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Demirel S. Vasorelaxant effects of biochemical constituents of various medicinal plants and their benefits in diabetes. World J Diabetes 2024; 15:1122-1141. [PMID: 38983824 PMCID: PMC11229960 DOI: 10.4239/wjd.v15.i6.1122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 03/07/2024] [Accepted: 05/06/2024] [Indexed: 06/11/2024] Open
Abstract
Endothelial function plays a pivotal role in cardiovascular health, and dysfunction in this context diminishes vasorelaxation concomitant with endothelial activity. The nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin-cyclic adenosine monophosphate pathway, inhibition of phosphodiesterase, and the opening of potassium channels, coupled with the reduction of calcium levels in the cell, constitute critical mechanisms governing vasorelaxation. Cardiovascular disease stands as a significant contributor to morbidity and mortality among individuals with diabetes, with adults afflicted by diabetes exhibiting a heightened cardiovascular risk compared to their non-diabetic counterparts. A plethora of medicinal plants, characterized by potent pharmacological effects and minimal side effects, holds promise in addressing these concerns. In this review, we delineate various medicinal plants and their respective biochemical constituents, showcasing concurrent vasorelaxant and anti-diabetic activities.
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Affiliation(s)
- Sadettin Demirel
- Medicine School, Physiology Department, Bursa Uludag University, Bursa 16059, Türkiye
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Tian X, Sang Z, Lan Z, Liu W, Feng Y, Hu J, Chen F, Liu Y. Fine-Scale analysis of both wild and cultivated horned galls provides insight into their quality differentiation. BMC PLANT BIOLOGY 2023; 23:426. [PMID: 37710158 PMCID: PMC10500821 DOI: 10.1186/s12870-023-04442-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 09/06/2023] [Indexed: 09/16/2023]
Abstract
BACKGROUND Galla chinensis is a traditional Chinese medicine (TCM) produced due to the interaction between the Fordinae aphids and the Rhus plant species. Horned galls with high tannin content are the most widely cultivated gall type, and Wufeng county of Hubei province in China is the center of cultivation. However, long-term artificial cultivation and domestication of horned galls to meet the increasing production demand have led to quality degradation. Understanding the reasons underlying quality degradation is urgent for horned gall production and application. The present study used a combination of metabolic, genetic, and ecological analyses to investigate the quality and genetic differentiation of the horned galls under long-term domestication as well as the potential relationships between them. RESULTS Analysis of gallic acid content and other three phenotypic traits (fresh weight, gall size, and wall thickness) revealed quality differentiation of horned galls collected from five locations in Wufeng, in which the cultivated samples from Wang Jiaping (WJP) showed the highest degradation. Genetic differentiation between the cultivated and wild Rhus chinensis trees in WJP, and between WJP and the other populations was detected based on SSR molecular markers, however, no significant difference in genetic structure was seen for the aphid populations. Among the various ecological factors examined, temperature was identified as the primary one affecting the quality of horned galls. CONCLUSIONS Both genetic and ecological factors caused quality differentiation of horned galls. The collection of diverse germplasm of host trees and aphids will help reduce the quality degradation of horned galls in Wufeng.
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Affiliation(s)
- Xufang Tian
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China
| | - Ziyang Sang
- Forestry Science Research Institute of Wufeng County, Yichang, 443400, People's Republic of China
| | - Zhaohui Lan
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China
| | - Wei Liu
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China
| | - Ying Feng
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China
| | - Juan Hu
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China
| | - Faju Chen
- Biotechnology Research Center, China Three Gorges University, Yichang, 443002, People's Republic of China
| | - Yifei Liu
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China.
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Wen C, Dechsupa N, Yu Z, Zhang X, Liang S, Lei X, Xu T, Gao X, Hu Q, Innuan P, Kantapan J, Lü M. Pentagalloyl Glucose: A Review of Anticancer Properties, Molecular Targets, Mechanisms of Action, Pharmacokinetics, and Safety Profile. Molecules 2023; 28:4856. [PMID: 37375411 DOI: 10.3390/molecules28124856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 06/07/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
Pentagalloyl glucose (PGG) is a natural hydrolyzable gallotannin abundant in various plants and herbs. It has a broad range of biological activities, specifically anticancer activities, and numerous molecular targets. Despite multiple studies available on the pharmacological action of PGG, the molecular mechanisms underlying the anticancer effects of PGG are unclear. Here, we have critically reviewed the natural sources of PGG, its anticancer properties, and underlying mechanisms of action. We found that multiple natural sources of PGG are available, and the existing production technology is sufficient to produce large quantities of the required product. Three plants (or their parts) with maximum PGG content were Rhus chinensis Mill, Bouea macrophylla seed, and Mangifera indica kernel. PGG acts on multiple molecular targets and signaling pathways associated with the hallmarks of cancer to inhibit growth, angiogenesis, and metastasis of several cancers. Moreover, PGG can enhance the efficacy of chemotherapy and radiotherapy by modulating various cancer-associated pathways. Therefore, PGG can be used for treating different human cancers; nevertheless, the data on the pharmacokinetics and safety profile of PGG are limited, and further studies are essential to define the clinical use of PGG in cancer therapies.
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Affiliation(s)
- Chengli Wen
- Department of Intensive Care Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
- Luzhou Key Laboratory of Human Microecology and Precision Diagnosis and Treatment, Luzhou 646000, China
| | - Nathupakorn Dechsupa
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Zehui Yu
- Laboratory Animal Center, Southwest Medical University, Luzhou 646000, China
| | - Xu Zhang
- Luzhou Key Laboratory of Human Microecology and Precision Diagnosis and Treatment, Luzhou 646000, China
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Sicheng Liang
- Luzhou Key Laboratory of Human Microecology and Precision Diagnosis and Treatment, Luzhou 646000, China
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Xianying Lei
- Department of Intensive Care Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Tao Xu
- Department of Intensive Care Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Xiaolan Gao
- Department of Intensive Care Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Qinxue Hu
- Department of Intensive Care Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Phattarawadee Innuan
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Jiraporn Kantapan
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Muhan Lü
- Luzhou Key Laboratory of Human Microecology and Precision Diagnosis and Treatment, Luzhou 646000, China
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
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Liu J, Li X, Bai H, Yang X, Mu J, Yan R, Wang S. Traditional uses, phytochemistry, pharmacology, and pharmacokinetics of the root bark of Paeonia x suffruticosa andrews: A comprehensive review. JOURNAL OF ETHNOPHARMACOLOGY 2023; 308:116279. [PMID: 36822345 DOI: 10.1016/j.jep.2023.116279] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/11/2023] [Accepted: 02/12/2023] [Indexed: 06/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Moutan Cortex (MC), commonly known as "Mu dan pi", refers to the dried root bark of Paeonia x suffruticosa Andrews and is broadly used as a traditional herbal medication in China, Japan, and Korea. For thousands of years, it has been utilized to treat female genital, extravasated blood, cardiovascular, and stagnant blood disorders. AIM OF THE REVIEW The purpose of this review article was to summarize information on the traditional uses, phytochemistry, pharmacology and pharmacokinetics of MC, as well as to outline the further research directions for the development of new drugs and the associations between traditional uses and pharmacological effects. MATERIALS AND METHODS The information involved in the study was gathered from a variety of electronic resources, including PubMed, Web of Science, ScienceDirect, SciFinder, China Knowledge Resource Integrated Database, and Google Scholar. The date was from 1992 to 2022. RESULTS Approximately 163 chemical compounds have been extracted and identified from MC, including monoterpenes, monoterpene glycosides, triterpenes, phenolics, flavonoids, volatile oils, alkaloids, and others. In these categories, the monoterpene glycosides and phenols being the most common. A wide variety of pharmacological effects have been described for MC crude extracts and active molecules, such as antioxidant, anti-inflammatory, antibacterial and antiviral, antitumor, antidiabetic, organ protection, and neuroprotective activities, as well as treating cardiovascular diseases. Pharmacokinetics has been also used in the study of MC, including its crude extracts or chemical constituents, in order to explore the therapeutic mechanism, direct clinically appropriate application and provide new ideas for the exploitation of innovative medicines. CONCLUSION Modern pharmacological research has demonstrated that MC, as a significant therapeutic resource, has the ability to heal a wide range of diseases, particularly female genital and cardiovascular problems. These researches propose therapeutic ideas for the development of novel MC medicines. Furthermore, preclinical and clinical study have verified several observed pharmacological properties related with the traditional usages of MC.
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Affiliation(s)
- Jincai Liu
- Northwest University Faculty of Life and Health Science, Northwest University, 229 Taibai Road, Xi'an, Shaanxi, 710069, China
| | - Xiang Li
- Northwest University Faculty of Life and Health Science, Northwest University, 229 Taibai Road, Xi'an, Shaanxi, 710069, China
| | - Huixin Bai
- Northwest University Faculty of Life and Health Science, Northwest University, 229 Taibai Road, Xi'an, Shaanxi, 710069, China
| | - Xu Yang
- Northwest University Faculty of Life and Health Science, Northwest University, 229 Taibai Road, Xi'an, Shaanxi, 710069, China
| | - Jun Mu
- Northwest University Faculty of Life and Health Science, Northwest University, 229 Taibai Road, Xi'an, Shaanxi, 710069, China
| | - Ruonan Yan
- Northwest University Faculty of Life and Health Science, Northwest University, 229 Taibai Road, Xi'an, Shaanxi, 710069, China
| | - Siwang Wang
- Northwest University Faculty of Life and Health Science, Northwest University, 229 Taibai Road, Xi'an, Shaanxi, 710069, China.
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Jin YH, Lee J, Jeon S, Kim S, Min JS, Kwon S. Natural Polyphenols, 1,2,3,4,6-O-Pentagalloyglucose and Proanthocyanidins, as Broad-Spectrum Anticoronaviral Inhibitors Targeting Mpro and RdRp of SARS-CoV-2. Biomedicines 2022; 10:biomedicines10051170. [PMID: 35625907 PMCID: PMC9138959 DOI: 10.3390/biomedicines10051170] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 02/04/2023] Open
Abstract
The natural plant dietary polyphenols 1,2,3,4,6-O-Pentagalloylglucose (PGG) and proanthocyanidin (PAC) have potent antioxidant activity and a variety of pharmacological activities, including antiviral activity. In this study, we examined the inhibitory effect of PGG and PAC on SARS-CoV-2 virus infection, and elucidated its mode of action. PGG and PAC have dose-dependent inhibitory activity against SARS-CoV-2 infection in Vero cells. PGG has a lower IC50 (15.02 ± 0.75 μM) than PAC (25.90 ± 0.81 μM), suggesting that PGG has better inhibitory activity against SARS-CoV-2 than PAC. The PGG and PAC inhibit similar Mpro activities in a protease activity assay, with IC50 values of 25–26 μM. The effects of PGG and PAC on the activity of the other essential SARS-CoV-2 viral protein, RdRp, were analyzed using a cell-based activity assay system. The activity of RdRp is inhibited by PGG and PAC, and PGG has a lower IC50 (5.098 ± 1.089 μM) than PAC (21.022 ± 1.202 μM), which is consistent with their inhibitory capacity of SARS-CoV-2 infection. PGG and PAC also inhibit infection by SARS-CoV and MERS-CoV. These data indicate that PGG and PAC may be candidate broad-spectrum anticoronaviral therapeutic agents, simultaneously targeting the Mpro and RdRp proteins of SARS-CoV-2.
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Affiliation(s)
- Young-Hee Jin
- KM Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Korea
- Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;
- Correspondence: (Y.-H.J.); (S.K.); Tel.: +82-(42)-610-8850 (Y.-H.J.); +82-(42)-868-9675 (S.K.)
| | - Jihye Lee
- Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam 13488, Korea; (J.L.); (S.J.); (S.K.)
| | - Sangeun Jeon
- Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam 13488, Korea; (J.L.); (S.J.); (S.K.)
| | - Seungtaek Kim
- Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam 13488, Korea; (J.L.); (S.J.); (S.K.)
| | - Jung Sun Min
- Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;
- KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
| | - Sunoh Kwon
- Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;
- KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
- Correspondence: (Y.-H.J.); (S.K.); Tel.: +82-(42)-610-8850 (Y.-H.J.); +82-(42)-868-9675 (S.K.)
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Marcińczyk N, Gromotowicz-Popławska A, Tomczyk M, Chabielska E. Tannins as Hemostasis Modulators. Front Pharmacol 2022; 12:806891. [PMID: 35095516 PMCID: PMC8793672 DOI: 10.3389/fphar.2021.806891] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 12/23/2021] [Indexed: 12/17/2022] Open
Abstract
The hemostasis system is often affected by complications associated with cardiovascular diseases, which results in thromboembolic events. Compounds of plant origin and plant extracts are considered as a promising source of substances that could modulate the functioning of the hemostasis system and thus reduce the risk of thromboembolism. Among them, tannins, which are plant-origin compounds with potential effects in hemostasis, deserve a special mention. This paper describes the hemostasis-modifying ability of three groups of tannins, namely ellagitannins, gallotannins, and procyanidins. The review highlights the desirable as well as undesirable influence of tannins on specific components of hemostasis, namely platelets, coagulation system, fibrinolysis system, and endothelium, and the multidirectional effect of these compounds on the thrombotic process. Studies performed under normal and pathological conditions such as diabetes or hypercoagulation are described, and the pathophysiology-dependent action of tannins is also highlighted. Most of the studies presented in the paper were performed in vitro, and due to the low bioavailability of tannins more studies should be conducted in the future to understand their actual activity in vivo.
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Affiliation(s)
- Natalia Marcińczyk
- Department of Biopharmacy, Medical University of Białystok, Białystok, Poland
| | | | - Michał Tomczyk
- Department of Pharmacognosy, Medical University of Białystok, Białystok, Poland
| | - Ewa Chabielska
- Department of Biopharmacy, Medical University of Białystok, Białystok, Poland
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Xiaoxuming Decoction Regulates Vascular Function by Modulating G Protein-Coupled Receptors: A Molecular Docking Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5575443. [PMID: 34195269 PMCID: PMC8203363 DOI: 10.1155/2021/5575443] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 04/03/2021] [Accepted: 05/28/2021] [Indexed: 01/13/2023]
Abstract
Xiaoxuming decoction (XXMD) is a traditional Chinese herbal medicine (CHM) that is used for the treatment of stroke in China. Stroke injury damages the cerebral vasculature and disrupts the autoregulation of vasoconstriction and vasodilatation, which is crucial for maintaining constant cerebral blood flow (CBF). It has been reported that XXMD exerts a positive effect on cerebral circulation in animal models of stroke. However, the mechanisms underlying the regulatory effect of XXMD on vascular tone, and the interactions among the multiple components of XXMD, remain unclear. In this study, XXMD was found to induce relaxation of the basilar artery rings of rats precontracted by 5-hydroxytryptamine (5-HT) in vitro, in a dose-dependent manner. The modulation of vascular tone and the process of cerebral ischemia are mediated via the interactions between G protein-coupled receptors (GPCRs) and their ligands, including 5-HT, angiotensin II (Ang II), and urotensin II (UII). Thus, the potential synergistic effects of the different components of XXMD on the regulation of vasoconstriction and vasodilation were further investigated by molecular docking based on network pharmacology. We constructed and analyzed a database comprising 963 compounds of XXMD and studied the interactions between five vascular GPCRs (5-HT1A receptor (5-HT1AR), 5-HT1B receptor (5-HT1BR), Ang II type 1 receptor (AT1R), beta 2-adrenergic receptor (β2-AR), and UII receptor (UTR)) and the various herbal constituents of XXMD using molecular docking. By constructing and analyzing the compound-target networks of XXMD, we found that Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, and Paeoniae Radix Alba were the three major herbs that contained a large number of compounds with high docking scores. We additionally observed that several constituents of XXMD, including gallotannin, liquiritin apioside, nariutin, 1,2,3,4,6-pentagalloylglucose, folic acid, and ginsenoside Rb1, targeted multiple vascular GPCRs. Moreover, the interactions between the components of XXMD and the targets related to vascular tone constituted the comprehensive cerebrovascular regulatory function of XXMD and provided a material basis of the vasoregulatory function of XXMD. The study reports the contributions of various components of XXMD to the regulatory effects on vascular tone and provides scientific evidence for the multicomponent and multitargeting characteristics of XXMD.
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Li P, Shen J, Wang Z, Liu S, Liu Q, Li Y, He C, Xiao P. Genus Paeonia: A comprehensive review on traditional uses, phytochemistry, pharmacological activities, clinical application, and toxicology. JOURNAL OF ETHNOPHARMACOLOGY 2021; 269:113708. [PMID: 33346027 DOI: 10.1016/j.jep.2020.113708] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 12/09/2020] [Accepted: 12/15/2020] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Paeonia, which comprises approximately 52 shrubs or herbaceous perennials around the world, is the only genus of the Paeoniaceae and is pervasively distributed in Asia, southern Europe, and North America. Many species of the genus Paeonia have been used for centuries in ethnomedical medical systems. AIM OF THE REVIEW The present study aims to summarize the traditional uses, clinical applications, and toxicology of the genus Paeonia, to critically evaluate the state-of-the-art phytochemical and pharmacological studies of this genus published between 2011 and 2020, and to suggest directions for further in-depth research on Paeonia medicinal resources. MATERIALS AND METHODS Popular and widely used databases such as PubMed, Scopus, Science Direct, and Google Scholar were searched using the various search strings; from these searches, a number of citations related to the traditional uses, phytochemistry, biological activities, clinical application, and toxicology of the genus Paeonia were retrieved. RESULTS The use of 21 species, 2 subspecies, and 7 varieties of the genus Paeonia as traditional herbal remedies has been reported, and many ethnomedicinal uses, such as the treatment of hematemesis, blood stasis, dysmenorrhea, amenorrhea, epilepsy, spasms, and gastritis, have been recorded. The roots and root bark are the most frequently reported parts of the plants used in medicinal applications. In phytochemical investigations, 451 compounds have been isolated from Paeonia plants to date, which contains monoterpenoid glucosides, flavonoids, tannins, stilbenes, triterpenoids and steroids, and phenols. Studies of their pharmacological activities have revealed the antioxidant, anti-inflammatory, antitumour, antibacterial, antiviral, cardiovascular protective, and neuroprotective properties of the genus Paeonia. In particular, some bioactive extracts and compounds (total glucosides of peony (TGP), paeonol, and paeoniflorin) have been used as therapeutic drugs or tested in clinical trials. In addition to the "incompatibility" of the combined use of "shaoyao" and Veratrum nigrum L. roots in traditional Chinese medicine theory, Paeonia was considered to have no obvious toxicity based on the available toxicological tests. CONCLUSION A large number of phytochemical and pharmacological reports have indicated that Paeonia is an important medicinal herb resource, and some of its traditional uses including the treatment of inflammation and cardiovascular diseases and its use as a neuroprotective agent, have been partially confirmed through modern pharmacological studies. Monoterpenoid glucosides are the main active constituents. Although many compounds have been isolated from Paeonia plants, the biological activities of only a few of these compounds (paeoniflorin, paeonol, and TGP) have been extensively investigated. Some paeoniflorin structural analogues and resveratrol oligomers have been preliminarily studied. With the exception of several species (P. suffruticosa, P. ostii, P. lactiflora, and P. emodi) that are commonly used in folk medicine, many medicinal species within the genus do not receive adequate attention. Conducting phytochemical and pharmacological experiments on these species can provide new clues that may lead to the discovery of medicinal resources. It is necessary to identify the effective phytoconstituents of crude extracts of Paeonia that displayed pharmacological activities by bioactivity-guided isolation. In addition, comprehensive plant quality control, and toxicology and pharmacokinetic studies are needed in the future studies.
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Affiliation(s)
- Pei Li
- Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Jie Shen
- Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Zhiqiang Wang
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
| | - Shuangshuang Liu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Qing Liu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Yue Li
- Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Chunnian He
- Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Peigen Xiao
- Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
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Welcome MO, Mastorakis NE. The taste of neuroinflammation: Molecular mechanisms linking taste sensing to neuroinflammatory responses. Pharmacol Res 2021; 167:105557. [PMID: 33737243 DOI: 10.1016/j.phrs.2021.105557] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 03/10/2021] [Accepted: 03/10/2021] [Indexed: 02/07/2023]
Abstract
Evidence indicates a critical role of neuroinflammatory response as an underlying pathophysiological process in several central nervous system disorders, including neurodegenerative diseases. However, the molecular mechanisms that trigger neuroinflammatory processes are not fully known. The discovery of bitter taste receptors in regions other than the oral cavity substantially increased research interests on their functional roles in extra-oral tissues. It is now widely accepted that bitter taste receptors, for instance, in the respiratory, intestinal, reproductive and urinary tracts, are crucial not only for sensing poisonous substances, but also, act as immune sentinels, mobilizing defense mechanisms against pathogenic aggression. The relatively recent discovery of bitter taste receptors in the brain has intensified research investigation on the functional implication of cerebral bitter taste receptor expression. Very recent data suggest that responses of bitter taste receptors to neurotoxins and microbial molecules, under normal condition, are necessary to prevent neuroinflammatory reactions. Furthermore, emerging data have revealed that downregulation of key components of the taste receptor signaling cascade leads to increased oxidative stress and inflammasome signaling in neurons that ultimately culminate in neuroinflammation. Nevertheless, the mechanisms that link taste receptor mediated surveillance of the extracellular milieu to neuroinflammatory responses are not completely understood. This review integrates new data on the molecular mechanisms that link bitter taste receptor sensing to neuroinflammatory responses. The role of bitter taste receptor-mediated sensing of toxigenic substances in brain disorders is also discussed. The therapeutic significance of targeting these receptors for potential treatment of neurodegenerative diseases is also highlighted.
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Affiliation(s)
- Menizibeya O Welcome
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Nile University of Nigeria, Abuja, Nigeria.
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Kim KH, Shim JS, Kim HJ, Son ED. Penta-O-galloyl-β-D-glucose from Paeonia lactiflora Pall. root extract enhances the expression of skin barrier genes via EGR3. JOURNAL OF ETHNOPHARMACOLOGY 2020; 248:112337. [PMID: 31655148 DOI: 10.1016/j.jep.2019.112337] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 09/10/2019] [Accepted: 10/21/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLIGICAL RELEVANCE Paeonia lactiflora Pall. has long been used to treat inflammatory skin diseases, such as psoriasis. AIM OF THE STUDY The skin acts as a barrier and provides protection against various stresses by expressing skin barrier genes during keratinocyte differentiation. However, the effect of Paeonia lactiflora Pall. root extract on the expression of skin barrier genes has not been investigated. Here, we aimed to show that treatment of keratinocytes with Paeonia lactiflora Pall. root can upregulate genes related to keratinocyte differentiation. MATERIALS AND METHODS To determine the effect Paeonia lactiflora Pall. root extract, RNA-Seq, gene ontology, and gene set enrichment analysis were performed. Reverse transcriptase quantitative polymerase chain reaction analysis was performed to confirm the increased expression of skin barrier genes. RESULTS Treatment with Paeonia lactiflora Pall. root enhanced the expression of skin barrier genes, including the filaggrin, loricrin, and involucrin. Moreover, we found that penta-O-galloyl-β-D-glucose (PGG), one of the ingredients in Paeonia lactiflora Pall. root, enhanced the expression of skin barrier genes, by upregulating the expression of the transcription factor EGR3. CONCLUSIONS PGG and Paeonia lactiflora Pall. root extract have therapeutic potential for the treatment of diseases related to skin barrier disruption and can be used in cosmetics to enhance skin barrier function.
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Affiliation(s)
- Kyu-Han Kim
- Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, 446-729, South Korea.
| | - Jin Sup Shim
- Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, 446-729, South Korea
| | - Hyoung-June Kim
- Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, 446-729, South Korea
| | - Eui Dong Son
- Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, 446-729, South Korea
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11
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Fais RS, Rodrigues FL, Pereira CA, Mendes AC, Mestriner F, Tostes RC, Carneiro FS. The inflammasome NLRP3 plays a dual role on mouse corpora cavernosa relaxation. Sci Rep 2019; 9:16224. [PMID: 31700106 PMCID: PMC6838322 DOI: 10.1038/s41598-019-52831-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 10/18/2019] [Indexed: 12/25/2022] Open
Abstract
NLRP3 plays a role in vascular diseases. Corpora cavernosa (CC) is an extension of the vasculature. We hypothesize that NLRP3 plays a deleterious role in CC relaxation. Male C57BL/6 (WT) and NLRP3 deficient (NLRP3−/−) mice were used. Intracavernosal pressure (ICP/MAP) measurement was performed. Functional responses were obtained from CC strips of WT and NLRP3−/− mice before and after MCC950 (NLRP3 inhibitor) or LPS + ATP (NLRP3 stimulation). NLRP3, caspase-1, IL-1β, eNOS, nNOS, guanylyl cyclase-β1 (GCβ1) and PKG1 protein expressions were determined. ICP/MAP and sodium nitroprusside (SNP)-induced relaxation in CC were decreased in NLRP3−/− mice. Caspase-1, IL-1β and eNOS activity were increased, but PKG1 was reduced in CC of NLRP3−/−. MCC950 decreased non-adrenergic non-cholinergic (NANC), acetylcholine (ACh), and SNP-induced relaxation in WT mice. MCC950 did not alter NLRP3, caspase-1 and IL-1β, but reduced GCβ1 expression. Although LPS + ATP decreased ACh- and SNP-, it increased NANC-induced relaxation in CC from WT, but not from NLRP3−/− mice. LPS + ATP increased NLRP3, caspase-1 and interleukin-1β (IL-1β). Conversely, it reduced eNOS activity and GCβ1 expression. NLRP3 plays a dual role in CC relaxation, with its inhibition leading to impairment of nitric oxide-mediated relaxation, while its activation by LPS + ATP causes decreased CC sensitivity to NO and endothelium-dependent relaxation.
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Affiliation(s)
- Rafael S Fais
- Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
| | - Fernanda L Rodrigues
- Departments of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
| | - Camila A Pereira
- Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
| | - Allan C Mendes
- Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
| | - Fabíola Mestriner
- Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
| | - Rita C Tostes
- Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
| | - Fernando S Carneiro
- Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil.
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12
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Pentagalloylglucose Inhibits the Replication of Rabies Virus via Mediation of the miR-455/SOCS3/STAT3/IL-6 Pathway. J Virol 2019; 93:JVI.00539-19. [PMID: 31243136 DOI: 10.1128/jvi.00539-19] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 06/23/2019] [Indexed: 02/07/2023] Open
Abstract
Our previous study showed that pentagalloylglucose (PGG), a naturally occurring hydrolyzable phenolic tannin, possesses significant anti-rabies virus (RABV) activity. In BHK-21 cells, RABV induced the overactivation of signal transducer and activator of transcription 3 (STAT3) by suppressing the expression of suppressor of cytokine signaling 3 (SOCS3). Inhibition of STAT3 by niclosamide, small interfering RNA, or exogenous expression of SOCS3 all significantly suppressed the replication of RABV. Additionally, RABV-induced upregulation of microRNA 455-5p (miR-455-5p) downregulated SOCS3 by directly binding to the 3' untranslated region (UTR) of SOCS3. Importantly, PGG effectively reversed the expression of miR-455-5p and its following SOCS3/STAT3 signaling pathway. Finally, activated STAT3 elicited the expression of interleukin-6 (IL-6), thereby contributing to RABV-associated encephalomyelitis; however, PGG restored the level of IL-6 in vitro and in vivo in a SOCS3/STAT3-dependent manner. Altogether, these data identify a new miR-455-5p/SOCS3/STAT3 signaling pathway that contributes to viral replication and IL-6 production in RABV-infected cells, with PGG exerting its antiviral effect by inhibiting the production of miR-455-5p and the activation of STAT3.IMPORTANCE Rabies virus causes lethal encephalitis in mammals and poses a serious public health threat in many parts of the world. Numerous strategies have been explored to combat rabies; however, their efficacy has always been unsatisfactory. We previously reported a new drug, PGG, which possesses a potent inhibitory activity on RABV replication. Herein, we describe the underlying mechanisms by which PGG exerts its anti-RABV activity. Our results show that RABV induces overactivation of STAT3 in BHK-21 cells, which facilitates viral replication. Importantly, PGG effectively inhibits the activity of STAT3 by disrupting the expression of miR-455-5p and increases the level of SOCS3 by directly targeting the 3' UTR of SOCS3. Furthermore, the downregulated STAT3 inhibits the production of IL-6, thereby contributing to a reduction in the inflammatory response in vivo Our study indicates that PGG effectively inhibits the replication of RABV by the miR-455-5p/SOCS3/STAT3/IL-6-dependent pathway.
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Biomechanical Restoration Potential of Pentagalloyl Glucose after Arterial Extracellular Matrix Degeneration. Bioengineering (Basel) 2019; 6:bioengineering6030058. [PMID: 31277241 PMCID: PMC6783915 DOI: 10.3390/bioengineering6030058] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 06/27/2019] [Accepted: 06/30/2019] [Indexed: 12/12/2022] Open
Abstract
The objective of this study was to quantify pentagalloyl glucose (PGG) mediated biomechanical restoration of degenerated extracellular matrix (ECM). Planar biaxial tensile testing was performed for native (N), enzyme-treated (collagenase and elastase) (E), and PGG (P) treated porcine abdominal aorta specimens (n = 6 per group). An Ogden material model was fitted to the stress-strain data and finite element computational analyses of simulated native aorta and aneurysmal abdominal aorta were performed. The maximum tensile stress of the N group was higher than that in both E and P groups for both circumferential (43.78 ± 14.18 kPa vs. 10.03 ± 2.68 kPa vs. 13.85 ± 3.02 kPa; p = 0.0226) and longitudinal directions (33.89 ± 8.98 kPa vs. 9.04 ± 2.68 kPa vs. 14.69 ± 5.88 kPa; p = 0.0441). Tensile moduli in the circumferential direction was found to be in descending order as N > P > E (195.6 ± 58.72 kPa > 81.8 ± 22.76 kPa > 46.51 ± 15.04 kPa; p = 0.0314), whereas no significant differences were found in the longitudinal direction (p = 0.1607). PGG binds to the hydrophobic core of arterial tissues and the crosslinking of ECM fibers is one of the possible explanations for the recovery of biomechanical properties observed in this study. PGG is a beneficial polyphenol that can be potentially translated to clinical practice for preventing rupture of the aneurysmal arterial wall.
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14
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Mikolajczyk TP, Nosalski R, Skiba DS, Koziol J, Mazur M, Justo-Junior AS, Kowalczyk P, Kusmierczyk Z, Schramm-Luc A, Luc K, Maffia P, Graham D, Kiss AK, Naruszewicz M, Guzik TJ. 1,2,3,4,6-Penta-O-galloyl-β-d-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension. Br J Pharmacol 2019; 176:1951-1965. [PMID: 30658013 PMCID: PMC6534792 DOI: 10.1111/bph.14583] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 10/26/2018] [Accepted: 12/02/2018] [Indexed: 12/16/2022] Open
Abstract
Background and Purpose Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production, and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6‐penta‐O‐galloyl‐β‐d‐glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. Experimental Approach PGG was administered to mice every 2 days at a dose of 10 mg·kg−1 i.p during 14 days of Ang II infusion. It was used at a final concentration of 20 μM for in vitro studies in cultured cells. Key Results Ang II administration increased leukocyte and T‐cell content in perivascular adipose tissue (pVAT), and administration of PGG significantly decreased total leukocyte and T‐cell infiltration in pVAT. This effect was observed in relation to all T‐cell subsets. PGG also decreased the content of T‐cells bearing CD25, CCR5, and CD44 receptors and the expression of both monocyte chemoattractant protein 1 (CCL2) in aorta and RANTES (CCL5) in pVAT. PGG administration decreased the content of TNF+ and IFN‐γ+ CD8 T‐cells and IL‐17A+ CD4+ and CD3+CD4−CD8− cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II‐infused animals independently of the BP increase. Mechanistically, PGG (20 μM) directly inhibited CD25 and CCR5 expression in cultured T‐cells. It also decreased the content of IFN‐γ+ CD8+ and CD3+CD4−CD8− cells and IL‐17A+ CD3+CD4−CD8− cells. Conclusion and Implication PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension. Linked Articles This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
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Affiliation(s)
- Tomasz P Mikolajczyk
- Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.,Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Ryszard Nosalski
- Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland.,Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Dominik S Skiba
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Joanna Koziol
- Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Magdalena Mazur
- Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Amauri S Justo-Junior
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Paulina Kowalczyk
- Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
| | - Zofia Kusmierczyk
- Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
| | - Agata Schramm-Luc
- Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Kevin Luc
- Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Pasquale Maffia
- Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.,Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.,Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Delyth Graham
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Anna K Kiss
- Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
| | - Marek Naruszewicz
- Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
| | - Tomasz J Guzik
- Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland.,Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
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15
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Patnaik SS, Simionescu DT, Goergen CJ, Hoyt K, Sirsi S, Finol EA. Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics. Ann Biomed Eng 2019; 47:39-59. [PMID: 30298373 PMCID: PMC6318003 DOI: 10.1007/s10439-018-02145-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 09/28/2018] [Indexed: 02/08/2023]
Abstract
Pentagalloyl glucose (PGG) is an elastin-stabilizing polyphenolic compound that has significant biomedical benefits, such as being a free radical sink, an anti-inflammatory agent, anti-diabetic agent, enzymatic resistant properties, etc. This review article focuses on the important benefits of PGG on vascular health, including its role in tissue mechanics, the different modes of pharmacological administration (e.g., oral, intravenous and endovascular route, intraperitoneal route, subcutaneous route, and nanoparticle based delivery and microbubble-based delivery), and its potential therapeutic role in vascular diseases such as abdominal aortic aneurysms (AAA). In particular, the use of PGG for AAA suppression and prevention has been demonstrated to be effective only in the calcium chloride rat AAA model. Therefore, in this critical review we address the challenges that lie ahead for the clinical translation of PGG as an AAA growth suppressor.
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Affiliation(s)
- Sourav S Patnaik
- Vascular Biomechanics and Biofluids Laboratory, Department of Mechanical Engineering, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX, 78249-0670, USA
| | - Dan T Simionescu
- Department of Bioengineering, Clemson University, Clemson, SC, USA
| | - Craig J Goergen
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Shashank Sirsi
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ender A Finol
- Vascular Biomechanics and Biofluids Laboratory, Department of Mechanical Engineering, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX, 78249-0670, USA.
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16
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Tu Z, Gong W, Zhang Y, Feng Y, Liu Y, Tu C. Inhibition of Rabies Virus by 1,2,3,4,6-Penta- O-galloyl-β-d-Glucose Involves mTOR-Dependent Autophagy. Viruses 2018; 10:v10040201. [PMID: 29673174 PMCID: PMC5923495 DOI: 10.3390/v10040201] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 04/04/2018] [Accepted: 04/14/2018] [Indexed: 12/25/2022] Open
Abstract
The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug.
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Affiliation(s)
- Zhongzhong Tu
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Jilin 130122, China.
| | - Wenjie Gong
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Jilin 130122, China.
| | - Yan Zhang
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Jilin 130122, China.
| | - Ye Feng
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Jilin 130122, China.
| | - Yan Liu
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Jilin 130122, China.
| | - Changchun Tu
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Jilin 130122, China.
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17
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Yu L, Yin M, Yang X, Lu M, Tang F, Wang H. Calpain inhibitor I attenuates atherosclerosis and inflammation in atherosclerotic rats through eNOS/NO/NF-κB pathway. Can J Physiol Pharmacol 2018; 96:60-67. [DOI: 10.1139/cjpp-2016-0652] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We previously reported that calpain, the Ca2+-sensitive cysteine protease, gets involved in atherogenesis. This study aimed to investigate the effects of calpain inhibitor I (CAI, 5 mg/kg per day) with or without NG-nitro-l-arginine-methyl ester (l-NAME) (100 mg/kg per day), the inhibitor of nitric oxide synthase (NOS), on atherosclerosis and inflammation in a rat model induced by high-cholesterol diet (HCD). The results demonstrated HCD increased protein expression of calpain-1 but not calpain-2 in aortic tissue. In addition, CAI reduced the thickness of atherosclerotic intima compared with HCD group, which was weakened by the l-NAME combination. CAI with or without l-NAME decreased the activity of calpain in the aorta. Also, CAI decreased the expressions of vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the aorta at the levels of both mRNA and protein. Furthermore, CAI increased the activity and the protein expression of endothelial NOS (eNOS) accompanied by increased content of NO and downregulated the protein expression of nuclear factor κB (NF-κB) of the nucleus in the aorta. However, the abovementioned effects were at least partly cancelled by l-NAME except for the protein expression of eNOS. The results suggested that CAI attenuated atherosclerosis and inflammation through eNOS/NO/NF-κB pathway.
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Affiliation(s)
- Lan Yu
- Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China
- Central Hospital of Yingkou Development Areas, Yingkou 115007, China
| | - Meihui Yin
- Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China
| | - Xueyan Yang
- Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China
- Internal Medicine-Cardiovascular Departments, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China
| | - Meili Lu
- Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China
| | - Futian Tang
- Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China
| | - Hongxin Wang
- Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China
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18
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Luo F, Liu J, Wang Y, Xu M, Ren Z. PGG impairs herpes simplex virus type 1 infection via blocking capsid assembly. Future Virol 2018. [DOI: 10.2217/fvl-2017-0109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aim: Pentagalloylglucose (PGG), a hydrolyzable polyphenol was isolated from Phyllanthus emblica, which exhibited a strong inhibitory activity on HSV-1 infection, but its underlying mechanisms have not been completely delineated. Results/methodology: Using TEM, we first observed that PGG blocked the formation and maturation of HSV-1 capsid particles. Hence, we engaged in exploring the molecular mechanisms of PGG on the capsid assembly. At last, we found that PGG also blocked the relocalization of capsid proteins from the cytoplasm to the nucleus where the assembly took place. Conclusion: The current studies, for the first time, demonstrated acetylated microtubules were needed at this process of capsid proteins nuclear translocation. PGG also impairs herpes simplex virus type 1 infection by blocking capsid assembly.
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Affiliation(s)
- Fan Luo
- Guangzhou Jinan Biomedicine Research & Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, Guangdong, China
- The Industry-Academia-Research Demonstration Base of Guangdong Higher Education Institutes (Namely Innovative Culturing Base of Graduates), Jinan University, Guangzhou, Guangdong, China
- College of Life Science & Technology, Jinan University, Guangzhou, Guangdong, China
| | - Junwei Liu
- Guangzhou Jinan Biomedicine Research & Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, Guangdong, China
| | - Yifei Wang
- Guangzhou Jinan Biomedicine Research & Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, Guangdong, China
- The Industry-Academia-Research Demonstration Base of Guangdong Higher Education Institutes (Namely Innovative Culturing Base of Graduates), Jinan University, Guangzhou, Guangdong, China
| | - Mingfang Xu
- College of Life Science & Technology, Jinan University, Guangzhou, Guangdong, China
| | - Zhe Ren
- Guangzhou Jinan Biomedicine Research & Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, Guangdong, China
- The Industry-Academia-Research Demonstration Base of Guangdong Higher Education Institutes (Namely Innovative Culturing Base of Graduates), Jinan University, Guangzhou, Guangdong, China
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19
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Galloylation of polyphenols alters their biological activity. Food Chem Toxicol 2017; 105:223-240. [DOI: 10.1016/j.fct.2017.04.021] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 03/23/2017] [Accepted: 04/15/2017] [Indexed: 01/08/2023]
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20
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Rodrigues AMG, Guimarães DO, Konno TUP, Tinoco LW, Barth T, Aguiar FA, Lopes NP, Leal ICR, Raimundo JM, Muzitano MF. Phytochemical Study of Tapirira guianensis Leaves Guided by Vasodilatory and Antioxidant Activities. Molecules 2017; 22:molecules22020304. [PMID: 28218702 PMCID: PMC6155791 DOI: 10.3390/molecules22020304] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 01/31/2017] [Accepted: 02/01/2017] [Indexed: 01/28/2023] Open
Abstract
The aim of this research was to perform a phytochemical study of the methanol leaves extract of T. guianensis (MET) guided by vasodilatory and antioxidant activities. The chemical profile of MET and the ethyl acetate fraction (EA fraction) was determined by HPLC-UV-MS and EA fraction guided fractionation by reverse-phase chromatography. The vasorelaxant effects of MET, fractions, sub-fractions and constituents were assessed on rat aorta pre-contracted with phenylephrine. Antioxidant activity was evaluated by using a DPPH assay. The results show that MET-induced vasodilation was dependent on NO/cGMP; and that the PI3K/Akt pathway seems to be the main route involved in eNOS activation. The EA fraction showed greater vasodilatory and antioxidant potency and was submitted to further fractionation. This allowed the isolation and characterization of quercetin, quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside and 1,4,6-tri-O-galloyl-β-d-glucose. Also, galloyl-HHDP-hexoside and myricetin deoxyhexoside were identified by HPLC-UV-MS. These compounds are being described for the first time for T. guianensis. 1,4,6-tri-O-galloyl-β-d-glucose and quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside showed no vasodilatory activity. Quercetin and myricetin glycoside seems to contribute to the MET activity, since they have been reported as vasodilatory flavonoids. MET-induced vasodilation could contribute to the hypotensive effect of T. guianensis previously reported.
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Affiliation(s)
- Amélia M G Rodrigues
- Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Av. Alberto Lamego, 2000, Parque Califórnia, Campos dos Goytacazes, 28013-602 Rio de Janeiro, Brazil.
- Laboratório Integrado de Pesquisa, Universidade Federal do Rio de Janeiro, Campus Macaé, Av. Aluízio da Silva Gomes, 50, Novo Cavaleiros, Macaé, 27930-560 Rio de Janeiro, Brazil.
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro-IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil.
| | - Denise O Guimarães
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro-IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil.
| | - Tatiana U P Konno
- Núcleo de Estudos em Ecologia e Desenvolvimento Sócio-Ambiental de Macaé, Universidade Federal do Rio de Janeiro, Av. São José Barreto, 764-São José do Barreto. Macaé, 27965-045 Rio de Janeiro, Brazil.
| | - Luzineide W Tinoco
- Instituto de Pesquisa de Produtos Naturais Walter Mors, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.
| | - Thiago Barth
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro-IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil.
| | - Fernando A Aguiar
- Núcleo de Pesquisa em Produtos Naturais e Sintéticos, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n. 14040-020 Ribeirão Preto, Brazil.
- Laboratório de Química, Universidade Federal do Rio de Janeiro-Campus Macaé, Av. Aluízio da Silva Gomes, 50, Novo Cavaleiros. Macaé, 27930-560 Rio de Janeiro, Brazil.
| | - Norberto P Lopes
- Núcleo de Pesquisa em Produtos Naturais e Sintéticos, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n. 14040-020 Ribeirão Preto, Brazil.
| | - Ivana C R Leal
- Laboratório de Produtos Naturais e Ensaios Biológicos, Departamento De Produtos Naturais e Alimentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.
| | - Juliana M Raimundo
- Laboratório Integrado de Pesquisa, Universidade Federal do Rio de Janeiro, Campus Macaé, Av. Aluízio da Silva Gomes, 50, Novo Cavaleiros, Macaé, 27930-560 Rio de Janeiro, Brazil.
| | - Michelle F Muzitano
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro-IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil.
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Rached I, Barros L, Fernandes IP, Santos-Buelga C, Rodrigues AE, Ferchichi A, Barreiro MF, Ferreira ICFR. Ceratonia siliqua L. hydroethanolic extract obtained by ultrasonication: antioxidant activity, phenolic compounds profile and effects in yogurts functionalized with their free and microencapsulated forms. Food Funct 2016; 7:1319-28. [PMID: 26887343 DOI: 10.1039/c6fo00100a] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Bioactive extracts were obtained from powdered carob pulp through an ultrasound extraction process and then evaluated in terms of antioxidant activity. Ten minutes of ultrasonication at 375 Hz were the optimal conditions leading to an extract with the highest antioxidant effects. After its chemical characterization, which revealed the preponderance of gallotannins, the extract (free and microencapsulated) was incorporated in yogurts. The microspheres were prepared using an extract/sodium alginate ratio of 100/400 (mg mg(-1)) selected after testing different ratios. The yogurts with the free extract exhibited higher antioxidant activity than the samples added with the encapsulated extracts, showing the preserving role of alginate as a coating material. None of the forms significantly altered the yogurt's nutritional value. This study confirmed the efficiency of microencapsulation to stabilize functional ingredients in food matrices maintaining almost the structural integrity of polyphenols extracted from carob pulp and furthermore improving the antioxidant potency of the final product.
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Affiliation(s)
- Irada Rached
- Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus Santa Apolónia, 1172, 5301-855 Bragança, Portugal. and Laboratory of Separation and Reaction Engineering (LSRE), Associate Laboratory LSRE/LCM, Polytechnic Institute of Bragança, Campus Santa Apolónia, 1134, 5301-857 Bragança, Portugal. and Rural Laboratory, National Institute of Agronomic of Tunisia, 43, Charles Nicolle, 1082, Tunis, Mahrajene, Tunisia
| | - Lillian Barros
- Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus Santa Apolónia, 1172, 5301-855 Bragança, Portugal. and Laboratory of Separation and Reaction Engineering (LSRE), Associate Laboratory LSRE/LCM, Polytechnic Institute of Bragança, Campus Santa Apolónia, 1134, 5301-857 Bragança, Portugal.
| | - Isabel P Fernandes
- Laboratory of Separation and Reaction Engineering (LSRE), Associate Laboratory LSRE/LCM, Polytechnic Institute of Bragança, Campus Santa Apolónia, 1134, 5301-857 Bragança, Portugal.
| | - Celestino Santos-Buelga
- GIP-USAL, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain
| | - Alírio E Rodrigues
- Laboratory of Separation and Reaction Engineering (LSRE), Associate Laboratory LSRE/LCM, Faculty of Engineering, University of Porto, Porto, Portugal
| | - Ali Ferchichi
- Rural Laboratory, National Institute of Agronomic of Tunisia, 43, Charles Nicolle, 1082, Tunis, Mahrajene, Tunisia
| | - Maria Filomena Barreiro
- Laboratory of Separation and Reaction Engineering (LSRE), Associate Laboratory LSRE/LCM, Polytechnic Institute of Bragança, Campus Santa Apolónia, 1134, 5301-857 Bragança, Portugal.
| | - Isabel C F R Ferreira
- Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus Santa Apolónia, 1172, 5301-855 Bragança, Portugal.
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In vitro glucuronidation of methyl gallate and pentagalloyl glucopyranose by liver microsomes. Drug Metab Pharmacokinet 2016; 31:292-303. [PMID: 27325020 DOI: 10.1016/j.dmpk.2016.04.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 04/04/2016] [Accepted: 04/06/2016] [Indexed: 11/23/2022]
Abstract
Methyl gallate (MG) and pentagalloyl glucopyranose (PGG) are bioactive phenolic compounds that possess various pharmacological activities. However, the knowledge of hepatic metabolism of MG and PGG is limited. The purpose of this study was to investigate the in vitro glucuronidation of MG and PGG using liver microsomes from human (HLMs) and rats (Sprague-Dawley, SDRLMs; Wistar, WRLMs; and Gunn, GRLMs), and recombinant human uridine 5'-diphospho-glucuronosyltransferases (UGT) 1A1 and 1A9. The results demonstrated that liver microsomes catalyzed two mono-glucuronided MG (M1 and M2) formations but that UGT1A1 and 1A9 catalyzed only M1 formation. For PGG, a mono-glucuronided metabolite was mediated by liver microsomes or UGT1A9. However, a PGG glucuronide was absent in the UGT1A1 system. Additionally, all metabolites showed susceptibility to β-glucuronidases. Furthermore, the glucuronidation activities of PGG were lower than those of MG. The kinetic parameters of MG glucuronidation demonstrated that the SDRLMs and GRLMs were more similar to the HLMs than the WRLMs for the formations of M1 and M2, respectively and that the SDRLMs and HLMs preferentially contributed to M1, whereas the WRLMs and GRLMs showed the favored formation of M2. In conclusion, MG and PGG were subjectively glucuronided by liver microsomes to demonstrate species- and strain-dependent metabolism.
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Zhao W, Haller V, Ritsch A. The polyphenol PGG enhances expression of SR-BI and ABCA1 in J774 and THP-1 macrophages. Atherosclerosis 2015; 242:611-7. [DOI: 10.1016/j.atherosclerosis.2015.08.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 08/09/2015] [Accepted: 08/18/2015] [Indexed: 12/01/2022]
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Jin F, Ma K, Chen M, Zou M, Wu Y, Li F, Wang Y. Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection. Jpn J Infect Dis 2015; 69:135-42. [PMID: 26166506 DOI: 10.7883/yoken.jjid.2015.137] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Herpes simplex virus type 1 (HSV-1), a widespread virus, causes a variety of human viral diseases worldwide. The serious threat of drug-resistance highlights the extreme urgency to develop novel antiviral drugs with different mechanisms of action. Pentagalloylglucose (PGG) is a natural polyphenolic compound with significant anti-HSV activity; however, the mechanisms underlying its antiviral activity need to be defined by further studies. In this study, we found that PGG treatment delays the nuclear transport process of HSV-1 particles by inhibiting the upregulation of dynein (a cellular major motor protein) induced by HSV-1 infection. Furthermore, PGG treatment affects the nucleocapsid egress of HSV-1 by inhibiting the expression and disrupting the cellular localization of pEGFP-UL31 and pEGFP-UL34, which are indispensable for HSV-1 nucleocapsid egress from the nucleus. However, the over-expression of pEGFP-UL31 and pEGFP-UL34 could decrease the antiviral effect of PGG. In this study, for the first time, the antiviral activity of PGG against acyclovir-resistant virus was demonstrated in vitro, and the possible mechanisms of its anti-HSV activities were identified based on the inhibition of nuclear transport and nucleocapsid egress in HSV-1. It was further confirmed that PGG could be a promising candidate for HSV therapy, especially for drug-resistant strains.
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Affiliation(s)
- Fujun Jin
- Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University
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1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:276946. [PMID: 25918543 PMCID: PMC4396556 DOI: 10.1155/2015/276946] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 11/20/2014] [Accepted: 11/20/2014] [Indexed: 12/28/2022]
Abstract
A characteristic feature of aggressive malignancy is the overexpression of lactic acid dehydrogenase- (LDH-) A, concomitant to pericellular accumulation of lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill.) gallnut (RCG) (also known as Galla Chinensis) extract as a potent (IC50 < 1 µg/mL) inhibitor of human LDH-A (hLDH-A). In this study, through bioactivity guided fractionation of the crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC50 = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of hLDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC50 = 94.18 µM), parallel to attenuated lactic acid production (IC50 = 97.81 µM). In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC50 = 1.2 µM) relative to paclitaxel (IC50 < 100 nM). In summary, these findings demonstrate that PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.
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The synthesis and antitumor activity of twelve galloyl glucosides. Molecules 2015; 20:2034-60. [PMID: 25633333 PMCID: PMC6272398 DOI: 10.3390/molecules20022034] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 01/05/2015] [Accepted: 01/21/2015] [Indexed: 12/31/2022] Open
Abstract
Twelve galloyl glucosides 1-12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9), ethyl 2,3-di-O-galloyl-α-D-glucopyranoside (11) and ethyl 2,3-di-O-galloyl-β-D-glucopyranoside (12), are new compounds and other six, 1,6-di-O-galloyl-β-D-glucopyranose (1), 1,4,6-tri-O-galloyl-β-D-glucopyranose (2), 1,2-di-O-galloyl-β-D-glucopyranose (3), 1,3-di-O-galloyl-β-D-glucopyranose (4), 1,2,3-tri-O-galloyl-α-D-glucopyranose (6) and methyl 3,4,6-tri-O-galloyl-α-D-glucopyranoside (10), were synthesized for the first time in the present study. In in vitro MTT assay, 1-12 inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC50 values were determined to be varied in 17.2-124.7 μM on the tested three human cancer cell lines. In addition, compounds 1-12 inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in the in vitro MTT assay, and in vivo antitumor activity of 1 and 2 was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control.
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Abstract
LPS (lipopolysaccharide), an outer membrane component of Gram-negative bacteria, plays an important role in the pathogenesis of sepsis and lipid A is known to be essential for its toxicity. Therefore it could be an effective measure to prevent sepsis by neutralizing or destroying LPS. Numerous studies have indicated that many traditional Chinese medicines are natural antagonists of LPS in vitro and in vivo. The goal of this study is to develop a rapid method to screen anti-sepsis components from Chinese herbs by use of a direct lipid A-based affinity biosensor technology based on a resonant mirror. The detergent OG (n-octyl β-D-glucopyranoside) was immobilized on a planar non-derivatized cuvette which provided an alternative surface to bind the terminal hydrophilic group of lipid A. A total of 78 herbs were screened based on the affinity biosensor with a target of lipid A. The aqueous extract of PSA (Paeonia suffruticosa Andr) was found to possess the highest capability of binding lipid A. Therefore an aqueous extraction from this plant was investigated further by our affinity biosensor, polyamide chromatography and IEC–HPLC. Finally, we obtained a component (PSA-I-3) from Paeonia suffruticosa Andr that was evaluated with the affinity biosensor. We also studied the biological activities of PSA-I-3 against sepsis in vitro and in vivo to further confirm the component we screened with the biosensor. In vitro, we found that PSA-I-3 could decrease TNFα (tumour necrosis factor α) release from RAW264.7 cells induced by LPS in a dose-dependent manner. In vivo, it increased remarkably the survival of KM (KunMing) mice by challenging both lethal-dose LPS and heat-killed Escherichia coli compared with control groups. Our results suggest that the constructed affinity biosensor can successfully screen the anti-sepsis component from Chinese herbs.
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Natural Compounds (Small Molecules) as Potential and Real Drugs of Alzheimer's Disease. ACTA ACUST UNITED AC 2014. [DOI: 10.1016/b978-0-444-63281-4.00006-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
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Vasodilator compounds derived from plants and their mechanisms of action. Molecules 2013; 18:5814-57. [PMID: 23685938 PMCID: PMC6270466 DOI: 10.3390/molecules18055814] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Revised: 04/24/2013] [Accepted: 05/07/2013] [Indexed: 12/31/2022] Open
Abstract
The present paper reviews vasodilator compounds isolated from plants that were reported in the past 22 years (1990 to 2012) and the different mechanisms of action involved in their vasodilator effects. The search for reports was conducted in a comprehensive manner, intending to encompass those metabolites with a vasodilator effect whose mechanism of action involved both vascular endothelium and arterial smooth muscle. The results obtained from our bibliographic search showed that over half of the isolated compounds have a mechanism of action involving the endothelium. Most of these bioactive metabolites cause vasodilation either by activating the nitric oxide/cGMP pathway or by blocking voltage-dependent calcium channels. Moreover, it was found that many compounds induced vasodilation by more than one mechanism. This review confirms that secondary metabolites, which include a significant group of compounds with extensive chemical diversity, are a valuable source of new pharmaceuticals useful for the treatment and prevention of cardiovascular diseases.
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Sáyago-Ayerdi SG, Moreno-Hernández CL, Montalvo-González E, García-Magaña ML, Mata-Montes de Oca M, Torres JL, Pérez-Jiménez J. Mexican ‘Ataulfo’ mango (Mangifera indica L) as a source of hydrolyzable tannins. Analysis by MALDI-TOF/TOF MS. Food Res Int 2013. [DOI: 10.1016/j.foodres.2012.11.034] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Wang Q, Kuang H, Su Y, Sun Y, Feng J, Guo R, Chan K. Naturally derived anti-inflammatory compounds from Chinese medicinal plants. JOURNAL OF ETHNOPHARMACOLOGY 2013; 146:9-39. [PMID: 23274744 DOI: 10.1016/j.jep.2012.12.013] [Citation(s) in RCA: 170] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2012] [Revised: 12/06/2012] [Accepted: 12/10/2012] [Indexed: 06/01/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Though inflammatory response is beneficial to body damage repair, if it is out of control, it can produce adverse effects on the body. Although purely western anti-inflammatory drugs, orthodox medicines, can control inflammation occurrence and development, it is not enough. The clinical efficacy of anti-inflammation therapies is unsatisfactory, thus the search for new anti-inflammation continues. Chinese Material Medica (CMM) remains a promising source of new therapeutic agents. CMM and herbal formulae from Traditional Chinese Medicine (TCM), unorthodox medicines, play an improtant anti-inflammatory role in multi-targets, multi-levels, and multi-ways in treating inflammation diseases in a long history in China, based on their multi-active ingredient characteristics. Due to these reasons, recently, CMM has been commercialized as an anti-inflammation agent which has become increasingly popular in the world health drug markets. Major research contributions in ethnopharmacology have generated vast amount of data associated with CMM in anti-inflammtion aspect. Therefore, a systematic introduction of CMM anti-inflammatory research progress is of great importance and necessity. AIM OF THE STUDY This paper strives to describe the progress of CMM in the treatment of inflammatory diseases from different aspects, and provide the essential theoretical support and scientific evidence for the further development and utilization of CMM resources as a potential anti-inflammation drug through a variety of databases. MATERIAL AND METHODS Literature survey was performed via electronic search (SciFinder®, Pubmed®, Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries. RESULTS This review mainly introduced the current research on the anti-inflammatory active ingredient, anti-inflammatory effects of CMM, their mechanism, anti-inflammatory drug development of CMM, and toxicological information. CONCLUSION CMM is used clinically to treat inflammation symptoms in TCM, and its effect is mediated by multiple targets through multiple active ingredients. Although scholars around the world have made studies on the anti-inflammatory studies of CMM from different pathways and aspects and have made substantial progress, further studies are warranted to delineate the inflammation actions in more cogency models, establish the toxicological profiles and quality standards, assess the potentials of CMM in clinical applications, and make more convenient preparations easy to administrate for patients. Development of the clinically anti-inflammatory drugs are also warranted.
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Affiliation(s)
- Qiuhong Wang
- Key Laboratory of Ministry of Education, Department of Pharmacology, Heilongjiang University of Chinese Medicine, Harbin, China
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Kiss AK, Filipek A, Żyżyńska‐Granica B, Naruszewicz M. Effects of Penta‐
O
‐galloyl‐β‐D‐glucose on Human Neutrophil Function: significant Down‐Regulation of L‐selectin Expression. Phytother Res 2012; 27:986-92. [DOI: 10.1002/ptr.4822] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Revised: 07/19/2012] [Accepted: 07/23/2012] [Indexed: 11/06/2022]
Affiliation(s)
- Anna K. Kiss
- Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy Medical University of Warsaw Poland
| | - Agnieszka Filipek
- Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy Medical University of Warsaw Poland
| | - Barbara Żyżyńska‐Granica
- Department of General and Nutritional Biochemistry, Faculty of Health Sciences Medical University of Warsaw Poland
| | - Marek Naruszewicz
- Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy Medical University of Warsaw Poland
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Frasca G, Cardile V, Puglia C, Bonina C, Bonina F. Gelatin tannate reduces the proinflammatory effects of lipopolysaccharide in human intestinal epithelial cells. Clin Exp Gastroenterol 2012; 5:61-67. [PMID: 22629114 PMCID: PMC3358810 DOI: 10.2147/ceg.s28792] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Gelatin tannate is a mixture of tannic acid and gelatin. Tannic acid has astringent properties, due to its capacity to form protein-macromolecular complexes, as well as antibacterial and antioxidant properties. However, little is known about its anti-inflammatory properties. PURPOSE To evaluate the anti-inflammatory activity of gelatin tannate by quantifying the suppression of key molecules produced during inflammatory events in lipopolysaccharide (LPS)-stimulated human intestinal cells. METHODS Intercellular adhesion molecule-1 (ICAM-1) expression was determined by Western blot analysis; interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) concentrations were measured by enzyme-linked immunosorbent assays in Caco-2 cells 24 hours after treatment with LPS (1 μg/mL) in presence of different concentrations of gelatin tannate. RESULTS ICAM-1 is induced on a wide variety of cells by inflammatory stimuli such as LPS. Our results have shown gelatin tannate as a potent inhibitor of ICAM-1 expression in LPS-stimulated Caco-2 cells. IL-8 and TNF-α are important inflammatory mediators, recruiting neutrophils and T-lymphocytes. Together with LPS, adding gelatin tannate at different concentrations induced a dose-dependent inhibition of IL-8 and TNF-α released by Caco-2 cells. CONCLUSION These results suggest that gelatin tannate exerts anti-inflammatory effects by inhibiting the specific cytokines and adhesion molecules involved in several inflammatory disorders.
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Affiliation(s)
- Giuseppina Frasca
- Department of Biomedical Sciences (Physiology), University of Catania, Catania, Italy
| | - Venera Cardile
- Department of Biomedical Sciences (Physiology), University of Catania, Catania, Italy
| | - Carmelo Puglia
- Department of Drug Sciences, University of Catania, Catania, Italy
| | - Claudia Bonina
- Department of Drug Sciences, University of Catania, Catania, Italy
| | - Francesco Bonina
- Department of Drug Sciences, University of Catania, Catania, Italy
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Liu G, Xiong S, Xiang YF, Guo CW, Ge F, Yang CR, Zhang YJ, Wang YF, Kitazato K. Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus. Arch Virol 2011; 156:1359-69. [DOI: 10.1007/s00705-011-0989-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2010] [Accepted: 03/21/2011] [Indexed: 10/18/2022]
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35
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Pei Y, Chen ZP, Ju HQ, Komatsu M, Ji YH, Liu G, Guo CW, Zhang YJ, Yang CR, Wang YF, Kitazato K. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro. Biochem Biophys Res Commun 2011; 405:186-91. [DOI: 10.1016/j.bbrc.2011.01.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2010] [Accepted: 01/02/2011] [Indexed: 10/18/2022]
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Inhibitory effects of 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose on biofilm formation by Staphylococcus aureus. Antimicrob Agents Chemother 2010; 55:1021-7. [PMID: 21173176 DOI: 10.1128/aac.00843-10] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose (PGG) is an active ingredient in plants that are commonly used in Chinese medicine to treat inflammation. We demonstrate here that PGG, at 6.25 μM, does not inhibit the growth of Staphylococcus aureus, and yet it prevents biofilm formation on polystyrene and polycarbonate surfaces. At the same concentration, PGG is not toxic to human epithelial and fibroblast cells. PGG has an IB₅₀ value, i.e., the PGG concentration that inhibits 50% biofilm formation, of 3.6 μM. The value is substantially lower than that of N-acetylcysteine, iodoacetamide, and N-phenyl maleimide, which are known to inhibit biofilm formation by S. aureus. Biochemical and scanning electron microscopy results also reveal that PGG inhibits initial attachment of the bacteria to solid surface and the synthesis of polysaccharide intercellular adhesin, explaining how PGG inhibits biofilm formation. The results of this study demonstrate that coating PGG on polystyrene and silicon rubber surfaces with polyaniline prevents biofilm formation, indicating that PGG is highly promising for clinical use in preventing biofilm formation by S. aureus.
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Djakpo O, Yao W. Rhus chinensis and Galla Chinensis--folklore to modern evidence: review. Phytother Res 2010; 24:1739-47. [PMID: 20564459 PMCID: PMC7167973 DOI: 10.1002/ptr.3215] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2010] [Revised: 03/29/2010] [Accepted: 04/11/2010] [Indexed: 11/10/2022]
Abstract
The species Rhus chinensis Mill. (Anacardiaceae) is an important representative of the genus Rhus, which contains over 250 individual species found in temperate and tropical regions worldwide. Rhus chinensis has long been used by folk medicine practitioners in Asia. Leaves, roots, stem, bark, fruit and particularly the galls on Rhus chinensis leaves, Galla chinensis, are recognized to have preventative and therapeutic effects on different ailments (such as diarrhea, dysentery, rectal and intestinal cancer, diabetes mellitus, sepsis, oral diseases and inflammation). However, it is critical to separate evidence from anecdote. Fortunately, recent scientific research has revealed that Rhus chinensis compounds possess strong antiviral, antibacterial, anticancer, hepatoprotective, antidiarrheal and antioxidant activities. Moreover, compounds isolated from the stem of Rhus chinensis significantly suppressed HIV-1 activity in vitro. Compounds from this plant were also found to inhibit enamel demineralization in vitro and enhance remineralization of dental enamel with fluoride. This review highlights claims from traditional and tribal medicinal lore and makes a contemporary summary of phytochemical, biological and pharmacological findings on this plant material. It aims to show that the pharmaceutical potential of this plant deserves closer attention.
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Affiliation(s)
- Odilon Djakpo
- School of Food Science and Technology, Jiangnan University, Food Safety and Quality Control Laboratory, Wuxi, 214122, Jiangsu Province, P.R. China.
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Larrosa M, García-Conesa MT, Espín JC, Tomás-Barberán FA. Ellagitannins, ellagic acid and vascular health. Mol Aspects Med 2010; 31:513-39. [PMID: 20837052 DOI: 10.1016/j.mam.2010.09.005] [Citation(s) in RCA: 265] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2010] [Revised: 09/06/2010] [Accepted: 09/06/2010] [Indexed: 01/08/2023]
Abstract
Hydrolysable tannins are phenolic phytochemicals that show high antioxidant and free-radical scavenging activities. For this reason their potential effects preventing oxidative related diseases, such as cardiovascular diseases, have been largely studied. In vitro studies show that ellagitannins, at concentrations in the range 10-100 μM, show some relevant anti-atherogenic, anti-thrombotic, anti-inflammatory and anti-angiogenic effects, supporting the molecular mechanisms for the vascular health benefits. While there is good evidence supporting the vascular effects in vitro, the evidence on animal models or humans is much scarcer. The in vitro results often do not match the findings in the in vivo studies. This could be explained by the low bioavailability of the antioxidant ellagitannins and ellagic acid. The main ellagitannin metabolites circulating in plasma are ellagic acid microbiota metabolites known as urolithins, and they have lost their free-radical scavenging activity. They are present in plasma as glucuronide or sulphate conjugates, at concentrations in the nM range. Future studies should focus in the bioavailable metabolites, urolithins, and in the form (conjugated with glucuronic acid or sulphate) and concentrations (nM range) in which they are found in plasma. In this review we critically discuss the role of ellagitannins and ellagic acid on vascular health.
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Affiliation(s)
- Mar Larrosa
- Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, P.O. Box 164, Murcia 30100, Spain
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39
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He CN, Peng Y, Zhang YC, Xu LJ, Gu J, Xiao PG. Phytochemical and biological studies of paeoniaceae. Chem Biodivers 2010; 7:805-38. [PMID: 20397219 DOI: 10.1002/cbdv.200800341] [Citation(s) in RCA: 95] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Chun-Nian He
- Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, 151 Malianwa North Road, Beijing 100193, P. R. China
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40
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Fujita K, Yamamoto T, Kamezaki T, Matsumura A. Efficacy of keishibukuryogan, a traditional Japanese herbal medicine, in treating cold sensation and numbness after stroke: clinical improvement and skin temperature normalization in 22 stroke patients. Neurol Med Chir (Tokyo) 2010; 50:1-5; discussion 5-6. [PMID: 20098017 DOI: 10.2176/nmc.50.1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Cold sensation and numbness have been reported as post-stroke sensory sequelae attributable to distal axonopathy, which is caused by chronic ischemia of diseased limbs resulting from dysfunction of vasomotor regulatory systems. Keishibukuryogan is a traditional herbal medicine used to treat symptoms of peripheral ischemia such as cold extremities. This study investigated clinical improvement and skin temperature in peripheral ischemia patients to determine the efficacy of keishibukuryogan in alleviating post-stroke cold sensation and numbness. Twenty-two stroke patients with cold sensation and/or numbness were enrolled in this study. Subjective cold sensation and numbness, evaluated using the visual analogue scale, were found in 21 and 31 limbs, respectively. The skin temperature of diseased and healthy limbs was recorded. We observed all patients for 4 weeks and 17 patients for 8 weeks after administration of keishibukuryogan. The skin temperature of diseased limbs was significantly higher than baseline at 4 weeks and 8 weeks, whereas that of healthy limbs did not change significantly. Cold sensation and numbness were significantly improved at 4 weeks and 8 weeks compared to baseline. Keishibukuryogan administration resulted in warming of diseased limbs and improved cold sensation and numbness, probably by increasing peripheral blood flow.
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Affiliation(s)
- Keishi Fujita
- Department of Neurosurgery, Ibaraki Seinan Medical Center Hospital, Ibaraki, Japan
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41
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Bing SJ, Kim MJ, Park E, Ahn G, Kim DS, Ko RK, Lee NH, Shin T, Park JW, Jee Y. 1,2,3,4,6-Penta-O-galloyl-.BETA.-D-glucose Protects Splenocytes against Radiation-Induced Apoptosis in Murine Splenocytes. Biol Pharm Bull 2010; 33:1122-7. [DOI: 10.1248/bpb.33.1122] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- So Jin Bing
- Department of Veterinary Medicine and Applied Radiological Science Research Institute, Jeju National University
| | - Min Ju Kim
- Department of Veterinary Medicine and Applied Radiological Science Research Institute, Jeju National University
| | - Eunjin Park
- Department of Veterinary Medicine and Applied Radiological Science Research Institute, Jeju National University
| | - Ginnae Ahn
- Faculty of Marine Life Sciences, Jeju National University
| | - Dae Seung Kim
- Department of Veterinary Medicine and Applied Radiological Science Research Institute, Jeju National University
| | - Ryeo Kyeong Ko
- Department of Chemistry, College of Natural Sciences, Jeju National University
| | - Nam Ho Lee
- Department of Chemistry, College of Natural Sciences, Jeju National University
| | - Taekyun Shin
- Department of Veterinary Medicine and Applied Radiological Science Research Institute, Jeju National University
| | - Jae Woo Park
- Department of Nuclear and Energy Engineering, Jeju National University
| | - Youngheun Jee
- Department of Veterinary Medicine and Applied Radiological Science Research Institute, Jeju National University
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Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-galloyl-β-d-glucose via blockade of NF-κB and STAT1 activation in the HaCaT cells. Biochem Biophys Res Commun 2009; 387:115-20. [DOI: 10.1016/j.bbrc.2009.06.137] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2009] [Accepted: 06/29/2009] [Indexed: 11/27/2022]
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Zhang J, Li L, Kim SH, Hagerman AE, Lü J. Anti-cancer, anti-diabetic and other pharmacologic and biological activities of penta-galloyl-glucose. Pharm Res 2009; 26:2066-80. [PMID: 19575286 PMCID: PMC2822717 DOI: 10.1007/s11095-009-9932-0] [Citation(s) in RCA: 205] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2009] [Accepted: 06/17/2009] [Indexed: 12/22/2022]
Abstract
1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose (PGG) is a polyphenolic compound highly enriched in a number of medicinal herbals. Several in vitro and a handful of in vivo studies have shown that PGG exhibits multiple biological activities which implicate a great potential for PGG in the therapy and prevention of several major diseases including cancer and diabetes. Chemically and functionally, PGG appears to be distinct from its constituent gallic acid or tea polyphenols. For anti-cancer activity, three published in vivo preclinical cancer model studies with PGG support promising efficacy to selectively inhibit malignancy without host toxicity. Potential mechanisms include anti-angiogenesis; anti-proliferative actions through inhibition of DNA replicative synthesis, S-phase arrest, and G(1) arrest; induction of apoptosis; anti-inflammation; and anti-oxidation. Putative molecular targets include p53, Stat3, Cox-2, VEGFR1, AP-1, SP-1, Nrf-2, and MMP-9. For anti-diabetic activity, PGG and analogues appear to improve glucose uptake. However, very little is known about the absorption, pharmacokinetics, and metabolism of PGG, or its toxicity profile. The lack of a large quantity of highly pure PGG has been a bottleneck limiting in vivo validation of cancer preventive and therapeutic efficacies in clinically relevant models.
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Affiliation(s)
- Jinhui Zhang
- The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
| | - Li Li
- The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
| | - Sung-Hoon Kim
- The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
- Cancer Preventive Material Development Research Center and Institute, College of Oriental Medicine, Kyunghee University, Republic of Korea
| | - Ann E. Hagerman
- Department of Chemistry & Biochemistry, Miami University, Oxford OH 45056
| | - Junxuan Lü
- The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
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Piao MJ, Kang KA, Zhang R, Ko DO, Wang ZH, Lee KH, Chang WY, Chae S, Jee Y, Shin T, Park JW, Lee NH, Hyun JW. Antioxidant properties of 1,2,3,4,6-penta-O-galloyl-β-d-glucose from Elaeocarpus sylvestris var. ellipticus. Food Chem 2009. [DOI: 10.1016/j.foodchem.2008.12.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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45
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Lee HG, Kim SY, Kim DS, Seo SR, Lee SI, Shin DM, De Smet P, Seo JT. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one inhibits neurite outgrowth and causes neurite retraction in PC12 cells independently of soluble guanylyl cyclase. J Neurosci Res 2009; 87:269-77. [PMID: 18711750 DOI: 10.1002/jnr.21838] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The effect of the potent soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) on neurite outgrowth and retraction was investigated in PC12 cells and SH-SY5Y human neuroblastoma cells. ODQ inhibited neurite outgrowth and triggered neurite retraction in the cells stimulated with nerve growth factor (NGF), staurosporine, or Y-27632. The nitric oxide (NO) scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO) had little effect on neurite outgrowth induced by Y-27632 or staurosporine. In the presence of ODQ, treatment of the cells with the cell-permeable cGMP analogue 8-bromo-cGMP failed to retrigger Y-27632- and staurosporine-induced neurite outgrowth. Furthermore, the depletion of sGC by RNA interference failed to prevent Y-27632- and staurosporine-induced neurite outgrowth. These results indicate that the NO/sGC/cGMP signaling cascade is not critically involved in ODQ-induced neurite remodeling. The MEK inhibitor PD98059 did not inhibit neurite outgrowth, and Y-27632 and staurosporine did not induce ERK phosphorylation, suggesting that the inhibitory effect of ODQ on neurite outgrowth is independent of the ERK signaling pathway. In contrast, pretreatment with dithionite or a hemin-glutathione mixture reversed the inhibitory effect of ODQ on Y-27632- and staurosporine-induced neurite outgrowth, indicating that ODQ might act on an intracellular redox-sensitive molecule. We conclude that ODQ inhibits Y-27632- and staurosporine-induced neurite outgrowth and triggers neurite retraction in an sGC-independent manner in neuronal cells and suggest that oxidation of unidentified redox-sensitive protein could be responsible for these effects.
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Affiliation(s)
- Han Gil Lee
- Department of Oral Biology, BK 21 Project for Yonsei Dental Sciences, Yonsei University College of Dentistry, Seoul, Korea
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46
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Lee JH, Yehl M, Ahn KS, Kim SH, Lieske JC. 1,2,3,4,6-penta-O-galloyl-beta-D-glucose attenuates renal cell migration, hyaluronan expression, and crystal adhesion. Eur J Pharmacol 2009; 606:32-7. [PMID: 19374853 DOI: 10.1016/j.ejphar.2009.01.024] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2008] [Revised: 12/15/2008] [Accepted: 01/09/2009] [Indexed: 11/30/2022]
Abstract
Calcium oxalate monohydrate (COM) crystals bind avidly to the surface of proliferating and migrating renal endothelial cells, and oxalate-induced peroxidative injury can promote crystal attachment to renal epithelial cells. 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), isolated from a traditional herbal remedy, inhibits vascular endothelial growth factor (VEGF) stimulated proliferation and migration of human umbilical vein endothelial cells (HUVECs) and has antioxidant activity. This study was performed to determine if PGG altered calcium oxalate monohydrate (COM) crystal adhesion to cells, perhaps via a change in cell surface properties. PGG significantly decreased COM crystal adhesion to cultured MDCK I cells at a low concentration (<10 microM) which was not cytotoxic. PGG exerted anti-adhesion effects whether cells or crystals were pre-coated. PGG also inhibited cell migration after scrape-wounding, decreased subsequent adhesion of crystals to proliferating and migrating cells, and decreased expression of the crystal binding molecule hyaluronan. These findings suggest that PGG represents a potential urolithiasis prevention compound. Anti-crystal adhesion effects appear multifaceted involving crystal coating by PGG, as well as decreased cell migration and the associated surface expression of hyaluronan. The latter represents a novel mechanism of nephrolithiasis prevention.
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Affiliation(s)
- Jae-Ho Lee
- Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
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Kim MS, Park SB, Suk K, Kim IK, Kim SY, Kim JA, Lee SH, Kim SH. Gallotannin Isolated from Euphorbia Species, 1,2,6-Tri-O-galloyl-.BETA.-D-allose, Decreases Nitric Oxide Production through Inhibition of Nuclear Factor-.KAPPA.>B and Downstream Inducible Nitric Oxide Synthase Expression in Macrophages. Biol Pharm Bull 2009; 32:1053-6. [DOI: 10.1248/bpb.32.1053] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Mi-Sun Kim
- CMRI, IHBR, Department of Pharmacology, School of Medicine, Kyungpook National University
| | - Seung-Bin Park
- CMRI, IHBR, Department of Pharmacology, School of Medicine, Kyungpook National University
| | - Kyoungho Suk
- CMRI, IHBR, Department of Pharmacology, School of Medicine, Kyungpook National University
| | - In Kyeom Kim
- CMRI, IHBR, Department of Pharmacology, School of Medicine, Kyungpook National University
| | - Sang-Yong Kim
- Division of Specimen and Genetic Resources, Korea National Arboretum
| | | | | | - Sang-Hyun Kim
- CMRI, IHBR, Department of Pharmacology, School of Medicine, Kyungpook National University
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48
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Al-Ayyoubi S, Gali-Muhtasib H. Differential apoptosis by gallotannin in human colon cancer cells with distinct p53 status. Mol Carcinog 2007; 46:176-86. [PMID: 17192871 DOI: 10.1002/mc.20252] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Gallotannin (GT), a plant polyphenol, has shown anticarcinogenic activities in several animal models including colon cancer. In our previous study, we showed that GT inhibits 1,2-dimethylhydrazine-induced colonic aberrant crypt foci and tumors in Balb/c mice, thus supporting a role for GT as a chemopreventive agent in colon cancer. However, at the molecular level, GT's mechanism of chemoprevention is still unclear. In this study, we aim at identifying GT's potential molecular mechanisms of action in in vitro studies. We show that GT differentially inhibits the growth of two isogenic HCT-116 (p53+/+, p53-/-) human colon cancer cells versus normal human intestinal epithelial cells (FHs 74Int). DNA flow cytometric analysis showed that GT induced S-phase arrest in both HCT-116 cell lines. Cell-cycle arrest in p53 (+/+) cells was associated with an increase in p53 protein levels and p21 transcript and protein levels. The inhibition of cell-cycle progression of HCT-116 p53 (+/+) cells by GT correlated with a reduction in the protein levels of cyclin D(1), pRb, and the Bax/Bcl-2 ratio. Although GT did not induce apoptosis in p53 (+/+) cells, a significant induction of apoptosis was observed in p53 (-/-) cells as shown by TUNEL staining and flow cytometry analysis. Apoptosis induction in p53 (-/-) cells was associated with a significant increase in Bax/Bcl-2 protein levels. Our results demonstrate that GT inhibits the growth of HCT-116 colon cancer cells in a p53-independent manner but exhibits differential sensitivity to apoptosis induction in HCT-116 cells with distinct p53 status.
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Affiliation(s)
- Sahar Al-Ayyoubi
- Department of Biology, The American University of Beirut, Beirut, Lebanon
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49
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An RB, Kim HC, Lee SH, Jeong GS, Sohn DH, Park H, Kwon DY, Lee JH, Kim YC. A new monoterpene glycoside and antibacterial monoterpene glycosides fromPaeonia suffruticosa. Arch Pharm Res 2006; 29:815-20. [PMID: 17121173 DOI: 10.1007/bf02973899] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Antibacterial activity-guided fractionation of the CHCI3-MeOH (1:1) extract of Paeonia suffruticosa root bark furnished three monoterpene glycosides, 6-O-vanillyoxypaeoniflorin (1), mudanpioside-H (2), and galloyl-oxypaeoniflorin (3). Of the isolated compounds, compound 1 is a new compound. All isolated compounds showed broad, but moderate, antibacterial activity with minimum inhibitory concentration (MIC) values in the range of 100 to 500 microg/mL against eighteen pathogenic microorganisms of concern for public health or zoonosis.
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Affiliation(s)
- Ren-Bo An
- College of Pharmacy, Wonkwang University, Iksan 570-749, Korea
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