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Bangar NS, Dixit A, Apte MM, Tupe RS. Syzygium cumini (L.) skeels mitigate diabetic nephropathy by regulating Nrf2 pathway and mitocyhondrial dysfunction: In vitro and in vivo studies. JOURNAL OF ETHNOPHARMACOLOGY 2025; 336:118684. [PMID: 39127117 DOI: 10.1016/j.jep.2024.118684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 07/12/2024] [Accepted: 08/07/2024] [Indexed: 08/12/2024]
Abstract
ETHNOPHARMACOLOGICAL PREVALENCE Hyperglycemia in diabetes increases the generation of advanced glycation end products (AGEs) through non-enzymatic reactions. The interaction between AGEs and their receptors (RAGE) leads to oxidative and inflammatory stress, which plays a pivotal role in developing diabetic nephropathy. Syzygium cumini (SC) L. (DC.) homeopathic preparations viz. 200C, 30C, and mother tincture [MT] are used to treat diabetes. This study aimed to elucidate the regulatory effects of SC preparations (200C, 30C, and MT) on the nuclear factor erythroid 2-related factor 2 (Nrf2) - nuclear factor-κB (NF-κB) pathways and mitochondrial dysfunction in mitigating diabetic nephropathy (DN). MATERIALS AND METHODS Streptozotocin-induced diabetic rats were treated with SC preparations (200C, 30C, MT; 1:20 dilution in distilled water; 600 μL/kg body weight) and metformin (45 mg/kg body weight) twice daily for 40 days. DN was evaluated through biochemical parameters and histological examination. Renal tissue lysates were analyzed for glycation markers. Protein and gene levels of Nrf2, NF-κB, and mitochondrial dysfunctional signaling were determined via western blotting and RT-qPCR. An immunohistochemical analysis of the kidneys was performed. In vitro, human serum albumin (HSA - 10 mg/ml) was glycated with methylglyoxal (MGO - 55 mM) in the presence of SC preparations (200C, 30C, MT) for eight days. Glycated samples (400 μg/mL) were incubated with renal cells (HEK-293) for 24 h. Further reactive oxygen species production, Nrf2 nuclear translocation, and protein or gene expression of Nrf2 and apoptosis markers were analyzed by western blotting, RT-qPCR, and flow cytometry. Molecular docking of gallic and ellagic acid with the HSA-MGO complex was performed. RESULT In vivo experiments using streptozotocin-induced diabetic rats treated with SC preparations exhibited improved biochemical parameters, preserved kidney function, and reduced glycation adduct formation in a dose-dependent manner. Furthermore, SC preparations downregulated inflammatory mediators such as RAGE, NF-κB, vascular endothelial growth factor (VEGF), and Tumor necrosis factor α (TNF-α) while upregulating the Nrf2-dependent antioxidant and detoxification pathways. They downregulated B-cell lymphoma 2 (Bcl-2) associated X-protein (BAX), C/EBP homologous protein (CHOP), Dynamin-related protein 1 (DRP1), and upregulated BCL 2 gene expression. Notably, SC preparations facilitated nuclear translocation of Nrf2, leading to the upregulation of antioxidant enzymes and the downregulation of oxidative stress markers. Molecular docking studies revealed favorable interactions between gallic (-5.26 kcal/mol) and ellagic acid (-4.71 kcal/mol) with the HSA-MGO complex. CONCLUSION SC preparations mitigate renal cell apoptosis and mitochondrial dysfunction through Nrf2-dependent mechanisms.
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Affiliation(s)
- Nilima S Bangar
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra State, India.
| | - Aditi Dixit
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra State, India.
| | - Mayura M Apte
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra State, India.
| | - Rashmi S Tupe
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra State, India.
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Ma Y, Li Y, Yao Y, Huang T, Lan C, Li L. Mechanistic studies on protective effects of total flavonoids from Ilex latifolia Thunb. on UVB-radiated human keratinocyte cell line (HaCaT cells) based on network pharmacology and molecular docking technique. Photochem Photobiol 2025; 101:70-82. [PMID: 38644599 DOI: 10.1111/php.13953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/28/2024] [Accepted: 03/29/2024] [Indexed: 04/23/2024]
Abstract
The aim of the present research is to investigate anti-UVB radiation activity of total flavonoids from Ilex latifolia Thunb. (namely large-leaved Kuding tea) on human keratinocyte cell line (HaCaT cells) based on network pharmacology and molecular docking technique. Network pharmacology was used to screen target genes of active ingredients from Ilex latifolia Thunb. associated with UVB irradiation. The possible signaling pathways were analyzed by KEGG enrichment and verified by cellular experiments. Molecular docking was used to assess the affinity between the active ingredients and the core targets. The prediction of network pharmacology and molecular docking was identified by series experiment in UVB-irradiated HaCaT cells. Network pharmacology results showed that the active ingredients of Ilex latifolia Thunb. for anti-UVB irradiation were mainly flavonoids, and the possible signaling pathways were involved in PI3K-AKT, apoptosis, MAPKs, NF-κB, and JAK-STAT3. Molecular docking indicated key binding activity between AKT1-Glycitein, STAT3-Formononetin, CASP3-Formononetin, TNF-Kaempferol, CASP3-Luteolin, and AKT1-Quercetin. The total flavonoid pretreatment (0.25-1.0 mg/mL) down-regulated the expression of IL-6, IL-1β, and TNF-α in the cells determined by ELISA. The expression of phosphor PI3K, phosphor AKT, phosphor JAK, phosphor STAT3, phosphor JNK, and phosphor p38 MAPKs and COX-2 proteins in cytosolic and NF-κB p65 protein in nucleus were down-regulated and determined by western blot. It also protected UVB-irradiated cells from apoptosis by reducing apoptosis rate and down-regulating active-caspase 3. In a word, the total flavonoid treatment protected HaCaT cells from UVB injuries effectively, and the potential mechanism involves PI3K-AKT, JAK-STAT3, MAPK, and NF-κB pathway by anti-inflammatory and apoptosis action in cells. The mechanism in vivo experiment needs to be further confirmed in future.
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Affiliation(s)
- Yunge Ma
- Pharmacy College, Henan University, Kaifeng, China
| | - Yingyan Li
- Pharmacy College, Henan University, Kaifeng, China
| | - Yike Yao
- Pharmacy College, Henan University, Kaifeng, China
| | - Tao Huang
- Medical School, Huanghe Science & Technology University, Zhengzhou, China
| | - Chong Lan
- Medical School, Huanghe Science & Technology University, Zhengzhou, China
- Zhengzhou Key Laboratory of Drug Screening and Activity Evaluation, Huanghe Science & Technology University, Zhengzhou, China
| | - Liyan Li
- Medical School, Huanghe Science & Technology University, Zhengzhou, China
- Zhengzhou Key Laboratory of Drug Screening and Activity Evaluation, Huanghe Science & Technology University, Zhengzhou, China
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Singh H, Mishra AK, Mohanto S, Kumar A, Mishra A, Amin R, Darwin CR, Emran TB. A recent update on the connection between dietary phytochemicals and skin cancer: emerging understanding of the molecular mechanism. Ann Med Surg (Lond) 2024; 86:5877-5913. [PMID: 39359831 PMCID: PMC11444613 DOI: 10.1097/ms9.0000000000002392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 07/08/2024] [Indexed: 10/04/2024] Open
Abstract
Constant exposure to harmful substances from both inside and outside the body can mess up the body's natural ways of keeping itself in balance. This can cause severe skin damage, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. However, plant-derived compounds found in fruits and vegetables have been shown to protect against skin cancer-causing free radicals and other harmful substances. It has been determined that these dietary phytochemicals are effective in preventing skin cancer and are widely available, inexpensive, and well-tolerated. Studies have shown that these phytochemicals possess anti-inflammatory, antioxidant, and antiangiogenic properties that can aid in the prevention of skin cancers. In addition, they influence crucial cellular processes such as angiogenesis and cell cycle control, which can halt the progression of skin cancer. The present paper discusses the benefits of specific dietary phytochemicals found in fruits and vegetables, as well as the signaling pathways they regulate, the molecular mechanisms involved in the prevention of skin cancer, and their drawbacks.
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Affiliation(s)
- Harpreet Singh
- School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh
| | | | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka
| | - Arvind Kumar
- School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh
| | - Amrita Mishra
- School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi
| | - Ruhul Amin
- Faculty of Pharmaceutical Science, Assam downtown University, Panikhaiti, Gandhinagar, Guwahati, Assam
| | | | - Talha Bin Emran
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
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Yang X, Chu F, Jiao Z, Yu H, Yang W, Li Y, Lu C, Ma H, Wang S, Liu Z, Qin S, Sun H. Ellagic acid ameliorates arsenic-induced neuronal ferroptosis and cognitive impairment via Nrf2/GPX4 signaling pathway. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 283:116833. [PMID: 39128446 DOI: 10.1016/j.ecoenv.2024.116833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 07/22/2024] [Accepted: 08/01/2024] [Indexed: 08/13/2024]
Abstract
Arsenic, a neurotoxic metalloid, poses significant health risks. However, ellagic acid, renowned for its antioxidant properties, has shown potential in neuroprotection. This study aimed to investigate the neuroprotective effects of ellagic acid against arsenic-induced neuronal ferroptosis and cognitive impairment and elucidate the underlying mechanisms. Using an arsenic-exposed Wistar rat model and an arsenic-induced HT22 cells model, we assessed cognitive ability, measured serum and brain arsenic levels, and evaluated pathological damage through histological analysis and transmission electron microscopy. Additionally, we examined oxidative stress and iron ion levels using GSH, MDA, ROS and tissue iron biochemical kits, and analyzed the expression of ferroptosis-related markers using western blot and qRT-PCR. Our results revealed that arsenic exposure increased both serum and brain arsenic levels, resulting in hippocampal pathological damage and subsequent decline in learning and memory abilities. Arsenic-induced neuronal ferroptosis was mediated by the inhibition of the xCT/GSH/GPX4/Nrf2 signaling axis and disruption of iron metabolism. Notably, ellagic acid intervention effectively reduced serum and brain arsenic levels, ameliorated neuronal damage, and improved oxidative stress, ferroptosis, and cognitive impairment. These beneficial effects were associated with the activation of the Nrf2/Keap1 signaling pathway, upregulation of GPX4 expression, and enhanced iron ion excretion. In conclusion, ellagic acid demonstrates promising neuroprotective effects against arsenic-induced neurotoxicity by mitigating neuronal ferroptosis and cognitive impairment.
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Affiliation(s)
- Xiyue Yang
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Fang Chu
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Zhe Jiao
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Hao Yu
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Wenjing Yang
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Yang Li
- The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu Distinct, Nanchang, Jiangxi 330006, China
| | - Chunqing Lu
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Hao Ma
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Sheng Wang
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Zhipeng Liu
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Shaoxiao Qin
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China
| | - Hongna Sun
- Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) & Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, China.
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Hu X, Chen M, Nawaz J, Duan X. Regulatory Mechanisms of Natural Active Ingredients and Compounds on Keratinocytes and Fibroblasts in Mitigating Skin Photoaging. Clin Cosmet Investig Dermatol 2024; 17:1943-1962. [PMID: 39224224 PMCID: PMC11368101 DOI: 10.2147/ccid.s478666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 08/16/2024] [Indexed: 09/04/2024]
Abstract
Background The mechanism underlying skin photoaging remains elusive because of the intricate cellular and molecular changes that contribute to this phenomenon, which have yet to be elucidated. In photoaging, the roles of keratinocytes and fibroblasts are vital for maintaining skin structure and elasticity. But these cells can get photo-induced damage during photoaging, causing skin morphological changes. Recently, the function of natural active ingredients in treating and preventing photoaging has drawn more attention, with researches often focusing on keratinocytes and fibroblasts. Methods We searched for studies published from 2007 to January 2024 in the Web of Science, PubMed, and ScienceDirect databases through the following keywords: natural plant, natural plant products or phytochemicals, traditional Chinese Medicine or Chinese herbal, plant extracts, solar skin aging, skin photoaging, and skin wrinkling. This review conducted the accordance of Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results In total, 87 researches were included in this review (Figure 1). In keratinocytes, natural compounds may primarily regulate signal pathways such as the NF-κB, MAPK, PI3K/AKT, and Nrf2/ARE pathways, reducing inflammation and cellular damage, thus slowing skin photoaging. Additionally, in fibroblasts, natural active ingredients primarily promote the TGF-β pathway, inhibit MMPs activity, and enhance collagen synthesis while potentially modulating the mTOR pathway, thereby protecting the dermal collagen network and reducing wrinkle formation. Several trials showed that natural compounds that regulate keratinocytes and fibroblasts responses have significant and safe therapeutic effects. Conclusion The demand for natural product-based ingredients in sunscreen formulations is rising. Natural compounds show promising anti-photoaging effects by targeting cellular pathways in keratinocytes and fibroblasts, providing potential therapeutic strategies. However, comprehensive clinical studies are needed to verify their efficacy and safety in mitigating photoaging, which should use advanced pharmacological methods to uncover the complex anti-photoaging mechanisms of natural compounds.
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Affiliation(s)
- Xinru Hu
- Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
| | - Meng Chen
- Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
| | - Jahanzeb Nawaz
- Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
| | - Xi Duan
- Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
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Farazi M, Houghton MJ, Nicolotti L, Murray M, Cardoso BR, Williamson G. Inhibition of human starch digesting enzymes and intestinal glucose transport by walnut polyphenols. Food Res Int 2024; 189:114572. [PMID: 38876610 DOI: 10.1016/j.foodres.2024.114572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 05/26/2024] [Accepted: 05/26/2024] [Indexed: 06/16/2024]
Abstract
One approach to controlling type 2 diabetes (T2D) is to lower postprandialglucose spikesby slowing down the digestion of carbohydrates and the absorption of glucose in the small intestine. The consumption of walnuts is associated with a reduced risk of chronic diseases such as T2D, suggested to be partly due to the high content of (poly)phenols. This study evaluated, for the first time, the inhibitory effect of a (poly)phenol-rich walnut extract on human carbohydrate digesting enzymes (salivary and pancreatic α-amylases, brush border sucrase-isomaltase) and on glucose transport across fully differentiated human intestinal Caco-2/TC7 monolayers. The walnut extract was rich in multiple (poly)phenols (70 % w/w) as analysed by Folin-Ciocalteau and by LCMS. It exhibited potent inhibition of both human salivary (IC50: 32.2 ± 2.5 µg walnut (poly)phenols (WP)/mL) and pancreatic (IC50: 56.7 ± 1.7 µg WP/mL) α-amylases, with weaker effects on human sucrase (IC50: 990 ± 20 µg WP/mL), maltase (IC50: 1300 ± 80 µg WP/mL), and isomaltase (IC25: 830 ± 60 µg WP/mL) activities. Selected individual walnut (poly)phenols inhibited human salivary α-amylase in the order: 1,3,4,6-tetragalloylglucose > ellagic acid pentoside > 1,2,6-tri-O-galloyl-β-D-glucopyranose, with no inhibition by ellagic acid, gallic acid and 4-O-methylgallic acid. The (poly)phenol-rich walnut extract also attenuated (up to 59 %) the transfer of 2-deoxy-D-glucose across differentiated Caco-2/TC7 cell monolayers. This is the first report on the effect of (poly)phenol-rich extracts from any commonly-consumed nut kernel on any human starch-digesting enzyme, and suggests a mechanism through which walnut consumption may lower postprandial glucose spikes and contribute to their proposed health benefits.
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Affiliation(s)
- Mena Farazi
- Department of Nutrition, Dietetics and Food, Monash University, BASE Facility, Level 1, 264 Ferntree Gully Road, Notting Hill, VIC 3168, Australia; Victorian Heart Institute, Monash University, Level 2, Victorian Heart Hospital, 631 Blackburn Road, Clayton, VIC 3168 Australia
| | - Michael J Houghton
- Department of Nutrition, Dietetics and Food, Monash University, BASE Facility, Level 1, 264 Ferntree Gully Road, Notting Hill, VIC 3168, Australia; Victorian Heart Institute, Monash University, Level 2, Victorian Heart Hospital, 631 Blackburn Road, Clayton, VIC 3168 Australia
| | - Luca Nicolotti
- The Australian Wine Research Institute, Adelaide, SA 5064, Australia; Metabolomics Australia, The Australian Wine Research Institute, Adelaide, SA 5064, Australia
| | - Margaret Murray
- Department of Nutrition, Dietetics and Food, Monash University, BASE Facility, Level 1, 264 Ferntree Gully Road, Notting Hill, VIC 3168, Australia; Department of Health Sciences and Biostatistics, Swinburne University of Technology, John St, Hawthorn, VIC 3122, Australia
| | - Barbara R Cardoso
- Department of Nutrition, Dietetics and Food, Monash University, BASE Facility, Level 1, 264 Ferntree Gully Road, Notting Hill, VIC 3168, Australia; Victorian Heart Institute, Monash University, Level 2, Victorian Heart Hospital, 631 Blackburn Road, Clayton, VIC 3168 Australia
| | - Gary Williamson
- Department of Nutrition, Dietetics and Food, Monash University, BASE Facility, Level 1, 264 Ferntree Gully Road, Notting Hill, VIC 3168, Australia; Victorian Heart Institute, Monash University, Level 2, Victorian Heart Hospital, 631 Blackburn Road, Clayton, VIC 3168 Australia.
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Gong Q, Wang X, Liu Y, Yuan H, Ge Z, Li Y, Huang J, Liu Y, Chen M, Xiao W, Liu R, Shi R, Wang L. Potential Hepatoprotective Effects of Allicin on Carbon Tetrachloride-Induced Acute Liver Injury in Mice by Inhibiting Oxidative Stress, Inflammation, and Apoptosis. TOXICS 2024; 12:328. [PMID: 38787107 PMCID: PMC11126064 DOI: 10.3390/toxics12050328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 04/27/2024] [Accepted: 04/28/2024] [Indexed: 05/25/2024]
Abstract
The global burden of liver disease is enormous, which highlights the need for effective hepatoprotective agents. It was reported that allicin exhibits protective effects against a range of diseases. In this study, we further evaluated allicin's effect and mechanism in acute hepatic injury. Liver injury in mice was induced by intraperitoneal injection with 1% CCl4 (10 mL/kg/day). When the first dose was given, CCl4 was given immediately after administration of different doses of allicin (40, 20, and 10 mg/kg/day) as well as compound glycyrrhizin (CGI, 80 mg/kg/day), and then different doses of allicin (40, 20, and 10 mg/kg/day) as well as compound glycyrrhizin (CGI, 80 mg/kg/day) were administrated every 12 h. The animals were dissected 24 h after the first administration. The findings demonstrated a significant inhibition of CCl4-induced acute liver injury following allicin treatment. This inhibition was evidenced by notable reductions in serum levels of transaminases, specifically aspartate transaminase, along with mitigated histological damage to the liver. In this protective process, allicin plays the role of reducing the amounts or the expression levels of proinflammatory cytokines, IL-1β, IL-6. Furthermore, allicin recovered the activities of the antioxidant enzyme catalase (CAT) and reduced the production of malondialdehyde (MDA) in a dose-dependent manner, and also reduced liver Caspase 3, Caspase 8, and BAX to inhibit liver cell apoptosis. Further analysis showed that the administration of allicin inhibited the increased protein levels of Nuclear factor-erythroid 2-related factor 2 (Nrf2) and NAD(P)H:quinone oxidoreductase 1 (NQO1), which is related to inflammation and oxidative stress. The in vitro study of the LPS-induced RAW264.7 inflammatory cell model confirmed that allicin can inhibit important inflammation-related factors and alleviate inflammation. This research firstly clarified that allicin has a significant protective effect on CCl4-induced liver injury via inhibiting the inflammatory response and hepatocyte apoptosis, alleviating oxidative stress associated with the progress of liver damage, highlighting the potential of allicin as a hepatoprotective agent.
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Affiliation(s)
- Qianmei Gong
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaoming Wang
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yongshi Liu
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Heling Yuan
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Zifeng Ge
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yuzhou Li
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Jinhu Huang
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yufan Liu
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Ming Chen
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Wenjun Xiao
- College of Pharmacy, Xinjiang Medical University, Urumqi 830017, China
| | - Ruiting Liu
- College of Pharmacy, Xinjiang Medical University, Urumqi 830017, China
| | - Rongmei Shi
- College of Pharmacy, Xinjiang Medical University, Urumqi 830017, China
| | - Liping Wang
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
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Dimitrijevic J, Tomovic M, Bradic J, Petrovic A, Jakovljevic V, Andjic M, Živković J, Milošević SĐ, Simanic I, Dragicevic N. Punica granatum L. (Pomegranate) Extracts and Their Effects on Healthy and Diseased Skin. Pharmaceutics 2024; 16:458. [PMID: 38675119 PMCID: PMC11054180 DOI: 10.3390/pharmaceutics16040458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/13/2024] [Accepted: 03/21/2024] [Indexed: 04/28/2024] Open
Abstract
The aim of this review is to provide a summary of the botany, phytochemistry and dermatological effects of Punica granatum (PG), with special emphasis on therapeutic mechanisms in various skin conditions. PG peel contains the highest levels of chemical compounds. Due to the high abundance of polyphenolic compounds, including phenolic acids, anthocyanins and flavonoids, exhibiting strong antioxidant properties, PG peel possesses significant health-promoting effects. Up until now, different parts of PG in the form of various extracts, fixed seed oil or individual active compounds have been investigated for various effects on skin conditions in in vitro and in vivo studies, such as antioxidant, anti-inflammatory, antimicrobial, chemoprotective and antiaging effects, as well as positive effects on striae distensae, skin repair mechanisms, erythema, pigmentation and psoriasis. Therefore, formulations containing PG active compounds have been used for skincare of diseased and healthy skin. Only a few effects have been confirmed on human subjects. Based on encouraging results obtained in in vitro and animal studies about the numerous substantial dermatological effects of PG active compounds, future perspectives should incorporate more in vivo investigations in human volunteers. This approach can aid in identifying the optimal concentrations and formulations that would be most efficacious in addressing specific skin conditions.
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Affiliation(s)
- Jovana Dimitrijevic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia; (J.D.); (J.B.); (A.P.)
| | - Marina Tomovic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia; (J.D.); (J.B.); (A.P.)
| | - Jovana Bradic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia; (J.D.); (J.B.); (A.P.)
- Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia;
| | - Anica Petrovic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia; (J.D.); (J.B.); (A.P.)
- Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia;
| | - Vladimir Jakovljevic
- Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia;
- Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia
- Department of Human Pathology, Sechenov First Moscow State Medical University, 8 Trubetskaya St., 119991 Moscow, Russia
| | - Marijana Andjic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia; (J.D.); (J.B.); (A.P.)
- Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia;
| | - Jelena Živković
- Institute for Medicinal Plants Research “Dr. Josif Pancic”, Tadeusa Koscuska 1, 11000 Belgrade, Serbia;
| | - Suzana Đorđević Milošević
- Environment and Sustainable Development, Singidunum University, Danijelova 32, 11000 Belgrade, Serbia;
| | - Igor Simanic
- Specialized Hospital for Rehabilitation and Orthopedic Prosthetics, Sokobanjska 17, 11000 Beograd, Serbia;
- Department of Physical Medicine and Rehabilitation, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia
| | - Nina Dragicevic
- Department of Pharmacy, Singidunum University, Danijelova 32, 11000 Belgrade, Serbia;
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9
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Zagórska-Dziok M, Ziemlewska A, Mokrzyńska A, Nizioł-Łukaszewska Z, Sowa I, Szczepanek D, Wójciak M. Comparative Study of Cytotoxicity and Antioxidant, Anti-Aging and Antibacterial Properties of Unfermented and Fermented Extract of Cornus mas L. Int J Mol Sci 2023; 24:13232. [PMID: 37686038 PMCID: PMC10487488 DOI: 10.3390/ijms241713232] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/21/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Due to the high demand for products that can help treat various skin conditions, the interest in plant extracts, which are a valuable source of phytochemicals, is constantly growing. In this work, the properties of extracts and ferments from Cornus mas L. and their potential use in cosmetic products were compared. For this purpose, their composition, antioxidant properties and cytotoxicity against skin cells, keratinocytes and fibroblasts were assessed in vitro. In addition, the ability to inhibit the activity of collagenase and elastase was compared, which enabled the assessment of their potential to inhibit skin aging. Microbiological analyses carried out on different bacterial strains were made in order to compare their antibacterial properties. The conducted analyses showed that both dogwood extract and ferment have antioxidant and anti-aging properties. In addition, they can have a positive effect on the viability of keratinocytes and fibroblasts and inhibit the proliferation of various pathogenic bacteria, which indicates their great potential as ingredients in skin care preparations. The stronger activity of the ferment compared to the extract indicates the legitimacy of carrying out the fermentation process of plant raw materials using kombucha in order to obtain valuable products for the cosmetics industry.
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Affiliation(s)
- Martyna Zagórska-Dziok
- Department of Technology of Cosmetic and Pharmaceutical Products, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland; (M.Z.-D.); (A.Z.); (A.M.); (Z.N.-Ł.)
| | - Aleksandra Ziemlewska
- Department of Technology of Cosmetic and Pharmaceutical Products, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland; (M.Z.-D.); (A.Z.); (A.M.); (Z.N.-Ł.)
| | - Agnieszka Mokrzyńska
- Department of Technology of Cosmetic and Pharmaceutical Products, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland; (M.Z.-D.); (A.Z.); (A.M.); (Z.N.-Ł.)
| | - Zofia Nizioł-Łukaszewska
- Department of Technology of Cosmetic and Pharmaceutical Products, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland; (M.Z.-D.); (A.Z.); (A.M.); (Z.N.-Ł.)
| | - Ireneusz Sowa
- Department of Analytical Chemistry, Medical University of Lublin, Aleje Raclawickie 1, 20-059 Lublin, Poland;
| | - Dariusz Szczepanek
- Chair and Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland;
| | - Magdalena Wójciak
- Department of Analytical Chemistry, Medical University of Lublin, Aleje Raclawickie 1, 20-059 Lublin, Poland;
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10
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Baloghová J, Michalková R, Baranová Z, Mojžišová G, Fedáková Z, Mojžiš J. Spice-Derived Phenolic Compounds: Potential for Skin Cancer Prevention and Therapy. Molecules 2023; 28:6251. [PMID: 37687080 PMCID: PMC10489044 DOI: 10.3390/molecules28176251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/20/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Skin cancer is a condition characterized by the abnormal growth of skin cells, primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Different types of skin cancer include melanoma, basal cell carcinoma, and squamous cell carcinoma. Despite the advancements in targeted therapies, there is still a need for a safer, highly efficient approach to preventing and treating cutaneous malignancies. Spices have a rich history dating back thousands of years and are renowned for their ability to enhance the flavor, taste, and color of food. Derived from various plant parts like seeds, fruits, bark, roots, or flowers, spices are important culinary ingredients. However, their value extends beyond the culinary realm. Some spices contain bioactive compounds, including phenolic compounds, which are known for their significant biological effects. These compounds have attracted attention in scientific research due to their potential health benefits, including their possible role in disease prevention and treatment, such as cancer. This review focuses on examining the potential of spice-derived phenolic compounds as preventive or therapeutic agents for managing skin cancers. By compiling and analyzing the available knowledge, this review aims to provide insights that can guide future research in identifying new anticancer phytochemicals and uncovering additional mechanisms for combating skin cancer.
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Affiliation(s)
- Janette Baloghová
- Department of Dermatovenerology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia; (J.B.); (Z.B.); (Z.F.)
| | - Radka Michalková
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia;
| | - Zuzana Baranová
- Department of Dermatovenerology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia; (J.B.); (Z.B.); (Z.F.)
| | - Gabriela Mojžišová
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia;
| | - Zuzana Fedáková
- Department of Dermatovenerology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia; (J.B.); (Z.B.); (Z.F.)
| | - Ján Mojžiš
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia;
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11
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Zuccari G, Alfei S. Development of Phytochemical Delivery Systems by Nano-Suspension and Nano-Emulsion Techniques. Int J Mol Sci 2023; 24:9824. [PMID: 37372971 DOI: 10.3390/ijms24129824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 06/01/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023] Open
Abstract
The awareness of the existence of plant bioactive compounds, namely, phytochemicals (PHYs), with health properties is progressively expanding. Therefore, their massive introduction in the normal diet and in food supplements and their use as natural therapeutics to treat several diseases are increasingly emphasized by several sectors. In particular, most PHYs possessing antifungal, antiviral, anti-inflammatory, antibacterial, antiulcer, anti-cholesterol, hypoglycemic, immunomodulatory, and antioxidant properties have been isolated from plants. Additionally, their secondary modification with new functionalities to further improve their intrinsic beneficial effects has been extensively investigated. Unfortunately, although the idea of exploiting PHYs as therapeutics is amazing, its realization is far from simple, and the possibility of employing them as efficient clinically administrable drugs is almost utopic. Most PHYs are insoluble in water, and, especially when introduced orally, they hardly manage to pass through physiological barriers and scarcely reach the site of action in therapeutic concentrations. Their degradation by enzymatic and microbial digestion, as well as their rapid metabolism and excretion, strongly limits their in vivo activity. To overcome these drawbacks, several nanotechnological approaches have been used, and many nanosized PHY-loaded delivery systems have been developed. This paper, by reporting various case studies, reviews the foremost nanosuspension- and nanoemulsion-based techniques developed for formulating the most relevant PHYs into more bioavailable nanoparticles (NPs) that are suitable or promising for clinical application, mainly by oral administration. In addition, the acute and chronic toxic effects due to exposure to NPs reported so far, the possible nanotoxicity that could result from their massive employment, and ongoing actions to improve knowledge in this field are discussed. The state of the art concerning the actual clinical application of both PHYs and the nanotechnologically engineered PHYs is also reviewed.
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Affiliation(s)
- Guendalina Zuccari
- Department of Pharmacy (DiFAR), University of Genoa, Viale Cembrano 4, I-16148 Genova, Italy
| | - Silvana Alfei
- Department of Pharmacy (DiFAR), University of Genoa, Viale Cembrano 4, I-16148 Genova, Italy
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12
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Lu W, Kong C, Cheng S, Xu X, Zhang J. Succinoglycan riclin relieves UVB-induced skin injury with anti-oxidant and anti-inflammatory properties. Int J Biol Macromol 2023; 235:123717. [PMID: 36806772 DOI: 10.1016/j.ijbiomac.2023.123717] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/19/2023] [Accepted: 02/12/2023] [Indexed: 02/19/2023]
Abstract
Excessive UVB exposure increases the production of reactive oxygen species (ROS), which causes oxidative damage and epidermal inflammation. Previous studies have identified that the succinoglycan riclin has potent anti-inflammatory properties. The current study aims to investigate whether riclin protects against UVB-induced photodamage. In vitro, riclin demonstrated excellent moisture-preserving properties, along with antioxidant potential by scavenging superoxide anions, hydroxyl and DPPH radicals. Riclin increased Col1α1 and Col3α1 expression in NIH3T3 cells, inhibited oxidation and melanin synthesis by B16F10 cells upon UVB irradiation. In vivo, topical application of riclin effectively attenuated UVB-induced skin damage in C57BL6 mice, which was characterized by erythema, epidermal hyperplasia, hydroxyproline loss and ROS production in skin tissue. Riclin suppressed skin inflammation by the elevation of TNF-α, IL-6, IL-β, and alleviated UVB-induced immune cell up-regulation. Moreover, treatment with a Dectin-1 inhibitor reversed the protective effect of riclin in THP-1 cells.
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Affiliation(s)
- Weiling Lu
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China
| | - Changchang Kong
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China
| | - Shijunyin Cheng
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China
| | - Xiaodong Xu
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China
| | - Jianfa Zhang
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China.
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13
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Naghibi N, Sadeghi A, Movahedinia S, Rahimi Naiini M, Rajizadeh MA, Bahri F, Nazari-Robati M. Ellagic acid ameliorates aging-induced renal oxidative damage through upregulating SIRT1 and NRF2. BMC Complement Med Ther 2023; 23:77. [PMID: 36899375 PMCID: PMC9999491 DOI: 10.1186/s12906-023-03907-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 03/03/2023] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND Aging is associated with impaired renal function and structural alterations. Oxidative stress plays a vital role in renal senescence and damage. Sirtuin 1 (SIRT1) is thought to protect cells from oxidative stress through nuclear factor erythroid 2-related factor 2 (NRF2). Ellagic acid (EA), a natural antioxidant, has been demonstrated to have renoprotective roles in vitro and in vivo. This study investigated if SIRT1 and NRF2 mediate the protective effects of EA in aged kidneys. METHODS Male Wistar rats were divided into three groups including young (4 months), old, and old + EA (25 months). Young and old groups received EA solvent, while the old + EA group was treated with EA (30 mg/kg) by gavage for 30 days. Then, the level of renal oxidative stress, SIRT1 and NRF2 expression, kidney function parameters, and histopathological indices were measured. RESULTS Treatment with EA significantly increased the level of antioxidant enzymes and reduced malondialdehyde concentration (P < 0.01). Moreover, EA administration remarkably upregulated mRNA and protein levels of SIRT1 and NRF2 as well as deacetylated NRF2 protein (P < 0.05). Additionally, EA treated rats improved kidney function and histopathological scores (P < 0.05). CONCLUSIONS These findings suggest that ellagic acid exerts protective effects on aged kidneys by activating SIRT1 and NRF2 signaling.
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Affiliation(s)
- Niloufar Naghibi
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Asie Sadeghi
- Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Sajjadeh Movahedinia
- Pathology and Stem Cell Research Center, Department of Pathology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahdis Rahimi Naiini
- Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Amin Rajizadeh
- Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Faegheh Bahri
- Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahdieh Nazari-Robati
- Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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14
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Liu HM, Cheng MY, Xun MH, Zhao ZW, Zhang Y, Tang W, Cheng J, Ni J, Wang W. Possible Mechanisms of Oxidative Stress-Induced Skin Cellular Senescence, Inflammation, and Cancer and the Therapeutic Potential of Plant Polyphenols. Int J Mol Sci 2023; 24:ijms24043755. [PMID: 36835162 PMCID: PMC9962998 DOI: 10.3390/ijms24043755] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/09/2023] [Accepted: 02/10/2023] [Indexed: 02/16/2023] Open
Abstract
As the greatest defense organ of the body, the skin is exposed to endogenous and external stressors that produce reactive oxygen species (ROS). When the antioxidant system of the body fails to eliminate ROS, oxidative stress is initiated, which results in skin cellular senescence, inflammation, and cancer. Two main possible mechanisms underlie oxidative stress-induced skin cellular senescence, inflammation, and cancer. One mechanism is that ROS directly degrade biological macromolecules, including proteins, DNA, and lipids, that are essential for cell metabolism, survival, and genetics. Another one is that ROS mediate signaling pathways, such as MAPK, JAK/STAT, PI3K/AKT/mTOR, NF-κB, Nrf2, and SIRT1/FOXO, affecting cytokine release and enzyme expression. As natural antioxidants, plant polyphenols are safe and exhibit a therapeutic potential. We here discuss in detail the therapeutic potential of selected polyphenolic compounds and outline relevant molecular targets. Polyphenols selected here for study according to their structural classification include curcumin, catechins, resveratrol, quercetin, ellagic acid, and procyanidins. Finally, the latest delivery of plant polyphenols to the skin (taking curcumin as an example) and the current status of clinical research are summarized, providing a theoretical foundation for future clinical research and the generation of new pharmaceuticals and cosmetics.
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Affiliation(s)
- Hui-Min Liu
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
- Engineering Research Center of Perfume & Aroma and Cosmetics, Ministry of Education, Shanghai 201418, China
| | - Ming-Yan Cheng
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
| | - Meng-Han Xun
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
| | - Zhi-Wei Zhao
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
| | - Yun Zhang
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
| | - Wei Tang
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
| | - Jun Cheng
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
| | - Jia Ni
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
| | - Wei Wang
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China
- Engineering Research Center of Perfume & Aroma and Cosmetics, Ministry of Education, Shanghai 201418, China
- Correspondence: ; Tel.: +86-18918830550
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15
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He B, Dai L, Jin L, Liu Y, Li X, Luo M, Wang Z, Kai G. Bioactive components, pharmacological effects, and drug development of traditional herbal medicine Rubus chingii Hu (Fu-Pen-Zi). Front Nutr 2023; 9:1052504. [PMID: 36698464 PMCID: PMC9868258 DOI: 10.3389/fnut.2022.1052504] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 12/12/2022] [Indexed: 01/11/2023] Open
Abstract
Rubus chingii Hu (Chinese Raspberry), known as Fu-Pen-Zi in Chinese, a woody perennial plant of the genus Rubus in the Rosaceae family, has specific nutritional and medicinal values, which is considered food-medicine herb in China for thousands of years to treat impotence, premature ejaculation, enuresis, frequent urination, and other diseases. This review aims to summarize recent advances in the bioactive components, pharmacological effects, and drug development and utilization of Rubus chingii Hu, hoping to provide useful support for its further research and clinical application. The bioactive components in Rubus chingii Hu contain mainly terpenoids, flavonoids, alkaloids, phenolic acids, polysaccharides, and steroids. The main pharmacological effects are their anti-oxidant, anti-inflammatory, and anti-tumor capacity on human health. Rubus chingii Hu is a very valuable food-medicine herb. The development of Rubus chingii Hu-related drugs is relatively single, which is limited to traditional Chinese medicine and prescriptions. Therefore, it is vital to pay interest to Rubus chingii Hu and its bioactive components in the future and extend its scientific application.
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Affiliation(s)
- Beihui He
- The First Affiliated Hospital, Zhejiang Provincial Hospital of Chinese Medicine, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Linghao Dai
- The First Affiliated Hospital, Zhejiang Provincial Hospital of Chinese Medicine, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Li Jin
- The First Affiliated Hospital, Zhejiang Provincial Hospital of Chinese Medicine, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yuan Liu
- The First Affiliated Hospital, Zhejiang Provincial Hospital of Chinese Medicine, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xiaojuan Li
- The First Affiliated Hospital, Zhejiang Provincial Hospital of Chinese Medicine, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Minmin Luo
- The First Affiliated Hospital, Zhejiang Provincial Hospital of Chinese Medicine, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Zhian Wang
- Zhejiang Research Institute of Traditional Chinese Medicine Co., Ltd., Hangzhou, China
| | - Guoyin Kai
- The First Affiliated Hospital, Zhejiang Provincial Hospital of Chinese Medicine, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- The Third Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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16
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Gao X, Zhang X, Jiang L, Xu J, Liu W, Qian Y, Jiang Y, Jin Q, Hong H, Chen M, Jin Z, Wei Z, Yang Z, Zhang H. Forsythin inhibits β-hydroxybutyrate-induced oxidative stress in bovine macrophages by regulating p38/ERK, PI3K/Akt, and Nrf2/HO-1 signaling pathways. Res Vet Sci 2023; 154:59-65. [PMID: 36463586 DOI: 10.1016/j.rvsc.2022.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 10/03/2022] [Accepted: 11/19/2022] [Indexed: 11/23/2022]
Abstract
Ketosis is a metabolic disease of dairy cows in the perinatal period, β-hydroxybutyrate (β-HB) is the main component of ketosis. High levels of β-HB can trigger oxidative stress and inflammatory response in dairy cows, leading to decreased milk yield and multiple postpartum diseases. Forsythin (FOR), the major constituent of the herbal medicine Forsythia, has anti-inflammatory, anti-oxidant, and antiviral effects. FOR was demonstrated to have an antioxidant effect on PC12 cells. However, the effects of FOR on β-HB-stimulated bovine macrophages (BMs) has not been reported. Thus, the aim of the present study was to investigate the effects of FOR on β-HB-stimulated BMs. Firstly, the CCK8 test confirmed that FOR (50, 100, 200 μg/mL) has no effect on BMs activity, and we selected these concentrations for subsequent experiments. Secondly, through detecting the oxidation indexes ROS, MDA and antioxidant indexes CAT and SOD, we confirmed the antioxidant effect of FOR on BMs. Next, qRT-PCR confirmed that FOR dramatically reduced the mRNA levels of IL-1β and IL-6. Furthermore, the western blotting confirmed that FOR observably down-regulated β-HB-stimulated phosphorylation of p38, ERK and Akt and up-regulated expression of Nrf2, and HO-1. Above results suggested that FOR plays antioxidant effects on β-HB-induced BMs through p38, ERK and PI3K/Akt, Nrf2 and HO-1 signaling pathways. Therefore, we speculated that FOR may be a potential medicine to alleviate β-HB-induced inflammatory response and provide a preliminary reference for the research and development of FOR.
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Affiliation(s)
- Xinxin Gao
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Xu Zhang
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
| | - Liqiang Jiang
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Jingnan Xu
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Wei Liu
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Yuxiao Qian
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Yuqian Jiang
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Qinqin Jin
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Hongrong Hong
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Meiyi Chen
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Zha Jin
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Zhengkai Wei
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Zhengtao Yang
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China.
| | - Haoji Zhang
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China.
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17
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Tanveer MA, Rashid H, Nazir LA, Archoo S, Shahid NH, Ragni G, Umar SA, Tasduq SA. Trigonelline, a plant derived alkaloid prevents ultraviolet-B-induced oxidative DNA damage in primary human dermal fibroblasts and BALB/c mice via modulation of phosphoinositide 3-kinase-Akt-Nrf2 signalling axis. Exp Gerontol 2023; 171:112028. [PMID: 36384201 DOI: 10.1016/j.exger.2022.112028] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/14/2022]
Abstract
BACKGROUND DNA is the main target for UV-B-irradiation-induced skin photodamage and accounts for 90 % of all the non-melanoma skin cancers. PURPOSE In this study, we explored the mechanistic basis of photoprotective effect of Trigonelline, a naturally occurring alkaloid from the Trigonella foenum-graecum, against UV-B-induced oxidative DNA Damage Response using Primary Human Dermal Fibroblasts (HDFs) and BALB/C mice as models of skin photodamage. METHODS Primary HDFs were subjected to UV-B exposure (10 mJ/cm2) with or without TG for 24 h. Effect of UV-B exposure and TG treatment was evaluated by analyzing the cell survival, cellular morphology, oxidative stress & DNA damage response markers by performing biochemical studies, florescent microscopy & protein expression studies. In in-vivo study, TG pre-treated BALB/c mice were -irradiated with 180 mJ/cm2 of UV-B dose thrice a week on alternative days for four months, followed by topical application of different concentrations of TG. The photodamage caused by UV-B exposure and its ameleoriation by topical treatment of TG was studied by physical and morphological appearance and analyzing the oxidative stress & DNA damage response markers from skin. RESULTS We found that TG significantly alleviates UV-B-induced cell death effects in HDFs. TG protects HDF cells and BALB/c mice from UV-B-induced DNA damage by regulating the expression profile of key protein markers of DNA damage which include P53, ATM, ATR, ϒH2AX, Chk1 and Chk2. We found that TG offers geno-protection to UV-B-irradiated HDFs by alleviating CPD induction, reducing the number of TUNEL positive cells and by decreasing the expression levels of DNA damage marker protein ϒH2AX in immunocytochemistry. Further, we found that TG prevents the UVB induced oxidative stress by activating the PI3K-AKT-Nrf2 signalling pathway. On employing PI3K inhibitor, LY294002, we found the expression of ϒH2AX and p-P53 is significantly increased compared to UV-B treated only, indicating that TG mediates the geno-protection against UV-B irradiation via PI3K-AKT-Nrf2 signalling pathway. CONCLUSION Current study presents for the first time the photo-protective role of TG against UV-B-induced oxidative DNA damage and provides its mechanistic insights also and provide strong evidence for TG to be carried forward as a potential remedial and cosmeceutical agent against UV-B-induced skin photodamage disorders.
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Affiliation(s)
- Malik A Tanveer
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, Jammu & Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Haroon Rashid
- Department of Hospital Adminstration, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Soura, Srinagar 190011, Jammu & Kashmir, India.
| | - Lone A Nazir
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, Jammu & Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Sajida Archoo
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, Jammu & Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Naiku H Shahid
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, Jammu & Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Gupta Ragni
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, Jammu & Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Sheikh A Umar
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, Jammu & Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Sheikh A Tasduq
- PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, Jammu & Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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ALTamimi JZ, Alshammari GM, AlFaris NA, Alagal RI, Aljabryn DH, Albekairi NA, Alkhateeb MA, Yahya MA. Ellagic acid protects against non-alcoholic fatty liver disease in streptozotocin-diabetic rats by activating AMPK. PHARMACEUTICAL BIOLOGY 2022; 60:25-37. [PMID: 34870551 PMCID: PMC8654409 DOI: 10.1080/13880209.2021.1990969] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 09/30/2021] [Accepted: 10/05/2021] [Indexed: 05/26/2023]
Abstract
CONTEXT Ellagic acid (EA) is used in traditional medicine to treated hyperlipidaemia. OBJECTIVE This study examined if AMPK mediates the anti-steatotic effect of ellagic acid (EA) in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats. MATERIALS AND METHODS Adult male Wistar rats (130 ± 10 g) were divided into 6 groups (n = 8 rats/group) as control, control + EA, control + EA + CC an AMPK inhibitor), T1DM, T1DM + EA, and T1DM + EA + CC. The treatments with EA (50 mg/kg/orally) and CC (200 ng/rat/i.p.) were given the desired groups for 12 weeks, daily. RESULTS In T1DM-rats, EA reduced fasting glucose levels (44.8%), increased fasting insulin levels (92.8%), prevented hepatic lipid accumulation, and decreased hepatic and serum levels of total triglycerides (54% & 61%), cholesterol (57% & 48%), and free fatty acids (40% & 37%). It also reduced hepatic levels of ROS (62%), MDA (52%), TNF-α (62%), and IL-6 (57.2%) and the nuclear activity of NF-κB p65 (54%) but increased the nuclear activity of Nrf-2 (4-fold) and levels of GSH (107%) and SOD (87%). Besides, EA reduced downregulated SREBP1 (35%), SREBP2 (34%), ACC-1 (36%), FAS (38%), and HMG-CoAR (49%) but stimulated mRNA levels of PPARα (1.7-fold) and CPT1a (1.8-fold), CPT1b (2.9-fold), and p-AMPK (4-fold). All these events were prevented by the co-administration of CC. DISCUSSION AND CONCLUSIONS These findings encourage the use of EA to treat hepatic disorders, and non-alcoholic fatty liver disease (NAFLD). Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.
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Affiliation(s)
- Jozaa Z. ALTamimi
- Nutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Ghedeir M. Alshammari
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Nora A. AlFaris
- Nutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Reham I. Alagal
- Nutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Dalal H. Aljabryn
- Nutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Norah A. Albekairi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Mahmoud Ahmad Alkhateeb
- Department of Basic Medical Sciences, College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
| | - Mohammed Abdo Yahya
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
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Wang Q, Botchway BOA, Zhang Y, Liu X. Ellagic acid activates the Keap1-Nrf2-ARE signaling pathway in improving Parkinson's disease: A review. Biomed Pharmacother 2022; 156:113848. [PMID: 36242848 DOI: 10.1016/j.biopha.2022.113848] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/26/2022] [Accepted: 10/06/2022] [Indexed: 12/14/2022] Open
Abstract
Parkinson's disease (PD) is a familiar neurodegenerative disease, accompanied by motor retardation, static tremor, memory decline and dementia. Heredity, environment, age and oxidative stress have been suggested as key factors in the instigation of PD. The Keap1-Nrf2-ARE signaling is one of the most significant anti- oxidative stress (OS) pathways. The Keap1 is a negative regulator of the Nrf2. The Keap1-Nrf2-ARE pathway can induce cell oxidation resistance and reduce nerve injury to treat neurodegenerative diseases. Ellagic acid (EA) can inhibit the Keap1 to accumulate the Nrf2 in the nucleus, and act on the ARE to produce target proteins, which in turn may alleviate the impact of OS on neuronal cells of PD. This review analyzes the structure and physiological role of EA, along with the structure, composition and functions of the Keap1-Nrf2-ARE signaling pathway. We further expound on the mechanism of ellagic acid in its activation of the Keap1-Nrf2-ARE signaling pathway, as well as the relationship between EA in impairing the TLR4/Myd88/NF-κB and Nrf2 pathways. Ellagic acid has the potentiality of improving PD by activating the Keap1-Nrf2-ARE signaling pathway and scavenging free radicals.
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Affiliation(s)
- Qianhui Wang
- Department of Histology and Embryology, Medical College, Shaoxing University, Zhejiang, China
| | - Benson O A Botchway
- Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China
| | - Yong Zhang
- Department of Histology and Embryology, Medical College, Shaoxing University, Zhejiang, China
| | - Xuehong Liu
- Department of Histology and Embryology, Medical College, Shaoxing University, Zhejiang, China.
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Kraokaew P, Manohong P, Prasertsuksri P, Jattujan P, Niamnont N, Tamtin M, Sobhon P, Meemon K. Ethyl Acetate Extract of Marine Algae, Halymenia durvillei, Provides Photoprotection against UV-Exposure in L929 and HaCaT Cells. Mar Drugs 2022; 20:707. [PMID: 36421985 PMCID: PMC9696495 DOI: 10.3390/md20110707] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/08/2022] [Accepted: 11/09/2022] [Indexed: 11/25/2023] Open
Abstract
Halymenia durvillei is a red alga distributed along the coasts of Southeast Asian countries including Thailand. Previous studies have shown that an ethyl acetate fraction of H. durvillei (HDEA), containing major compounds including n-hexadecanoic acid, 2-butyl-5-hexyloctahydro-1H-indene, 3-(hydroxyacetyl) indole and indole-3-carboxylic acid, possesses high antioxidant and anti-lung cancer activities. The present study demonstrated that HDEA could protect mouse skin fibroblasts (L929) and human immortalized keratinocytes (HaCaT) against photoaging due to ultraviolet A and B (UVA and UVB) by reducing intracellular reactive oxygen species (ROS) and expressions of matrix metalloproteinases (MMP1 and MMP3), as well as increasing Nrf2 nuclear translocation, upregulations of mRNA transcripts of antioxidant enzymes, including superoxide dismutase (SOD), heme oxygenase (HMOX) and glutathione S-transferase pi1 (GSTP1), and procollagen synthesis. The results indicate that HDEA has the potential to protect skin cells from UV irradiation through the activation of the Nrf2 pathway, which leads to decreasing intracellular ROS and MMP production, along with the restoration of skin collagen.
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Affiliation(s)
- Pichnaree Kraokaew
- Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand
| | - Preeyanuch Manohong
- Department of Chemistry, Faculty of Science, King Mongkut’s University of Technology Thonburi, Bang Mod, Bangkok 10140, Thailand
| | | | - Prapaporn Jattujan
- Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Nakhon Niamnont
- Department of Chemistry, Faculty of Science, King Mongkut’s University of Technology Thonburi, Bang Mod, Bangkok 10140, Thailand
| | - Montakan Tamtin
- Kung Krabean Bay Royal Development Center, Department of Fisheries, Khlong Khut Sub-District, Tha Mai, Chantaburi 22000, Thailand
| | - Prasert Sobhon
- Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand
| | - Krai Meemon
- Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand
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21
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Adebayo AA, Oboh G, Ademosun AO. Nutraceutical potential of almond fruits in managing diabetes‐related erectile dysfunction: Effect on Nrf‐2 level and smooth muscle/collagen ratio. Andrologia 2022; 54:e14636. [DOI: 10.1111/and.14636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/28/2022] [Accepted: 10/29/2022] [Indexed: 11/11/2022] Open
Affiliation(s)
- Adeniyi A. Adebayo
- Department of Chemical Sciences (Biochemistry Unit) Joseph Ayo Babalola University Ikeji Arakeji Nigeria
- Functional Foods and Nutraceutical Unit, Department of Biochemistry Federal University of Technology Akure Nigeria
| | - Ganiyu Oboh
- Functional Foods and Nutraceutical Unit, Department of Biochemistry Federal University of Technology Akure Nigeria
| | - Ayokunle O. Ademosun
- Functional Foods and Nutraceutical Unit, Department of Biochemistry Federal University of Technology Akure Nigeria
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22
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Brancaccio M, Milito A, Viegas CA, Palumbo A, Simes DC, Castellano I. First evidence of dermo-protective activity of marine sulfur-containing histidine compounds. Free Radic Biol Med 2022; 192:224-234. [PMID: 36174879 DOI: 10.1016/j.freeradbiomed.2022.09.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 09/06/2022] [Accepted: 09/17/2022] [Indexed: 10/31/2022]
Abstract
Among natural products, ovothiol (ovo), produced by marine invertebrates, bacteria, and microalgae, is receiving increasing interest for its unique antioxidant properties. Recently, ovo has been shown to exhibit anti-inflammatory activity in an in vitro model of endothelial dysfunction and in an in vivo model of liver fibrosis. The aim of this study was to evaluate the effect of ovo and its precursor 5-thiohistidine (5-thio) in comparison with ergothioneine (erg), in human skin cells and tissues upon inflammation. We used both an in vitro and ex vivo model of human skin, represented by a keratinocytes cell line (HaCaT) and skin biopsies, respectively. We observed that ovo, 5-thio, and erg were not cytotoxic in HaCaT cells, but instead exerted a protective function against TNF-α -induced inflammation. In order to get insights on their mechanism of action, we performed western blot analysis of ERK and JNK, as well as sub-cellular localization of Nrf2, a key mediator of the anti-inflammatory response. The results indicated that the pre-treatment with ovo, 5-thio, and erg differently affected the phosphorylation of ERK and JNK. However, all the three molecules promoted the accumulation of Nrf2 in the nucleus of HaCaT cells. In addition, gene expression analysis by RTqPCR and ELISA assays performed in ex vivo human skin tissues pre-treated with thiohistidines and then inflamed with IL-1β revealed a significant downregulation of IL-8, TNF-α and COX-2 genes and a concomitant significant decrease in the cytokines IL-6, IL-8 and TNF-α production. Moreover, the protective action of ovo and 5-thio resulted to be stronger when compared with dexamethasone, a corticosteroid drug currently used to treat skin inflammatory conditions. Our findings suggest that ovo and 5-thio can ameliorate skin damage and may be used to develop natural skin care products to prevent the inflammatory status induced by environmental stressors and aging.
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Affiliation(s)
- Mariarita Brancaccio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131, Naples, Italy
| | - Alfonsina Milito
- Centre for Research in Agricultural Genomics - CRAG, Barcelona, Catalonia, Spain
| | - Carla Alexandra Viegas
- Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal; GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal
| | - Anna Palumbo
- Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, Naples, Italy
| | - Dina Costa Simes
- Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal; GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal
| | - Immacolata Castellano
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131, Naples, Italy; Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, Naples, Italy.
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23
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Wang S, Du Q, Meng X, Zhang Y. Natural polyphenols: a potential prevention and treatment strategy for metabolic syndrome. Food Funct 2022; 13:9734-9753. [PMID: 36134531 DOI: 10.1039/d2fo01552h] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Metabolic syndrome (MS) is the term for a combination of hypertension, dyslipidemia, insulin resistance, and central obesity as factors leading to cardiovascular and metabolic disease. Epidemiological investigation has shown that polyphenol intake is negatively correlated with the incidence of MS. Natural polyphenols are widely found in cocoa beans, tea, vegetables, fruits, and some Chinese herbal medicines; they are a class of plant compounds containing a variety of phenolic structural units, which are potent antioxidants and anti-inflammatory agents in plants. Polyphenols are composed of flavonoids (such as flavanols, anthocyanidins, anthocyanins, isoflavones, etc.) and non-flavonoids (such as phenolic acids, stilbenes, and lignans). Modern pharmacological studies have proved that polyphenols can reduce blood pressure, improve lipid metabolism, lower blood glucose, and reduce body weight, thereby preventing and improving MS. Due to the unique characteristics and potential development and application value of polyphenols, this review summarizes some natural polyphenols that could treat MS, including their chemical properties, plant sources, and pharmacological action against MS, to provide a basis for the further study of polyphenols in MS.
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Affiliation(s)
- Shaohui Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Qinyun Du
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xianli Meng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Yi Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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Bai S, Yu Y, An L, Wang W, Fu X, Chen J, Ma J. Ellagic Acid Increases Stress Resistance via Insulin/IGF-1 Signaling Pathway in Caenorhabditis elegans. Molecules 2022; 27:molecules27196168. [PMID: 36234702 PMCID: PMC9571563 DOI: 10.3390/molecules27196168] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/10/2022] [Accepted: 09/14/2022] [Indexed: 11/16/2022] Open
Abstract
Ellagic acid is a natural polyphenol found in various fruits and vegetables. Numerous studies have shown that ellagic acid has beneficial effects on human health. In this study, we investigated the stress resistant action of ellagic acid in Caenorhabditis elegans (C. elegans). Notably, 50 μM ellagic acid prolonged the lifespan of C. elegans by 36.25%, 36.22%, 155.1%, and 79.07% under ultraviolet radiation stress, heat stress, oxidative stress, and Pseudomonas aeruginosa infection stress, respectively. Furthermore, the mechanism by which ellagic acid reduces the damage caused by ultraviolet radiation in C. elegans was explored. Ellagic acid could significantly induce the nucleus translocation of DAF-16 and, thereby, activate a series of target genes to resist ultraviolet radiation stress. Moreover, ellagic acid also significantly increased the expression of SOD-3 by 3.61 times and the activity of superoxide dismutase by 3.70 times to clean out harmful reactive oxygen species in C. elegans exposed to ultraviolet radiation stress. In both daf-16 mutant and daf-2; daf-16 double-mutant worms exposed to ultraviolet radiation, ellagic acid could no longer prolong their lifespan. These results indicate that ellagic acid plays an important role in resisting ultraviolet radiation stress in C. elegans, probably in an insulin/IGF-1 signaling pathway-dependent way.
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Ellagic Acid and Its Anti-Aging Effects on Central Nervous System. Int J Mol Sci 2022; 23:ijms231810937. [PMID: 36142849 PMCID: PMC9502104 DOI: 10.3390/ijms231810937] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/09/2022] [Accepted: 09/10/2022] [Indexed: 11/25/2022] Open
Abstract
Aging is an unavoidable biological process that leads to the decline of human function and the reduction in people’s quality of life. Demand for anti-aging medicines has become very urgent. Many studies have shown that ellagic acid (EA), a phenolic compound widely distributed in dicotyledonous plants, has powerful anti-inflammation and antioxidant properties. Moreover, it has been demonstrated that EA can enhance neuronal viability, reduce neuronal defects, and alleviate damage in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. This paper reviews the biochemical functions and neuroprotective effects of EA, showing the clinical value of its application.
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LIU X, CHENG C, DENG B, LIU M. Ellagic acid attenuates muscle atrophy in STZ-induced diabetic mice. Physiol Res 2022; 71:631-641. [PMID: 36047725 PMCID: PMC9841811 DOI: 10.33549/physiolres.934918] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Diabetes is closely connected with skeletal muscle dysfunction. Ellagic acid (EA) possesses a variety of bio-effects and is applied to the improvement of diabetes. The purpose of this study was to explore the potential improvement effect and mechanisms of EA in streptozotocin (STZ)-induced diabetic muscle atrophy. The model of diabetic mice was established by intra-peritoneal STZ to evaluate treatment effect of EA (100 mg/kg/d for 8 weeks) on muscle atrophy. Our data exhibited that EA enhanced fiber size and weight of gastrocnemius, and promoted grip strength to relieve STZ-induced muscle lesions. In serum, the levels of Creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) were inhibited, while high-density lipoprotein cholesterol (HDL) level was enhanced by EA treatment in diabetic mice. In gastrocnemius, EA decreased Atrogin-1 and MuRF-1 expressions to relieve STZ-induced muscle atrophy. Moreover, EA increased NRF-1 and PGC-1alpha expressions to alleviate mitochondrial disorder. Meanwhile, EA suppressed CHOP and GRP-87 levels to relieve ER stress. Lastly, EA inhibited BAX expressions and enhanced Bcl-2 expressions to mitigate apoptosis. In conclusion, EA is preventing the event of STZ-induced gastrocnemia by amelioration of mitochondrial dysfunction, ER stress and apoptosis, and could be used in the protection and therapeutic of muscle atrophy in diabetes.
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Affiliation(s)
- Xianchu LIU
- Institute of Physical Culture, Hunan University of Arts and Science, Changde, China
| | - Changhao CHENG
- Institute of Physical Culture, Hunan University of Arts and Science, Changde, China
| | - Beiwang DENG
- Institute of Physical Culture, Hunan University of Arts and Science, Changde, China
| | - Ming LIU
- Faculty of Science, College of Furong, Hunan University of Arts and Science, Changde, China
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Chaiprasongsuk A, Panich U. Role of Phytochemicals in Skin Photoprotection via Regulation of Nrf2. Front Pharmacol 2022; 13:823881. [PMID: 35645796 PMCID: PMC9133606 DOI: 10.3389/fphar.2022.823881] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 04/11/2022] [Indexed: 12/13/2022] Open
Abstract
Ethnopharmacological studies have become increasingly valuable in the development of botanical products and their bioactive phytochemicals as novel and effective preventive and therapeutic strategies for various diseases including skin photoaging and photodamage-related skin problems including abnormal pigmentation and inflammation. Exploring the roles of phytochemicals in mitigating ultraviolet radiation (UVR)-induced skin damage is thus of importance to offer insights into medicinal and ethnopharmacological potential for development of novel and effective photoprotective agents. UVR plays a role in the skin premature aging (or photoaging) or impaired skin integrity and function through triggering various biological responses of skin cells including apoptosis, oxidative stress, DNA damage and inflammation. In addition, melanin produced by epidermal melanocytes play a protective role against UVR-induced skin damage and therefore hyperpigmentation mediated by UV irradiation could reflect a sign of defensive response of the skin to stress. However, alteration in melanin synthesis may be implicated in skin damage, particularly in individuals with fair skin. Oxidative stress induced by UVR contributes to the process of skin aging and inflammation through the activation of related signaling pathways such as the mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1), the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), the nuclear factor kappa B (NF-κB) and the signal transducer and activator of transcription (STAT) in epidermal keratinocytes and dermal fibroblasts. ROS formation induced by UVR also plays a role in regulation of melanogenesis in melanocytes via modulating MAPK, PI3K/Akt and the melanocortin 1 receptor (MC1R)-microphthalmia-associated transcription factor (MITF) signaling cascades. Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated antioxidant defenses can affect the major signaling pathways involved in regulation of photoaging, inflammation associated with skin barrier dysfunction and melanogenesis. This review thus highlights the roles of phytochemicals potentially acting as Nrf2 inducers in improving photoaging, inflammation and hyperpigmentation via regulation of cellular homeostasis involved in skin integrity and function. Taken together, understanding the role of phytochemicals targeting Nrf2 in photoprotection could provide an insight into potential development of natural products as a promising strategy to delay skin photoaging and improve skin conditions.
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Affiliation(s)
| | - Uraiwan Panich
- Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- *Correspondence: Uraiwan Panich,
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Zhu W, Tang H, Li J, Guedes RM, Cao L, Guo C. Ellagic acid attenuates interleukin-1β-induced oxidative stress and exerts protective effects on chondrocytes through the Kelch-like ECH-associated protein 1 (Keap1)/ Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Bioengineered 2022; 13:9233-9247. [PMID: 35378052 PMCID: PMC9162011 DOI: 10.1080/21655979.2022.2059995] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Osteoarthritis (OA) is the most prevalent type of degenerative joint disease, and its pathological progression is highly associated with oxidative stress. Natural antioxidants can attenuate oxidative stress and chondrocyte injury, suggesting that antioxidants have potential applications in the management of OA. Ellagic acid (EA), a natural polyphenol derived from fruits or nuts, exerts antioxidant and anti-inflammatory effects in diseases related to oxidative stress. Herein, we investigated the effects of EA on interleukin-1β (IL-1β)-induced oxidative stress and degeneration in C28/I2 human chondrocytes. EA efficiently suppressed IL-1β-induced oxidative stress and ameliorated oxidative stress-induced dysfunction of chondrocytes, as indicated by the promotion of cartilage matrix secretion. Moreover, EA remarkably suppressed cell apoptosis and senescence, and reduced the expression of proinflammatory factors and metalloproteinases, suggesting that EA could alleviate chondrocyte injury under oxidative stress. Mechanistically, EA upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as its downstream targets NADPH quinone oxidoreductase 1 and heme oxygenase-1. ML385, a specific Keap1/Nrf2 pathway inhibitor, blocked the antioxidant and chondroprotective effects of EA. Our findings demonstrated that EA could attenuate oxidative stress and exert protective effects on chondrocytes by upregulating the Keap1/Nrf2 signaling pathway.
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Affiliation(s)
- Wenrun Zhu
- Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Han Tang
- Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Juncheng Li
- Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rui Miranda Guedes
- LABIOMEP, UMAI-INEGI, Faculty of Engineering of the University of Porto, Porto, Portugal
| | - Lu Cao
- Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Changan Guo
- Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Sharifi-Rad J, Quispe C, Castillo CMS, Caroca R, Lazo-Vélez MA, Antonyak H, Polishchuk A, Lysiuk R, Oliinyk P, De Masi L, Bontempo P, Martorell M, Daştan SD, Rigano D, Wink M, Cho WC. Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:3848084. [PMID: 35237379 PMCID: PMC8885183 DOI: 10.1155/2022/3848084] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/31/2022] [Indexed: 12/18/2022]
Abstract
Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.
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Affiliation(s)
| | - Cristina Quispe
- Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda. Arturo Prat 2120, Iquique 1110939, Chile
| | | | - Rodrigo Caroca
- Biotechnology and Genetic Engineering Group, Science and Technology Faculty, Universidad del Azuay, Av. 24 de Mayo 7-77, Cuenca, Ecuador
- Universidad del Azuay, Grupos Estratégicos de Investigación en Ciencia y Tecnología de Alimentos y Nutrición Industrial (GEICA-UDA), Av. 24 de Mayo 7-77, Apartado 01.01.981, Cuenca, Ecuador
| | - Marco A. Lazo-Vélez
- Universidad del Azuay, Grupos Estratégicos de Investigación en Ciencia y Tecnología de Alimentos y Nutrición Industrial (GEICA-UDA), Av. 24 de Mayo 7-77, Apartado 01.01.981, Cuenca, Ecuador
| | | | | | - Roman Lysiuk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Petro Oliinyk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Luigi De Masi
- National Research Council (CNR), Institute of Biosciences and Bioresources (IBBR), Via Università 133, 80055 Portici, Naples, Italy
| | - Paola Bontempo
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, 4070386 Concepción, Chile
| | - Sevgi Durna Daştan
- Department of Biology, Faculty of Science, Sivas Cumhuriyet University, 58140 Sivas, Turkey
- Beekeeping Development Application and Research Center, Sivas Cumhuriyet University, 58140 Sivas, Turkey
| | - Daniela Rigano
- Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano, 49 80131 Naples, Italy
| | - Michael Wink
- Heidelberg University, Institute of Pharmacy and Molecular Biotechnology, INF 329, D-69120 Heidelberg, Germany
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
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Qi M, Wang N, Xiao Y, Deng Y, Zha A, Tan B, Wang J, Yin Y, Liao P. Ellagic acid ameliorates paraquat-induced liver injury associated with improved gut microbial profile. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2022; 293:118572. [PMID: 34838710 DOI: 10.1016/j.envpol.2021.118572] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 11/13/2021] [Accepted: 11/23/2021] [Indexed: 06/13/2023]
Abstract
Paraquat, a widely used herbicide, causes environmental pollution, and liver injury in humans and animals. As a natural compound in fruits, ellagic acid (EA) shows anti-inflammatory and antioxidant effects. This study examines the beneficial effects of dietary EA against the paraquat-induced hepatic injury and further explores the underlying molecular mechanisms using a piglet model. Post-weaning piglets are fed basal diet supplemented with 50 mg/kg, 100 mg/kg, or 200 mg/kg EA for 3 weeks. At week 2, hepatic injury is induced by 4 mg/kg paraquat followed by 7 days recovery. EA supplementation significantly mitigates paraquat-induced hepatic fibrosis, steatosis, and high apoptotic rate. In agreement, EA supplementation reduces serum pro-inflammatory levels, ameliorates inflammatory cells infiltration into hepatic tissue, which are associated with suppressed NF-κB signaling during paraquat exposure. In addition, EA supplementation significantly improves activities of antioxidative enzymes which were correlated with activated Nrf2/Keap 1 signaling during paraquat exposure. Furthermore, EA supplementation restores cecal microbial community during paraquat exposure. The protective effect of EA is strongly linked with increased relative abundance of Lactobacillus reuteri and Lactobacillus amylovorus. Taken together, EA supplementation effectively reduced the occurrence of hepatic oxidative damage and inflammation induced by paraquat through modulating cecal microbial communities, which provides a novel nutritional therapeutic strategy for hepatic injury.
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Affiliation(s)
- Ming Qi
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410000, Hunan, China; University of Chinese Academy of Sciences, Beijing, 100008, China
| | - Nan Wang
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410000, Hunan, China
| | - Yuxin Xiao
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410000, Hunan, China
| | - Yuankun Deng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410000, Hunan, China
| | - Andong Zha
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China; University of Chinese Academy of Sciences, Beijing, 100008, China
| | - Bie Tan
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410000, Hunan, China
| | - Jing Wang
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410000, Hunan, China.
| | - Yulong Yin
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410000, Hunan, China; University of Chinese Academy of Sciences, Beijing, 100008, China
| | - Peng Liao
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China; University of Chinese Academy of Sciences, Beijing, 100008, China
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Abstract
There are many extrinsic factors that can contribute to the premature aging of the skin. In recent years, the demand for natural cosmetic from the general population has noticeable grow. Therefore, this research aimed to investigate the bioproperties of sky fruit (Swietenia macrophylla) seed extract that could help to inhibit premature skin aging. Firstly, the extract and its fractions were tested on HaCaT cells for their wound healing properties. The presence of sky fruit’s extract and its fractions on scratch wound significantly improved cellular proliferation, migration, and closure of the wound. These effects were distinctly observed following the treatment with S. macrophylla hexane fraction (SMHF) and S. macrophylla water fraction (SMWF). Our continuous research study revealed that SMWF had antioxidant properties, which might be one of the factors contributing to its emerging wound healing properties because antioxidants are known to act as suppressors of the inflammatory pathway and aid the transition towards cell proliferation. In addition, all samples had critical wavelengths that indicated that they were able to absorb the whole UVB range and some parts of the UVA wavelength. This suggested that S. macrophylla might contain potential photoprotective bioactive compounds, which could be developed into anti-UVB photoprotective sunscreens. Thus, this warrants further studies focusing on isolation and identifications of the bioactive compounds responsible for both its photoprotective and wound healing properties. A deeper study on mechanisms of the pathways that were affected by these compounds should be conducted as well to better understand this natural product and develop it into a potential cosmeceutical ingredient.
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Chun KS, Raut PK, Kim DH, Surh YJ. Role of chemopreventive phytochemicals in NRF2-mediated redox homeostasis in humans. Free Radic Biol Med 2021; 172:699-715. [PMID: 34214633 DOI: 10.1016/j.freeradbiomed.2021.06.031] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/14/2021] [Accepted: 06/24/2021] [Indexed: 12/17/2022]
Abstract
While functioning as a second messenger in the intracellular signaling, ROS can cause oxidative stress when produced in excess or not neutralized/eliminated properly. Excessive ROS production is implicated in multi-stage carcinogenesis. Our body is equipped with a defense system to cope with constant oxidative stress caused by the external insults, including redox-cycling chemicals, radiation, and microbial infection as well as endogenously generated ROS. The transcription factor, nuclear transcription factor erythroid 2-related factor 2 (NRF2) is a master switch in the cellular antioxidant signaling and plays a vital role in adaptive survival response to ROS-induced oxidative stress. Although NRF2 is transiently activated when cellular redox balance is challenged, this can be overwhelmed by massive oxidative stress. Therefore, it is necessary to maintain the NRF2-mediated antioxidant defense capacity at an optimal level. This review summarizes the natural NRF2 inducers/activators, especially those present in the plant-based diet, in relation to their cancer chemopreventive potential in humans. The molecular mechanisms underlying their stabilization or activation of NRF2 are also discussed.
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Affiliation(s)
- Kyung-Soo Chun
- College of Pharmacy, Keimyung University, Daegu 42691, South Korea
| | - Pawan Kumar Raut
- College of Pharmacy, Keimyung University, Daegu 42691, South Korea
| | - Do-Hee Kim
- Department of Chemistry, College of Convergence and Integrated Science, Kyonggi University, Suwon, Gyeonggi-do 16227, South Korea
| | - Young-Joon Surh
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, South Korea; Cancer Research Institute, Seoul National University, Seoul 03080, South Korea.
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Ryšavá A, Vostálová J, Rajnochová Svobodová A. Effect of ultraviolet radiation on the Nrf2 signaling pathway in skin cells. Int J Radiat Biol 2021; 97:1383-1403. [PMID: 34338112 DOI: 10.1080/09553002.2021.1962566] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE Excessive exposure of skin to solar radiation is associated with greatly increased production of reactive oxygen and nitrogen species (ROS, RNS) resulting in oxidative stress (OS), inflammation, immunosuppression, the production of matrix metalloproteinase, DNA damage and mutations. These events lead to increased incidence of various skin disorders including photoaing and both non-melanoma and melanoma skin cancers. The ultraviolet (UV) part of sunlight, in particular, is responsible for structural and cellular changes across the different layers of the skin. Among other effects, UV photons stimulate oxidative damage to biomolecules via the generation of unstable and highly reactive compounds. In response to oxidative damage, cytoprotective pathways are triggered. One of these is the pathway driven by the nuclear factor erythroid-2 related factor 2 (Nrf2). This transcription factor translocates to the nucleus and drives the expression of numerous genes, among them various detoxifying and antioxidant enzymes. Several studies concerning the effects of UV radiation on Nrf2 activation have been published, but different UV wavelengths, skin cells or tissues and incubation periods were used in the experiments that complicate the evaluation of UV radiation effects. CONCLUSIONS This review summarizes the effects of UVB (280-315 nm) and UVA (315-400 nm) radiation on the Nrf2 signaling pathway in dermal fibroblasts and epidermal keratinocytes and melanocytes. The effects of natural compounds (pure compounds or mixtures) on Nrf2 activation and level as well as on Nrf2-driven genes in UV irradiated human skin fibroblasts, keratinocytes and melanocytes are briefly mentioned as well.HighlightsUVB radiation is a rather poor activator of the Nrf2-driven pathway in fibroblastsUVA radiation stimulates Nrf2 activation in dermal fibroblastsEffects of UVA on the Nrf2 pathway in keratinocytes and melanocytes remain unclearLong-term Nrf2 activation in keratinocytes disturbs their normal differentiationPharmacological activation of Nrf2 in the skin needs to be performed carefully.
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Affiliation(s)
- Alena Ryšavá
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
| | - Jitka Vostálová
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
| | - Alena Rajnochová Svobodová
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
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Chansriniyom C, Nooin R, Nuengchamnong N, Wongwanakul R, Petpiroon N, Srinuanchai W, Chantarasuwan B, Pitchakarn P, Temviriyanukul P, Nuchuchua O. Tandem mass spectrometry of aqueous extract from Ficus dubia sap and its cell-based assessments for use as a skin antioxidant. Sci Rep 2021; 11:16899. [PMID: 34413383 PMCID: PMC8377047 DOI: 10.1038/s41598-021-96261-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/04/2021] [Indexed: 12/11/2022] Open
Abstract
Since 2006, Ficus dubia has been reported as a new Ficus species in Thailand. As per our recent report, the red-brown aqueous extract of F. dubia sap (FDS) has been determined to strongly exhibit in vitro anti-radicals. However, the phytochemicals in the FDS extract related to health-promoting antioxidation have not been explored. Thus, in this study, we aimed to investigate the chemical components of the F. dubia sap extract by liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-MS/QTOF-MS) and its potential use in cosmetics in terms of cellular antioxidation on keratinocytes (HaCaT), phototoxicity, and irritation on 3D skin cell models following standard tests suggested by the Organization for Economic Cooperation and Development (OECD). It was found that the sap extract was composed of quinic acid and caffeoyl derivatives (e.g., syringoylquinic acid, 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, and dimeric forms of caffeoylquinic acids). The extract has significantly exhibited antioxidant activity against H2O2-induced oxidative stress in HaCaT cells. The cellular antioxidative effect of the FDS extract was remarkably dependent on the presence of 3- and 4-O-caffeoylquinic acid in the extract. Furthermore, the FDS extract showed negative results on skin phototoxicity and irritation. Overall, the results reveal that the FDS extract could be developed as a new antioxidant candidate for a skin healthcare product.
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Affiliation(s)
- Chaisak Chansriniyom
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
- Natural Products and Nanoparticles Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Rawiwan Nooin
- Nano Agricultural Chemistry and Processing Research Team, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand
| | - Nitra Nuengchamnong
- Science Laboratory Center, Faculty of Science, Naresuan University, Phitsanulok, Thailand
| | - Ratjika Wongwanakul
- Nano Environmental and Health Safety Research Team, Advanced Nanocharacterization and Safety Research Group , National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand
| | - Nalinrat Petpiroon
- Nano Environmental and Health Safety Research Team, Advanced Nanocharacterization and Safety Research Group , National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand
| | - Wanwisa Srinuanchai
- Nano Agricultural Chemistry and Processing Research Team, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand
| | | | - Pornsiri Pitchakarn
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Piya Temviriyanukul
- Food and Nutrition Academic and Research Cluster, Institute of Nutrition, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom, Thailand
| | - Onanong Nuchuchua
- Nano Agricultural Chemistry and Processing Research Team, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand.
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35
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Guo H, Liu C, Tang Q, Li D, Wan Y, Li JH, Gao XH, Seeram NP, Ma H, Chen HD. Pomegranate (Punica granatum) extract and its polyphenols reduce the formation of methylglyoxal-DNA adducts and protect human keratinocytes against methylglyoxal-induced oxidative stress. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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36
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Alfei S, Schito AM, Zuccari G. Nanotechnological Manipulation of Nutraceuticals and Phytochemicals for Healthy Purposes: Established Advantages vs. Still Undefined Risks. Polymers (Basel) 2021; 13:2262. [PMID: 34301020 PMCID: PMC8309409 DOI: 10.3390/polym13142262] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 07/07/2021] [Accepted: 07/08/2021] [Indexed: 12/12/2022] Open
Abstract
Numerous foods, plants, and their bioactive constituents (BACs), named nutraceuticals and phytochemicals by experts, have shown many beneficial effects including antifungal, antiviral, anti-inflammatory, antibacterial, antiulcer, anti-cholesterol, hypoglycemic, immunomodulatory, and antioxidant activities. Producers, consumers, and the market of food- and plant-related compounds are increasingly attracted by health-promoting foods and plants, thus requiring a wider and more fruitful exploitation of the healthy properties of their BACs. The demand for new BACs and for the development of novel functional foods and BACs-based food additives is pressing from various sectors. Unfortunately, low stability, poor water solubility, opsonization, and fast metabolism in vivo hinder the effective exploitation of the potential of BACs. To overcome these issues, researchers have engineered nanomaterials, obtaining food-grade delivery systems, and edible food- and plant-related nanoparticles (NPs) acting as color, flavor, and preservative additives and natural therapeutics. Here, we have reviewed the nanotechnological transformations of several BACs implemented to increase their bioavailability, to mask any unpleasant taste and flavors, to be included as active ingredients in food or food packaging, to improve food appearance, quality, and resistance to deterioration due to storage. The pending issue regarding the possible toxic effect of NPs, whose knowledge is still limited, has also been discussed.
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Affiliation(s)
- Silvana Alfei
- Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy;
| | - Anna Maria Schito
- Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV 6, I-16132 Genoa, Italy;
| | - Guendalina Zuccari
- Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy;
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37
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Wei X, Luo C, He Y, Huang H, Ran F, Liao W, Tan P, Fan S, Cheng Y, Zhang D, Lin J, Han L. Hepatoprotective Effects of Different Extracts From Triphala Against CCl 4-Induced Acute Liver Injury in Mice. Front Pharmacol 2021; 12:664607. [PMID: 34290606 PMCID: PMC8287969 DOI: 10.3389/fphar.2021.664607] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 04/06/2021] [Indexed: 02/01/2023] Open
Abstract
Background:Triphala is a traditional polyherbal formula used in Indian Ayurvedic and Chinese Tibetan medicine. A wide range of biological activities have been attributed to Triphala, but the impact of various extraction methods on efficacy has not been determined. Purpose: The study aimed to evaluate Triphala extracts obtained by various methods for their hepatoprotective effects and molecular mechanisms in a mouse model of carbon tetrachloride (CCl4)-induced liver injury. Methods: HPLC fingerprinting was used to characterize the chemical characteristics of Triphala extracts obtained by (a) 0.5 h ultrasonication, (b) 2 h reflux, and (c) 4 h reflux. Hepatoprotective efficacy was evaluated in a mouse model of CCl4-induced liver damage. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured, as well as the liver antioxidant and inflammatory markers malondialdehyde superoxide dismutase glutathione peroxidase (GSH-Px), TNF-α, and IL-6. Gene and protein expression of Nrf-2 signaling components Nrf-2, heme oxygenase (HO-1), and NADPH Quinone oxidoreductase (NQO-1) in liver tissue were evaluated by real-time PCR and western blotting. Results: Chemical analysis showed a clear difference in content between extracts produced by ultrasonic and reflux methods. The pharmacological analysis showed that all three Triphala extracts reduced ALT, AST, MDA, TNF-α, and IL-6 levels and increased SOD and GSH-Px. Triphala extracts also induced transcript and protein expression of Nrf-2, HO-1, and NQO-1. Conclusion: Triphala extract prevents CCl4-induced acute liver injury. The ultrasonic extract of Triphala was most effective, suggesting that hepatoprotection may be related to the larger tannins via activation of Nrf-2 signaling.
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Affiliation(s)
- Xichuan Wei
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuanhong Luo
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanan He
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haozhou Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Fei Ran
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wei Liao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Peng Tan
- Sichuan Academy of Traditional Chinese Medicine, State Key Laboratory of Quality Evaluation of Traditional Chinese Medicine, Chengdu, China
| | - Sanhu Fan
- Sanajon Pharmaceutical Group, Chengdu, China
| | - Yuan Cheng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Dingkun Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Li Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Liu HM, Xu PF, Cheng MY, Lei SN, Liu QL, Wang W. Optimization of Fermentation Process of Pomegranate Peel and Schisandra Chinensis and the Biological Activities of Fermentation Broth: Antioxidant Activity and Protective Effect Against H 2O 2-induced Oxidative Damage in HaCaT Cells. Molecules 2021; 26:molecules26113432. [PMID: 34198860 PMCID: PMC8201020 DOI: 10.3390/molecules26113432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/31/2021] [Accepted: 06/01/2021] [Indexed: 12/29/2022] Open
Abstract
In this study, the lactobacillus fermentation process of pomegranate (Punica granatum L.) peel and Schisandra chinensis (Turcz.) Baill (PP&SC) was optimized by using the response surface method (RSM) coupled with a Box-Behnken design. The optimum fermentation condition with the maximal yield of ellagic acid (99.49 ± 0.47 mg/g) was as follows: 1:1 (w:w) ratio of pomegranate peel to Schisandra chinensis, 1% (v:v) of strains with a 1:1 (v:v) ratio of Lactobacillus Plantarum to Streptococcus Thermophilus, a 37 °C fermentation temperature, 33 h of fermentation time, 1:20 (g:mL) of a solid–liquid ratio and 3 g/100 mL of a glucose dosage. Under these conditions, the achieved fermentation broth (FB) showed stronger free radical scavenging abilities than the water extract (WE) against the ABTS+, DPPH, OH− and O2− radicals. The cytotoxicity and the protective effect of FB on the intracellular ROS level in HaCaT cells were further detected by the Cell Counting Kit-8 (CCK-8) assay. The results showed that FB had no significant cytotoxicity toward HaCaT cells when its content was no more than 8 mg/mL. The FB with a concentration of 8 mg/mL had a good protective effect against oxidative damage, which can effectively reduce the ROS level to 125.94% ± 13.46% (p < 0.001) compared with 294.49% ± 11.54% of the control group in H2O2-damaged HaCaT cells. The outstanding antioxidant ability and protective effect against H2O2-induced oxidative damage in HaCaT cells promote the potential for the FB of PP&SC as a functional raw material of cosmetics.
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Affiliation(s)
- Hui-Min Liu
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
- Engineering Research Center of Perfume & Aroma and Cosmetics, Ministry of Education, Shanghai 201418, China
| | - Peng-Fei Xu
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
| | - Ming-Yan Cheng
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
| | - Sheng-Nan Lei
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
| | - Qing-Lei Liu
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
| | - Wei Wang
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
- Engineering Research Center of Perfume & Aroma and Cosmetics, Ministry of Education, Shanghai 201418, China
- Correspondence: ; Tel.: +86-18918830550
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Kirenol Inhibits B[a]P-Induced Oxidative Stress and Apoptosis in Endothelial Cells via Modulation of the Nrf2 Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:5585303. [PMID: 33981385 PMCID: PMC8088375 DOI: 10.1155/2021/5585303] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/18/2021] [Accepted: 04/15/2021] [Indexed: 12/20/2022]
Abstract
Atherosclerosis is a persistent inflammatory disorder specified by the dysfunction of the arteries, the world's leading cause of cardiovascular diseases. We sought to determine the effectiveness of KRL in B[a]P-induced oxidative stress and programmed cell death in endothelial cells. Western blotting, real-time PCR, DCFH2-DA, and TUNEL staining were performed to detect pPI3K, pAKT, Nrf2, HO-1, NQO-1, Bcl2, Bax, and caspase-3 on the HUVECs. Through the pretreatment of KRL, a drastic enhancement was observed in the cell viability of HUVECs, whereas DNA damage and generation of reactive oxygen species induced by B[a]P was suppressed. KRL's potential use as an antioxidant was observed to have a direct correlation with an antioxidant gene's augmented expression and the nuclear translocation activation of Nrf2, even during the event when B[a]P was found to be absent. In addition, this study proved that the signaling cascades of PI3K/AKT mediated Nrf2 translocation. Activation of suppressed nuclear Nrf2 and reduced antioxidant genes across cells interacting with an LY294002 confirmed this phenomenon. In addition, knockdown of Nrf2 by Nrf2-siRNA transfection abolished the protective effects of KRL on HUVECs cells against oxidative damage. Finally, the expression of apoptotic proteins also supported the hypothesis that KRL may inhibit endothelial dysfunction. This study showed that KRL potentially prevents B[a]P-induced redox imbalance in the vascular endothelium by inducing the Nrf2 signaling via the PI3K/AKT pathway.
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40
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Fu H, You S, Zhao D, An Q, Zhang J, Wang C, Wang D, Li M. Tremella fuciformis polysaccharides inhibit UVA-induced photodamage of human dermal fibroblast cells by activating up-regulating Nrf2/Keap1 pathways. J Cosmet Dermatol 2021; 20:4052-4059. [PMID: 33686752 DOI: 10.1111/jocd.14051] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 02/14/2021] [Accepted: 02/24/2021] [Indexed: 01/09/2023]
Abstract
BACKGROUND UVA radiation can cause skin oxidative stress. Tremella fuciformis polysaccharides (TFPS) are the main active ingredient in Tremella. Previous studies have shown that TFPS have protective effects on UVA-induced oxidative stress cells, but the specific protective mechanism has not been clarified. OBJECTIVE This study aims to explore the potential protective mechanism of Tremella fuciformis polysaccharides on UVA-induced damage to human dermal fibroblasts cells. METHODS We evaluated the protective ability of TFPS against UVA-induced damage by detecting cell survival rate, the content of reactive oxygen species (ROS) and malondialdehyde (MDA) in the cells, and the scavenging activity of ABTS free radicals, as well as the enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the Nrf2-Keap-1 pathway protein and gene were measured to study the protective mechanism of TFPS from photodamage. RESULTS TFPS pretreatment can reduce the oxidative stress of UVA-treated human dermal fibroblasts cells. After TFPS pretreatment, the content of ROS and MDA in the cell decreased significantly and the total antioxidant activity was increased. Among them, the active of CAT, SOD, and GSH-Px in the cells increased significantly. TFPS can also protect fibroblasts by up-regulating Nrf2 and down-regulating Keap1 expression. Finally, it was also found that TFPS pretreatment increased the content of collagen I, elastin, and hyaluronic acid (HA) in skin fibroblasts treated with UVA. CONCLUSION These results indicate that a certain concentration of TFPS can effectively alleviate skin damage caused by UVA, and they may be used as an effective component of cosmetics.
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Affiliation(s)
- Hao Fu
- Beijing Key Lab of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, China
| | - ShiQuan You
- Beijing Key Lab of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, China
| | - Dan Zhao
- Beijing Key Lab of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, China.,Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China
| | - Quan An
- Yunnan Baiyao Group Co., Ltd., Kunming, China
| | - Jiachan Zhang
- Beijing Key Lab of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, China.,Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China
| | - Changtao Wang
- Beijing Key Lab of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, China.,Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China
| | - Dongdong Wang
- Beijing Key Lab of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, China
| | - Meng Li
- Beijing Key Lab of Plant Resource Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, China
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Yang HL, Lin CP, Vudhya Gowrisankar Y, Huang PJ, Chang WL, Shrestha S, Hseu YC. The anti-melanogenic effects of ellagic acid through induction of autophagy in melanocytes and suppression of UVA-activated α-MSH pathways via Nrf2 activation in keratinocytes. Biochem Pharmacol 2021; 185:114454. [PMID: 33545118 DOI: 10.1016/j.bcp.2021.114454] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/13/2022]
Abstract
Ellagic acid (EA) is a natural phenol antioxidant in different fruits, vegetables, and nuts. As a copper iron chelator from the tyrosinase enzyme's active site, EA was reported to inhibit melanogenesis in melanocytes. Here, we demonstrated the anti-melanogenic mechanisms of EA through autophagy induction in melanoma B16F10 cells and the role of Nrf2 and UVA (3 J/cm2)-activated α-melanocyte stimulating hormone (α-MSH) pathways in keratinocyte HaCaT cells. In vitro data showed that EA suppressed the tyrosinase activity and melanogenesis by suppressing cAMP-mediated CREB and MITF signaling mechanisms in α-MSH-stimulated B16F10 cells. ERK, JNK, and AKT pathways were involved in this EA-regulated MITF downregulation. Notably, EA induced autophagy in B16F10 cells was evidenced from increased LC3-II accumulation, p62/SQSTM1 activation, ATG4B downregulation, acidic vesicular organelle (AVO) formation, PI3K/AKT/mTOR inhibition, and Beclin-1/Bcl-2 dysregulation. Interestingly, 3-MA (an autophagy inhibitor) pretreatment or LC3 silencing (siRNA transfection) of B16F10 cells significantly reduced EA-induced anti-melanogenic activity. Besides this, in UVA-irradiated keratinocyte HaCaT cells, EA suppressed ROS production and α-MSH generation. Moreover, EA mediated the activation and nuclear translocation of Nrf2, leading to antioxidant γ-GCLC, HO-1, and NQO-1 protein expression in HaCaT cells. However, Nrf2 knockdown has significantly impaired this effect, and there was an uncontrolled ROS generation following UVA irradiation. JNK, PKC, and ROS pathways were involved in the activation of Nrf2 in HaCaT cells. In vivo experiments using the zebrafish model confirmed that EA inhibited tyrosinase activity and endogenous pigmentation. In conclusion, ellagic acid is an effective skin-whitening agent and might be used as a topical applicant.
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Affiliation(s)
- Hsin-Ling Yang
- Institute of Nutrition, College of Healthcare, China Medical University, Taichung 40402, Taiwan
| | - Chia-Pei Lin
- Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan
| | | | - Pei-Jane Huang
- Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan
| | - Wan-Lin Chang
- Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan
| | - Sirjana Shrestha
- Institute of Nutrition, College of Healthcare, China Medical University, Taichung 40402, Taiwan
| | - You-Cheng Hseu
- Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan; Research Center of Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan.
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42
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Nakata M, Shimoda M, Yamamoto S. UV-Induced Neuronal Degeneration in the Rat Cerebral Cortex. Cereb Cortex Commun 2021; 2:tgab006. [PMID: 34296154 PMCID: PMC8152860 DOI: 10.1093/texcom/tgab006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/19/2021] [Accepted: 01/20/2021] [Indexed: 12/01/2022] Open
Abstract
Irradiation with ultraviolet (UV) light on the cortical surface can induce a focal brain lesion (UV lesion) in rodents. In the present study, we investigated the process of establishing a UV lesion. Rats underwent UV irradiation (365-nm wavelength, 2.0 mWh) over the dura, and time-dependent changes in the cortical tissue were analyzed histologically. We found that the majority of neurons in the lesion started to degenerate within 24 h and the rest disappeared within 5 days after irradiation. UV-induced neuronal degeneration progressed in a layer-dependent manner. Moreover, UV-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity and heme oxygenase-1 (HO-1) immunoreactivity were also detected. These findings suggest that UV irradiation in the brain can induce gradual neural degeneration and oxidative stress. Importantly, UV vulnerability may vary among cortical layers. UV-induced cell death may be due to apoptosis; however, there remains a possibility that UV-irradiated cells were degenerated via processes other than apoptosis. The UV lesion technique will not only assist in investigating brain function at a targeted site but may also serve as a pathophysiological model of focal brain injury and/or neurodegenerative disorders.
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Affiliation(s)
- Mariko Nakata
- Integrative Neuroscience Research Group, Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8568, Japan
| | - Masayuki Shimoda
- Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Shinya Yamamoto
- Integrative Neuroscience Research Group, Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8568, Japan
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Cock IE, Cheesman M. Plants of the genus Terminalia: Phytochemical and antioxidant profiles, proliferation, and cancer. Cancer 2021. [DOI: 10.1016/b978-0-12-819547-5.00044-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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do Nascimento MF, Cardoso JC, Santos TS, Tavares LA, Pashirova TN, Severino P, Souto EB, de Albuquerque-Junior RLC. Development and Characterization of Biointeractive Gelatin Wound Dressing Based on Extract of Punica granatum Linn. Pharmaceutics 2020; 12:E1204. [PMID: 33322458 PMCID: PMC7763089 DOI: 10.3390/pharmaceutics12121204] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 12/05/2020] [Accepted: 12/07/2020] [Indexed: 12/17/2022] Open
Abstract
Punica granatum Linn (pomegranate) extracts have been proposed for wound healing due to their antimicrobial, antioxidant, and anti-inflammatory properties. In this work, we designed biointeractive membranes that contain standard extracts of P. granatum for the purpose of wound healing. The used standard extract contained 32.24 mg/g of gallic acid and 41.67 mg/g of ellagic acid, and it showed high antioxidant activity (the concentration of the extract that produces 50% scavenging (IC50) 1.715 µg/mL). Compared to the gelatin-based membranes (GEL), membranes containing P. granatum extracts (GELPG) presented a higher maximal tension (p = 0.021) and swelling index (p = 0.033) and lower water vapor permeability (p = 0.003). However, no difference was observed in the elongation and elastic modulus of the two types of membranes (p > 0.05). Our wound-healing assay showed that a GELPG-treated group experienced a significant increase compared to that of the control group in their wound contraction rates on days 3 (p < 0.01), 7 (p < 0.001), and on day 14 (p < 0.001). The GELPG membranes promoted major histological changes in the dynamics of wound healing, such as improvements in the formation of granular tissue, better collagen deposition and arrangement, and earlier development of cutaneous appendages. Our results suggest that a biointeractive gelatin-based membrane containing P. granatum extracts has a promising potential application for dressings that are used to treat wounds.
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Affiliation(s)
- Marismar F. do Nascimento
- Health and Environment Post-Graduating Program, University Tiradentes (UNIT), Aracaju 49032-490, Sergipe, Brazil; (M.F.d.N.); (J.C.C.); (T.S.S.); (L.A.T.)
- School of Nursing, University of Pernambuco, Brazil BR 203, Km 2, s/n, Petrolina 56328-903, Pernambuco, Brazil
| | - Juliana C. Cardoso
- Health and Environment Post-Graduating Program, University Tiradentes (UNIT), Aracaju 49032-490, Sergipe, Brazil; (M.F.d.N.); (J.C.C.); (T.S.S.); (L.A.T.)
- Institute of Research and Technology (ITR), Av. Murilo Dantas 300, Aracaju 49032-490, Sergipe, Brazil
| | - Tarsizio S. Santos
- Health and Environment Post-Graduating Program, University Tiradentes (UNIT), Aracaju 49032-490, Sergipe, Brazil; (M.F.d.N.); (J.C.C.); (T.S.S.); (L.A.T.)
| | - Lívia A. Tavares
- Health and Environment Post-Graduating Program, University Tiradentes (UNIT), Aracaju 49032-490, Sergipe, Brazil; (M.F.d.N.); (J.C.C.); (T.S.S.); (L.A.T.)
| | - Tatiana N. Pashirova
- Department of Pharmaceutical Technology, Faculty of Pharmacy (FFUC), University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov St., 8, 420088 Kazan, Russia
| | - Patricia Severino
- School of Pharmacy, Industrial Biotechnology Post-Graduating Program, University Tiradentes, Aracaju 49032-490, Sergipe, Brazil;
- Tiradentes Institute, 150 Mt Vernon St, Dorchester, MA 02125, USA
- Center for Biomedical Engineering, Department of Medicine, Brigham and Women & Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
| | - Eliana B. Souto
- Department of Pharmaceutical Technology, Faculty of Pharmacy (FFUC), University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;
- CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
| | - Ricardo L. C. de Albuquerque-Junior
- Health and Environment Post-Graduating Program, University Tiradentes (UNIT), Aracaju 49032-490, Sergipe, Brazil; (M.F.d.N.); (J.C.C.); (T.S.S.); (L.A.T.)
- Institute of Research and Technology (ITR), Av. Murilo Dantas 300, Aracaju 49032-490, Sergipe, Brazil
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Choi DW, Jung SY, Lee SY, Shon DH, Shin HS. Rosae multiflorae Fructus Extract Improves Trimellitic Anhydride-Induced Atopic Dermatitis-Like Symptoms. J Med Food 2020; 23:1287-1295. [PMID: 33185498 DOI: 10.1089/jmf.2020.4767] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Allergic disorders, including atopic dermatitis (AD), are closely linked to the activation of type 2 helper T (Th2) cells. The aim of this study was to investigate the possibility of using Rosae multiflorae fructus extract (RMFE) for AD treatment in the AD-like mouse model induced by treatment with trimellitic anhydride (TMA). Oral treatment of RMFE reduced the increase in ear thickness and suppressed inflammatory cytokine expression (interleukin [IL]-1β and tumor necrosis factor [TNF]-α) and Th2-associated immune responses (immunoglobulin [Ig] E and IL-4) in mouse ears. Furthermore, messenger RNA (mRNA) expression levels such as IL-4, IL-5, and IL-13, in draining lymph nodes were decreased by RMFE. Furthermore, we found that RMFE increased the level of heme oxygenase-1 (HO-1) through ERK and p38 pathways, reducing IL-2 production and CD4+ T cell proliferation, and inhibited STAT6 phosphorylation. Therefore, this study suggested that RMFE could be an effective treatment of AD induced by Th2-mediated immune responses by suppressing proliferation of CD4+ T cells via increased HO-1.
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Affiliation(s)
- Dae Woon Choi
- Food Biotechnology Program, KFRI School, Korea University of Science and Technology, Daejeon, Korea.,Division of Functional Food Research, Korea Food Research Institute, Wanju-gun, Korea
| | - Sun Young Jung
- Food Biotechnology Program, KFRI School, Korea University of Science and Technology, Daejeon, Korea.,Division of Functional Food Research, Korea Food Research Institute, Wanju-gun, Korea
| | - So-Young Lee
- Food Biotechnology Program, KFRI School, Korea University of Science and Technology, Daejeon, Korea.,Division of Functional Food Research, Korea Food Research Institute, Wanju-gun, Korea
| | - Dong-Hwa Shon
- Department of Food Processing and Distribution, Gangneung-Wonju National University, Gangneung, Korea
| | - Hee Soon Shin
- Food Biotechnology Program, KFRI School, Korea University of Science and Technology, Daejeon, Korea.,Division of Functional Food Research, Korea Food Research Institute, Wanju-gun, Korea
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Physical formulation approaches for improving aqueous solubility and bioavailability of ellagic acid: A review. Eur J Pharm Biopharm 2020; 159:198-210. [PMID: 33197529 DOI: 10.1016/j.ejpb.2020.11.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 10/10/2020] [Accepted: 11/07/2020] [Indexed: 01/16/2023]
Abstract
Ellagic acid (EA) is a polyphenolic active compound with antimalarial and other promising therapeutic activities. However, its solubility and its permeability are both low (BCS IV). These properties greatly compromise its oral bioavailability and clinical utilizations. To overcome these limitations of the physicochemical parameters, several formulation approaches, including particle size reduction, amorphization and lipid-based formulations, have been used. Although these strategies have not yet led to a clinical application, some of them have resulted in significant improvements in the solubility and bioavailability of EA. This critical review reports and analyses the different formulation approaches used by scientists to improve both the biopharmaceutical properties and the clinical use of EA.
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Bianchini Silva LS, Perasoli FB, Carvalho KV, Vieira KM, Paz Lopes MT, Bianco de Souza GH, Henrique Dos Santos OD, Freitas KM. Melaleuca leucadendron (L.) L. flower extract exhibits antioxidant and photoprotective activities in human keratinocytes exposed to ultraviolet B radiation. Free Radic Biol Med 2020; 159:54-65. [PMID: 32745772 DOI: 10.1016/j.freeradbiomed.2020.07.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 07/08/2020] [Accepted: 07/12/2020] [Indexed: 12/24/2022]
Abstract
Recently, there has been a demand for the replacement of chemical sunscreens with natural compounds that could prevent or restore UV-induced skin damage. Here, we investigated the photoprotective influence of the Melaleuca leucadendron ethanolic flower extract (EEMec) on factors involved in cellular and molecular UVB-induced oxidative stress in human skin keratinocytes (HaCaT). The phytochemical constituents, antioxidant potential by DPPH assay, content of total phenolic and flavonoid compounds in EEMec were evaluated. HaCaT cells were treated with EEMec followed by irradiation with UVB. CAT activity; GSH and ROS levels; and SOD1, GPx, CAT and COX-2 expression assays were employed to verify the oxidative stress, as well as EEMec effect on transmembrane transport, and pro-inflammatory and pro-apoptotic protein expression. EEMec reverted the viability loss of HaCaT cells after irradiation with UVB, exhibited significant antioxidant capacity and free radical scavenging activity in vitro, inhibited COX-2 expression and ensure protection of DNA-damage. EEMec shown a great photoprotective property to prevent keratinocytes damage induced by UV radiation and, thus a candidate potential to application as an adjuvant in sunscreen formulations as a strategy to reduce risk of sunburn and prevent skin diseases associated with UV-induced inflammation and cancer.
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Affiliation(s)
- Luan Silvestro Bianchini Silva
- Laboratório de Fitotecnologia, Departamento de Farmácia, Universidade Federal de Ouro Preto, Campus Morro Do Cruzeiro, Ouro Preto, Minas Gerais, CEP 35400-000, Brazil
| | - Fernanda Barçante Perasoli
- Laboratório de Fitotecnologia, Departamento de Farmácia, Universidade Federal de Ouro Preto, Campus Morro Do Cruzeiro, Ouro Preto, Minas Gerais, CEP 35400-000, Brazil
| | - Karen Vitor Carvalho
- Laboratório de Fitotecnologia, Departamento de Farmácia, Universidade Federal de Ouro Preto, Campus Morro Do Cruzeiro, Ouro Preto, Minas Gerais, CEP 35400-000, Brazil
| | - Karla Murata Vieira
- Laboratório de Fitotecnologia, Departamento de Farmácia, Universidade Federal de Ouro Preto, Campus Morro Do Cruzeiro, Ouro Preto, Minas Gerais, CEP 35400-000, Brazil
| | - Miriam Teresa Paz Lopes
- Laboratório de Substâncias Antitumorais, Departamento de Farmacologia, Universidade Federal de Minas Gerais, Campus Pampulha, Belo Horizonte, Minas Gerais, CEP 31270-901, Brazil
| | - Gustavo Henrique Bianco de Souza
- Laboratório de Fitotecnologia, Departamento de Farmácia, Universidade Federal de Ouro Preto, Campus Morro Do Cruzeiro, Ouro Preto, Minas Gerais, CEP 35400-000, Brazil
| | - Orlando David Henrique Dos Santos
- Laboratório de Fitotecnologia, Departamento de Farmácia, Universidade Federal de Ouro Preto, Campus Morro Do Cruzeiro, Ouro Preto, Minas Gerais, CEP 35400-000, Brazil.
| | - Kátia Michelle Freitas
- Laboratório de Fitotecnologia, Departamento de Farmácia, Universidade Federal de Ouro Preto, Campus Morro Do Cruzeiro, Ouro Preto, Minas Gerais, CEP 35400-000, Brazil
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Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management? Antioxidants (Basel) 2020; 9:antiox9100973. [PMID: 33050575 PMCID: PMC7600646 DOI: 10.3390/antiox9100973] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/04/2020] [Accepted: 10/07/2020] [Indexed: 12/25/2022] Open
Abstract
The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cell signaling mechanism in maintaining redox homeostasis in humans. The role of dietary flavonoids in activating Nrf2/ARE in relation to cancer chemoprevention or cancer promotion is not well established. Here we summarize the dual effects of flavonoids in cancer chemoprevention and cancer promotion with respect to the regulation of the Nrf2/ARE pathway, while underlying the possible cellular mechanisms. Luteolin, apigenin, quercetin, myricetin, rutin, naringenin, epicatechin, and genistein activate the Nrf2/ARE pathway in both normal and cancer cells. The hormetic effect of flavonoids has been observed due to their antioxidant or prooxidant activity, depending on the concentrations. Reported in vitro and in vivo investigations suggest that the activation of the Nrf2/ARE pathway by either endogenous or exogenous stimuli under normal physiological conditions contributes to redox homeostasis, which may provide a mechanism for cancer chemoprevention. However, some flavonoids, such as luteolin, apigenin, myricetin, quercetin, naringenin, epicatechin, genistein, and daidzein, at low concentrations (1.5 to 20 µM) facilitate cancer cell growth and proliferation in vitro. Paradoxically, some flavonoids, including luteolin, apigenin, and chrysin, inhibit the Nrf2/ARE pathway in vitro. Therefore, even though flavonoids play a major role in cancer chemoprevention, due to their possible inducement of cancer cell growth, the effects of dietary flavonoids on cancer pathophysiology in patients or appropriate experimental animal models should be investigated systematically.
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Natural Nrf2 Modulators for Skin Protection. Antioxidants (Basel) 2020; 9:antiox9090812. [PMID: 32882952 PMCID: PMC7556038 DOI: 10.3390/antiox9090812] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 08/26/2020] [Accepted: 08/26/2020] [Indexed: 02/06/2023] Open
Abstract
Since the discovery of antioxidant responsive elements (ARE), which are commonly found in the promoter of the Phase II metabolism/antioxidant enzymes, and nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor that binds to ARE, the study conducted in this field has expanded remarkably over the decades, and the Nrf2-mediated pathway is now recognized to occupy a central position in cell defense mechanisms. Induction of the Phase II metabolism/antioxidant enzymes through direct activation of Nrf2 can be a promising strategy for preventing degenerative diseases in general, but a dark side of this strategy should be considered, as Nrf2 activation can enhance the survival of cancer cells. In this review, we discuss the historical discovery of Nrf2 and the regulatory mechanism of the Nrf2-mediated pathway, focusing on the interacting proteins and post-translational modifications. In addition, we discuss the latest studies that examined various natural Nrf2 modulators for the protective roles in the skin, in consideration of their dermatological and cosmetic applications. Studies are reviewed in the order of time of research as much as possible, to help understand how and why such studies were conducted under the circumstances of that time. We hope that this review can serve as a steppingstone in conducting more advanced research by providing a scientific basis for researchers newly entering this field.
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Alfei S, Marengo B, Zuccari G. Oxidative Stress, Antioxidant Capabilities, and Bioavailability: Ellagic Acid or Urolithins? Antioxidants (Basel) 2020; 9:E707. [PMID: 32759749 PMCID: PMC7465258 DOI: 10.3390/antiox9080707] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 07/24/2020] [Accepted: 08/03/2020] [Indexed: 12/14/2022] Open
Abstract
Oxidative stress (OS), triggered by overproduction of reactive oxygen and nitrogen species, is the main mechanism responsible for several human diseases. The available one-target drugs often face such illnesses, by softening symptoms without eradicating the cause. Differently, natural polyphenols from fruits and vegetables possess multi-target abilities for counteracting OS, thus representing promising therapeutic alternatives and adjuvants. Although in several in vitro experiments, ellagitannins (ETs), ellagic acid (EA), and its metabolites urolithins (UROs) have shown similar great potential for the treatment of OS-mediated human diseases, only UROs have demonstrated in vivo the ability to reach tissues to a greater extent, thus appearing as the main molecules responsible for beneficial activities. Unfortunately, UROs production depends on individual metabotypes, and the consequent extreme variability limits their potentiality as novel therapeutics, as well as dietary assumption of EA, EA-enriched functional foods, and food supplements. This review focuses on the pathophysiology of OS; on EA and UROs chemical features and on the mechanisms of their antioxidant activity. A discussion on the clinical applicability of the debated UROs in place of EA and on the effectiveness of EA-enriched products is also included.
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Affiliation(s)
- Silvana Alfei
- Department of Pharmacy, University of Genoa, Viale Cembrano, 4, I-16148 Genoa, Italy;
| | - Barbara Marengo
- Department of Experimental Medicine—DIMES, Via Alberti L.B. 2, I-16132 Genoa, Italy;
| | - Guendalina Zuccari
- Department of Pharmacy, University of Genoa, Viale Cembrano, 4, I-16148 Genoa, Italy;
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