|
1
|
Huang YL, Morikawa-Ichinose T, Lee SU, Tatsumi Y, Ichitani M, Kumazoe M, Tachibana H, Fujimura Y. Comprehensive microRNA analysis toward exploring a new functional component in Matcha green tea. FOOD CHEMISTRY. MOLECULAR SCIENCES 2025; 10:100265. [PMID: 40530395 PMCID: PMC12171767 DOI: 10.1016/j.fochms.2025.100265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 05/07/2025] [Accepted: 05/27/2025] [Indexed: 06/20/2025]
Abstract
Matcha, a traditional Japanese green tea, has health-promoting effects. However, little is known about its bioactive components, except for polyphenols, caffeine, and amino acids. Here, we revealed the presence of diverse miRNAs, a type of functional RNAs, as new components of Matcha, using next-generation sequencing. Quantitative reverse-transcription PCR analysis of 10 different Matcha showed that miRNA levels varied depending on the cultivar and harvest season. As extraction methods of miRNAs, we found that soaking at 95 °C significantly enhanced total RNA and miRNA yields. Furthermore, a positive correlation was observed between total RNA and miRNA yields extracted from 27 plant-based dried powders. Notably, Matcha exhibited the highest levels of four representative miRNAs: lja-miR166-3p, csn-miR396d-5p, gma-miR396e, and csn-miRn409. The miRNA yields in Matcha were correlated with the major Matcha components. These results highlight Matcha as a source of miRNAs and candidate bioactive components. These findings provide new insights into the functionality of Matcha.
Collapse
Affiliation(s)
- Yi-Lan Huang
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| | - Tomomi Morikawa-Ichinose
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| | - Seong-Uk Lee
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| | - Yuka Tatsumi
- Central Research Institute, ITOEN, Ltd., 21 Mekami, Makinohara-shi, Shizuoka 421-0516, Japan
| | - Masaki Ichitani
- Central Research Institute, ITOEN, Ltd., 21 Mekami, Makinohara-shi, Shizuoka 421-0516, Japan
| | - Motofumi Kumazoe
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| | - Yoshinori Fujimura
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| |
Collapse
|
|
2
|
Qutub M, Hussain UM, Tatode A, Premchandani T, Khan R, Umekar M, Taksande J, Singanwad P. Nano-Engineered Epigallocatechin Gallate (EGCG) Delivery Systems: Overcoming Bioavailability Barriers to Unlock Clinical Potential in Cancer Therapy. AAPS PharmSciTech 2025; 26:137. [PMID: 40379893 DOI: 10.1208/s12249-025-03145-0] [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: 03/27/2025] [Accepted: 05/05/2025] [Indexed: 05/19/2025] Open
Abstract
Epigallocatechin gallate (EGCG), a bioactive polyphenol derived from Camellia sinensis, exhibits multimodal anticancer activity through mechanisms such as apoptosis induction, metastasis suppression, and chemoresistance reversal. Despite its therapeutic promise, clinical application is constrained by rapid metabolism, poor bioavailability, and inconsistent biodistribution. Recent advances in nanotechnology have enabled the development of innovative delivery systems including pH-responsive nanoparticles, lipid-polymer hybrids, and ligand-functionalized carriers that enhance EGCG stability, tumor targeting, and bioavailability by 3- to fivefold in preclinical models. These platforms also facilitate synergistic co-delivery with chemotherapeutics like doxorubicin, amplifying cytotoxicity and overcoming multidrug resistance. Mechanistically, EGCG modulates oncogenic pathways via NF-κB suppression, caspase activation, and MMP-9 downregulation, demonstrating efficacy across diverse cancer types. However, translational challenges persist, such as nanoparticle toxicity, variable tumor accumulation, and insufficient penetration in hypoxic microenvironments. Regulatory hurdles, including the lack of harmonized global standards for herbal medicinal products, further complicate clinical adoption. To bridge these gaps, future research must prioritize scalable cGMP-compliant manufacturing, rigorous preclinical toxicity profiling, and robust clinical trials to validate safety and efficacy. Addressing these issues could position nanoengineered EGCG as a paradigm-shifting therapy in precision oncology, aligning with ESCOP's mission to integrate evidence-based phytomedicines into conventional cancer care. This review underscores the necessity of interdisciplinary collaboration to standardize phytopreparations, refine regulatory frameworks, and advance biomarker-driven clinical validation, ultimately unlocking the full potential of EGCG in modern therapeutics.
Collapse
Affiliation(s)
- Mohammad Qutub
- Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, 441002, India
| | - Ujban Md Hussain
- Department of Pharmaceutical Sciences, Rashtrasant Tukdoji Maharaj Nagpur University, Nagpur, Maharashtra, India
| | - Amol Tatode
- Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, 441002, India.
| | - Tanvi Premchandani
- Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, 441002, India
| | - Rahmuddin Khan
- Department of Pharmaceutics, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi, 110062, India
| | - Milind Umekar
- Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, 441002, India
| | - Jayshree Taksande
- Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, 441002, India
| | - Priyanka Singanwad
- Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, 441002, India
| |
Collapse
|
|
3
|
Kato Y, Suzuki S, Higashiyama A, Kaneko I, Akagawa M, Nishikawa M, Ikushiro S. Tea Catechins in Green Tea Inhibit the Activity of SARS-CoV-2 Main Protease via Covalent Adduction. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:4116-4125. [PMID: 39907399 DOI: 10.1021/acs.jafc.4c11685] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
We herein examined the inhibitory effects of tea catechins on the SARS-CoV-2 main protease (Mpro). Among the catechins analyzed, epigallocatechin 3-(3″-O-methyl)gallate, epigallocatechin gallate (EGCG), gallocatechin, gallocatechin gallate, and epigallocatechin inhibited recombinant Mpro in a dose-dependent manner. Peptide mapping revealed that catechins preferentially formed covalent bonds with five sequences with the strongest activity at the C145 active site. Fragmentation analysis indicated 184 cleavages from peptides containing C145, corresponding to the D ring, suggesting that the B ring was attached to C145. When 10 bottled teas were incubated with Mpro, four green teas inhibited the enzyme by over 80%, whereas the blended and barley teas showed no effect. EGCG reacted covalently with SARS-CoV-2 Mpro within cells when incubated with cultured cells expressing Mpro. This is the first study to report direct covalent binding between tea catechins and Mpro in cells. This suggests that catechins from green tea can inhibit Mpro in infected cells.
Collapse
Affiliation(s)
- Yoji Kato
- School of Human Science and Environment, University of Hyogo, Himeji, Hyogo 670-0092, Japan
- Research Institute for Food and Nutritional Sciences, University of Hyogo, Himeji, Hyogo 670-0092, Japan
| | - Sakiko Suzuki
- School of Human Science and Environment, University of Hyogo, Himeji, Hyogo 670-0092, Japan
| | - Akari Higashiyama
- School of Human Science and Environment, University of Hyogo, Himeji, Hyogo 670-0092, Japan
| | - Ichiro Kaneko
- School of Human Science and Environment, University of Hyogo, Himeji, Hyogo 670-0092, Japan
- Research Institute for Food and Nutritional Sciences, University of Hyogo, Himeji, Hyogo 670-0092, Japan
| | - Mitsugu Akagawa
- Department of Food and Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8501, Japan
| | - Miyu Nishikawa
- Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, Imizu, Toyama 939-0398, Japan
| | - Shinichi Ikushiro
- Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, Imizu, Toyama 939-0398, Japan
| |
Collapse
|
|
4
|
Tachibana H. Future outlook for food function research. Biosci Biotechnol Biochem 2025; 89:201-204. [PMID: 39322238 DOI: 10.1093/bbb/zbae137] [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: 09/11/2024] [Accepted: 09/20/2024] [Indexed: 09/27/2024]
Abstract
The results of research on food functionality in Japan have been passed on to society in the form of Foods for Specified Health Uses and Foods with Functional Claims. However, it is also true that there are people who do not experience any health benefits even when they consume these foods. To clarify the factors that cause such individual differences in the health benefits of food, research into the following points is important: (1) Elucidation of the molecular mechanisms behind why food factors exert their functionality. (2) Research into the functional interactions between food factors that exert their functionality in multi-component systems. (3) Research into the functionality of food factors that have not been the subject of research until now. We will introduce the results of our research in these areas. We will also discuss our expectations for the application of food functionality research to pharmaceutical development as an extension of this research.
Collapse
Affiliation(s)
- Hirofumi Tachibana
- Division of Applied Biological Chemistry, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| |
Collapse
|
|
5
|
Koyama S, Weber EL, Heinbockel T. Possible Combinatorial Utilization of Phytochemicals and Extracellular Vesicles for Wound Healing and Regeneration. Int J Mol Sci 2024; 25:10353. [PMID: 39408681 PMCID: PMC11476926 DOI: 10.3390/ijms251910353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 10/20/2024] Open
Abstract
Organ and tissue damage can result from injury and disease. How to facilitate regeneration from damage has been a topic for centuries, and still, we are trying to find agents to use for treatments. Two groups of biological substances are known to facilitate wound healing. Phytochemicals with bioactive properties form one group. Many phytochemicals have anti-inflammatory effects and enhance wound healing. Recent studies have described their effects at the gene and protein expression levels, highlighting the receptors and signaling pathways involved. The extremely large number of phytochemicals and the multiple types of receptors they activate suggest a broad range of applicability for their clinical use. The hydrophobic nature of many phytochemicals and the difficulty with chemical stabilization have been a problem. Recent developments in biotechnology and nanotechnology methods are enabling researchers to overcome these problems. The other group of biological substances is extracellular vesicles (EVs), which are now known to have important biological functions, including the improvement of wound healing. The proteins and nanoparticles contained in mammalian EVs as well as the specificity of the targets of microRNAs included in the EVs are becoming clear. Plant-derived EVs have been found to contain phytochemicals. The overlap in the wound-healing capabilities of both phytochemicals and EVs and the differences in their nature suggest the possibility of a combinatorial use of the two groups, which may enhance their effects.
Collapse
Affiliation(s)
- Sachiko Koyama
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Erin L. Weber
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - Thomas Heinbockel
- Department of Anatomy, College of Medicine, Howard University, Washington, DC 20059, USA
| |
Collapse
|
|
6
|
Zhang W, Wang J, Shan C. The eEF1A protein in cancer: Clinical significance, oncogenic mechanisms, and targeted therapeutic strategies. Pharmacol Res 2024; 204:107195. [PMID: 38677532 DOI: 10.1016/j.phrs.2024.107195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 04/09/2024] [Accepted: 04/22/2024] [Indexed: 04/29/2024]
Abstract
Eukaryotic elongation factor 1A (eEF1A) is among the most abundant proteins in eukaryotic cells. Evolutionarily conserved across species, eEF1A is in charge of translation elongation for protein biosynthesis as well as a plethora of non-translational moonlighting functions for cellular homeostasis. In malignant cells, however, eEF1A becomes a pleiotropic driver of cancer progression via a broad diversity of pathways, which are not limited to hyperactive translational output. In the past decades, mounting studies have demonstrated the causal link between eEF1A and carcinogenesis, gaining deeper insights into its multifaceted mechanisms and corroborating its value as a prognostic marker in various cancers. On the other hand, an increasing number of natural and synthetic compounds were discovered as anticancer eEF1A-targeting inhibitors. Among them, plitidepsin was approved for the treatment of multiple myeloma whereas metarrestin was currently under clinical development. Despite significant achievements in these two interrelated fields, hitherto there lacks a systematic examination of the eEF1A protein in the context of cancer research. Therefore, the present work aims to delineate its clinical implications, molecular oncogenic mechanisms, and targeted therapeutic strategies as reflected in the ever expanding body of literature, so as to deepen mechanistic understanding of eEF1A-involved tumorigenesis and inspire the development of eEF1A-targeted chemotherapeutics and biologics.
Collapse
Affiliation(s)
- Weicheng Zhang
- The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People's Republic of China.
| | - Jiyan Wang
- The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People's Republic of China
| | - Changliang Shan
- The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People's Republic of China.
| |
Collapse
|
|
7
|
Iloki Assanga SB, Lewis Luján LM, McCarty MF. Targeting beta-catenin signaling for prevention of colorectal cancer - Nutraceutical, drug, and dietary options. Eur J Pharmacol 2023; 956:175898. [PMID: 37481200 DOI: 10.1016/j.ejphar.2023.175898] [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: 03/11/2023] [Revised: 06/09/2023] [Accepted: 06/29/2023] [Indexed: 07/24/2023]
Abstract
Progressive up-regulation of β-catenin signaling is very common in the transformation of colorectal epithelium to colorectal cancer (CRC). Practical measures for opposing such signaling hence have potential for preventing or slowing such transformation. cAMP/PKA activity in colon epithelium, as stimulated by COX-2-generated prostaglandins and β2-adrenergic signaling, boosts β-catenin activity, whereas cGMP/PKG signaling has the opposite effect. Bacterial generation of short-chain fatty acids (as supported by unrefined high-carbohydrate diets, berberine, and probiotics), dietary calcium, daily aspirin, antioxidants opposing cox-2 induction, and nicotine avoidance, can suppress cAMP production in colonic epithelium, whereas cGMP can be boosted via linaclotides, PDE5 inhibitors such as sildenafil or icariin, and likely high-dose biotin. Selective activation of estrogen receptor-β by soy isoflavones, support of adequate vitamin D receptor activity with UV exposure or supplemental vitamin D, and inhibition of CK2 activity with flavanols such as quercetin, can also oppose β-catenin signaling in colorectal epithelium. Secondary bile acids, the colonic production of which can be diminished by low-fat diets and berberine, can up-regulate β-catenin activity by down-regulating farnesoid X receptor expression. Stimulation of PI3K/Akt via insulin, IGF-I, TLR4, and EGFR receptors boosts β-catenin levels via inhibition of glycogen synthase-3β; plant-based diets can down-regulate insulin and IGF-I levels, exercise training and leanness can keep insulin low, anthocyanins and their key metabolite ferulic acid have potential for opposing TLR4 signaling, and silibinin is a direct antagonist for EGFR. Partially hydrolyzed phytate can oppose growth factor-mediated down-regulation of β-catenin by inhibiting Akt activation. Multifactorial strategies for safely opposing β-catenin signaling can be complemented with measures that diminish colonic mutagenesis and DNA hypomethylation - such as avoidance of heme-rich meat and charred or processed meats, consumption of phase II-inductive foods and nutraceuticals (e.g., Crucifera), and assurance of adequate folate status.
Collapse
Affiliation(s)
- Simon Bernard Iloki Assanga
- Departamento de Ciencias Químico Biológicas, Universidad de Sonora, Blvd Luis Encinas y Rosales S/N Col. Centro, Hermosillo, Sonora, C.P. 83000, Mexico.
| | - Lidianys María Lewis Luján
- Technological Institute of Hermosillo (ITH), Ave. Tecnológico y Periférico Poniente S/N, Col. Sahuaro, Hermosillo, Sonora, C.P. 83170, México.
| | | |
Collapse
|
|
8
|
Bae J, Kumazoe M, Lee KW, Fujimura Y, Tachibana H. 67-kDa laminin receptor mediates oolonghomobisflavan B-induced cell growth inhibition in melanoma. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 118:154970. [PMID: 37516056 DOI: 10.1016/j.phymed.2023.154970] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 06/12/2023] [Accepted: 07/15/2023] [Indexed: 07/31/2023]
Abstract
BACKGROUND Oolonghomobisflavans are unique polyphenols found in oolong teas. Oolonghomobisflavan B (OHBFB), a dimer of (-)-epigallocatechin-3-O-gallate (EGCG), is an active compound found in green tea. PURPOSE OHBFB has been reported to exert an inhibitory effect on lipase enzyme activity. However, little is known regarding its intercellular signaling induction effect. Further, there are no reports describing the anti-cancer effects of OHBFB. METHODS The effect of OFBFB on B16 melanoma cells was evaluated by cell counting, and its mechanisms were determined by western blot analysis with or without protein phosphatase 2A (PP2A) inhibitor treatment. Intracellular cyclic adenosine monophosphate (cAMP) levels were evaluated by time-resolved fluorescence resonance energy transfer analysis. Quartz crystal microbalance (QCM) analysis was performed to assess the binding of OHBFB to 67LR. RESULTS Cell growth assay and western blot analyses showed that OHBFB inhibited melanoma cell growth, followed by myosin phosphatase target subunit 1 (MYPT1) and myosin regulatory light chain (MRLC) dephosphorylation via protein phosphatase 2A (PP2A)-dependent mechanisms. These effects are mediated by intracellular cAMP- and protein kinase A (PKA) A-dependent mechanisms. QCM analysis identified the 67-kDa laminin receptor (67LR) as an OHBFB receptor with a Kd of 3.7 µM. We also demonstrated for the first time that OHBFB intake suppresses tumor growth in vivo. CONCLUSIONS Taken together, these results indicate that the cAMP/PKA/PP2A/MYPT1/MRLC pathway is a key mediator of melanoma cell growth inhibition following OHBFB binding to 67LR and that OHBFB suppresses tumor growth in vivo.
Collapse
Affiliation(s)
- Jaehoon Bae
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan; Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si, Jeonbuk 580-185, Republic of Korea
| | - Motofumi Kumazoe
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Kwan-Woo Lee
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Yoshinori Fujimura
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan.
| |
Collapse
|
|
9
|
Kciuk M, Alam M, Ali N, Rashid S, Głowacka P, Sundaraj R, Celik I, Yahya EB, Dubey A, Zerroug E, Kontek R. Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications. Molecules 2023; 28:5246. [PMID: 37446908 PMCID: PMC10343677 DOI: 10.3390/molecules28135246] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 06/30/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical and clinical studies suggest that EGCG may be used in the treatment of numerous disorders, including cancer. This review aims to summarize the existing knowledge regarding the biological properties of EGCG, especially in the context of cancer treatment and prophylaxis.
Collapse
Affiliation(s)
- Mateusz Kciuk
- Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland; (M.K.); (R.K.)
- Doctoral School of Exact and Natural Sciences, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
| | - Manzar Alam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India;
| | - Nemat Ali
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Summya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia
| | - Pola Głowacka
- Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 90-001 Lodz, Poland;
- Doctoral School of Medical University of Lodz, Hallera 1 Square, 90-700 Lodz, Poland
| | - Rajamanikandan Sundaraj
- Department of Biochemistry, Centre for Drug Discovery, Karpagam Academy of Higher Education, Coimbatore 641021, India;
| | - Ismail Celik
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38280, Turkey;
| | - Esam Bashir Yahya
- Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Penang 11800, Malaysia;
| | - Amit Dubey
- Computational Chemistry and Drug Discovery Division, Quanta Calculus, Greater Noida 201310, India;
- Department of Pharmacology, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospital, Chennai 600077, India
| | - Enfale Zerroug
- LMCE Laboratory, Group of Computational and Pharmaceutical Chemistry, University of Biskra, Biskra 07000, Algeria;
| | - Renata Kontek
- Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland; (M.K.); (R.K.)
| |
Collapse
|
|
10
|
Fujimura Y, Yoshimoto T, Fujino K, Nezu A, Marugame Y, Bae J, Kumazoe M, Tachibana H. Bioactivity-boosting strategy based on combination of anti-allergic O-methylated catechin with a Citrus flavanone, hesperetin. J Nat Med 2023; 77:363-369. [PMID: 36494586 DOI: 10.1007/s11418-022-01668-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/30/2022] [Indexed: 12/13/2022]
Abstract
Many patients with allergies have anxiety about taking anti-allergic medicines due to their side effects and increased medical expenses. Thus, developing functional foods/agricultural products for allergy prevention is strongly desired. In this study, we revealed that a Citrus flavanone, hesperetin, amplified IgE/antigen-mediated degranulation-inhibitory potency of anti-allergic catechin, (-)-epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3''Me), in the rat basophilic/mast cell line RBL-2H3. Hesperetin also significantly elevated the activation of acid sphingomyelinase (ASM), essential for eliciting anti-allergic effect of EGCG3''Me through the cell surficial protein, 67-kDa laminin receptor (67LR). Furthermore, oral administration of the highly absorbent hesperidin, α-glucosyl hesperidin, also enhanced the inhibitory potency of EGCG3''Me-rich 'Benifuuki' green tea (Camellia sinensis L.) on passive cutaneous anaphylaxis (PCA) reaction evoked by IgE/antigen in BALB/c mice. These observations indicate that hesperetin amplifies the ability of EGCG3''Me to inhibit the IgE/antigen-mediated degranulation through activating ASM signaling.
Collapse
Affiliation(s)
- Yoshinori Fujimura
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan
| | - Takanori Yoshimoto
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan
| | - Konatsu Fujino
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan
| | - Ayaka Nezu
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan
| | - Yuki Marugame
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan
| | - Jaehoon Bae
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan
| | - Motofumi Kumazoe
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan.
| |
Collapse
|
|
11
|
Bernitsa S, Dayan R, Stephanou A, Tzvetanova ID, Patrikios IS. Natural biomolecules and derivatives as anticancer immunomodulatory agents. Front Immunol 2023; 13:1070367. [PMID: 36700235 PMCID: PMC9868674 DOI: 10.3389/fimmu.2022.1070367] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 12/05/2022] [Indexed: 01/11/2023] Open
Abstract
Despite advancements in chemotherapy, the issue of resistance and non-responsiveness to many chemotherapeutic drugs that are currently in clinical use still remains. Recently, cancer immunotherapy has gathered attention as a novel treatment against select cancers. Immunomodulation is also emerging as an effective strategy to improve efficacy. Natural phytochemicals, with known anticancer properties, been reported to mediate their effects by modulating both traditional cancer pathways and immunity. The mechanism of phytochemical mediated-immunomodulatory activity may be attributed to the remodeling of the tumor immunosuppressive microenvironment and the sensitization of the immune system. This allows for improved recognition and targeting of cancer cells by the immune system and synergy with chemotherapeutics. In this review, we will discuss several well-known plant-derived biomolecules and examine their potential as immunomodulators, and therefore, as novel immunotherapies for cancer treatment.
Collapse
Affiliation(s)
| | - Rotem Dayan
- School of Medicine, European University Cyprus, Nicosia, Cyprus
| | | | | | | |
Collapse
|
|
12
|
Therapeutic Effects of Green Tea Polyphenol (‒)-Epigallocatechin-3-Gallate (EGCG) in Relation to Molecular Pathways Controlling Inflammation, Oxidative Stress, and Apoptosis. Int J Mol Sci 2022; 24:ijms24010340. [PMID: 36613784 PMCID: PMC9820274 DOI: 10.3390/ijms24010340] [Citation(s) in RCA: 89] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/20/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
(‒)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. Thanks to multiple interactions with cell surface receptors, intracellular signaling pathways, and nuclear transcription factors, EGCG possesses a wide variety of anti-inflammatory, antioxidant, antifibrotic, anti-remodelation, and tissue-protective properties which may be useful in the treatment of various diseases, particularly in cancer, and neurological, cardiovascular, respiratory, and metabolic disorders. This article reviews current information on the biological effects of EGCG in the above-mentioned disorders in relation to molecular pathways controlling inflammation, oxidative stress, and cell apoptosis.
Collapse
|
|
13
|
Hayashi D, Mouchlis VD, Okamoto S, Namba T, Wang L, Li S, Ueda S, Yamanoue M, Tachibana H, Arai H, Ashida H, Dennis EA, Shirai Y. Vitamin E functions by association with a novel binding site on the 67 kDa laminin receptor activating diacylglycerol kinase. J Nutr Biochem 2022; 110:109129. [PMID: 35977663 PMCID: PMC10243646 DOI: 10.1016/j.jnutbio.2022.109129] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 03/27/2022] [Accepted: 07/16/2022] [Indexed: 01/13/2023]
Abstract
It is generally recognized that the main function of α-tocopherol (αToc), which is the most active form of vitamin E, is its antioxidant effect, while non-antioxidant effects have also been reported. We previously found that αToc ameliorates diabetic nephropathy via diacylglycerol kinase alpha (DGKα) activation in vivo, and the activation was not related to the antioxidant effect. However, the underlying mechanism of how αToc activates DGKα have been enigmatic. We report that the membrane-bound 67 kDa laminin receptor (67LR), which has previously been shown to serve as a receptor for epigallocatechin gallate (EGCG), also contains a novel binding site for vitamin E, and its association with Vitamin E mediates DGKα activation by αToc. We employed hydrogen-deuterium exchange mass spectrometry (HDX/MS) and molecular dynamics (MD) simulations to identify the specific binding site of αToc on the 67LR and discovered the conformation of the specific hydrophobic pocket that accommodates αToc. Also, HDX/MS and MD simulations demonstrated the detailed binding of EGCG to a water-exposed hydrophilic site on 67LR, while in contrast αToc binds to a distinct hydrophobic site. We demonstrated that 67LR triggers an important signaling pathway mediating non-antioxidant effects of αToc, such as DGKα activation. This is the first evidence demonstrating a membrane receptor for αToc and one of the underlying mechanisms of a non-antioxidant function for αToc.
Collapse
Affiliation(s)
- Daiki Hayashi
- Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Faculty of Agriculture, Kobe University, Kobe, Japan; Department of Pharmacology, and Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA
| | - Varnavas D Mouchlis
- Department of Pharmacology, and Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA
| | - Seika Okamoto
- Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Faculty of Agriculture, Kobe University, Kobe, Japan
| | - Tomoka Namba
- Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Faculty of Agriculture, Kobe University, Kobe, Japan
| | - Liuqing Wang
- Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Faculty of Agriculture, Kobe University, Kobe, Japan
| | - Sheng Li
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Shuji Ueda
- Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Faculty of Agriculture, Kobe University, Kobe, Japan
| | - Minoru Yamanoue
- Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Faculty of Agriculture, Kobe University, Kobe, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Hiroyuki Arai
- Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo Japan
| | - Hitoshi Ashida
- Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Faculty of Agriculture, Kobe University, Kobe, Japan
| | - Edward A Dennis
- Department of Pharmacology, and Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA
| | - Yasuhito Shirai
- Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Faculty of Agriculture, Kobe University, Kobe, Japan.
| |
Collapse
|
|
14
|
Chattree V, Singh K, Singh K, Goel A, Maity A, Lone A. A comprehensive review on modulation of SIRT1 signaling pathways in the immune system of COVID-19 patients by phytotherapeutic melatonin and epigallocatechin-3-gallate. J Food Biochem 2022; 46:e14259. [PMID: 35662052 PMCID: PMC9347991 DOI: 10.1111/jfbc.14259] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 04/30/2022] [Accepted: 05/10/2022] [Indexed: 01/13/2023]
Abstract
SARS-CoV-2 infection has now become the world's most significant health hazard, with the World Health Organization declaring a pandemic on March 11, 2020. COVID-19 enters the lungs through angiotensin-converting enzyme 2 (ACE2) receptors, alters various signaling pathways, and causes immune cells to overproduce cytokines, resulting in mucosal inflammation, lung damage, and multiple organ failure in COVID-19 patients. Although several antiviral medications have been effective in managing the virus, they have not been effective in lowering the inflammation and symptoms of the illness. Several studies have found that epigallocatechin-3-gallate and melatonin upregulate sirtuins proteins, which leads to downregulation of pro-inflammatory gene transcription and NF-κB, protecting organisms from oxidative stress in autoimmune, respiratory, and cardiovascular illnesses. As a result, the purpose of this research is to understand more about the molecular pathways through which these phytochemicals affect COVID-19 patients' impaired immune systems, perhaps reducing hyperinflammation and symptom severity. PRACTICAL APPLICATIONS: Polyphenols are natural secondary metabolites that are found to be present in plants. EGCG a polyphenol belonging to the flavonoid family in tea has potent anti-inflammatory and antioxidative properties that helps to counter the inflammation and oxidative stress associated with many neurodegenerative diseases. Melatonin, another strong antioxidant in plants, has been shown to possess antiviral function and alleviate oxidative stress in many inflammatory diseases. In this review, we propose an alternative therapy for COVID-19 patients by supplementing their diet with these nutraceuticals that perhaps by modulating sirtuin signaling pathways counteract cytokine storm and oxidative stress, the root causes of severe inflammation and symptoms in these patients.
Collapse
Affiliation(s)
- Vineeta Chattree
- Department of Biochemistry, Deshbandhu CollegeDelhi UniversityNew DelhiIndia
| | - Kamana Singh
- Department of Biochemistry, Deshbandhu CollegeDelhi UniversityNew DelhiIndia
| | - Kanishk Singh
- Department of Biochemistry, Deshbandhu CollegeDelhi UniversityNew DelhiIndia
| | - Aayush Goel
- Department of Biochemistry, Deshbandhu CollegeDelhi UniversityNew DelhiIndia
| | - Amritaparna Maity
- Department of Biochemistry, Deshbandhu CollegeDelhi UniversityNew DelhiIndia
| | - Asif Lone
- Department of Biochemistry, Deshbandhu CollegeDelhi UniversityNew DelhiIndia
| |
Collapse
|
|
15
|
The Role of Diacylglycerol Kinase in the Amelioration of Diabetic Nephropathy. Molecules 2022; 27:molecules27206784. [PMID: 36296376 PMCID: PMC9607625 DOI: 10.3390/molecules27206784] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/05/2022] [Accepted: 10/07/2022] [Indexed: 12/02/2022] Open
Abstract
The drastic increase in the number of patients with diabetes and its complications is a global issue. Diabetic nephropathy, the leading cause of chronic kidney disease, significantly affects patients’ quality of life and medical expenses. Furthermore, there are limited drugs for treating diabetic nephropathy patients. Impaired lipid signaling, especially abnormal protein kinase C (PKC) activation by de novo-synthesized diacylglycerol (DG) under high blood glucose, is one of the causes of diabetic nephropathy. DG kinase (DGK) is an enzyme that phosphorylates DG and generates phosphatidic acid, i.e., DGK can inhibit PKC activation under diabetic conditions. Indeed, it has been proven that DGK activation ameliorates diabetic nephropathy. In this review, we summarize the involvement of PKC and DGK in diabetic nephropathy as therapeutic targets, and its mechanisms, by referring to our recent study.
Collapse
|
|
16
|
Fujimura Y, Kumazoe M, Tachibana H. 67-kDa Laminin Receptor-Mediated Cellular Sensing System of Green Tea Polyphenol EGCG and Functional Food Pairing. Molecules 2022; 27:molecules27165130. [PMID: 36014370 PMCID: PMC9416087 DOI: 10.3390/molecules27165130] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 08/07/2022] [Accepted: 08/10/2022] [Indexed: 11/16/2022] Open
Abstract
The body is equipped with a “food factor-sensing system” that senses food factors, such as polyphenols, sulfur-containing compounds, and vitamins, taken into the body, and plays an essential role in manifesting their physiological effects. For example, (–)-epigallocatechin-3-O-gallate (EGCG), the representative catechin in green tea (Camellia sinensi L.), exerts various effects, including anti-cancer, anti-inflammatory, and anti-allergic effects, when sensed by the cell surficial protein 67-kDa laminin receptor (67LR). Here, we focus on three representative effects of EGCG and provide their specific signaling mechanisms, the 67LR-mediated EGCG-sensing systems. Various components present in foods, such as eriodictyol, hesperetin, sulfide, vitamin A, and fatty acids, have been found to act on the food factor-sensing system and affect the functionality of other foods/food factors, such as green tea extract, EGCG, or its O-methylated derivative at different experimental levels, i.e., in vitro, animal models, and/or clinical trials. These phenomena are observed by increasing or decreasing the activity or expression of EGCG-sensing-related molecules. Such functional interaction between food factors is called “functional food pairing”. In this review, we introduce examples of functional food pairings using EGCG.
Collapse
|
|
17
|
Japanese soup stocks (katsuo-dashi and kombu-dashi) modulate food factor sensing-related gene expression in mice. Int J Gastron Food Sci 2022. [DOI: 10.1016/j.ijgfs.2022.100573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
|
|
18
|
Yang CS, Chen T, Ho CT. Redox and Other Biological Activities of Tea Catechins That May Affect Health: Mechanisms and Unresolved Issues. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:7887-7899. [PMID: 35727888 DOI: 10.1021/acs.jafc.2c02527] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The beneficial health effects of green tea have been attributed to tea catechins. However, the molecular mechanisms of action, especially those in vivo, remain unclear. This article reviews the redox and other activities of tea catechins, using (-)-epigallocatechin-3-gallate (EGCG), as an example. EGCG is a well-known antioxidant. However, EGCG can be oxidized to generate reactive oxygen species and EGCG quinone. We propose that EGCG quinone can react with Keap-1 to activate Nrf2-regulated cytoprotective enzymes. Tissue levels of catechins are important for their biological activities; a section is devoted to reviewing the biological fates of tea catechins after ingestion. Possible EGCG oxidation in vivo and whether the oligomeric forms are biologically active in animals are discussed. We also review the effects of EGCG on the activities of enzymes, receptors, and other signaling molecules through binding and raise a question about whether the autoxidation of EGCG in vitro may lead to artifacts or misinterpretation in some studies. Finally, we discuss the challenges in the extrapolation of in vitro results to situations in vivo and the translation of laboratory studies to humans.
Collapse
Affiliation(s)
- Chung S Yang
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States
| | - Tingting Chen
- School of Food Science & Technology, State Key Laboratory of Food Science & Technology, Nanchang University, Nanchang 330047, China
| | - Chi-Tang Ho
- Department of Food Science, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, United States
| |
Collapse
|
|
19
|
Sahadevan R, Singh S, Binoy A, Sadhukhan S. Chemico-biological aspects of (-)-epigallocatechin- 3-gallate (EGCG) to improve its stability, bioavailability and membrane permeability: Current status and future prospects. Crit Rev Food Sci Nutr 2022; 63:10382-10411. [PMID: 35491671 DOI: 10.1080/10408398.2022.2068500] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Natural products have been a bedrock for drug discovery for decades. (-)-Epigallocatechin-3-gallate (EGCG) is one of the widely studied natural polyphenolic compounds derived from green tea. It is the key component believed to be responsible for the medicinal value of green tea. Significant studies implemented in in vitro, in cellulo, and in vivo models have suggested its anti-oxidant, anti-cancer, anti-diabetic, anti-inflammatory, anti-microbial, neuroprotective activities etc. Despite having such a wide array of therapeutic potential and promising results in preclinical studies, its applicability to humans has encountered with rather limited success largely due to the poor bioavailability, poor membrane permeability, rapid metabolic clearance and lack of stability of EGCG. Therefore, novel techniques are warranted to address those limitations so that EGCG or its modified analogs can be used in the clinical setup. This review comprehensively covers different strategies such as structural modifications, nano-carriers as efficient drug delivery systems, synergistic studies with other bioactivities to improve the chemico-biological aspects (e.g., stability, bioavailability, permeability, etc.) of EGCG for its enhanced pharmacokinetics and pharmacological properties, eventually enhancing its therapeutic potentials. We think this review article will serve as a strong platform with comprehensive literature on the development of novel techniques to improve the bioavailability of EGCG so that it can be translated to the clinical applications.
Collapse
Affiliation(s)
- Revathy Sahadevan
- Department of Chemistry, Indian Institute of Technology Palakkad, Kerala, India
| | - Satyam Singh
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Madhya Pradesh, India
| | - Anupama Binoy
- Department of Chemistry, Indian Institute of Technology Palakkad, Kerala, India
| | - Sushabhan Sadhukhan
- Department of Chemistry, Indian Institute of Technology Palakkad, Kerala, India
- Department of Biological Sciences and Engineering, Indian Institute of Technology Palakkad, Kerala, India
| |
Collapse
|
|
20
|
Fan X, Fan Z, Yang Z, Huang T, Tong Y, Yang D, Mao X, Yang M. Flavonoids-Natural Gifts to Promote Health and Longevity. Int J Mol Sci 2022; 23:ijms23042176. [PMID: 35216290 PMCID: PMC8879655 DOI: 10.3390/ijms23042176] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/08/2022] [Accepted: 02/14/2022] [Indexed: 02/01/2023] Open
Abstract
The aging of mammals is accompanied by the progressive atrophy of tissues and organs and the accumulation of random damage to macromolecular DNA, protein, and lipids. Flavonoids have excellent antioxidant, anti-inflammatory, and neuroprotective effects. Recent studies have shown that flavonoids can delay aging and prolong a healthy lifespan by eliminating senescent cells, inhibiting senescence-related secretion phenotypes (SASPs), and maintaining metabolic homeostasis. However, only a few systematic studies have described flavonoids in clinical treatment for anti-aging, which needs to be explored further. This review first highlights the association between aging and macromolecular damage. Then, we discuss advances in the role of flavonoid molecules in prolonging the health span and lifespan of organisms. This study may provide crucial information for drug design and developmental and clinical applications based on flavonoids.
Collapse
Affiliation(s)
- Xiaolan Fan
- Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; (X.F.); (Z.F.); (Z.Y.); (T.H.); (Y.T.); (D.Y.); (X.M.)
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Ziqiang Fan
- Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; (X.F.); (Z.F.); (Z.Y.); (T.H.); (Y.T.); (D.Y.); (X.M.)
| | - Ziyue Yang
- Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; (X.F.); (Z.F.); (Z.Y.); (T.H.); (Y.T.); (D.Y.); (X.M.)
| | - Tiantian Huang
- Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; (X.F.); (Z.F.); (Z.Y.); (T.H.); (Y.T.); (D.Y.); (X.M.)
| | - Yingdong Tong
- Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; (X.F.); (Z.F.); (Z.Y.); (T.H.); (Y.T.); (D.Y.); (X.M.)
| | - Deying Yang
- Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; (X.F.); (Z.F.); (Z.Y.); (T.H.); (Y.T.); (D.Y.); (X.M.)
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Xueping Mao
- Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; (X.F.); (Z.F.); (Z.Y.); (T.H.); (Y.T.); (D.Y.); (X.M.)
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
| | - Mingyao Yang
- Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China; (X.F.); (Z.F.); (Z.Y.); (T.H.); (Y.T.); (D.Y.); (X.M.)
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
- Correspondence:
| |
Collapse
|
|
21
|
Aoi W, Iwasa M, Marunaka Y. Metabolic functions of flavonoids: From human epidemiology to molecular mechanism. Neuropeptides 2021; 88:102163. [PMID: 34098453 DOI: 10.1016/j.npep.2021.102163] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 05/11/2021] [Accepted: 05/19/2021] [Indexed: 12/12/2022]
Abstract
Dietary flavonoid intake is associated with the regulation of nutrient metabolism in the living body. Observational and cohort studies have reported a negative association between flavonoid intake and the risk of metabolic and cardiovascular diseases. Several intervention trials in humans have also supported the benefits of dietary flavonoids. In experimental studies using animal models, a daily diet rich in typical flavonoids such as catechins, anthocyanin, isoflavone, and quercetin was shown to improve whole-body energy expenditure, mitochondrial activity, and glucose tolerance. For some flavonoids, molecular targets for the metabolic modulations have been suggested. Although the effect of flavonoids on neurons has been unclear, several flavonoids have been shown to regulate thermogenesis and feeding behavior through modulating autonomic and central nervous systems. Based on epidemiological and experimental studies, this review summarizes the evidence on the metabolic benefits of flavonoids and their potential mechanism of action in metabolic regulation.
Collapse
Affiliation(s)
- Wataru Aoi
- Laboratory of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto 606-8522, Japan.
| | - Masayo Iwasa
- Laboratory of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto 606-8522, Japan
| | - Yoshinori Marunaka
- Medical Research Institute, Kyoto Industrial Health Association, Kyoto 604-8472, Japan; Research Center for Drug Discovery and Pharmaceutical Development Science, Research Organization of Science and Technology, Ritsumeikan University, Kusatsu 525-8577, Japan; Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; International Research Center for Food Nutrition and Safety, College of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| |
Collapse
|
|
22
|
Fujimura Y, Fujino K, Yoshimoto T, Nezu A, Marugame Y, Bae J, Kumazoe M, Tachibana H. Eriodictyol-Amplified 67-kDa Laminin Receptor Signaling Potentiates the Antiallergic Effect of O-Methylated Catechin. JOURNAL OF NATURAL PRODUCTS 2021; 84:1823-1830. [PMID: 34106718 DOI: 10.1021/acs.jnatprod.1c00337] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
(-)-Epigallocatechin-3-O-(3-O-methyl) gallate (1, EGCG3″Me), an antiallergic O-methylated catechin, is present in high quantities in the green tea cultivar "Benifuuki" (Camellia sinensis L.). Previous studies have shown that EGCG3″Me inhibited basophil degranulation mediated through the cell-surface 67-kDa laminin receptor (67LR), but the mechanisms are not fully elucidated. This study aimed to investigate the mechanisms underlying the inhibitory effect of EGCG3″Me on IgE/antigen (Ag)-mediated degranulation and the combined effect of EGCG3″Me with eriodictyol (2), a bioactive flavanone. EGCG3″Me inhibited β-hexosaminidase release from the rat basophilic/mast cell line RBL-2H3 stimulated by IgE/Ag and induced acid sphingomyelinase (ASM) activity. This induction was inhibited by anti-67LR antibody treatment. The ASM-specific inhibitor desipramine inhibited EGCG3″Me-induced suppression of degranulation. The soluble guanylate cyclase (sGC) inhibitor NS2028 weakened the potency of EGCG3″Me, and the sGC activator BAY41-2272 suppressed degranulation. The ability of EGCG3″Me to induce ASM activity and inhibit degranulation was amplified by eriodictyol. Furthermore, oral administration of the lemon-peel-derived eriodyctiol-7-O-glucoside (3) potentiated the suppressive effect of EGCG3″Me-rich "Benifuuki" green tea on the IgE/Ag-induced passive cutaneous anaphylaxis (PCA) reaction in BALB/c mice. These results suggest that EGCG3″Me inhibits IgE/Ag-mediated degranulation by inducing the 67LR/sGC/ASM signaling pathway, and eriodictyol amplifies this signaling.
Collapse
Affiliation(s)
- Yoshinori Fujimura
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Konatsu Fujino
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Takanori Yoshimoto
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Ayaka Nezu
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Yuki Marugame
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Jaehoon Bae
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Motofumi Kumazoe
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan
| |
Collapse
|
|
23
|
Yang Y, Han X, Chen Y, Wu J, Li M, Yang H, Xu W, Wei L. EGCG Induces Pro-inflammatory Response in Macrophages to Prevent Bacterial Infection through the 67LR/p38/JNK Signaling Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:5638-5651. [PMID: 33993695 DOI: 10.1021/acs.jafc.1c01353] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Extensive studies focused on the therapeutic efficacy of epigallocatechin-3-gallate (EGCG) against bacterial infection. However, little is known about its prophylactic efficacy against bacterial infection. Herein, we found that EGCG showed an effective prophylactic efficacy against bacterial infection with a broad spectrum, including Gram-negative, Gram-positive, and drug-resistant bacteria. Pretreatment with EGCG through intraperitoneal injection, intravenous injection, or intragastric administration significantly reduced the bacterial load, inflammatory response, and mortality in mouse abdominal infection models induced by bacterial inoculation or cecal ligation and puncture. Pretreatment with EGCG by intraperitoneal injection significantly increased the numbers of neutrophils and monocytes/macrophages in the abdominal cavity and peripheral blood of mice, and depletion of neutrophils and monocytes/macrophages by specific antibodies or chemical drugs obviously increased the bacterial load in mice. Of note, EGCG did not directly induce neutrophil and macrophage migration, and it just induced phagocyte migration in the presence of macrophages in a co-cultured system, implying that EGCG-induced phagocyte migration relies on its immunoregulatory effects on macrophages. EGCG markedly induced the production of cytokines and chemokines in macrophages and mouse peritoneal lavage, including tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β), IL-6, CXC chemokine ligands 1 and 2 (CXCL1 and 2), and monocyte chemotactic protein-1 (MCP-1). EGCG significantly induced the phosphorylation of p38 and JNK mitogen-activated protein kinases (MAPKs) in macrophages, and inhibition of p38 and JNK MAPKs markedly reduced EGCG-induced chemokine and cytokine production. Anti-67-kDa laminin receptor (67LR) antibody treatment significantly reduced EGCG-induced chemokine production and p38 and JNK phosphorylation in macrophages. Together, EGCG showed an obvious prophylactic efficacy against bacterial infection by inducing a pro-inflammatory response in macrophages through the 67LR/p38/JNK signaling pathway, supporting the further development of EGCG as a potent prophylaxis for bacterial infection and providing new clues to understand the healthcare function of green tea.
Collapse
Affiliation(s)
- Yang Yang
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu, China
| | - Xiaoyang Han
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu, China
| | - Yue Chen
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu, China
| | - Jing Wu
- School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Min Li
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu, China
| | - Hailong Yang
- School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Wei Xu
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu, China
| | - Lin Wei
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu, China
| |
Collapse
|
|
24
|
Della Via FI, Shiraishi RN, Santos I, Ferro KP, Salazar-Terreros MJ, Franchi Junior GC, Rego EM, Saad STO, Torello CO. (-)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1. Sci Rep 2021; 11:9103. [PMID: 33907248 PMCID: PMC8079435 DOI: 10.1038/s41598-021-88478-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/01/2021] [Indexed: 02/02/2023] Open
Abstract
(-)-Epigallocatechin-3-gallate (EGCG), the major active polyphenol extracted from green tea, has been shown to induce apoptosis and inhibit cell proliferation, cell invasion, angiogenesis and metastasis. Herein, we evaluated the in vivo effects of EGCG in acute myeloid leukaemia (AML) using an acute promyelocytic leukaemia (APL) experimental model (PML/RARα). Haematological analysis revealed that EGCG treatment reversed leucocytosis, anaemia and thrombocytopenia, and prolonged survival of PML/RARα mice. Notably, EGCG reduced leukaemia immature cells and promyelocytes in the bone marrow while increasing mature myeloid cells, possibly due to apoptosis increase and cell differentiation. The reduction of promyelocytes and neutrophils/monocytes increase detected in the peripheral blood, in addition to the increased percentage of bone marrow cells with aggregated promyelocytic leukaemia (PML) bodies staining and decreased expression of PML-RAR oncoprotein corroborates our results. In addition, EGCG increased expression of neutrophil differentiation markers such as CD11b, CD14, CD15 and CD66 in NB4 cells; and the combination of all-trans retinoic acid (ATRA) plus EGCG yield higher increase the expression of CD15 marker. These findings could be explained by a decrease of peptidyl-prolyl isomerase NIMA-interacting 1 (PIN1) expression and reactive oxygen species (ROS) increase. EGCG also decreased expression of substrate oncoproteins for PIN1 (including cyclin D1, NF-κB p65, c-MYC, and AKT) and 67 kDa laminin receptor (67LR) in the bone marrow cells. Moreover, EGCG showed inhibition of ROS production in NB4 cells in the presence of N-acetyl-L-cysteine (NAC), as well as a partial blockage of neutrophil differentiation and apoptosis, indicating that EGCG-activities involve/or are in response of oxidative stress. Furthermore, apoptosis of spleen cells was supported by increasing expression of BAD and BAX, parallel to BCL-2 and c-MYC decrease. The reduction of spleen weights of PML/RARα mice, as well as apoptosis induced by EGCG in NB4 cells in a dose-dependent manner confirms this assumption. Our results support further evaluation of EGCG in clinical trials for AML, since EGCG could represent a promising option for AML patient ineligible for current mainstay treatments.
Collapse
Affiliation(s)
- Fernanda Isabel Della Via
- grid.411087.b0000 0001 0723 2494Haematology and Transfusion Medicine Centre – Hemocentro, University of Campinas, Campinas, 13083-878 Brazil
| | - Rodrigo Naoto Shiraishi
- grid.411087.b0000 0001 0723 2494Haematology and Transfusion Medicine Centre – Hemocentro, University of Campinas, Campinas, 13083-878 Brazil
| | - Irene Santos
- grid.411087.b0000 0001 0723 2494Haematology and Transfusion Medicine Centre – Hemocentro, University of Campinas, Campinas, 13083-878 Brazil
| | - Karla Priscila Ferro
- grid.411087.b0000 0001 0723 2494Haematology and Transfusion Medicine Centre – Hemocentro, University of Campinas, Campinas, 13083-878 Brazil
| | - Myriam Janeth Salazar-Terreros
- grid.411087.b0000 0001 0723 2494Haematology and Transfusion Medicine Centre – Hemocentro, University of Campinas, Campinas, 13083-878 Brazil
| | - Gilberto Carlos Franchi Junior
- grid.411087.b0000 0001 0723 2494Onco-Haematological Child Centre, Faculty of Medical Sciences, University of Campinas, Campinas, 13083-970 Brazil
| | - Eduardo Magalhães Rego
- grid.11899.380000 0004 1937 0722Haematology and Clinical Oncology Division, Department of Internal Medicine, University of São Paulo, Ribeirão Preto, 14048-900 Brazil
| | - Sara Teresinha Olalla Saad
- grid.411087.b0000 0001 0723 2494Haematology and Transfusion Medicine Centre – Hemocentro, University of Campinas, Campinas, 13083-878 Brazil
| | - Cristiane Okuda Torello
- grid.411087.b0000 0001 0723 2494Haematology and Transfusion Medicine Centre – Hemocentro, University of Campinas, Campinas, 13083-878 Brazil
| |
Collapse
|
|
25
|
Tada R, Ogasawara M, Yamanaka D, Sakurai Y, Negishi Y, Kiyono H, Ohno N, Kunisawa J, Aramaki Y. Enzymatically polymerised polyphenols prepared from various precursors potentiate antigen-specific immune responses in both mucosal and systemic compartments in mice. PLoS One 2021; 16:e0246422. [PMID: 33556119 PMCID: PMC7870002 DOI: 10.1371/journal.pone.0246422] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 01/19/2021] [Indexed: 12/20/2022] Open
Abstract
Despite significant modern medicine progress, having an infectious disease is a major risk factor for humans. Mucosal vaccination is now widely considered as the most promising strategy to defeat infectious diseases; however, only live-attenuated and inactivated mucosal vaccines are used in the clinical field. To date, no subunit mucosal vaccine was approved mainly because of the lack of safe and effective methodologies to either activate or initiate host mucosal immune responses. We have recently elucidated that intranasal administration of enzymatically polymerised caffeic acid potentiates antigen-specific mucosal and systemic antibody responses in mice. However, our earlier study has not confirmed whether these effects are specific to the polymer synthesised from caffeic acid. Here, we show that enzymatically polymerised polyphenols (EPPs) from various phenolic compounds possess mucosal adjuvant activities when administered nasally with an antigen to mice. Potentiation of antigen-specific immune responses by all EPPs tested in this study showed no clear difference among the precursors used. We found that intranasal administration of ovalbumin as the antigen, in combination with all enzymatically polymerised polyphenols used in this study, induced ovalbumin-specific mucosal IgA in the nasal cavity, bronchoalveolar lavage fluid, vaginal fluids, and systemic IgG, especially IgG1, in sera. Our results demonstrate that the mucosal adjuvant activities of polyphenols are not limited to polymerised caffeic acid but are broadly observable across the studied polyphenols. These properties of polyphenols may be advantageous for the development of safe and effective nasal vaccine systems to prevent and/or treat various infectious diseases.
Collapse
Affiliation(s)
- Rui Tada
- Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
- * E-mail:
| | - Miki Ogasawara
- Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Daisuke Yamanaka
- Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Yasuhiro Sakurai
- Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Yoichi Negishi
- Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Hiroshi Kiyono
- Division of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Naohito Ohno
- Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Jun Kunisawa
- Division of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan
| | - Yukihiko Aramaki
- Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| |
Collapse
|
|
26
|
Hayakawa S, Ohishi T, Miyoshi N, Oishi Y, Nakamura Y, Isemura M. Anti-Cancer Effects of Green Tea Epigallocatchin-3-Gallate and Coffee Chlorogenic Acid. Molecules 2020; 25:molecules25194553. [PMID: 33027981 PMCID: PMC7582793 DOI: 10.3390/molecules25194553] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 09/24/2020] [Accepted: 09/28/2020] [Indexed: 02/07/2023] Open
Abstract
Tea and coffee are consumed worldwide and epidemiological and clinical studies have shown their health beneficial effects, including anti-cancer effects. Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA) are the major components of green tea polyphenols and coffee polyphenols, respectively, and believed to be responsible for most of these effects. Although a large number of cell-based and animal experiments have provided convincing evidence to support the anti-cancer effects of green tea, coffee, EGCG, and CGA, human studies are still controversial and some studies have suggested even an increased risk for certain types of cancers such as esophageal and gynecological cancers with green tea consumption and bladder and lung cancers with coffee consumption. The reason for these inconsistent results may have been arisen from various confounding factors. Cell-based and animal studies have proposed several mechanisms whereby EGCG and CGA exert their anti-cancer effects. These components appear to share the common mechanisms, among which one related to reactive oxygen species is perhaps the most attractive. Meanwhile, EGCG and CGA have also different target molecules which might explain the site-specific differences of anti-cancer effects found in human studies. Further studies will be necessary to clarify what is the mechanism to cause such differences between green tea and coffee.
Collapse
Affiliation(s)
- Sumio Hayakawa
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan;
- Correspondence: (S.H.); (M.I.); Tel.: +81-3-3822-2131 (S.H.); +81-54-264-5920 (M.I.)
| | - Tomokazu Ohishi
- Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Shizuoka 410-0301, Japan;
| | - Noriyuki Miyoshi
- School of Nutritional and Environmental Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan; (N.M.); (Y.N.)
| | - Yumiko Oishi
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan;
| | - Yoriyuki Nakamura
- School of Nutritional and Environmental Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan; (N.M.); (Y.N.)
| | - Mamoru Isemura
- School of Nutritional and Environmental Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan; (N.M.); (Y.N.)
- Correspondence: (S.H.); (M.I.); Tel.: +81-3-3822-2131 (S.H.); +81-54-264-5920 (M.I.)
| |
Collapse
|
|
27
|
Wang R, Zhu W, Peng J, Li K, Li C. Lipid rafts as potential mechanistic targets underlying the pleiotropic actions of polyphenols. Crit Rev Food Sci Nutr 2020; 62:311-324. [PMID: 32951435 DOI: 10.1080/10408398.2020.1815171] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Polyphenols have attracted a lot of global attention due to their diverse biological actions against cancer, obesity, and cardiovascular diseases. Although extensive research has been carried out to elucidate the mechanisms of pleiotropic actions of polyphenols, this remains unclear. Lipid rafts are distinct nanodomains enriched in cholesterol and sphingolipids, present in the inner and outer leaflets of cell membranes, forming functional platforms for the regulation of cellular processes and diseases. Recent studies focusing on the interaction between polyphenols and cellular lipid rafts shed new light on the pleiotropic actions of polyphenols. Polyphenols are postulated to interact with lipid rafts in two ways: first, they interfere with the structural integrity of lipid rafts, by disrupting their structure and clustering of the ordered domains; second, they modulate the downstream signaling pathways mediated by lipid rafts, by binding to receptor proteins associated with lipid rafts, such as the 67 kDa laminin receptor (67LR), epidermal growth factor receptor (EGFR), and others. This study aims to elaborate the mechanism of interaction between polyphenols and lipid rafts, and describe pleiotropic preventive effects of polyphenols.
Collapse
Affiliation(s)
- Ruifeng Wang
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Wei Zhu
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Jinming Peng
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Kaikai Li
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Chunmei Li
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.,Key Laboratory of Environment Correlative Food Science, Huazhong Agricultural University, Ministry of Education, Wuhan, China
| |
Collapse
|
|
28
|
Kumazoe M, Fujimura Y, Tachibana H. 67-kDa Laminin Receptor Mediates the Beneficial Effects of Green Tea Polyphenol EGCG. ACTA ACUST UNITED AC 2020. [DOI: 10.1007/s40495-020-00228-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
|
|
29
|
Uddin MS, Hossain MF, Mamun AA, Shah MA, Hasana S, Bulbul IJ, Sarwar MS, Mansouri RA, Ashraf GM, Rauf A, Abdel-Daim MM, Bin-Jumah MN. Exploring the multimodal role of phytochemicals in the modulation of cellular signaling pathways to combat age-related neurodegeneration. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 725:138313. [PMID: 32464743 DOI: 10.1016/j.scitotenv.2020.138313] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 03/27/2020] [Accepted: 03/28/2020] [Indexed: 06/11/2023]
Abstract
Neurodegeneration is the progressive loss of neuronal structures and functions that lead to copious disorders like Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), amyotrophic lateral sclerosis (ALS), and other less recurring diseases. Aging is the prime culprit for most neurodegenerative events. Moreover, the shared pathogenic factors of many neurodegenerative processes are inflammatory responses and oxidative stress (OS). Unfortunately, it is very complicated to treat neurodegeneration and there is no effective remedy. The rapid progression of the neurodegenerative diseases that exacerbate the burden and the concurrent absence of effective treatment strategies force the researchers to investigate more therapeutic approaches that ultimately target the causative factors of the neurodegeneration. Phytochemicals have great potential to exert their neuroprotective effects by targeting various mechanisms, such as OS, neuroinflammation, abnormal protein aggregation, neurotrophic factor deficiency, disruption in mitochondrial function, and apoptosis. Therefore, this review represents the molecular mechanisms of neuroprotection by multifunctional phytochemicals to combat age-linked neurodegenerative disorders.
Collapse
Affiliation(s)
- Md Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh; Pharmakon Neuroscience Research Network, Dhaka, Bangladesh.
| | - Md Farhad Hossain
- Pharmakon Neuroscience Research Network, Dhaka, Bangladesh; Department of Physical Therapy, Graduate School of Inje University, Gimhae, South Korea
| | - Abdullah Al Mamun
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh; Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
| | - Muhammad Ajmal Shah
- Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan
| | - Sharifa Hasana
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
| | | | - Md Shahid Sarwar
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Rasha A Mansouri
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ghulam Md Ashraf
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar, Khyber Pakhtunkhwa, Pakistan
| | - Mohamed M Abdel-Daim
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - May N Bin-Jumah
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11474, Saudi Arabia
| |
Collapse
|
|
30
|
Castejón-Vega B, Giampieri F, Alvarez-Suarez JM. Nutraceutical Compounds Targeting Inflammasomes in Human Diseases. Int J Mol Sci 2020; 21:E4829. [PMID: 32650482 PMCID: PMC7402342 DOI: 10.3390/ijms21144829] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 07/02/2020] [Accepted: 07/03/2020] [Indexed: 12/19/2022] Open
Abstract
The macromolecular complex known as "inflammasome" is defined as an intracellular multi-protein complex composed of a sensor receptor (PRR), an adaptor protein and an effector enzyme (caspase-1), which oligomerize when they sense danger, such as how the NLR family, AIM-2 and RIG-1 receptors protect the body against danger via cytokine secretion. Within the NLR members, NLRP3 is the most widely known and studied inflammasome and has been linked to many diseases. Nowadays, people's interest in their lifestyles and nutritional habits is increasing, mainly due to the large number of diseases that seem to be related to both. The term "nutraceutical" has recently emerged as a hybrid term between "nutrition" and "pharmacological" and it refers to a wide range of bioactive compounds contained in food with relevant effects on human health. The relationship between these compounds and diseases based on inflammatory processes has been widely exposed and the compounds stand out as an alternative to the pathological consequences that inflammatory processes may have, beyond their defense and repair action. Against this backdrop, here we review the results of studies using several nutraceutical compounds in common diseases associated with the inflammation and activation of the NLRP3 inflammasomes complex. In general, it was found that there is a wide range of nutraceuticals with effects through different molecular pathways that affect the activation of the inflammasome complex, with positive effects mainly in cardiovascular, neurological diseases, cancer and type 2 diabetes.
Collapse
Affiliation(s)
- Beatriz Castejón-Vega
- Research Laboratory, Oral Medicine Department, University of Sevilla, 41009 Sevilla, Spain;
| | - Francesca Giampieri
- Nutrition and Food Science Group, Department of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, 36310 Vigo, Spain;
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez, Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, 60131 Ancona, Italy
- College of Food Science and Technology, Northwest University, Xi’an 710069, China
| | - José M. Alvarez-Suarez
- Facultad de Ingeniería y Ciencias Aplicadas (FICA), AgroScience & Food Research Group, Universidad de Las Américas, 170125 Quito, Ecuador
- King Fahd Medical Research Center, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
| |
Collapse
|
|
31
|
EGCG down-regulates MuRF1 expression through 67-kDa laminin receptor and the receptor signaling is amplified by eriodictyol. J Nat Med 2020; 74:673-679. [DOI: 10.1007/s11418-020-01417-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 05/17/2020] [Indexed: 12/18/2022]
|
|
32
|
Zhang J, Li X, Huang L. Anticancer activities of phytoconstituents and their liposomal targeting strategies against tumor cells and the microenvironment. Adv Drug Deliv Rev 2020; 154-155:245-273. [PMID: 32473991 PMCID: PMC7704676 DOI: 10.1016/j.addr.2020.05.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 05/07/2020] [Accepted: 05/20/2020] [Indexed: 12/13/2022]
Abstract
Various bioactive ingredients have been extracted from Chinese herbal medicines (CHMs) that affect tumor progression and metastasis. To further understand the mechanisms of CHMs in cancer therapy, this article summarizes the effects of five categories of CHMs and their active ingredients on tumor cells and the tumor microenvironment. Despite their treatment potential, the undesirable physicochemical properties (poor permeability, instability, high hydrophilicity or hydrophobicity, toxicity) and unwanted pharmacokinetic profiles (short half-life in blood and low bioavailability) restrict clinical studies of CHMs. Therefore, development of liposomes through relevant surface modifying techniques to achieve targeted CHM delivery for cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature, have been reviewed. Current challenges of liposomal targeting of these phytoconstituents and future perspective of CHM applications are discussed to provide an informative reference for interested readers.
Collapse
Affiliation(s)
- Jing Zhang
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, China
| | - Xiang Li
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, China
| | - Leaf Huang
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
| |
Collapse
|
|
33
|
McCarty MF, Lerner A. Nutraceuticals Targeting Generation and Oxidant Activity of Peroxynitrite May Aid Prevention and Control of Parkinson's Disease. Int J Mol Sci 2020; 21:3624. [PMID: 32455532 PMCID: PMC7279222 DOI: 10.3390/ijms21103624] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 04/29/2020] [Accepted: 05/18/2020] [Indexed: 12/14/2022] Open
Abstract
Parkinson's disease (PD) is a chronic low-grade inflammatory process in which activated microglia generate cytotoxic factors-most prominently peroxynitrite-which induce the death and dysfunction of neighboring dopaminergic neurons. Dying neurons then release damage-associated molecular pattern proteins such as high mobility group box 1 which act on microglia via a range of receptors to amplify microglial activation. Since peroxynitrite is a key mediator in this process, it is proposed that nutraceutical measures which either suppress microglial production of peroxynitrite, or which promote the scavenging of peroxynitrite-derived oxidants, should have value for the prevention and control of PD. Peroxynitrite production can be quelled by suppressing activation of microglial NADPH oxidase-the source of its precursor superoxide-or by down-regulating the signaling pathways that promote microglial expression of inducible nitric oxide synthase (iNOS). Phycocyanobilin of spirulina, ferulic acid, long-chain omega-3 fatty acids, good vitamin D status, promotion of hydrogen sulfide production with taurine and N-acetylcysteine, caffeine, epigallocatechin-gallate, butyrogenic dietary fiber, and probiotics may have potential for blunting microglial iNOS induction. Scavenging of peroxynitrite-derived radicals may be amplified with supplemental zinc or inosine. Astaxanthin has potential for protecting the mitochondrial respiratory chain from peroxynitrite and environmental mitochondrial toxins. Healthful programs of nutraceutical supplementation may prove to be useful and feasible in the primary prevention or slow progression of pre-existing PD. Since damage to the mitochondria in dopaminergic neurons by environmental toxins is suspected to play a role in triggering the self-sustaining inflammation that drives PD pathogenesis, there is also reason to suspect that plant-based diets of modest protein content, and possibly a corn-rich diet high in spermidine, might provide protection from PD by boosting protective mitophagy and thereby aiding efficient mitochondrial function. Low-protein diets can also promote a more even response to levodopa therapy.
Collapse
Affiliation(s)
| | - Aaron Lerner
- B. Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa 3525422, Israel
| |
Collapse
|
|
34
|
(-)-Epigallocatechin-3-gallate (EGCG) attenuates salt-induced hypertension and renal injury in Dahl salt-sensitive rats. Sci Rep 2020; 10:4783. [PMID: 32179848 PMCID: PMC7075996 DOI: 10.1038/s41598-020-61794-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 03/03/2020] [Indexed: 12/23/2022] Open
Abstract
Epigallocatechin-3-gallate (EGCG), a main active catechin in green tea, was reported to attenuate renal injury and hypertension. However, its effects on salt-induced hypertension and renal injury remain unclear. In the present study, we explored its effects on hypertension and renal damage in Dahl rats with salt-sensitive hypertension. We found that EGCG could lower blood pressure after 6 weeks of oral administration, reduce 24 h urine protein levels and decrease creatinine clearance, and attenuate renal fibrosis, indicating that it could attenuate hypertension by protecting against renal damage. Furthermore, we studied the renal protective mechanisms of EGCG, revealing that it could lower malondialdehyde levels, reduce the numbers of infiltrated macrophages and T cells, and induce the apoptosis of NRK-49F cells. Considering that the 67 kD laminin receptor (67LR) binds to EGCG, its role in EGCG-induced fibroblast apoptosis was also investigated. The results showed that an anti-67LR antibody partially abrogated the apoptosis-inducing effects of EGCG on NRK-49F cells. In summary, EGCG may attenuate renal damage and salt-sensitive hypertension via exerting anti-oxidant, anti-inflammatory, and apoptosis-inducing effects on fibroblasts; the last effect is partially mediated by 67LR, suggesting that EGCG represents a potential strategy for treating salt-sensitive hypertension.
Collapse
|
|
35
|
Bae J, Kumazoe M, Murata K, Fujimura Y, Tachibana H. Procyanidin C1 Inhibits Melanoma Cell Growth by Activating 67-kDa Laminin Receptor Signaling. Mol Nutr Food Res 2020; 64:e1900986. [PMID: 32103628 DOI: 10.1002/mnfr.201900986] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 02/06/2020] [Indexed: 12/11/2022]
Abstract
SCOPE Procyanidin C1 (PC1) is an epicatechin trimer found mainly in grapes that is reported to provide several health benefits. However, little is known about the molecular mechanisms underlying these benefits. The aim of this study is to demonstrate the molecular mechanisms by which PC1 operates. METHODS AND RESULTS A 67-kDa laminin receptor (67LR) is identified as a cell surface receptor of PC1, with a Kd value of 2.8 µm. PC1 induces an inhibitory effect on growth, accompanied by dephosphorylation of the C-kinase potentiated protein phosphatase-1 inhibitor protein of 17 kDa (CPI17) and myosin regulatory light chain (MRLC) proteins, followed by actin cytoskeleton remodeling in melanoma cells. These actions are mediated by protein kinase A (PKA) and protein phosphatase 2A (PP2A) activation once PC1 is bound to 67LR. CONCLUSION It is demonstrated that PC1 elicits melanoma cell growth inhibition by activating the 67LR/PKA/PP2A/CPI17/MRLC pathway.
Collapse
Affiliation(s)
- Jaehoon Bae
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Motofumi Kumazoe
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Kyosuke Murata
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Yoshinori Fujimura
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| |
Collapse
|
|
36
|
Estrogenic biological activity and underlying molecular mechanisms of green tea constituents. Trends Food Sci Technol 2020. [DOI: 10.1016/j.tifs.2019.11.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
37
|
Bae J, Kumazoe M, Takeuchi C, Hidaka S, Fujimura Y, Tachibana H. Epigallocatechin-3-O-gallate induces acid sphingomyelinase activation through activation of phospholipase C. Biochem Biophys Res Commun 2019; 520:186-191. [PMID: 31585731 DOI: 10.1016/j.bbrc.2019.09.102] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 09/24/2019] [Indexed: 02/06/2023]
Abstract
Epigallocatechin-3-O-gallate (EGCG)-induced cyclic guanosine monophosphate (cGMP) plays a crucial role in EGCG-induced cell death in various types of cancer cells. However, little is known regarding the early molecular events after cGMP induction. In this study, we showed that cGMP induction is sufficient to induce the phosphorylation of protein kinase C delta (PKCδ) at Ser664, the crucial kinase for EGCG-induced activation of acid sphingomyelinase (ASM). Using a chemical inhibitor library, we revealed that the inhibitors of the negative regulators of diacylglycerol strongly increase the effect of EGCG. We also showed that EGCG treatment increased phospholipase C (PLC) activity, and the same results were obtained with cGMP inducer treatment. EGCG-induced ASM activation was completely suppressed by pharmacological inhibition of PLC. Collectively, EGCG-induced cGMP activated the cGMP/PLC/PKCδ/ASM signaling axis in multiple myeloma cells.
Collapse
Affiliation(s)
- Jaehoon Bae
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Motofumi Kumazoe
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Chieri Takeuchi
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Shiori Hidaka
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Yoshinori Fujimura
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan.
| |
Collapse
|
|
38
|
Naoi M, Shamoto-Nagai M, Maruyama W. Neuroprotection of multifunctional phytochemicals as novel therapeutic strategy for neurodegenerative disorders: antiapoptotic and antiamyloidogenic activities by modulation of cellular signal pathways. FUTURE NEUROLOGY 2019. [DOI: 10.2217/fnl-2018-0028] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
In neurodegenerative disorders, including Alzheimer's and Parkinson's disease, neuroprotection by diet and natural bioactive compounds has been proposed to prevent the onset and progress of neurodegeneration by modification of pathogenic factors. Plant food-derived phytochemicals protect neurons via targeting oxidative stress, mitochondrial dysfunction, neurotrophic factor deficit, apoptosis and abnormal protein accumulation. This review presents the molecular mechanism of neuroprotection by phytochemicals: direct regulation of mitochondrial apoptotic machinery, modification of cellular signal pathways, induction of antiapoptotic Bcl-2 protein family and prosurvival neurotrophic factors, such as brain- and glial cell line-derived neurotrophic factor, and prevention of protein aggregation. Multitargeted neuroprotective agents are under development based on the structure of blood–brain barrier-permeable phytochemicals to ameliorate brain dysfunction and prevent neurodegeneration.
Collapse
Affiliation(s)
- Makoto Naoi
- Department of Health & Nutrition, Faculty of Psychological & Physical Science, Aichi Gakuin University, Nisshin, Aichi, Japan
| | - Masayo Shamoto-Nagai
- Department of Health & Nutrition, Faculty of Psychological & Physical Science, Aichi Gakuin University, Nisshin, Aichi, Japan
| | - Wakako Maruyama
- Department of Health & Nutrition, Faculty of Psychological & Physical Science, Aichi Gakuin University, Nisshin, Aichi, Japan
| |
Collapse
|
|
39
|
Molecular Targets of Epigallocatechin-Gallate (EGCG): A Special Focus on Signal Transduction and Cancer. Nutrients 2018; 10:nu10121936. [PMID: 30563268 PMCID: PMC6315581 DOI: 10.3390/nu10121936] [Citation(s) in RCA: 178] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 11/30/2018] [Accepted: 12/04/2018] [Indexed: 12/15/2022] Open
Abstract
Green tea is a beverage that is widely consumed worldwide and is believed to exert effects on different diseases, including cancer. The major components of green tea are catechins, a family of polyphenols. Among them, epigallocatechin-gallate (EGCG) is the most abundant and biologically active. EGCG is widely studied for its anti-cancer properties. However, the cellular and molecular mechanisms explaining its action have not been completely understood, yet. EGCG is effective in vivo at micromolar concentrations, suggesting that its action is mediated by interaction with specific targets that are involved in the regulation of crucial steps of cell proliferation, survival, and metastatic spread. Recently, several proteins have been identified as EGCG direct interactors. Among them, the trans-membrane receptor 67LR has been identified as a high affinity EGCG receptor. 67LR is a master regulator of many pathways affecting cell proliferation or apoptosis, also regulating cancer stem cells (CSCs) activity. EGCG was also found to be interacting directly with Pin1, TGFR-II, and metalloproteinases (MMPs) (mainly MMP2 and MMP9), which respectively regulate EGCG-dependent inhibition of NF-kB, epithelial-mesenchimal transaction (EMT) and cellular invasion. EGCG interacts with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which modulates epigenetic changes. The bulk of this novel knowledge provides information about the mechanisms of action of EGCG and may explain its onco-suppressive function. The identification of crucial signalling pathways that are related to cancer onset and progression whose master regulators interacts with EGCG may disclose intriguing pharmacological targets, and eventually lead to novel combined treatments in which EGCG acts synergistically with known drugs.
Collapse
|
|
40
|
Wang YQ, Lu JL, Liang YR, Li QS. Suppressive Effects of EGCG on Cervical Cancer. Molecules 2018; 23:E2334. [PMID: 30213130 PMCID: PMC6225117 DOI: 10.3390/molecules23092334] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 09/05/2018] [Accepted: 09/11/2018] [Indexed: 02/07/2023] Open
Abstract
Cervical cancer is the fourth most common gynecological cancer worldwide. Although prophylactic vaccination presents the most effective method for cervical cancer prevention, chemotherapy is still the primary invasive intervention. It is urgent to exploit low-toxic natural anticancer drugs on account of high cytotoxicity and side-effects of conventional agents. As a natural product, (-)-epigallocatechingallate (EGCG) has abilities in anti-proliferation, anti-metastasis and pro-apoptosis of cervical cancer cells. Moreover, EGCG also has pharmaceutical synergistic effects with conventional agents such as cisplatin (CDDP) and bleomycin (BLM). The underlying mechanisms of EGCG suppressive effects on cervical cancer are reviewed in this article. Further research directions and ambiguous results are also discussed.
Collapse
Affiliation(s)
- Ying-Qi Wang
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Jian-Liang Lu
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Yue-Rong Liang
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Qing-Sheng Li
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| |
Collapse
|
|
41
|
Yamashita S, Hirashima A, Lin IC, Bae J, Nakahara K, Murata M, Yamada S, Kumazoe M, Yoshitomi R, Kadomatsu M, Sato Y, Nezu A, Hikida A, Fujino K, Murata K, Maeda-Yamamoto M, Tachibana H. Saturated fatty acid attenuates anti-obesity effect of green tea. Sci Rep 2018; 8:10023. [PMID: 29968774 PMCID: PMC6030063 DOI: 10.1038/s41598-018-28338-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 06/18/2018] [Indexed: 12/11/2022] Open
Abstract
Green tea and its major polyphenol epigallocatechin-3-O-gallate (EGCG) have suppressive effect on dietary obesity. However, it remains unsolved what type of diet on which they exhibit high or low anti-obesity effect. In the present study, we investigated whether anti-obesity effect of green tea differs depending on composition of fats or fatty acids that consist high-fat (HF) diet in mouse model. Green tea extract (GTE) intake dramatically suppressed weight gain and fat accumulation induced by olive oil-based HF diet, whereas the effects on those induced by beef tallow-based HF diet were weak. GTE also effectively suppressed obesity induced by unsaturated fatty acid-enriched HF diet with the stronger effect compared with that induced by saturated fatty acid-enriched HF diet. These differences would be associated with the increasing action of GTE on expression of PPARδ signaling pathway-related genes in the white adipose tissue. Expressions of genes relating to EGCG signaling pathway that is critical for exhibition of physiological effects of EGCG were also associated with the different effects of GTE. Here, we show that anti-obesity effect of GTE differs depending on types of fats or fatty acids that consist HF diet and could be attenuated by saturated fatty acid.
Collapse
Affiliation(s)
- Shuya Yamashita
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan.,Institute of Fruit Tree and Tea Science, National Agriculture and Food Research Organization (NARO), Makurazaki, 898-0087, Japan
| | - Asami Hirashima
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - I-Chian Lin
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Jaehoon Bae
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Kanami Nakahara
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Motoki Murata
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Shuhei Yamada
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Motofumi Kumazoe
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Ren Yoshitomi
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Mai Kadomatsu
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Yuka Sato
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Ayaka Nezu
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Ai Hikida
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Konatsu Fujino
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Kyosuke Murata
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan
| | - Mari Maeda-Yamamoto
- Agri-Food Business Innovation Center, National Agriculture and Food Research Organization (NARO), Tsukuba, 305-8517, Japan
| | - Hirofumi Tachibana
- Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan.
| |
Collapse
|
|
42
|
Cagnetta R, Frese CK, Shigeoka T, Krijgsveld J, Holt CE. Rapid Cue-Specific Remodeling of the Nascent Axonal Proteome. Neuron 2018; 99:29-46.e4. [PMID: 30008298 PMCID: PMC6048689 DOI: 10.1016/j.neuron.2018.06.004] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Revised: 12/24/2017] [Accepted: 05/31/2018] [Indexed: 01/13/2023]
Abstract
Axonal protein synthesis and degradation are rapidly regulated by extrinsic signals during neural wiring, but the full landscape of proteomic changes remains unknown due to limitations in axon sampling and sensitivity. By combining pulsed stable isotope labeling of amino acids in cell culture with single-pot solid-phase-enhanced sample preparation, we characterized the nascent proteome of isolated retinal axons on an unparalleled rapid timescale (5 min). Our analysis detects 350 basally translated axonal proteins on average, including several linked to neurological disease. Axons stimulated by different cues (Netrin-1, BDNF, Sema3A) show distinct signatures with more than 100 different nascent protein species up- or downregulated within the first 5 min followed by further dynamic remodeling. Switching repulsion to attraction triggers opposite regulation of a subset of common nascent proteins. Our findings thus reveal the rapid remodeling of the axonal proteomic landscape by extrinsic cues and uncover a logic underlying attraction versus repulsion.
Collapse
Affiliation(s)
- Roberta Cagnetta
- Department of Physiology Development and Neuroscience, Downing Street, University of Cambridge, Cambridge CB2 3DY, UK
| | - Christian K Frese
- European Molecular Biology Laboratory (EMBL), Meyerhofstr. 1, Heidelberg 69117, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany; CECAD Research Center, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany
| | - Toshiaki Shigeoka
- Department of Physiology Development and Neuroscience, Downing Street, University of Cambridge, Cambridge CB2 3DY, UK
| | - Jeroen Krijgsveld
- European Molecular Biology Laboratory (EMBL), Meyerhofstr. 1, Heidelberg 69117, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany; Excellence Cluster CellNetworks, University of Heidelberg, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
| | - Christine E Holt
- Department of Physiology Development and Neuroscience, Downing Street, University of Cambridge, Cambridge CB2 3DY, UK.
| |
Collapse
|
|
43
|
Avtanski D, Poretsky L. Phyto-polyphenols as potential inhibitors of breast cancer metastasis. Mol Med 2018; 24:29. [PMID: 30134816 PMCID: PMC6016885 DOI: 10.1186/s10020-018-0032-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 05/27/2018] [Indexed: 12/31/2022] Open
Abstract
Breast cancer is the most common cancer among women as metastasis is currently the main cause of mortality. Breast cancer cells undergoing metastasis acquire resistance to death signals and increase of cellular motility and invasiveness.Plants are rich in polyphenolic compounds, many of them with known medicinal effects. Various phyto-polyphenols have also been demonstrated to suppress cancer growth. Their mechanism of action is usually pleiotropic as they target multiple signaling pathways regulating key cellular processes such as proliferation, apoptosis and differentiation. Importantly, some phyto- polyphenols show low level of toxicity to untransformed cells, but selective suppressing effects on cancer cells proliferation and differentiation.In this review, we summarize the current information about the mechanism of action of some phyto-polyphenols that have demonstrated anti-carcinogenic activities in vitro and in vivo. Gained knowledge of how these natural polyphenolic compounds work can give us a clue for the development of novel anti-metastatic agents.
Collapse
Affiliation(s)
- Dimiter Avtanski
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, 10022, USA.
- Division of Endocrinology and Metabolism, Department of Medicine, Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, 110 E 59th Street, Suite 8B, Room 837, New York, NY, 10022, USA.
| | - Leonid Poretsky
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, 10022, USA
| |
Collapse
|
|
44
|
Kumar BNP, Puvvada N, Rajput S, Sarkar S, Mahto MK, Yallapu MM, Pathak A, Emdad L, Das SK, Reis RL, Kundu SC, Fisher PB, Mandal M. Targeting of EGFR, VEGFR2, and Akt by Engineered Dual Drug Encapsulated Mesoporous Silica-Gold Nanoclusters Sensitizes Tamoxifen-Resistant Breast Cancer. Mol Pharm 2018; 15:2698-2713. [PMID: 29787277 DOI: 10.1021/acs.molpharmaceut.8b00218] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Tamoxifen administration enhanced overall disease-free survival and diminished mortality rates in cancer patients. However, patients with breast cancer often fail to respond for tamoxifen therapy due to the development of a drug-resistant phenotype. Functional analysis and molecular studies suggest that protein mutation and dysregulation of survival signaling molecules such as epidermal growth factor receptor, vascular endothelial growth factor receptor 2, and Akt contribute to tamoxifen resistance. Various strategies, including combinatorial therapies, show chemosensitize tamoxifen-resistant cancers. Based on chemotoxicity issues, researchers are actively investigating alternative therapeutic strategies. In the current study, we fabricate a mesoporous silica gold cluster nanodrug delivery system that displays exceptional tumor-targeting capability, thus promoting accretion of drug indices at the tumor site. We employ dual drugs, ZD6474, and epigallocatechin gallate (EGCG) that inhibit EGFR2, VEGFR2, and Akt signaling pathways since changes in these signaling pathways confer tamoxifen resistance in MCF 7 and T-47D cells. Mesoporous silica gold cluster nanodrug delivery of ZD6474 and EGCG sensitize tamoxifen-resistant cells to apoptosis. Western and immune-histochemical analyses confirmed the apoptotic inducing properties of the nanoformulation. Overall, results with these silica gold nanoclusters suggest that they may be a potent nanoformulation against chemoresistant cancers.
Collapse
Affiliation(s)
- B N Prashanth Kumar
- Department of Pharmaceutical Sciences and Center for Cancer Research , University of Tennessee Health Science Center , Memphis , Tennessee 38163 , United States
| | - Nagaprasad Puvvada
- Chemical Biology , CSIR-Indian Institute of Chemical Technology , Uppal Road , Hyderabad 500007 , India
| | - Shashi Rajput
- Tumor Initiation and Maintenance , Sanford-Burnham Medical Research Institute , La Jolla , California 92037 , United States
| | - Siddik Sarkar
- Department of Human and Molecular Genetics , VCU Institute of Molecular Genetics, VCU Massey Cancer, Virginia Commonwealth University, School of Medicine , Richmond , Virginia 23298 , United States
| | | | - Murali M Yallapu
- Department of Pharmaceutical Sciences and Center for Cancer Research , University of Tennessee Health Science Center , Memphis , Tennessee 38163 , United States
| | | | - Luni Emdad
- Department of Human and Molecular Genetics , VCU Institute of Molecular Genetics, VCU Massey Cancer, Virginia Commonwealth University, School of Medicine , Richmond , Virginia 23298 , United States
| | - Swadesh K Das
- Department of Human and Molecular Genetics , VCU Institute of Molecular Genetics, VCU Massey Cancer, Virginia Commonwealth University, School of Medicine , Richmond , Virginia 23298 , United States
| | - Rui L Reis
- 3Bs Research Group , Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho , Avepark - 4805-017 , Barco, Guimaraes, Portugal
| | - S C Kundu
- 3Bs Research Group , Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho , Avepark - 4805-017 , Barco, Guimaraes, Portugal
| | - Paul B Fisher
- Department of Human and Molecular Genetics , VCU Institute of Molecular Genetics, VCU Massey Cancer, Virginia Commonwealth University, School of Medicine , Richmond , Virginia 23298 , United States
| | | |
Collapse
|
|
45
|
Kato Y, Suga N. Covalent adduction of endogenous and food-derived quinones to a protein: its biological significance. J Clin Biochem Nutr 2018; 62:213-220. [PMID: 29892159 PMCID: PMC5990407 DOI: 10.3164/jcbn.18-26] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Accepted: 03/05/2018] [Indexed: 01/09/2023] Open
Abstract
There are many chemically reactive compounds, including quinone, in living systems and also food. Even after the ingestion of food polyphenols, quinones derived from catechol moieties could form endogenously in the body. Dopaquinone, dopamine quinone, estrogen-derived quinones, tryptamine-4,5-dione, and ubiquinone are examples of an endogenous quinone. These indicate that quinone is ubiquitously formed or present in living systems and food. Quinones can induce a variety of hazardous effects and also could have beneficial physiological effects. This review focuses on the chemical reactivity of quinone toward a biomolecule and its biological action.
Collapse
Affiliation(s)
- Yoji Kato
- Laboratory of Free Radical and Food Function, School of Human Science and Environment, University of Hyogo, 1-1-12 Shinzaike-honcho, Himeji, Hyogo 670-0092, Japan.,Research Institute of Food and Nutrition, University of Hyogo, 1-1-12 Shinzaike-honcho, Himeji, Hyogo 670-0092, Japan
| | - Naoko Suga
- Laboratory of Free Radical and Food Function, School of Human Science and Environment, University of Hyogo, 1-1-12 Shinzaike-honcho, Himeji, Hyogo 670-0092, Japan
| |
Collapse
|
|
46
|
Sugiyama I, Kaihatsu K, Soma Y, Kato N, Sadzuka Y. Dual-effect liposomes with increased antitumor effects against 67-kDa laminin receptor-overexpressing tumor cells. Int J Pharm 2018; 541:206-213. [DOI: 10.1016/j.ijpharm.2018.02.041] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 02/13/2018] [Accepted: 02/23/2018] [Indexed: 12/01/2022]
|
|
47
|
Umbaugh CS, Diaz-Quiñones A, Neto MF, Shearer JJ, Figueiredo ML. A dock derived compound against laminin receptor (37 LR) exhibits anti-cancer properties in a prostate cancer cell line model. Oncotarget 2017; 9:5958-5978. [PMID: 29464047 PMCID: PMC5814187 DOI: 10.18632/oncotarget.23236] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 07/16/2017] [Indexed: 11/25/2022] Open
Abstract
Laminin receptor (67 LR) is a 67 kDa protein derived from a 37 kDa precursor (37 LR). 37/67 LR is a strong clinical correlate for progression, aggression, and chemotherapeutic relapse of several cancers including breast, prostate, and colon. The ability of 37/67 LR to promote cancer cell aggressiveness is further increased by its ability to transduce physiochemical and mechanosensing signals in endothelial cells and modulate angiogenesis. Recently, it was demonstrated that 37/67 LR modulates the anti-angiogenic potential of the secreted glycoprotein pigment epithelium-derived factor (PEDF). Restoration of PEDF balance is a desirable therapeutic outcome, and we sought to identify a small molecule that could recapitulate known signaling properties of PEDF but without the additional complications of peptide formulation or gene delivery safety validation. We used an in silico drug discovery approach to target the interaction interface between PEDF and 37 LR. Following cell based counter screening and binding validation, we characterized a hit compound's anti-viability, activation of PEDF signaling-related genes, anti-wound healing, and anti-cancer signaling properties. This hit compound has potential for future development as a lead compound for treating tumor growth and inhibiting angiogenesis.
Collapse
Affiliation(s)
- Charles Samuel Umbaugh
- Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, USA
| | - Adriana Diaz-Quiñones
- Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, USA
| | - Manoel Figueiredo Neto
- Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, USA
| | - Joseph J Shearer
- Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, USA
| | - Marxa L Figueiredo
- Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, USA
| |
Collapse
|
|
48
|
Boratkó A, Csortos C. TIMAP, the versatile protein phosphatase 1 regulator in endothelial cells. IUBMB Life 2017; 69:918-928. [DOI: 10.1002/iub.1695] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 10/26/2017] [Indexed: 01/28/2023]
Affiliation(s)
- Anita Boratkó
- Department of Medical Chemistry; Faculty of Medicine, University of Debrecen, Egyetem tér 1; Debrecen Hungary
| | - Csilla Csortos
- Department of Medical Chemistry; Faculty of Medicine, University of Debrecen, Egyetem tér 1; Debrecen Hungary
| |
Collapse
|
|
49
|
Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential. BIOMED RESEARCH INTERNATIONAL 2017; 2017:1047523. [PMID: 29201895 PMCID: PMC5672119 DOI: 10.1155/2017/1047523] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 09/12/2017] [Indexed: 12/28/2022]
Abstract
The present paper investigated the efficiency of Urtica dioica (U. dioica) on hemostatic and wound healing activities. U. dioica leaf extracts were evaluated for their antibacterial and antioxidant effects as well as their flavonoid and polyphenol content. The hydroethanolic extract (EtOH-H2OE), showing the most potent antibacterial and antioxidant activities in vitro, thanks to its flavonoid and polyphenol richness, was selected for hemostatic and wound healing evaluation. Twenty-four rats completing full-thickness wounds were split into four groups. The wounds were topically treated with saline solution, glycerol, “CICAFLORA,” and U. dioica EtOH-H2OE (50 µL/mm2) until day 11. The wound healing effect was assessed by macroscopic, histological, and biochemical parameters. Rats treated with EtOH-H2OE showed fast wound closure (92.39%) compared to the control animals (60.91%) on the 11th day of wounding (P < 0.01). Histopathological and biochemical explorations showed full epidermal regeneration and an improvement of the hydroxyproline content in the U. dioica EtOH-H2OE treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of unsaturated fatty acids and a high concentration of lupeol known for their involvement in reepithelialization. These results prove the efficiency of U. dioica EtOH-H2OE in wound healing and supported its traditional use.
Collapse
|
|
50
|
Mao X, Gu C, Chen D, Yu B, He J. Oxidative stress-induced diseases and tea polyphenols. Oncotarget 2017; 8:81649-81661. [PMID: 29113421 PMCID: PMC5655316 DOI: 10.18632/oncotarget.20887] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 08/26/2017] [Indexed: 12/24/2022] Open
Abstract
Reactive oxide species are the middle products of normal metabolism, and play a crucial role in cell signaling transduction. On the contrary, accumulation of excess reactive oxide species results in oxidative stress that often brings multifarious impairment to cells, including decrease of ATP level in cells, elevation of cytosolic Ca2+, DNA damage, dysfunction of biological function in lipid bilayer and so on. These effects will finally lead to all kinds of diseases. Tea polyphenols are widely considered as a kind of excellent antioxidant agents. It can be antioxidants by directly scavenging reactive oxide species or chelating transition metals, and indirectly upregulating the activity of antioxidant enzymes. In addition, tea polyphenols have also been observed a potent pro-oxidant capacity, which directly leads to the generation of reactive oxide species, and indirectly induces apoptosis and death of cancer cells. The underlying characters of its pro-oxidant activity in some diseases is not well understood. The present review we will discuss the dual character of tea polyphenols, both antioxidant and pro-oxidant properties, in some human diseases induced by oxidative stress.
Collapse
Affiliation(s)
- Xiangbing Mao
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, People's Republic of China
- Key Laboratory of Animal Disease-Resistance Nutrition, Chinese Ministry of Education, Chengdu, 611130, People's Republic of China
| | - Changsong Gu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, People's Republic of China
- Key Laboratory of Animal Disease-Resistance Nutrition, Chinese Ministry of Education, Chengdu, 611130, People's Republic of China
| | - Daiwen Chen
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, People's Republic of China
- Key Laboratory of Animal Disease-Resistance Nutrition, Chinese Ministry of Education, Chengdu, 611130, People's Republic of China
| | - Bing Yu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, People's Republic of China
- Key Laboratory of Animal Disease-Resistance Nutrition, Chinese Ministry of Education, Chengdu, 611130, People's Republic of China
| | - Jun He
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, People's Republic of China
- Key Laboratory of Animal Disease-Resistance Nutrition, Chinese Ministry of Education, Chengdu, 611130, People's Republic of China
| |
Collapse
|