quercetin did not affect NET formation; however, NET formation was inhibited by exposure to culture supernatant from peripheral blood mononuclear cells (PBMCs) treated with quercetin. By contrast, culture supernatant from PBMCs treated with lipopolysaccharide (LPS) induced high levels of NET formation of PMNs, and this effect was reduced by co-treatment with LPS and quercetin. In addition, treatment of PMNs with recombinant porcine (rp) TNF-α induced high levels of NET formation. PBMCs treated with LPS increased higher levels of TNF-α mRNA and protein, but this effect was weakened when they were co-treated with quercetin. These findings indicated that quercetin inhibits NET formation of PMNs by suppressing production of TNF-α from LPS-stimulated PBMCs. These results suggest that quercetin exerts an anti-inflammatory effect, mediated by down-regulation of TNF-α production from LPS-stimulated PBMCs, which inhibits NET formation in PMNs.
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Affiliation(s)
- Hyun-Min Jo
- Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea
| | - Changhwan Ahn
- Department of Veterinary Medicine, College of Veterinary Medicine, Jeju National University, Jeju Special Self Governing Province, 63243, Republic of Korea
| | - Hakhyun Kim
- Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea
| | - Byeong-Teck Kang
- Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea
| | - Eui-Bae Jeung
- Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea
| | - Mhan-Pyo Yang
- Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
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Leischner C, Burkard M, Michel A, Berchtold S, Niessner H, Marongiu L, Busch C, Frank J, Lauer UM, Venturelli S. Comparative Analysis of the Antitumor Activity of Cis- and Trans-Resveratrol in Human Cancer Cells with Different p53 Status. Molecules 2021; 26:5586. [PMID: 34577057 PMCID: PMC8466563 DOI: 10.3390/molecules26185586] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 09/06/2021] [Accepted: 09/09/2021] [Indexed: 11/17/2022] Open
Abstract
Resveratrol, a natural plant phytoalexin, is produced in response to fungal infection or- UV irradiation. It exists as an isomeric pair with cis- and trans-conformation. Whereas multiple physiological effects of the trans-form, including a pronounced anti-tumoral activity, are nowadays elucidated, much less knowledge exists concerning the cis-isomer. In our work, we analyzed the antiproliferative and cytotoxic properties of cis-resveratrol in four different human tumor entities in direct comparison to trans-resveratrol. We used human cell lines as tumor models for hepatocellular carcinoma (HCC; HepG2, Hep3B), colon carcinoma (HCT-116, HCT-116/p53(-/-)), pancreatic carcinoma (Capan-2, MiaPaCa-2), and renal cell carcinoma (A498, SN12C). Increased cytotoxicity in all investigated tumor cells was observed for the trans-isomer. To verify possible effects of the tumor suppressor p53 on resveratrol-induced cell death, we used wild type and p53-deleted or -mutated cell lines for every tested tumor entity. Applying viability and cytotoxicity assays, we demonstrated a differential, dose-dependent sensitivity towards cis- or trans-resveratrol among the respective tumor types.
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Affiliation(s)
- Christian Leischner
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany; (C.L.); (M.B.); (A.M.); (H.N.); (L.M.)
| | - Markus Burkard
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany; (C.L.); (M.B.); (A.M.); (H.N.); (L.M.)
| | - Anja Michel
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany; (C.L.); (M.B.); (A.M.); (H.N.); (L.M.)
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany;
| | - Susanne Berchtold
- Department of Internal Medicine VIII, University Hospital Tuebingen, 72076 Tuebingen, Germany; (S.B.); (U.M.L.)
| | - Heike Niessner
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany; (C.L.); (M.B.); (A.M.); (H.N.); (L.M.)
- Division of Dermatooncology, Department of Dermatology, University of Tuebingen, 72076 Tuebingen, Germany
| | - Luigi Marongiu
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany; (C.L.); (M.B.); (A.M.); (H.N.); (L.M.)
| | | | - Jan Frank
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany;
| | - Ulrich M. Lauer
- Department of Internal Medicine VIII, University Hospital Tuebingen, 72076 Tuebingen, Germany; (S.B.); (U.M.L.)
- German Cancer Consortium (DKTK), DKFZ Partner Site, 72076 Tuebingen, Germany
| | - Sascha Venturelli
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany; (C.L.); (M.B.); (A.M.); (H.N.); (L.M.)
- Department of Vegetative and Clinical Physiology, Institute of Physiology, University of Tuebingen, 72074 Tuebingen, Germany
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15
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Quercetin Reduces Hepatic Fibrogenesis by Inhibiting TGF-β/Smad3 Signaling Pathway in LX-2 Cell Line. Jundishapur J Nat Pharm Prod 2021. [DOI: 10.5812/jjnpp.113484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Liver fibrosis has become one of the leading causes of morbidity and mortality in the world. Liver fibrosis progresses to cirrhosis and can eventually lead to hepatocellular carcinoma (HCC). During fibrogenesis, the hepatic stellate cells (HSCs) remain active and continuously produce more extracellular matrix (ECM). Quercetin, one of the main flavonoids in vegetables, has shown hepatoprotective potential, but its effects on liver fibrosis are not apparent. Objectives: In this study, we investigated the antifibrotic activity of quercetin following stimulation of TGF-β in the LX-2 cell line (a type of HSC-derived cell line) and its underlying mechanism in vitro. Methods: The LX-2 cells were treated with TGF-β1 (2 ng/mL) for 24 h. Next, the cells were treated with quercetin for 24 h, and the mRNA expression of α-smooth muscle actin (α-SMA), collagen1α1, and p-Smad3 protein levels were measured. Results: The results showed that the expression of α-SMA, collagen 1α1 (COL1α1) genes, and also the level of p-Smad3 protein in the presence of TGF-β increased significantly compared to the control group. Moreover, quercetin in concentrations of 75 and 100 μM inhibited TGF-β1-induced expression of α-SMA and COL1α1 genes and the p-Smad3 protein in LX-2 cells. Conclusions: We conclude that quercetin inhibits further activation of HSCs by inhibiting the TGF-β/Smad3 signaling pathway and reduces ECM accumulation during liver fibrosis in vitro, and may prevent the progression of liver fibrosis. Thus, the use of quercetin is suggested as a potential therapeutic agent in the treatment of liver fibrosis.
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Abstract
The use of calendula for its lenitive properties’ dates to the XII century. This plant contains several bioactive compounds, including terpenoids, terpenes, carotenoids, flavonoids and polyunsaturated fatty acids. Calendula flower extract is used in soothing cosmetics, such as after-sun, sensitive skin and eye contour products. The anti-inflammatory properties of this ingredient were demonstrated in an animal model, but the mechanism of action is poorly understood. Therefore, our work explored the effect of a calendula flower extract on NO production, a pro-inflammatory radical produced by nitric oxide synthase (iNOS) and highly released by innate immune cells in inflammatory-related pathologies. NO production was evoked by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) in macrophages, using concentrations that did not compromise cells viability. This ingredient exhibited a dose-dependent NO inhibition, reaching 50% at 147 μL/mL without cytotoxicity. Together with previous literature, these results provide experimental evidence on the anti-inflammatory properties of calendula flower extract, as well as its usefulness in cosmetics with soothing properties and adjunctive skin care in the treatment of the diseases associated with dysregulation of the NO signaling cascade.
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Intracellular Redox-Modulated Pathways as Targets for Effective Approaches in the Treatment of Viral Infection. Int J Mol Sci 2021; 22:ijms22073603. [PMID: 33808471 PMCID: PMC8036776 DOI: 10.3390/ijms22073603] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/19/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023] Open
Abstract
Host-directed therapy using drugs that target cellular pathways required for virus lifecycle or its clearance might represent an effective approach for treating infectious diseases. Changes in redox homeostasis, including intracellular glutathione (GSH) depletion, are one of the key events that favor virus replication and contribute to the pathogenesis of virus-induced disease. Redox homeostasis has an important role in maintaining an appropriate Th1/Th2 balance, which is necessary to mount an effective immune response against viral infection and to avoid excessive inflammatory responses. It is known that excessive production of reactive oxygen species (ROS) induced by viral infection activates nuclear factor (NF)-kB, which orchestrates the expression of viral and host genes involved in the viral replication and inflammatory response. Moreover, redox-regulated protein disulfide isomerase (PDI) chaperones have an essential role in catalyzing formation of disulfide bonds in viral proteins. This review aims at describing the role of GSH in modulating redox sensitive pathways, in particular that mediated by NF-kB, and PDI activity. The second part of the review discusses the effectiveness of GSH-boosting molecules as broad-spectrum antivirals acting in a multifaceted way that includes the modulation of immune and inflammatory responses.
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Wang Q, Xie C, Xi S, Qian F, Peng X, Huang J, Tang F. Radioprotective Effect of Flavonoids on Ionizing Radiation-Induced Brain Damage. Molecules 2020; 25:5719. [PMID: 33287417 PMCID: PMC7730479 DOI: 10.3390/molecules25235719] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/25/2020] [Accepted: 12/02/2020] [Indexed: 01/27/2023] Open
Abstract
Patients receiving brain radiotherapy may suffer acute or chronic side effects. Ionizing radiation induces the production of intracellular reactive oxygen species and pro-inflammatory cytokines in the central nervous system, leading to brain damage. Complementary Chinese herbal medicine therapy may reduce radiotherapy-induced side effects. Flavonoids are a class of natural products which can be extracted from Chinese herbal medicine and have been shown to have neuroprotective and radioprotective properties. Flavonoids are effective antioxidants and can also inhibit regulatory enzymes or transcription factors important for controlling inflammatory mediators, affect oxidative stress through interaction with DNA and enhance genomic stability. In this paper, radiation-induced brain damage and the relevant molecular mechanism were summarized. The radio-neuro-protective effect of flavonoids, i.e., antioxidant, anti-inflammatory and maintaining genomic stability, were then reviewed. We concluded that flavonoids treatment may be a promising complementary therapy to prevent radiotherapy-induced brain pathophysiological changes and cognitive impairment.
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Affiliation(s)
- Qinqi Wang
- Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China; (Q.W.); (C.X.); (S.X.)
- Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Chenghao Xie
- Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China; (Q.W.); (C.X.); (S.X.)
- Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Shijun Xi
- Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China; (Q.W.); (C.X.); (S.X.)
- Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Feng Qian
- Department of Physiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China;
| | - Xiaochun Peng
- Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China; (Q.W.); (C.X.); (S.X.)
- Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Jiangrong Huang
- Department of Integrative Medicine, School of Health Sciences, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Fengru Tang
- Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Initiative, National University of Singapore, 1 CREATE Way #04-01, CREATE Tower, Singapore 138602, Singapore
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Hahn D, Shin SH, Bae JS. Natural Antioxidant and Anti-Inflammatory Compounds in Foodstuff or Medicinal Herbs Inducing Heme Oxygenase-1 Expression. Antioxidants (Basel) 2020; 9:E1191. [PMID: 33260980 PMCID: PMC7761319 DOI: 10.3390/antiox9121191] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/20/2020] [Accepted: 11/24/2020] [Indexed: 02/06/2023] Open
Abstract
Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme that catalyzes heme group degradation. Decreased level of HO-1 is correlated with disease progression, and HO-1 induction suppresses development of metabolic and neurological disorders. Natural compounds with antioxidant activities have emerged as a rich source of HO-1 inducers with marginal toxicity. Here we discuss the therapeutic role of HO-1 in obesity, hypertension, atherosclerosis, Parkinson's disease and hepatic fibrosis, and present important signaling pathway components that lead to HO-1 expression. We provide an updated, comprehensive list of natural HO-1 inducers in foodstuff and medicinal herbs categorized by their chemical structures. Based on the continued research in HO-1 signaling pathways and rapid development of their natural inducers, HO-1 may serve as a preventive and therapeutic target for metabolic and neurological disorders.
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Affiliation(s)
- Dongyup Hahn
- School of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu 41566, Korea;
- Department of Integrative Biology, Kyungpook National University, Daegu 41566, Korea
| | - Seung Ho Shin
- Department of Food and Nutrition, Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Korea;
| | - Jong-Sup Bae
- College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Korea
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Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NF κB Signaling Pathways in Primary Splenocytes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:3476212. [PMID: 32617135 PMCID: PMC7306849 DOI: 10.1155/2020/3476212] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 05/02/2020] [Accepted: 05/18/2020] [Indexed: 01/06/2023]
Abstract
Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 μM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1β protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA's potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF-α/IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.
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Martins-Perles JVC, Bossolani GDP, Zignani I, de Souza SRG, Frez FCV, de Souza Melo CG, Barili E, de Souza Neto FP, Guarnier FA, Armani ALC, Cecchini R, Zanoni JN. Quercetin increases bioavailability of nitric oxide in the jejunum of euglycemic and diabetic rats and induces neuronal plasticity in the myenteric plexus. Auton Neurosci 2020; 227:102675. [PMID: 32474374 DOI: 10.1016/j.autneu.2020.102675] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 03/06/2020] [Accepted: 04/24/2020] [Indexed: 02/08/2023]
Abstract
Considering the antioxidant, neuroprotective, inflammatory and nitric oxide modulatory actions of quercetin, the aim of this study was to test the effect of quercetin administration in drinking water (40 mg/day/rat) on neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), overall population of myenteric neurons (HuC/D) and nitric oxide (NO) levels in the jejunal samples from diabetic rats. Male Wistar rats were distributed into four groups (8 rats per group): euglycemic (E), euglycemic administered with quercetin (E+Q), diabetic (D) and diabetic administered with quercetin (D+Q). Rats were induced to diabetes with streptozotocin (35mg/kg/iv) and, after 120 days, the proximal jejunum were collected and processed for immunohistochemical (VIP, nNOS and HuC/D) and chemiluminescence (quantification of tissue NO levels) techniques. Diabetes mellitus reduced the number of nNOS-IR (immunoreactive) (p <0.05) and HuC/D-IR (p <0.001) neurons, however, promoted an increased morphometric area of nNOS-IR neurons (p <0.001) and VIP-IR varicosities (p <0.05). In D+Q group, neuroplasticity effects were observed on HuC/D-IR neurons, accompanied by a reduction of cell body area of neurons nNOS- and VIP-IR varicosities (p <0.05). The NO levels were increased in the E+Q (p <0.05) and D+Q group (p <0.001) compared to the control group. In conclusion, the results showed that quercetin supplementation increased the bioavailability of NO in the jejunum in euglycemic and mitigate the effects of diabetes on nNOS-IR neurons and VIP-IR varicosities in the myenteric plexus of diabetic rats.
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Affiliation(s)
| | - Gleison Daion Piovezana Bossolani
- Department of Morphological Sciences, Universidade Estadual de Maringá, Avenida Colombo, n 5790 Bloco O-33, Maringá, PR CEP 87020-900, Brazil
| | - Isabela Zignani
- Department of Morphological Sciences, Universidade Estadual de Maringá, Avenida Colombo, n 5790 Bloco O-33, Maringá, PR CEP 87020-900, Brazil
| | - Sara Raquel Garcia de Souza
- Department of Morphological Sciences, Universidade Estadual de Maringá, Avenida Colombo, n 5790 Bloco O-33, Maringá, PR CEP 87020-900, Brazil
| | - Flávia Cristina Vieira Frez
- Department of Morphological Sciences, Universidade Estadual de Maringá, Avenida Colombo, n 5790 Bloco O-33, Maringá, PR CEP 87020-900, Brazil
| | - Carina Guimarães de Souza Melo
- Department of Morphological Sciences, Universidade Estadual de Maringá, Avenida Colombo, n 5790 Bloco O-33, Maringá, PR CEP 87020-900, Brazil
| | - Emerson Barili
- Department of Statistic, Universidade Estadual de Maringá, Avenida Colombo, n 5790, Maringá, PR CEP 87020-900, Brazil
| | - Fernando Pinheiro de Souza Neto
- Department of Pathology Sciences, Universidade Estadual de Londrina (UEL), Rodovia Celso Garcia Cid
- Pr 445 Km 380, Londrina, PR CEP 86.057-970, Brazil
| | - Flávia Alessandra Guarnier
- Department of Pathology Sciences, Universidade Estadual de Londrina (UEL), Rodovia Celso Garcia Cid
- Pr 445 Km 380, Londrina, PR CEP 86.057-970, Brazil
| | - Alessandra Lourenço Cecchini Armani
- Department of Pathology Sciences, Universidade Estadual de Londrina (UEL), Rodovia Celso Garcia Cid
- Pr 445 Km 380, Londrina, PR CEP 86.057-970, Brazil
| | - Rubens Cecchini
- Department of Pathology Sciences, Universidade Estadual de Londrina (UEL), Rodovia Celso Garcia Cid
- Pr 445 Km 380, Londrina, PR CEP 86.057-970, Brazil
| | - Jacqueline Nelisis Zanoni
- Department of Morphological Sciences, Universidade Estadual de Maringá, Avenida Colombo, n 5790 Bloco O-33, Maringá, PR CEP 87020-900, Brazil.
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22
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Belchamber KBR, Donnelly LE. Targeting defective pulmonary innate immunity - A new therapeutic option? Pharmacol Ther 2020; 209:107500. [PMID: 32061706 DOI: 10.1016/j.pharmthera.2020.107500] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 01/31/2020] [Indexed: 12/11/2022]
Abstract
Chronic pulmonary conditions now account for 1 in 15 deaths in the US and mortality is increasing. Chronic obstructive pulmonary disease (COPD) is due to become the 3rd largest cause of mortality by 2030 and mortality from other respiratory conditions such as asthma, idiopathic pulmonary fibrosis and cystic fibrosis are not reducing. There is an urgent need for novel therapies to address this problem as many of the current strategies targeting inflammation are not sufficient. The innate immune system of the lung is an important defence against invading pathogens, but in many chronic pulmonary diseases, this system mounts an inappropriate response. In COPD, macrophages are increased in number, but fail to clear pathogens correctly and become highly activated. This leads to increased damage and remodelling of the airways. In idiopathic fibrosis, there is a switch of macrophage phenotype to a cell that promotes abnormal repair. Neutrophils also display dysfunction in COPD where aberrant migratory profiles may lead to increased damage to lung tissue and emphysema; while in cystic fibrosis the proteolytic lung environment damages neutrophil receptors leading to ineffective phagocytosis and migration. Targeting the innate immune system to restore 'normal function' could have enormous benefits. Improving phagocytosis of pathogens could reduce exacerbations and hence the associated decline in lung function, and novel therapeutics such as sulforaphane appear to do this in vitro. Other natural products such as resveratrol and derivatives also have anti-inflammatory properties. Statins have traditionally been used to manage cholesterol levels in hypercholesterolaemia, however these molecules also have beneficial effects on the innate immune cells. Statins have been shown to be anti-inflammatory and restore aberrant neutrophil chemotaxis in aged cells. Other possible agents that may be efficacious are senolytics. These compounds include natural products such as quercetin which have anti-inflammatory properties but can also suppress viral replication. As viruses have been shown to suppress phagocytosis of macrophages, it is possible that these compounds could have benefit during viral exacerbations to protect this innate response. These compounds demonstrate that it is possible to address defective innate responses in the lung but a better understanding of the mechanisms driving defective innate immunity in pulmonary disease may lead to improved therapeutics.
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Affiliation(s)
- Kylie B R Belchamber
- National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
| | - Louise E Donnelly
- National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.
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23
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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.
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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.
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24
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Phytofabrication of Nanoparticles as Novel Drugs for Anticancer Applications. Molecules 2019; 24:molecules24234246. [PMID: 31766544 PMCID: PMC6930546 DOI: 10.3390/molecules24234246] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 10/30/2019] [Accepted: 11/08/2019] [Indexed: 02/05/2023] Open
Abstract
Cancer is one of the foremost causes of death globally and also the major stumbling block of increasing life expectancy. Although the primary treatment of surgical resection, chemotherapy, and radiotherapy have greatly reduced the mortality of cancer, the survival rate is still low because of the metastasis of tumor, a range of adverse drug reactions, and drug resistance. For all this, it is relevant to mention that a growing amount of research has shown the anticarcinogenic effect of phytochemicals which can modulate the molecular pathways and cellular events include apoptosis, cell proliferation, migration, and invasion. However, their pharmacological potential is hindered by their low water solubility, low stability, poor absorption, and rapid metabolism. In this scenario, the development of nanotechnology has created novel formulations to maximize the potential use of phytochemicals in anticancer treatment. Nanocarriers can enhance the solubility and stability of phytochemicals, prolong their half-life in blood and even achieve site-targeting delivery. This review summarizes the advances in utilizing nanoparticles in cancer therapy. In particular, we introduce several applications of nanoparticles combined with apigenin, resveratrol, curcumin, epigallocatechin-3-gallate, 6-gingerol, and quercetin in cancer treatment.
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25
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Ksouri R. Food components and diet habits: chief factors of cancer development. FOOD QUALITY AND SAFETY 2019. [DOI: 10.1093/fqsafe/fyz021] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Abstract
Food is a vital need for everyone. Today, there is food for all, but the world still suffers from under- and over-nutrition and risk of cancer development and chronic diseases can follow both cases. Worldwide, cancer is a leading cause of mortality after cardiovascular disease; it is considered the second reason for death globally. Role of nutritional habits, the quality of food, the consumption of canned foods, genetically modified fruits and vegetables and exposed food to certain pesticides and carcinogens agents, and unhealthy lifestyle behaviours such as smoking, alcohol, obesity, and fast-foods consumption may be at risk to the development of some cancers. In recent decades, researchers have carried out attention in this field to improve the quality of life and to limit nutrition problems. Thus, this study aims to summarize current evidence on the relationship between nutritional factors and cancer expansion, how nutrition can be a heal and a source of fatal illness leading to death. In detail, this review will highlight the influence of specific foodstuffs on the threat of cancer incidence and recurrence by providing some examples of most carcinogenic compounds.
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Affiliation(s)
- Rihab Ksouri
- Department of Biotechnology, Biotechnology Institute, Ankara University, Turkey
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26
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Nutrition and Breast Cancer: A Literature Review on Prevention, Treatment and Recurrence. Nutrients 2019; 11:nu11071514. [PMID: 31277273 PMCID: PMC6682953 DOI: 10.3390/nu11071514] [Citation(s) in RCA: 232] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 06/28/2019] [Accepted: 07/01/2019] [Indexed: 12/13/2022] Open
Abstract
Breast cancer (BC) is the second most common cancer worldwide and the most commonly occurring malignancy in women. There is growing evidence that lifestyle factors, including diet, body weight and physical activity, may be associated with higher BC risk. However, the effect of dietary factors on BC recurrence and mortality is not clearly understood. Here, we provide an overview of the current evidence obtained from the PubMed databases in the last decade, assessing dietary patterns, as well as the consumption of specific food-stuffs/food-nutrients, in relation to BC incidence, recurrence and survival. Data from the published literature suggest that a healthy dietary pattern characterized by high intake of unrefined cereals, vegetables, fruit, nuts and olive oil, and a moderate/low consumption of saturated fatty acids and red meat, might improve overall survival after diagnosis of BC. BC patients undergoing chemotherapy and/or radiotherapy experience a variety of symptoms that worsen patient quality of life. Studies investigating nutritional interventions during BC treatment have shown that nutritional counselling and supplementation with some dietary constituents, such as EPA and/or DHA, might be useful in limiting drug-induced side effects, as well as in enhancing therapeutic efficacy. Therefore, nutritional intervention in BC patients may be considered an integral part of the multimodal therapeutic approach. However, further research utilizing dietary interventions in large clinical trials is required to definitively establish effective interventions in these patients, to improve long-term survival and quality of life.
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Luzardo-Álvarez A, Lamela-Gómez I, Otero-Espinar F, Blanco-Méndez J. Development, Characterization, and In Vitro Evaluation of Resveratrol-Loaded Poly-(ε-caprolactone) Microcapsules Prepared by Ultrasonic Atomization for Intra-Articular Administration. Pharmaceutics 2019; 11:E249. [PMID: 31141945 PMCID: PMC6631008 DOI: 10.3390/pharmaceutics11060249] [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: 04/23/2019] [Revised: 05/22/2019] [Accepted: 05/23/2019] [Indexed: 12/14/2022] Open
Abstract
: Intra-articular administration of drugs to the joint in the treatment of joint disease has the potential to minimize the systemic bioavailability and the usual side-effects associated with oral drug administration. In this work, a drug delivery system is proposed to achieve an anti-inflammatory local effect using resveratrol (RSV). This study aims to develop microcapsules made of poly-(ε-caprolactone) (PCL) by ultrasonic atomization to preserve the antioxidant activity of RSV, to prevent its degradation and to suppress the inflammatory response in activated RAW 264.7 macrophages. An experimental design was performed to build a mathematical model that could estimate the effect of nozzle power and polymer concentration on particle size and encapsulation efficiency. RSV-loaded microcapsules showed adequate morphology, particle size, and loading efficiency properties. RSV formulations exhibited negligible cytotoxicity and an efficient amelioration of inflammatory responses, in terms of Nitric Oxide (NO), ROS (Reactive Oxygen Species), and lipid peroxidation in macrophages. Thus, RSV-loaded microcapsules merit consideration as a drug delivery system suitable for intra-articular administration in inflammatory disorders affecting the joint.
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Affiliation(s)
- Asteria Luzardo-Álvarez
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Sciences, Campus de Lugo, University of Santiago de Compostela, Lugo 27002, Spain.
| | - Iván Lamela-Gómez
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Sciences, Campus de Lugo, University of Santiago de Compostela, Lugo 27002, Spain.
| | - Francisco Otero-Espinar
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy, Campus de Santiago de Compostela, University of Santiago de Compostela, Santiago de Compostela 14875, Spain.
| | - José Blanco-Méndez
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Sciences, Campus de Lugo, University of Santiago de Compostela, Lugo 27002, Spain.
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy, Campus de Santiago de Compostela, University of Santiago de Compostela, Santiago de Compostela 14875, Spain.
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28
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Rodriguez-Muñiz GM, Miranda MA, Marin ML. A Time-Resolved Study on the Reactivity of Alcoholic Drinks with the Hydroxyl Radical. Molecules 2019; 24:E234. [PMID: 30634584 PMCID: PMC6359750 DOI: 10.3390/molecules24020234] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Revised: 12/28/2018] [Accepted: 01/07/2019] [Indexed: 01/19/2023] Open
Abstract
Reactive oxygen species (ROS) can provoke damage to cells, where their concentrations are regulated by antioxidants. As the hydroxyl radical (•OH) is the most oxidizing ROS, we have focused our attention on the use of a mechanistically based time-resolved methodology, such as laser flash photolysis, to determine the relative reactivity of alcoholic beverages towards •OH as an indicator of their antioxidant potential. The selected drinks were of two different origins: (i) those derived from grapes such as red wine, white wine, white vermouth, marc and brandy and (ii) spirits not derived from grapes: triple sec, gin, whisky, and rum. Initially, we determined the quenching rate constant of ethanol with •OH and then we explored the reactivity of the different beverages, which was higher than expected based on their alcoholic content. This can be attributed to the presence of antioxidants and was especially remarkable for the grape-derived drinks.
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Affiliation(s)
- Gemma M Rodriguez-Muñiz
- Instituto de Tecnología Química, Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas, Avda. de los Naranjos s/n, E-46022 Valencia, Spain.
| | - Miguel A Miranda
- Instituto de Tecnología Química, Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas, Avda. de los Naranjos s/n, E-46022 Valencia, Spain.
| | - M Luisa Marin
- Instituto de Tecnología Química, Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas, Avda. de los Naranjos s/n, E-46022 Valencia, Spain.
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29
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Flavonoids Ability to Disrupt Inflammation Mediated by Lipid and Cholesterol Oxidation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1161:243-253. [PMID: 31562634 DOI: 10.1007/978-3-030-21735-8_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Flavonoids are plant secondary metabolites that act as protectants against harmful effects of UV-B radiation inasmuch as biotic stress, conferring at the same time pigmentation of fruits and leaves [67]. The term "flavonoid" refers to phenolics having a basic skeleton of diphenylpropane (C6-C3-C6), which consists of two aromatic rings linked through three carbons that usually form an oxygenated heterocycle [25, 52]. Flavonoids are broken down into several different sub-categories based on their chemical structure. The main subclasses commonly found in food items are: flavonols, flavones, flavanones, flavan-3-ols, proanthocyanidins, and anthocyanins [44, 67]. Figure 19.1 depicts the major classification of flavonoids according to their chemical structure. Their occurrence in food matrices has been extensively reviewed [39, 44], and has been subject of extensive research in the last decades. Table 19.1 contains a few examples of compounds from each of the subcategory, with the fruit (berry) in which they are commonly found. The monomeric unit of flavonoids can dimerize and polymerize to form other important high molecular weight molecules; this is the case of proanthocyanidins, that are polymers of flavan-3-ols or flavanols. Not only do these compounds act as plant protectants, but they can also be very beneficial to human health. Cohorts studies performed in the early '90 have shown that dietary consumption of flavonoids was inversely associated with morbidity and mortality from coronary heart disease [31, 32]. These findings have opened an intensive field of research on the effects of flavonoids and flavonoids-rich food extracts in cardiovascular diseases (CVD) progression, particularly in the modulating CVD-associated oxidative stress and inflammation. In this short review, we will summarize the current findings in flavonoids beneficial effects in preventing CVD through inhibition of initial stages of CVD progression. Given the magnitude of scientific literature in the field, we will focus on two strictly mechanistic aspects: inhibition of chemical-induced LDL oxidation, and the effect of flavonoids in the monocyte/macrophages activation pathways.
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30
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Fischer N, Seo EJ, Efferth T. Prevention from radiation damage by natural products. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2018; 47:192-200. [PMID: 30166104 DOI: 10.1016/j.phymed.2017.11.005] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Revised: 10/20/2017] [Accepted: 11/12/2017] [Indexed: 06/08/2023]
Abstract
BACKGROUND Radiotherapy is a mainstay of cancer treatment since decades. Ionizing radiation (IR) is used for destruction of cancer cells and shrinkage of tumors. However, the increase of radioresistance in cancer cells and radiation toxicity to normal tissues are severe concerns. The exposure to radiation generates intracellular reactive oxygen species (ROS), which leads to DNA damage by lipid peroxidation, removal of thiol groups from cellular and membrane proteins, strand breaks and base alterations. HYPOTHESIS Plants have to deal with radiation-induced damage (UV-light of sun, other natural radiation sources). Therefore, it is worth speculating that radioprotective mechanisms have evolved during evolution of life. We hypothesize that natural products from plants may also protect from radiation damage caused as adverse side effects of cancer radiotherapy. METHODS The basis of this systematic review, we searched the relevant literature in the PubMed database. RESULTS Flavonoids, such as genistein, epigallocatechin-3-gallate, epicatechin, apigenin and silibinin mainly act as antioxidant, free radical scavenging and anti-inflammatory compounds, thus, providing cytoprotection in addition to downregulation of several pro-inflammatory cytokines. Comparable effects have been found in phenylpropanoids, especially caffeic acid phenylethylester, curcumin, thymol and zingerone. Besides, resveratrol and quercetin are the most important cytoprotective polyphenols. Their radioprotective effects are mediated by a wide range of mechanisms mainly leading to direct or indirect reduction of cellular stress. Ascorbic acid is broadly used as antioxidant, but it has also shown activity in reducing cellular damage after irradiation mainly due to its antioxidant capabilities. The metal ion chelator, gallic acid, represents another natural product attenuating cellular damage caused by radiation. CONCLUSIONS Some secondary metabolites from plants reveal radioprotective features against cellular damage caused by irradiation. These results warrant further analysis to develop phytochemicals as radioprotectors for clinical use.
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Affiliation(s)
- Nicolas Fischer
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
| | - Ean-Jeong Seo
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
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31
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Li ZP, Liu HB, Zhang QW, Li LF, Bao WR, Ma DL, Leung CH, Bian ZX, Lu AP, Han QB. Interference of Quercetin on Astragalus Polysaccharide-Induced Macrophage Activation. Molecules 2018; 23:E1563. [PMID: 29958399 PMCID: PMC6100010 DOI: 10.3390/molecules23071563] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 06/22/2018] [Accepted: 06/26/2018] [Indexed: 01/24/2023] Open
Abstract
Polysaccharides, which exert immunoregulatory effects, are becoming more and more popular as food supplements; however, certain components of ordinary foods could be reducing the polysaccharides beneficial effects. Quercetin, a flavonoid found in common fruits and vegetables, is one such component. This study investigated the effects of quercetin on Astragalus polysaccharide RAP induced-macrophage activation. The results show quercetin decreases the NO production and iNOS gene expression in RAW264.7 cells, and it inhibits the production of cytokines in RAW264.7 cells and peritoneal macrophages. Western blot analysis results suggest that quercetin inhibits the phosphorylation of Akt/mTORC1, MAPKs, and TBK1, but has no effect on NF-κB in RAP-induced RAW264.7 cells. Taken together, the results show that quercetin partly inhibits macrophage activation by the Astragalus polysaccharide RAP. This study demonstrates that quercetin-containing foods may interfere with the immune-enhancing effects of Astragalus polysaccharide RAP to a certain extent.
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Affiliation(s)
- Zhi-Peng Li
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
| | - Hong-Bing Liu
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
| | - Quan-Wei Zhang
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
| | - Li-Feng Li
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
| | - Wan-Rong Bao
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
| | - Dik-Lung Ma
- Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
| | - Chung-Hang Leung
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
| | - Zhao-Xiang Bian
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
| | - Ai-Ping Lu
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
| | - Quan-Bin Han
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
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32
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Hatahet T, Morille M, Hommoss A, Devoisselle J, Müller R, Bégu S. Liposomes, lipid nanocapsules and smartCrystals®: A comparative study for an effective quercetin delivery to the skin. Int J Pharm 2018; 542:176-185. [DOI: 10.1016/j.ijpharm.2018.03.019] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 03/12/2018] [Accepted: 03/12/2018] [Indexed: 02/07/2023]
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33
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Meng Q, Guo T, Li G, Sun S, He S, Cheng B, Shi B, Shan A. Dietary resveratrol improves antioxidant status of sows and piglets and regulates antioxidant gene expression in placenta by Keap1-Nrf2 pathway and Sirt1. J Anim Sci Biotechnol 2018; 9:34. [PMID: 29713468 PMCID: PMC5909222 DOI: 10.1186/s40104-018-0248-y] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 03/05/2018] [Indexed: 12/29/2022] Open
Abstract
Background Resveratrol, a plant phenol, affords protection against inflammation and oxidative stress. The objective of this study was to investigate the effects of dietary resveratrol supplementation during pregnancy and lactation on the antioxidant status of sows and piglets and on antioxidant gene expression and pathway in placenta. Methods Forty sows were allotted to 2 dietary treatments 20 d after breeding. Sows were fed a control diet and a control diet with 300 mg/kg resveratrol. Oxidative stress biomarkers and antioxidant enzymes were measured in the placenta, milk, and plasma of sows and piglets. Antioxidant gene expression and protein expression of Kelch-like ECH-associated protein 1-Nuclear factor E2-related factor 2 (Keap1-Nrf2), nuclear factor kappa B-p65 (NFκB-p65) and sirtuin1 (Sirt1) were quantified in the placenta. Results Dietary resveratrol increased the litter and piglets weaning weights. Antioxidant status in the milk, placenta and plasma of sows and piglets was partially improved by dietary resveratrol. In placenta, Nrf2 protein expression was increased and Keap1 protein expression was decreased by dietary resveratrol. The mRNA expression of antioxidant genes including catalase (CAT), glutathione peroxidase 1 (GPX1), GPX4, superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO1), and phase 2 detoxification genes, including glutamate-cysteine ligase modifier (GCLM), microsomal glutathione S-transferase 1(MGST1) and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), was increased by dietary resveratrol. Dietary resveratrol also increased Sirt1 and phosphorylated NFκB-p65 protein expression in the placenta. We failed to observe any influences of dietary resveratrol on pro-inflammatory cytokine levels, including those of interleukin 1β (IL-1β), IL-6, IL-8 and tumor necrosis factor α (TNF-α). However, we observed that the mRNA expression of IL-8 in placenta was reduced by maternal resveratrol. In addition, dietary resveratrol showed interactive effects with day of lactation on activities of SOD and CAT and levels of malonaldehyde (MDA) and hydrogen peroxide (H2O2) in milk. Conclusions Dietary resveratrol supplementation during pregnancy and lactation improves the antioxidant status of sows and piglets, which is beneficial to the reproductive performance of sows. Dietary resveratrol regulates placental antioxidant gene expression by the Keap1-Nrf2 pathway and Sirt1 in placenta.
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Affiliation(s)
- Qingwei Meng
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang People's Republic of China
| | - Tao Guo
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang People's Republic of China
| | - Gaoqiang Li
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang People's Republic of China
| | - Shishuai Sun
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang People's Republic of China
| | - Shiqi He
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang People's Republic of China
| | - Baojing Cheng
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang People's Republic of China
| | - Baoming Shi
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang People's Republic of China
| | - Anshan Shan
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, Heilongjiang People's Republic of China
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Medjeber O, Touri K, Rafa H, Djeraba Z, Belkhelfa M, Boutaleb AF, Arroul-Lammali A, Belguendouz H, Touil-Boukoffa C. Ex vivo immunomodulatory effect of ethanolic extract of propolis during Celiac Disease: involvement of nitric oxide pathway. Inflammopharmacology 2018. [PMID: 29516252 DOI: 10.1007/s10787-018-0460-6] [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: 02/06/2023]
Abstract
Celiac Disease (CeD) is a chronic immune-mediated enteropathy, in which dietary gluten induces an inflammatory reaction, predominantly in the duodenum. Propolis is a resinous hive product, collected by honeybees from various plant sources. Propolis is well-known for its anti-inflammatory, anti-oxidant and immunomodulatory effects, due to its major compounds, polyphenols and flavonoids. The aim of our study was to assess the ex vivo effect of ethanolic extract of propolis (EEP) upon the activity and expression of iNOS, along with IFN-γ and IL-10 production in Algerian Celiac patients. In this context, PBMCs isolated from peripheral blood of Celiac patients and healthy controls were cultured with different concentrations of EEP. NO production was measured using the Griess method, whereas quantitation of IFN-γ and IL-10 levels was performed by ELISA. Inducible nitric oxide synthase (iNOS) expression, NFκB and pSTAT-3 activity were analyzed by immunofluorescence assay. Our results showed that PBMCs from Celiac patients produced high levels of NO and IFN-γ compared with healthy controls (HC). Interestingly, EEP reduced significantly, NO and IFN-γ levels and significantly increased IL-10 levels at a concentration of 50 µg/mL. Importantly, EEP downmodulated the iNOS expression as well as the activity of NFκB and pSTAT-3 transcription factors. Altogether, our results highlight the immunomodulatory effect of propolis on NO pathway and on pro-inflammatory cytokines. Therefore, we suggest that propolis may constitute a potential candidate to modulate inflammation during Celiac Disease and has a potential therapeutic value.
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Affiliation(s)
- Oussama Medjeber
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia Bab-Ezzouar, Algiers, Algeria
| | - Kahina Touri
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia Bab-Ezzouar, Algiers, Algeria
| | - Hayet Rafa
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia Bab-Ezzouar, Algiers, Algeria
| | - Zineb Djeraba
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia Bab-Ezzouar, Algiers, Algeria
| | - Mourad Belkhelfa
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia Bab-Ezzouar, Algiers, Algeria
| | | | - Amina Arroul-Lammali
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia Bab-Ezzouar, Algiers, Algeria
| | - Houda Belguendouz
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia Bab-Ezzouar, Algiers, Algeria
| | - Chafia Touil-Boukoffa
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia Bab-Ezzouar, Algiers, Algeria.
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Lee PJ, Tsai TY, Chen S. Analysis of NO-suppressing activity of Strawberry Wine supplemented with ball-milled achenes. Journal of Food Science and Technology 2018; 55:1285-1294. [PMID: 29606742 DOI: 10.1007/s13197-018-3039-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 05/17/2017] [Accepted: 01/12/2018] [Indexed: 10/18/2022]
Abstract
Inflammation is generally thought to be involved in the development of several chronical diseases, therefore, phytochemicals to modulate immune responses has attracted great interests. The objective of the present study was to evaluate the potential anti-inflammatory effects of wine supplemented using ball-milled achene on modulating NO production and inducible nitric oxide synthase (iNOS) expression. Ball-milled achenes were added in strawberry must prior to fermentation, and the wine samples were then concentrated and extracted with water and/or ethanol prior to analysis. Bioactivities of wine extracts were evaluated using the cell viability assay, cell cycle measurements, NO production and iNOS expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Treatments of achenes supplemented strawberry wine extract up to 100 μg/mL inhibited the proliferation of LPS-stimulated RAW264.7 cell via affecting the progression of cell cycle. Moreover, no detectable cytotoxicity in RAW264.7 cells was observed. The supplemented wine extract suppressed the action of LPS and led to a decreased NO production in stimulated cells. The inhibitory effect of the wine extract on NO production was determined to be a 25-40% decrease in the level of 25-100 μg/mL, in contrast to a 10% decrease for conventional wine samples. Additionally, an alcoholic wine extract (100 μg/mL) led to a 40.31% decrease in iNOS expression in LPS-stimulated cells, which was more effective than the same dose of tocopherol. The results show that strawberry wine supplemented with ball-milled achenes causes a substantial inhibition of NO production, and this biofunction is exerted via the down-regulation of iNOS expression.
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Affiliation(s)
- Pao-Ju Lee
- 1Ph.D. Program in Nutrition and Food Sciences, Fu Jen Catholic University, New Taipei City, 24205 Taiwan
| | - Tsung-Yu Tsai
- 1Ph.D. Program in Nutrition and Food Sciences, Fu Jen Catholic University, New Taipei City, 24205 Taiwan.,2EP 305, Department of Food Science, Fu Jen Catholic University, # 510 Chungcheng Road, Hsinchuan District, New Taipei City, 24205 Taiwan
| | - Shaun Chen
- 1Ph.D. Program in Nutrition and Food Sciences, Fu Jen Catholic University, New Taipei City, 24205 Taiwan.,2EP 305, Department of Food Science, Fu Jen Catholic University, # 510 Chungcheng Road, Hsinchuan District, New Taipei City, 24205 Taiwan
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36
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Ko JH, Sethi G, Um JY, Shanmugam MK, Arfuso F, Kumar AP, Bishayee A, Ahn KS. The Role of Resveratrol in Cancer Therapy. Int J Mol Sci 2017; 18:ijms18122589. [PMID: 29194365 PMCID: PMC5751192 DOI: 10.3390/ijms18122589] [Citation(s) in RCA: 493] [Impact Index Per Article: 61.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 11/27/2017] [Accepted: 11/29/2017] [Indexed: 12/26/2022] Open
Abstract
Natural product compounds have recently attracted significant attention from the scientific community for their potent effects against inflammation-driven diseases, including cancer. A significant amount of research, including preclinical, clinical, and epidemiological studies, has indicated that dietary consumption of polyphenols, found at high levels in cereals, pulses, vegetables, and fruits, may prevent the evolution of an array of diseases, including cancer. Cancer development is a carefully orchestrated progression where normal cells acquires mutations in their genetic makeup, which cause the cells to continuously grow, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Compounds that modulate these oncogenic processes can be considered as potential anti-cancer agents that may ultimately make it to clinical application. Resveratrol, a natural stilbene and a non-flavonoid polyphenol, is a phytoestrogen that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. It has been reported that resveratrol can reverse multidrug resistance in cancer cells, and, when used in combination with clinically used drugs, it can sensitize cancer cells to standard chemotherapeutic agents. Several novel analogs of resveratrol have been developed with improved anti-cancer activity, bioavailability, and pharmacokinetic profile. The current focus of this review is resveratrol’s in vivo and in vitro effects in a variety of cancers, and intracellular molecular targets modulated by this polyphenol. This is also accompanied by a comprehensive update of the various clinical trials that have demonstrated it to be a promising therapeutic and chemopreventive agent.
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Affiliation(s)
- Jeong-Hyeon Ko
- College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
| | - Gautam Sethi
- Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam.
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam.
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
| | - Jae-Young Um
- College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
| | - Muthu K Shanmugam
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
| | - Frank Arfuso
- Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth WA 6009, Australia.
| | - Alan Prem Kumar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
| | - Anupam Bishayee
- Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA.
| | - Kwang Seok Ahn
- College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
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Khampeerathuch T, Mudsak A, Srikok S, Vannamahaxay S, Chotinun S, Chuammitri P. Differential gene expression in heterophils isolated from commercial hybrid and Thai indigenous broiler chickens under quercetin supplementation. JOURNAL OF APPLIED ANIMAL RESEARCH 2017. [DOI: 10.1080/09712119.2017.1405814] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Tanakrit Khampeerathuch
- Department of Veterinary Biosciences and Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Acharaporn Mudsak
- Department of Veterinary Biosciences and Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Suphakit Srikok
- Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Soulasack Vannamahaxay
- Department of Livestock and Fisheries, Faculty of Agriculture, National University of Laos, Vientiane, Laos
| | - Suwit Chotinun
- Department of Food Animal Clinics, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
- Integrative Research Center for Veterinary Preventive Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Phongsakorn Chuammitri
- Department of Veterinary Biosciences and Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
- Excellent Center in Veterinary Biosciences (ECVB), Chiang Mai University, Chiang Mai, Thailand
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38
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Li ZP, Zhang QW, Wei W, Li LF, Ma DL, Leung CH, Lu AP, Bian ZX, Han QB. Luteolin exerted less inhibitory effect on macrophage activation induced by Astragalus polysaccharide than by lipopolysaccharide. J Funct Foods 2017. [DOI: 10.1016/j.jff.2017.08.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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39
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Evaluation of nitric oxide inhibition effect in LPS-stimulated RAW 264.7 macrophages by phytochemical constituents from Mesua beccariana, Mesua congestiflora, and Mesua ferrea. Med Chem Res 2017. [DOI: 10.1007/s00044-017-2017-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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40
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Choi JG, Lee H, Hwang YH, Lee JS, Cho WK, Ma JY. Eupatorium fortunei and Its Components Increase Antiviral Immune Responses against RNA Viruses. Front Pharmacol 2017; 8:511. [PMID: 28824435 PMCID: PMC5541272 DOI: 10.3389/fphar.2017.00511] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 07/20/2017] [Indexed: 11/17/2022] Open
Abstract
Eupatorium fortunei (EF) has long been used as herbal medicine in Korea, China, and Asian countries to treat a variety of diseases. Recent studies have reported that EF has anti-metastatic, anti-angiogenic, anti-bacterial, and anti-oxidant activities, as well as activities against malignant metastatic human cancers. The effect of EF and its components on viruses has not been reported. In the present study, the antiviral activity and mechanism of action of an aqueous extract of EF (WEF) and its components were evaluated in vitro. We found that pretreatment with WEF markedly reduced viral replication, as evaluated using a green fluorescent protein (GFP)-tagged virus (influenza A virus, Newcastle disease virus, and vesicular stomatitis virus) in murine RAW 264.7 macrophage cells. We demonstrated that WEF induces the production of type I IFN including pro-inflammatory cytokines. Additionally, we identified the active anti-viral components of WEF as quercetin, psoralen, and quercitrin. Thus, WEF and its active components are immunomodulators of the innate immune response in murine macrophages, a finding that is potentially useful to developing prophylactic or therapeutic treatments against a range of viruses.
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Affiliation(s)
- Jang-Gi Choi
- Korean Medicine Application Center, Korea Institute of Oriental MedicineDaegu, South Korea
| | - Heeeun Lee
- Korean Medicine Application Center, Korea Institute of Oriental MedicineDaegu, South Korea
| | - Youn-Hwan Hwang
- Korean Medicine Application Center, Korea Institute of Oriental MedicineDaegu, South Korea
| | - Jong-Soo Lee
- College of Veterinary Medicine, Chungnam National UniversityDaejeon, South Korea
| | - Won-Kyung Cho
- Korean Medicine Application Center, Korea Institute of Oriental MedicineDaegu, South Korea
| | - Jin Yeul Ma
- Korean Medicine Application Center, Korea Institute of Oriental MedicineDaegu, South Korea
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41
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A multifunctional alanine-rich anti-inflammatory peptide BCP61 showed potent inhibitory effects by inhibiting both NF-κB and MAPK expression. Inflammation 2017; 40:688-696. [PMID: 28214973 DOI: 10.1007/s10753-017-0515-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The purified BCP61 was reported to be a unique low-molecular-weight (MW) anti-microbial peptide because of its non-identical alanine-rich N-terminal sequence. In this study, we investigated the anti-inflammatory effects of BCP61 on induction of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. The treatment with BCP61, with varying concentrations of 10, 50, and 100 μg/mL, inhibited levels of expression of LPS-induced NF-κB and MAPKs (extracellular signal-related kinases (ERKs), c-Jun NH2-terminal kinase (JNK), and mitogen-activated protein (p38)) as well as production of pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). The results suggested that BCP61 prevents inhibitor of kappa B (IκBα) phosphorylation and degradation, thereby inhibiting the nuclear translocation of the p65 protein. We do report that the use of BCP61 in the treatment of inflammation as well as microbial infection could be a potent therapeutic candidate.
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42
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Kim IH, Kwon MJ, Nam TJ. Differences in cell death and cell cycle following fucoidan treatment in high-density HT-29 colon cancer cells. Mol Med Rep 2017; 15:4116-4122. [PMID: 28487956 PMCID: PMC5436236 DOI: 10.3892/mmr.2017.6520] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 02/27/2017] [Indexed: 12/16/2022] Open
Abstract
Fucoidan, a sulfated polysaccharide present in marine brown seaweed, has been demonstrated to inhibit in vivo and in vitro growth of cells. The present study was conducted in HT-29 human colon cancer cells cultured at a high density, and examined the potential underlying mechanisms by which fucoidan exerts its anti-proliferative effects, which remain poorly understood. Fucoidan treatment of high-density HT-29 cells resulted in the inhibition of cell growth and increased apoptotic cell death. Flow cytometric analysis revealed that fucoidan treatment led to sub-G1 phase cell cycle arrest. This was associated with decreased protein expression levels of Retinoblastoma protein and E2 factor protein. In conclusion, the results of the present study demonstrated that fucoidan possesses anticancer activity against high density HT-29 cells by inhibiting cell growth and cell cycle progression.
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Affiliation(s)
- In-Hye Kim
- Cell Biology Laboratory, Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Republic of Korea
| | - Mi-Jin Kwon
- Cell Biology Laboratory, Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Republic of Korea
| | - Taek-Jeong Nam
- Cell Biology Laboratory, Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Republic of Korea
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43
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Cho S, Namkoong K, Shin M, Park J, Yang E, Ihm J, Thu VT, Kim HK, Han J. Cardiovascular Protective Effects and Clinical Applications of Resveratrol. J Med Food 2017; 20:323-334. [PMID: 28346848 DOI: 10.1089/jmf.2016.3856] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Resveratrol is a naturally occurring phenol that is generated by plant species following injury or attack by bacterial and fungal pathogens. This compound was first described as the French Paradox in 1992. Later in 2003, resveratrol was reported to activate sirtuins in yeast cells. Recent experimental studies have found that resveratrol offers a variety of benefits that include both anticarcinogenic and anti-inflammatory effects in addition to the ability to reverse obesity, attenuate hyperglycemia and hyperinsulinemia, protect heart and endothelial function, and increase the life span. Multiple molecular targets are associated with the cardioprotective capabilities of resveratrol, and therefore, resveratrol has potential for a wide range of new therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, cardiac failure, and inflammatory alterations during aging. Expectations for application in human patients, however, suffer from a lack of sufficient clinical evidence in support of these beneficial effects. This article reviews recently reported basic research results that describe the beneficial effects of resveratrol in an attempt to condense the evidence observed in clinical trials and provide support for the future development of novel clinical therapeutics in patients with cardiovascular diseases.
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Affiliation(s)
- Sanghyun Cho
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea
| | - Kyung Namkoong
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea
| | - Minji Shin
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea
| | - Jueun Park
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea
| | - Eunyeong Yang
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea
| | - Jinsoo Ihm
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea
| | - Vu Thi Thu
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea.,2 Key Laboratory of Enzyme and Protein Technology, Faculty of Biology, VNU University of Science , Hanoi, Vietnam
| | - Hyoung Kyu Kim
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea.,3 Department of Integrated Biomedical Science, College of Medicine, Inje University , Busan, Korea
| | - Jin Han
- 1 National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, BK21 Project Team, Department of Physiology, College of Medicine, Inje University , Busan, Korea
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44
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Yoon DH, Han C, Fang Y, Gundeti S, Han Lee IS, Song WO, Hwang KC, Kim TW, Sung GH, Park H. Inhibitory Activity ofCordyceps bassianaExtract on LPS-induced Inflammation in RAW 264.7 Cells by Suppressing NF-κB Activation. ACTA ACUST UNITED AC 2017. [DOI: 10.20307/nps.2017.23.3.162] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Deok Hyo Yoon
- Department of Biochemistry, Kangwon National University, Chunchon 200-701, Republic of Korea
| | - Changwoo Han
- College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea
| | - Yuanying Fang
- College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea
| | - Shankariah Gundeti
- College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea
| | - In-Sook Han Lee
- Department of Science Education, Kangwon National University, Chunchon 200-701, Republic of Korea
| | - Won O Song
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI48824, USA
| | - Ki-Chul Hwang
- Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon 404-834, Republic of Korea
| | - Tae Woong Kim
- Department of Biochemistry, Kangwon National University, Chunchon 200-701, Republic of Korea
| | - Gi-Ho Sung
- Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon 404-834, Republic of Korea
| | - Haeil Park
- College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea
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Romero M, Vera B, Galisteo M, Toral M, Gálvez J, Perez-Vizcaino F, Duarte J. Protective vascular effects of quercitrin in acute TNBS-colitis in rats: the role of nitric oxide. Food Funct 2017; 8:2702-2711. [DOI: 10.1039/c7fo00755h] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Quercitrin (quercetin 3-rhamnoside) is a bioflavonoid with anti-inflammatory activity in experimental colitis.
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Affiliation(s)
- Miguel Romero
- Department of Pharmacology
- School of Pharmacy
- University of Granada
- 18071 Granada
- Spain
| | - Beatriz Vera
- Department of Pharmacology
- School of Pharmacy
- University of Granada
- 18071 Granada
- Spain
| | - Milagros Galisteo
- Department of Pharmacology
- School of Pharmacy
- University of Granada
- 18071 Granada
- Spain
| | - Marta Toral
- Department of Pharmacology
- School of Pharmacy
- University of Granada
- 18071 Granada
- Spain
| | - Julio Gálvez
- Department of Pharmacology
- School of Pharmacy
- University of Granada
- 18071 Granada
- Spain
| | - Francisco Perez-Vizcaino
- Department of Pharmacology
- School of Medicine
- University Complutense of Madrid
- Ciber Enfermedades Respiratorias (Ciberes) and Instituto de Investigación Sanitaria Gregorio Marañón (IISGM)
- Spain
| | - Juan Duarte
- Department of Pharmacology
- School of Pharmacy
- University of Granada
- 18071 Granada
- Spain
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Gardener SL, Rainey-Smith SR, Martins RN. Diet and Inflammation in Alzheimer's Disease and Related Chronic Diseases: A Review. J Alzheimers Dis 2016; 50:301-34. [PMID: 26682690 DOI: 10.3233/jad-150765] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Inflammation is one of the pathological features of the neurodegenerative disease, Alzheimer's disease (AD). A number of additional disorders are likewise associated with a state of chronic inflammation, including obesity, cardiovascular disease, and type-2 diabetes, which are themselves risk factors for AD. Dietary components have been shown to modify the inflammatory process at several steps of the inflammatory pathway. This review aims to evaluate the published literature on the effect of consumption of pro- or anti-inflammatory dietary constituents on the severity of both AD pathology and related chronic diseases, concentrating on the dietary constituents of flavonoids, spices, and fats. Diet-based anti-inflammatory components could lead to the development of potent novel anti-inflammatory compounds for a range of diseases. However, further work is required to fully characterize the therapeutic potential of such compounds, including gaining an understanding of dose-dependent relationships and limiting factors to effectiveness. Nutritional interventions utilizing anti-inflammatory foods may prove to be a valuable asset in not only delaying or preventing the development of age-related neurodegenerative diseases such as AD, but also treating pre-existing conditions including type-2 diabetes, cardiovascular disease, and obesity.
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Affiliation(s)
- Samantha L Gardener
- Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Perth, Australia.,Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Australia
| | - Stephanie R Rainey-Smith
- Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Perth, Australia.,Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Australia
| | - Ralph N Martins
- Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Perth, Australia.,Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Australia
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47
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The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms. Nutrients 2016; 8:nu8090581. [PMID: 27657126 PMCID: PMC5037565 DOI: 10.3390/nu8090581] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 08/25/2016] [Accepted: 09/09/2016] [Indexed: 02/07/2023] Open
Abstract
The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs) via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer.
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Mya Mya Mu, Chakravortty D, Sugiyama T, Koide N, Takahashi K, Mori I, Yoshida T, Yokochi T. The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/09680519010070060601] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The effect of quercetin on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was studied. Quercetin pretreatment significantly inhibited NO production in an LPS-stimulated RAW 264.7 murine macrophage cell line. Post-treatment with quercetin partially inhibited NO production. The inhibitory action of quercetin was due to neither the cytotoxic action nor altered LPS binding. The expression of inducible-type NO synthase (iNOS) was markedly down-regulated by quercetin. Quercetin suppressed the release of free nuclear factor (NF)-κB by preventing degradation of IκB-α and IκB-β. Moreover, quercetin blocked the phosphorylation of extracellular signal regulated kinase 1/2 (Erk1/2), p38, and c-Jun NH 2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and, further, the activity of tyrosine kinases in LPS-stimulated RAW cells. Quercetin also inhibited interferon (IFN)-γ-induced NO production. Taken together, these results indicate that the inhibitory action of quercetin on NO production in LPS- and/or IFN-γ-stimulated macrophages might be due to abrogation of iNOS protein induction by impairment of a series of intracellular signal pathways.
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Affiliation(s)
- Mya Mya Mu
- Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Dipshikha Chakravortty
- Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Tsuyoshi Sugiyama
- Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Naoki Koide
- Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Kazuko Takahashi
- Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Isamu Mori
- Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Tomoaki Yoshida
- Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Takashi Yokochi
- Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan, -med-u.ac.jp
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Kann B, Spengler C, Coradini K, Rigo LA, Bennink ML, Jacobs K, Offerhaus HL, Beck RCR, Windbergs M. Intracellular Delivery of Poorly Soluble Polyphenols: Elucidating the Interplay of Self-Assembling Nanocarriers and Human Chondrocytes. Anal Chem 2016; 88:7014-22. [PMID: 27329347 DOI: 10.1021/acs.analchem.6b00199] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Increased molecular understanding of multifactorial diseases paves the way for novel therapeutic approaches requiring sophisticated carriers for intracellular delivery of actives. We designed and characterized self-assembling lipid-core nanocapsules for coencapsulation of two poorly soluble natural polyphenols curcumin and resveratrol. The polyphenols were identified as high-potential therapeutic candidates intervening in the intracellular inflammation cascade of chondrocytes during the progress of osteoarthritis. To elucidate the interplay between chondrocytes and nanocapsules and their therapeutic effect, we pursued a complementary analytical approach combining label-free visualization with biological assays. Primary human chondrocytes did not show any adverse effects upon nanocapsule application and coherent anti-Stokes Raman scattering images visualized their intracellular uptake. Further, by systematically blocking different uptake mechanisms, an energy independent uptake into the cells could be identified. Additionally, we tested the therapeutic effect of the polyphenol-loaded carriers on inflamed chondrocytes. Treatment with nanocapsules resulted in a major reduction of nitric oxide levels, a well-known apoptosis trigger during the course of osteoarthritis. For a more profound examination of this protective effect on joint cells, we pursued studies with atomic force microscopy investigations. Significant changes in the cell cytoskeleton as well as prominent dents in the cell membrane upon induced apoptosis were revealed. Interestingly, these effects could not be detected for chondrocytes which were pretreated with the nanocapsules. Overall, besides presenting a sophisticated carrier system for joint application, these results highlight the necessity of establishing combinatorial analytical approaches to elucidate cellular uptake, the interplay of codelivered drugs and their therapeutic effect on the subcellular level.
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Affiliation(s)
- Birthe Kann
- Saarland University , Department of Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany.,University of Twente , Optical Sciences Group, MESA+ Institute for Nanotechnology, P.O. Box 217, 7500 AE Enschede, The Netherlands
| | - Christian Spengler
- Saarland University , Experimental Physics, Campus E2.9, 66123 Saarbruecken, Germany
| | - Karine Coradini
- Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Federal University of Rio Grande do Sul (UFRGS) , 90610-000, Porto Alegre, Rio Grande do Sul, Brazil
| | - Lucas A Rigo
- Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Federal University of Rio Grande do Sul (UFRGS) , 90610-000, Porto Alegre, Rio Grande do Sul, Brazil
| | - Martin L Bennink
- University of Twente , Nanobiophysics Group, MESA+ Institute for Nanotechnology, P.O. Box 217, 7500 AE Enschede, The Netherlands
| | - Karin Jacobs
- Saarland University , Experimental Physics, Campus E2.9, 66123 Saarbruecken, Germany
| | - Herman L Offerhaus
- University of Twente , Optical Sciences Group, MESA+ Institute for Nanotechnology, P.O. Box 217, 7500 AE Enschede, The Netherlands
| | - Ruy C R Beck
- Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Federal University of Rio Grande do Sul (UFRGS) , 90610-000, Porto Alegre, Rio Grande do Sul, Brazil
| | - Maike Windbergs
- Saarland University , Department of Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany.,Helmholtz Centre for Infection Research and Helmholtz Institute for Pharmaceutical Research Saarland , Department of Drug Delivery, Campus E 8.1, 66123 Saarbruecken, Germany.,PharmBioTec GmbH , Department of Drug Delivery, Science Park 1, 66123 Saarbruecken, Germany
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50
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Liu CW, Lin HW, Yang DJ, Chen SY, Tseng JK, Chang TJ, Chang YY. Luteolin inhibits viral-induced inflammatory response in RAW264.7 cells via suppression of STAT1/3 dependent NF-κB and activation of HO-1. Free Radic Biol Med 2016; 95:180-9. [PMID: 27016074 DOI: 10.1016/j.freeradbiomed.2016.03.019] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 03/13/2016] [Accepted: 03/21/2016] [Indexed: 12/11/2022]
Abstract
Luteolin is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-virus inflammatory capacity of luteolin and its molecular mechanisms of action were analyzed. The cytotoxic effects of luteolin were assessed in the presence or absence of pseudorabies virus (PRV) via LDH and MTT assays. The results showed that luteolin (<10μM) had no toxic effects and there were tendencies toward higher cell survival. In PRV-infected RAW264.7 cells, luteolin potently inhibited the production of NO, iNOS, COX-2 and inflammatory cytokine production. Luteolin did not inhibit the phosphorylation of ERK 1/2, p38, and JNK 1/2 either. We found that PRV-induced NF-κB activation is regulated through inhibition of STAT1and STAT3 phosphorylation in response to luteolin. Additionally, luteolin caused the induction of HO-1 via upregulation of Nrf2, both of which are involved in the secretion of proinflammatory mediators. The blockade of HO-1 expression with SnPP, a HO-1 inhibitor, attenuated HO-1 induction by luteolin and thus mitigated its anti-inflammatory effects during PRV-infected RAW264.7 cells. Taken together, our data indicate that luteolin diminishes the proinflammatory mediators NO, inflammatory cytokines and the expression of their regulatory genes, iNOS and COX-2, in PRV-infected RAW264.7 cells by inhibiting STAT1/3 dependent NF-κB activation and inducing Nrf2mediated HO-1 expression.
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Affiliation(s)
- Cheng-Wei Liu
- Department of Post-Modern Agriculture, MingDao University, Changhua 52345, Taiwan
| | - Hui-Wen Lin
- Department of Optometry, Asia University, Taichung 413, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 402, Taiwan
| | - Deng-Jye Yang
- School of Health Diet and Industry Management and Department of Nutrition, Chung Shan Medical University and Chung Shan Medical University Hospital, 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan
| | - Shih-Yin Chen
- Genetics Center, Department of Medical Research, China Medical University Hospital, and School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Jung-Kai Tseng
- Department of Optometry, Asia University, Taichung 413, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 402, Taiwan
| | - Tien-Jye Chang
- Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan
| | - Yuan-Yen Chang
- Department of Microbiology and Immunology, School of Medicine, Chung-Shan Medical University, and Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
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