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1
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Bourquin RA, Sorenson AE, Schaeffer PM. Fluorescent HIV-1 integrases for a suite of new user-friendly stability, nucleic acid binding and strand transfer activity assays. Int J Biol Macromol 2025; 309:142859. [PMID: 40216138 DOI: 10.1016/j.ijbiomac.2025.142859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 03/26/2025] [Accepted: 04/03/2025] [Indexed: 04/15/2025]
Abstract
Human immunodeficiency virus (HIV) infects CD4+ T-cells, causing acquired immunodeficiency syndrome. Despite advances in antiretroviral therapy, drug resistance remains a critical issue. HIV integrase is a key therapeutic target. Resistance to integrase strand transfer inhibitors requires development of new drugs with distinct mechanisms. Integrases tethered with GFP (IN-GFP) and mCherry (IN-mCherry) were evaluated for the development of a comprehensive suite of user-friendly assays. A new fluorescent protein-based stability assay (FP-Basta) effectively assessed protein thermal stability, revealing aggregation midpoints of 45.0 °C for IN-GFP and 45.4 °C for IN-mCherry. FP-Basta showed that IN-mCherry was stabilized by a target DNA and viral LTR, confirming protein-DNA interactions. A new qPCR-based integrase activity assay demonstrated robust detection of strand transfer activity, with a ∼21,500-fold sensitivity over background. Manganese ions were essential, enhancing integrase activity 56-fold compared to magnesium ions, while Zn2+ impaired functionality. The integrase activity assay can distinguish 3'-processing and strand transfer activities and was validated for inhibitor screening. The combination of FP-Basta and qPCR-based integrase activity assay provides a comprehensive, cost-effective platform for evaluating IN function and inhibitor efficacy. These tools, leveraging GFP- and mCherry-tagged IN, offer potential for future high-throughput applications in HIV drug discovery and the development of therapies addressing resistance challenges.
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Affiliation(s)
- Rebecca A Bourquin
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Douglas, QLD 4811, Australia
| | - Alanna E Sorenson
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Douglas, QLD 4811, Australia
| | - Patrick M Schaeffer
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Douglas, QLD 4811, Australia.
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Wang Z, Cai X, Ren Z, Shao Y, Xu Y, Fu L, Zhu Y. Piceatannol as an Antiviral Inhibitor of PRV Infection In Vitro and In Vivo. Animals (Basel) 2023; 13:2376. [PMID: 37508153 PMCID: PMC10375968 DOI: 10.3390/ani13142376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/17/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiviral activity of piceatannol. The results showed that piceatannol could restrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. Piceatannol could exert an anti-PRV effect by reducing the transcription level of viral genes, inhibiting PRV-induced apoptosis and elevating the levels of IL-4, TNF-α and IFN-γ in the serum of mice. Animal experiments showed that piceatannol could delay the onset of disease, reduce the viral load in the brain and kidney and reduce the pathological changes in the tissues and organs of the mice to improve the survival rate of the mice (14.3%). Therefore, the anti-PRV activity of piceatannol in vivo and in vitro was systematically evaluated in this study to provide scientific data for developing a new alternative measure for controlling PRV infection.
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Affiliation(s)
- Zhiying Wang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150038, China
| | - Xiaojing Cai
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150038, China
| | - Zhiyuan Ren
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150038, China
| | - Yi Shao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150038, China
| | - Yongkang Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150038, China
| | - Lian Fu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150038, China
| | - Yan Zhu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150038, China
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Wang S, Zhou X, He X, Ma S, Sun C, Zhang J, Xu X, Jin W, Yan J, Lin P, Mao G. Suppressive effects of pterostilbene on human cytomegalovirus (HCMV) infection and HCMV-induced cellular senescence. Virol J 2022; 19:224. [PMID: 36564838 PMCID: PMC9782289 DOI: 10.1186/s12985-022-01954-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Human cytomegalovirus (HCMV), a member of the β-herpesvirus family, causes the establishment of a latent infection that persists throughout the life of the host and can be reactivated when immunity is weakened. To date, there is no vaccine to prevent HCMV infection, and clinically approved drugs target the stage of viral replication and have obvious adverse reactions. Thus, development of novel therapeutics is urgently needed. METHODS In the current study, we identified a naturally occurring pterostilbene that inhibits HCMV Towne strain replication in human diploid fibroblast WI-38 cells through Western blotting, qPCR, indirect immunofluorescence assay, tissue culture infective dose assays. The time-of-addition experiment was carried out to identify the stage at which pterostilbene acted. Finally, the changes of cellular senescence biomarkers and reactive oxygen species production brought by pterostilbene supplementation were used to partly elucidate the mechanism of anti-HCMV activity. RESULTS Our findings revealed that pterostilbene prevented lytic cytopathic changes, inhibited the expression of viral proteins, suppressed the replication of HCMV DNA, and significantly reduced the viral titre in WI-38 cells. Furthermore, our data showed that pterostilbene predominantly acted after virus cell entry and membrane fusion. The half-maximal inhibitory concentration was determined to be 1.315 μM and the selectivity index of pterostilbene was calculated as 26.73. Moreover, cell senescence induced by HCMV infection was suppressed by pterostilbene supplementation, as shown by a decline in senescence-associated β-galactosidase activity, decreased production of reactive oxygen species and reduced expression of p16, p21 and p53, which are considered biomarkers of cellular senescence. CONCLUSION Together, our findings identify pterostilbene as a novel anti-HCMV agent that may prove useful in the treatment of HCMV replication.
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Affiliation(s)
- Sanying Wang
- grid.417400.60000 0004 1799 0055Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030 People’s Republic of China
| | - Xuqiang Zhou
- grid.417400.60000 0004 1799 0055Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030 People’s Republic of China ,grid.268505.c0000 0000 8744 8924College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053 People’s Republic of China
| | - Xinyue He
- grid.469325.f0000 0004 1761 325XCollege of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014 People’s Republic of China
| | - Shushu Ma
- grid.417400.60000 0004 1799 0055Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030 People’s Republic of China
| | - Chuan Sun
- grid.417400.60000 0004 1799 0055Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030 People’s Republic of China
| | - Jing Zhang
- grid.417400.60000 0004 1799 0055Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030 People’s Republic of China
| | - Xiaogang Xu
- grid.417400.60000 0004 1799 0055Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030 People’s Republic of China
| | - Weihua Jin
- grid.469325.f0000 0004 1761 325XCollege of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014 People’s Republic of China
| | - Jin Yan
- grid.417400.60000 0004 1799 0055Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030 People’s Republic of China
| | - Ping Lin
- Geriatric Department of the 3rd Hospital of Hangzhou, 310009 Hangzhou, People’s Republic of China
| | - Genxiang Mao
- grid.417400.60000 0004 1799 0055Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030 People’s Republic of China ,grid.268505.c0000 0000 8744 8924College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053 People’s Republic of China
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Benabbes R, Ouahhoud S, Moueqqit M, Addi M, Hano C, Delporte C, Nacoulma AP, Megalizzi V. The Major Stilbene Compound Accumulated in the Roots of a Resistant Variety of Phoenix dactylifera L. Activates Proteasome for a Path in Anti-Aging Strategy. Cells 2022; 12:cells12010071. [PMID: 36611864 PMCID: PMC9818208 DOI: 10.3390/cells12010071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 12/14/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
The main objective of the present study is to estimate, through differential analysis, various biological activities of total phenolics content in alcoholic extracts of three date palm varieties sensitive or resistant to Fusarium oxysporum. sp Albidinis. Here, stilbene products with antioxidant and bioactive capacities were evidenced in resistant variety Taabdount (TAAR). Furthermore, the methanolic fraction of the TAAR-resistant date palm variety contains a significant product, determined by LC-MS/MS and 1H, 13C NMR, belonging to the family of hydroxystilbenes, which exhibits antioxidant capacities, inhibits the mushroom tyrosinase activity, and activates and exerts a protective effect on hypochlorite-induced damage in 20S proteasome of human dermal fibroblast aged cells. Altogether, the present results indicate that hydroxystilbene present in resistant Phoenix dactylifera L. should be studied to understand the way that the stilbene could exert anti-aging ability.
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Affiliation(s)
- Redouane Benabbes
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Université Mohamed Premier, BV Mohammed VI BP 717, Oujda 60000, Morocco
| | - Sabir Ouahhoud
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Université Mohamed Premier, BV Mohammed VI BP 717, Oujda 60000, Morocco
| | - Mohammed Moueqqit
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Université Mohamed Premier, BV Mohammed VI BP 717, Oujda 60000, Morocco
| | - Mohamed Addi
- Laboratory of Improvement of Agricultural Production, Biotechnology and Environment, Department of Biology, Faculty of Sciences, Université Mohamed Premier, Oujda 60000, Morocco
| | - Christophe Hano
- Laboratoire de Biologie des Ligneux et des Grandes Cultures, INRA USC1328, Orleans University, CEDEX 2, 45067 Orléans, France
- Correspondence:
| | - Cédric Delporte
- Microbiology, Bioorganic and Macromolecular Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, Bvd du Triomphe, 1050 Brussels, Belgium
| | - Aminata P. Nacoulma
- The Unit Pharmacognosy, Bioanalysis & Drug Discovery (PBDD), Department of Drug Research and Development, Faculty of Pharmacy, Université Libre de Bruxelles, Bvd du Triomphe, 1050 Brussels, Belgium
| | - Véronique Megalizzi
- Microbiology, Bioorganic and Macromolecular Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, Bvd du Triomphe, 1050 Brussels, Belgium
- The Unit Pharmacognosy, Bioanalysis & Drug Discovery (PBDD), Department of Drug Research and Development, Faculty of Pharmacy, Université Libre de Bruxelles, Bvd du Triomphe, 1050 Brussels, Belgium
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Richetta C, Tu NQ, Delelis O. Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance. Viruses 2022; 14:v14122591. [PMID: 36560595 PMCID: PMC9785060 DOI: 10.3390/v14122591] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/17/2022] [Accepted: 11/19/2022] [Indexed: 11/23/2022] Open
Abstract
Integrase Strand Transfer Inhibitors (INSTIs) are currently used as the most effective therapy in the treatment of human immunodeficiency virus (HIV) infections. Raltegravir (RAL) and Elvitegravir (EVG), the first generation of INSTIs used successfully in clinical treatment, are susceptible to the emergence of viral resistance and have a high rate of cross-resistance. To counteract these resistant mutants, second-generation INSTI drugs have been developed: Dolutegravir (DTG), Cabotegravir (CAB), and Bictegravir (BIC). However, HIV is also able to develop resistance mechanisms against the second-generation of INSTIs. This review describes the mode of action of INSTIs and then summarizes and evaluates some typical resistance mutations, such as substitution and insertion mutations. The role of unintegrated viral DNA is also discussed as a new pathway involved in conferring resistance to INSTIs. This allows us to have a more detailed understanding of HIV resistance to these inhibitors, which may contribute to the development of new INSTIs in the future.
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Teka T, Zhang L, Ge X, Li Y, Han L, Yan X. Stilbenes: Source plants, chemistry, biosynthesis, pharmacology, application and problems related to their clinical Application-A comprehensive review. PHYTOCHEMISTRY 2022; 197:113128. [PMID: 35183567 DOI: 10.1016/j.phytochem.2022.113128] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 02/08/2022] [Accepted: 02/09/2022] [Indexed: 06/14/2023]
Abstract
Stilbenes are some of the important phenolic compounds originating from plant families like Vitaceae, Leguminaceae, Gnetaceae, and Dipterocarpaceae. Structurally, they have a C6-C2-C6 skeleton, usually with two isomeric forms. Stilbenes are biosynthesized due to biotic and abiotic stresses such as microbial infections, high temperatures, and oxidation. This review aims to provide a comprehensive overview of stilbenes' botanical sources, chemistry, biosynthetic pathways, pharmacology, and clinical applications and challenges based on up-to-date data. All included studies were collected from PubMed, ScienceDirect, Google Scholar, and CNKI, and the presented data from these indexed studies were analyzed and summarized. A total of 459 natural stilbene compounds from 45 plant families and 196 plant species were identified. Pharmacological studies also show that stilbenes have various activities such as anticancer, antimicrobial, antioxidant, anti-inflammatory, anti-degenerative diseases, anti-diabetic, neuroprotective, anti-aging, and cardioprotective effects. Stilbene synthase (STS) is the key enzyme involved in stilbene biosynthetic pathways. Studies on the therapeutic application of stilbenes pinpoint that challenges such as low bioavailability and isomerization are the major bottlenecks for their development as therapeutic drugs. Although the medicinal uses of several stilbenes have been demonstrated in vivo and in vitro, studies on the development of stilbenes deserve more attention in the future.
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Affiliation(s)
- Tekleab Teka
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China; Department of Pharmacy, College of Medicine and Health Sciences, Wollo University, P. O. Box 1145, Dessie, Ethiopia
| | - Lele Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China
| | - Xiaoyan Ge
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China
| | - Yanjie Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China
| | - Lifeng Han
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China.
| | - Xiaohui Yan
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China.
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HIV-1 Integrase Inhibitory Effects of Major Compounds Present in CareVid™: An Anti-HIV Multi-Herbal Remedy. Life (Basel) 2022; 12:life12030417. [PMID: 35330168 PMCID: PMC8950597 DOI: 10.3390/life12030417] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 11/21/2022] Open
Abstract
In our continued study on the anti-HIV activity of compounds present in CareVidTM, we report the HIV-1 integrase ((HIV-1 IN) inhibitory effects of pellitorine (1), oleuropein (2), magnoflorine (3), crotepoxide (4), ent-kaurane-16β,17-diol (5), crotocorylifuran (6), lupeol (7), betulin (8), and ellagic acid (9) in an in vitro enzyme assay, and in an in silico study. Ellagic acid, pellitorine, lupeol, and betulin showed an in vitro percentage inhibition against HIV-1 IN of 21.1%, 19.0%, 18.5%, and 16.8%, respectively, at a standard concentration of 25 μg/mL. However, from a pharmacokinetic perspective, ellagic acid has poor bioavailability, due to rapid elimination in metabolism in the gut microbiome. It was postulated that known gut catabolites of ellagic acid, urolithin A (10) and urolithin B (11) could be more promising candidates in exploring the anti-HIV activity of ellagic acid-rich medicinal species consumed orally. On the contrary, urolithin A and urolithin B demonstrated lower activity with comparison to ellagic acid. The binding affinity of compounds 1–9, urolithin A, and urolithin B against the catalytic domain of HIV-1 IN was also explored by in silico methods. Docking studies showed oleuropein as the best candidate, with a predicted energy of binding of ΔG −5.81 kcal/mol, while ellagic acid showed moderate predicted inhibition (ΔG −4.38 kcal/mol) caused by the interaction between the carbonyl and the key Mg2+ ion in the active site.
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Souid I, Korchef A, Souid S. In silico evaluation of Vitis amurensis Rupr. polyphenol compounds for their inhibition potency against CoVID-19 main enzymes Mpro and RdRp. Saudi Pharm J 2022; 30:570-584. [PMID: 35250347 PMCID: PMC8883852 DOI: 10.1016/j.jsps.2022.02.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 02/21/2022] [Indexed: 02/07/2023] Open
Abstract
The rapid transmission of the pneumonia (COVID-19) emerged as an entire worldwide health concern and it was declared as pandemic by the World Health Organization (WHO) as a consequence of the increasing reported infections number. COVID-19 disease is caused by the novel SARS-CoV-2 virus, and unfortunatly no drugs are currently approved against this desease. Accordingly, it is of outmost importance to review the possible therapeutic effects of naturally-occuring compounds that showed approved antiviral activities. The molecular docking approach offers a rapid prediction of a possible inhibition of the main enzymes Mpro and RdRp that play crucial role in the SARS-CoV-2 replication and transcription. In the present work, we review the anti-viral activities of polyphenol compounds (phenolic acids, flavonoids and stilbene) derived from the traditional Chinese medicinal Vitis amurensis. Recent molecular docking studies reported the possible binding of these polyphenols on SARS-CoV-2 enzymes Mpro and RdRp active sites and showed interesting inhibitory effects. This antiviral activity was explained by the structure-activity relationships of the studied compounds. Also, pharmacokinetic analysis of the studied molecules is simulated in the present work. Among the studied polyphenol compounds, only five, namely caffeic acid, ferulic acid, quercetin, naringenin and catechin have drug-likeness characteristics. These five polyphenols derived from Vitis amurensis are promising drug candidates for the COVID-19 treatment.
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Wang Y, Lv W, Li Y, Liu D, He X, Liu T. Ampelopsin Improves Cognitive Impairment in Alzheimer's Disease and Effects of Inflammatory Cytokines and Oxidative Stress in the Hippocampus. Curr Alzheimer Res 2021; 17:44-51. [PMID: 31797758 DOI: 10.2174/1567205016666191203153447] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 11/17/2019] [Accepted: 12/02/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Neuroinflammation and oxidative stress have significant effects on cognitive deficiency in the pathophysiological development of Alzheimer's disease (AD). In the present study, we studied the influences of Ampelopsin (AMP) on proinflammatory cytokines (PICs, IL-1β, IL-6 and TNF-α), and products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, a product of oxidative stress); and 8-hydroxy-2'-deoxyguanosine (8-OHdG, a key biomarker of protein oxidation) in the hippocampus using a rat model of AD. METHODS ELISA was used to examine PICs and oxidative stress production; and western blotting to examine NADPH oxidase (NOXs). The Spatial working memory tests and Morris water maze were utilized to assess cognitive functions. RESULTS We observed amplification of IL-1β, IL-6 and TNF-α as well as 8-iso PGF2α and 8-OHdG in the hippocampus of AD rats. AMP attenuated upregulation of PICs and oxidative stress production. AMP also inhibited NOX4 in the AD rat hippocampus. Notably, AMP mostly improved learning performance in AD rat and this was linked to signal pathways of PIC and oxidative stress. CONCLUSION AMP plays a significant role in improving the memory deficiency in AD rats via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that AMP is likely to prospect in preventing and relieving development of the cognitive dysfunctions in AD as a complementary alternative intervention.
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Affiliation(s)
- Yan Wang
- Department of Geriatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Wei Lv
- Department of Geriatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Yueyang Li
- Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Dandan Liu
- Center of Physical Examination, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Xiuting He
- Department of Geriatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Ting Liu
- Department of Geriatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, China
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Joshi RS, Jagdale SS, Bansode SB, Shankar SS, Tellis MB, Pandya VK, Chugh A, Giri AP, Kulkarni MJ. Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease. J Biomol Struct Dyn 2021; 39:3099-3114. [PMID: 32329408 PMCID: PMC7212545 DOI: 10.1080/07391102.2020.1760137] [Citation(s) in RCA: 168] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 04/20/2020] [Indexed: 12/24/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected over 2.5 million individuals with a mortality rate ranging from 5 to 10%. There are several efforts going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (MPro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of MPro, we have performed phylogenetic and Sequence Similarity Network analysis, that depicted divergence of Coronaviridae MPro in five clusters specific to viral hosts. This clustering was corroborated with the comparison of MPro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. These attributes can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 MPro. In agreement with this, we performed screening of ∼7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 MPro as the primary target. We identified several natural molecules like δ-viniferin, myricitrin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, hesperidin and phyllaemblicin B that strongly binds to SARS-CoV-2 MPro. Intrestingly, these molecules also showed strong binding with other potential targets of SARS-CoV-2 infection like viral receptor human angiotensin-converting enzyme 2 (hACE-2) and RNA dependent RNA polymerase (RdRp). We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Rakesh S. Joshi
- Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Shounak S. Jagdale
- Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India
| | - Sneha B. Bansode
- Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India
| | - S. Shiva Shankar
- Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Meenakshi B. Tellis
- Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India
- Department of Botany, Savitribai Phule Pune University, Pune, India
| | | | | | - Ashok P. Giri
- Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Mahesh J. Kulkarni
- Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
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11
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Pappalardo AM, Ferrito V, Biscotti MA, Canapa A, Capriglione T. Transposable Elements and Stress in Vertebrates: An Overview. Int J Mol Sci 2021; 22:1970. [PMID: 33671215 PMCID: PMC7922186 DOI: 10.3390/ijms22041970] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/13/2021] [Accepted: 02/14/2021] [Indexed: 12/17/2022] Open
Abstract
Since their identification as genomic regulatory elements, Transposable Elements (TEs) were considered, at first, molecular parasites and later as an important source of genetic diversity and regulatory innovations. In vertebrates in particular, TEs have been recognized as playing an important role in major evolutionary transitions and biodiversity. Moreover, in the last decade, a significant number of papers has been published highlighting a correlation between TE activity and exposition to environmental stresses and dietary factors. In this review we present an overview of the impact of TEs in vertebrate genomes, report the silencing mechanisms adopted by host genomes to regulate TE activity, and finally we explore the effects of environmental and dietary factor exposures on TE activity in mammals, which is the most studied group among vertebrates. The studies here reported evidence that several factors can induce changes in the epigenetic status of TEs and silencing mechanisms leading to their activation with consequent effects on the host genome. The study of TE can represent a future challenge for research for developing effective markers able to detect precocious epigenetic changes and prevent human diseases.
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Affiliation(s)
- Anna Maria Pappalardo
- Department of Biological, Geological and Environmental Sciences-Section of Animal Biology "M. La Greca", University of Catania, Via Androne 81, 95124 Catania, Italy
| | - Venera Ferrito
- Department of Biological, Geological and Environmental Sciences-Section of Animal Biology "M. La Greca", University of Catania, Via Androne 81, 95124 Catania, Italy
| | - Maria Assunta Biscotti
- Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy
| | - Adriana Canapa
- Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy
| | - Teresa Capriglione
- Department of Biology, University of Naples "Federico II", Via Cinthia 21-Ed7, 80126 Naples, Italy
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Jeandet P, Vannozzi A, Sobarzo-Sánchez E, Uddin MS, Bru R, Martínez-Márquez A, Clément C, Cordelier S, Manayi A, Nabavi SF, Rasekhian M, El-Saber Batiha G, Khan H, Morkunas I, Belwal T, Jiang J, Koffas M, Nabavi SM. Phytostilbenes as agrochemicals: biosynthesis, bioactivity, metabolic engineering and biotechnology. Nat Prod Rep 2021; 38:1282-1329. [PMID: 33351014 DOI: 10.1039/d0np00030b] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Covering: 1976 to 2020. Although constituting a limited chemical family, phytostilbenes represent an emblematic group of molecules among natural compounds. Ever since their discovery as antifungal compounds in plants and their ascribed role in human health and disease, phytostilbenes have never ceased to arouse interest for researchers, leading to a huge development of the literature in this field. Owing to this, the number of references to this class of compounds has reached the tens of thousands. The objective of this article is thus to offer an overview of the different aspects of these compounds through a large bibliography analysis of more than 500 articles. All the aspects regarding phytostilbenes will be covered including their chemistry and biochemistry, regulation of their biosynthesis, biological activities in plants, molecular engineering of stilbene pathways in plants and microbes as well as their biotechnological production by plant cell systems.
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Affiliation(s)
- Philippe Jeandet
- Research Unit "Induced Resistance and Plant Bioprotection", EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687 Reims Cedex 2, France.
| | - Alessandro Vannozzi
- Department of Agronomy, Food, Natural Resources, Animals, and Environment (DAFNAE), University of Padova, 35020 Legnaro, PD, Italy
| | - Eduardo Sobarzo-Sánchez
- Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain and Instituto de Investigación e Innovación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Chile
| | - Md Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh and Neuroscience Research Network, Dhaka, Bangladesh
| | - Roque Bru
- Plant Proteomics and Functional Genomics Group, Department of Agrochemistry and Biochemistry, Faculty of Science, University of Alicante, Alicante, Spain
| | - Ascension Martínez-Márquez
- Plant Proteomics and Functional Genomics Group, Department of Agrochemistry and Biochemistry, Faculty of Science, University of Alicante, Alicante, Spain
| | - Christophe Clément
- Research Unit "Induced Resistance and Plant Bioprotection", EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687 Reims Cedex 2, France.
| | - Sylvain Cordelier
- Research Unit "Induced Resistance and Plant Bioprotection", EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687 Reims Cedex 2, France.
| | - Azadeh Manayi
- Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, 1417614411 Tehran, Iran
| | - Seyed Fazel Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-16471, Iran
| | - Mahsa Rasekhian
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt
| | - Haroon Khan
- Department of Pharmacy, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, 23200, Pakistan
| | - Iwona Morkunas
- Department of Plant Physiology, Poznań University of Life Sciences, Wołyńska 35, 60-637 Poznań, Poland
| | - Tarun Belwal
- Zhejiang University, College of Biosystems Engineering and Food Science, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agri-Food Processing, Hangzhou 310058, The People's Republic of China
| | - Jingjie Jiang
- Dorothy and Fred Chau '71 Constellation Professor, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Room 4005D, 110 8th Street, Troy, NY 12180, USA
| | - Mattheos Koffas
- Dorothy and Fred Chau '71 Constellation Professor, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Room 4005D, 110 8th Street, Troy, NY 12180, USA
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-16471, Iran
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Šikuten I, Štambuk P, Andabaka Ž, Tomaz I, Marković Z, Stupić D, Maletić E, Kontić JK, Preiner D. Grapevine as a Rich Source of Polyphenolic Compounds. Molecules 2020; 25:E5604. [PMID: 33260583 PMCID: PMC7731206 DOI: 10.3390/molecules25235604] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 11/21/2020] [Accepted: 11/25/2020] [Indexed: 12/26/2022] Open
Abstract
Grapes are rich in primary and secondary metabolites. Among the secondary metabolites, polyphenolic compounds are the most abundant in grape berries. Besides their important impacts on grape and wine quality, this class of compounds has beneficial effects on human health. Due to their antioxidant activity, polyphenols and phenolic acids can act as anti-inflammatory and anticancerogenic agents, and can modulate the immune system. In grape berries, polyphenols and phenolic acids can be located in the pericarp and seeds, but distribution differs considerably among these tissues. Although some classes of polyphenols and phenolic acids are under strict genetic control, the final content is highly influenced by environmental factors, such as climate, soil, vineyard, and management. This review aims to present the main classes of polyphenolic compounds and phenolic acids in different berry tissues and grape varieties and special emphasis on their beneficial effect on human health.
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Affiliation(s)
- Iva Šikuten
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
- Centre of Excellence for Biodiversity and Molecular Plant Breeding, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia
| | - Petra Štambuk
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
- Centre of Excellence for Biodiversity and Molecular Plant Breeding, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia
| | - Željko Andabaka
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
| | - Ivana Tomaz
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
- Centre of Excellence for Biodiversity and Molecular Plant Breeding, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia
| | - Zvjezdana Marković
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
- Centre of Excellence for Biodiversity and Molecular Plant Breeding, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia
| | - Domagoj Stupić
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
| | - Edi Maletić
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
- Centre of Excellence for Biodiversity and Molecular Plant Breeding, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia
| | - Jasminka Karoglan Kontić
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
- Centre of Excellence for Biodiversity and Molecular Plant Breeding, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia
| | - Darko Preiner
- Department of Viticulture and Enology, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia; (I.Š.); (P.Š.); (Ž.A.); (Z.M.); (D.S.); (E.M.); (J.K.K.); (D.P.)
- Centre of Excellence for Biodiversity and Molecular Plant Breeding, Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Croatia
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Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol. Molecules 2020; 25:molecules25215166. [PMID: 33171952 PMCID: PMC7664215 DOI: 10.3390/molecules25215166] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 12/15/2022] Open
Abstract
Pterostilbene is a natural 3,5-dimethoxy analog of resveratrol. This stilbene compound has a strong bioactivity and exists widely in Dalbergia and Vaccinium spp. Besides natural extraction, pterostilbene can be obtained by biosynthesis. Pterostilbene has become popular because of its remarkable pharmacological activities, such as anti-tumor, anti-oxidation, anti-inflammation, and neuroprotection. Pterostilbene can be rapidly absorbed and is widely distributed in tissues, but it does not seriously accumulate in the body. Pterostilbene can easily pass through the blood-brain barrier because of its low molecular weight and good liposolubility. In this review, the studies performed in the last three years on resources, synthesis, bioactivity, and pharmacokinetics of pterostilbene are summarized. This review focuses on the effects of pterostilbene on certain diseases to explore its targets, explain the possible mechanism, and look for potential therapeutic applications.
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Mattio LM, Catinella G, Pinto A, Dallavalle S. Natural and nature-inspired stilbenoids as antiviral agents. Eur J Med Chem 2020; 202:112541. [PMID: 32652408 PMCID: PMC7335248 DOI: 10.1016/j.ejmech.2020.112541] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/24/2020] [Accepted: 06/04/2020] [Indexed: 12/12/2022]
Abstract
Viruses continue to be a major threat to human health. In the last century, pandemics occurred and resulted in significant mortality and morbidity. Natural products have been largely screened as source of inspiration for new antiviral agents. Within the huge class of plant secondary metabolites, resveratrol-derived stilbenoids present a wide structural diversity and mediate a great number of biological responses relevant for human health. However, whilst the antiviral activity of resveratrol has been extensively studied, little is known about the efficacy of its monomeric and oligomeric derivatives. The purpose of this review is to provide an overview of the achievements in this field, with particular emphasis on the source, chemical structures and the mechanism of action of resveratrol-derived stilbenoids against the most challenging viruses. The collected results highlight the therapeutic versatility of stilbene-containing compounds and provide a prospective insight into their potential development as antiviral agents.
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Affiliation(s)
- Luce M Mattio
- Department of Food, Environmental and Nutritional Sciences, Università Degli Studi di Milano, Via Celoria 2, 20133, Milano, Italy
| | - Giorgia Catinella
- Department of Food, Environmental and Nutritional Sciences, Università Degli Studi di Milano, Via Celoria 2, 20133, Milano, Italy
| | - Andrea Pinto
- Department of Food, Environmental and Nutritional Sciences, Università Degli Studi di Milano, Via Celoria 2, 20133, Milano, Italy
| | - Sabrina Dallavalle
- Department of Food, Environmental and Nutritional Sciences, Università Degli Studi di Milano, Via Celoria 2, 20133, Milano, Italy.
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16
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A Reference List of Phenolic Compounds (Including Stilbenes) in Grapevine ( Vitis vinifera L.) Roots, Woods, Canes, Stems, and Leaves. Antioxidants (Basel) 2020; 9:antiox9050398. [PMID: 32397203 PMCID: PMC7278806 DOI: 10.3390/antiox9050398] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 05/01/2020] [Accepted: 05/05/2020] [Indexed: 01/19/2023] Open
Abstract
Due to their biological activities, both in plants and in humans, there is a great interest in finding natural sources of phenolic compounds or ways to artificially manipulate their levels. During the last decade, a significant amount of these compounds has been reported in the vegetative organs of the vine plant. In the roots, woods, canes, stems, and leaves, at least 183 phenolic compounds have been identified, including 78 stilbenes (23 monomers, 30 dimers, 8 trimers, 16 tetramers, and 1 hexamer), 15 hydroxycinnamic acids, 9 hydroxybenzoic acids, 17 flavan-3-ols (of which 9 are proanthocyanidins), 14 anthocyanins, 8 flavanones, 35 flavonols, 2 flavones, and 5 coumarins. There is great variability in the distribution of these chemicals along the vine plant, with leaves and stems/canes having flavonols (83.43% of total phenolic levels) and flavan-3-ols (61.63%) as their main compounds, respectively. In light of the pattern described from the same organs, quercetin-3-O-glucuronide, quercetin-3-O-galactoside, quercetin-3-O-glucoside, and caftaric acid are the main flavonols and hydroxycinnamic acids in the leaves; the most commonly represented flavan-3-ols and flavonols in the stems and canes are catechin, epicatechin, procyanidin B1, and quercetin-3-O-galactoside. The main stilbenes (trans-ε-viniferin, trans-resveratrol, isohopeaphenol/hopeaphenol, vitisin B, and ampelopsins) accumulate primarily in the woods, followed by the roots, the canes, and the stems, whereas the leaves, which are more exposed to environmental stresses, have a low concentration of these compounds. Data provided in this review could be used as (i) a metabolomic tool for screening in targeted and untargeted analyses and (ii) a reference list in studies aimed at finding ways to induce naturally occurring polyphenols on an industrial scale for pant and human disease control.
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Kotipalli T, Hou D. Synthesis of 3‐Bromoindenes from 4‐Alkynyl Alcohols/Sulfonamides and Aldehydes via Prins Cyclization, Ring‐Opening and Friedel‐Crafts Reactions. ASIAN J ORG CHEM 2019. [DOI: 10.1002/ajoc.201900292] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- Trimurtulu Kotipalli
- Department of ChemistryNational Central University Jhong-Li City Taoyuan Taiwan 32001
| | - Duen‐Ren Hou
- Department of ChemistryNational Central University Jhong-Li City Taoyuan Taiwan 32001
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18
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Salehi B, Kumar NVA, Şener B, Sharifi-Rad M, Kılıç M, Mahady GB, Vlaisavljevic S, Iriti M, Kobarfard F, Setzer WN, Ayatollahi SA, Ata A, Sharifi-Rad J. Medicinal Plants Used in the Treatment of Human Immunodeficiency Virus. Int J Mol Sci 2018; 19:E1459. [PMID: 29757986 PMCID: PMC5983620 DOI: 10.3390/ijms19051459] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 04/29/2018] [Accepted: 05/07/2018] [Indexed: 12/20/2022] Open
Abstract
Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.
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Affiliation(s)
- Bahare Salehi
- Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, 88777539 Tehran, Iran.
- Student Research Committee, Shahid Beheshti University of Medical Sciences, 22439789 Tehran, Iran.
| | - Nanjangud V Anil Kumar
- Department of Chemistry, Manipal Institute of Technology, Manipal University, Manipal 576104, India.
| | - Bilge Şener
- Department of Pharmacognosy, Gazi University, Faculty of Pharmacy, 06330 Ankara, Turkey.
| | - Mehdi Sharifi-Rad
- Department of Medical Parasitology, Zabol University of Medical Sciences, 61663-335 Zabol, Iran.
| | - Mehtap Kılıç
- Department of Pharmacognosy, Gazi University, Faculty of Pharmacy, 06330 Ankara, Turkey.
| | - Gail B Mahady
- PAHO/WHO Collaborating Centre for Traditional Medicine, College of Pharmacy, University of Illinois, 833 S. Wood St., Chicago, IL 60612, USA.
| | - Sanja Vlaisavljevic
- Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovica 3, 21000 Novi Sad, Serbia.
| | - Marcello Iriti
- Department of Agricultural and Environmental Sciences, Milan State University, 20133 Milan, Italy.
| | - Farzad Kobarfard
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, 11369 Tehran, Iran.
- Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 11369 Tehran, Iran.
| | - William N Setzer
- Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA.
| | - Seyed Abdulmajid Ayatollahi
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, 11369 Tehran, Iran.
- Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 11369 Tehran, Iran.
- Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB R3B 2G3, Canada.
| | - Athar Ata
- Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB R3B 2G3, Canada.
| | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, 11369 Tehran, Iran.
- Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB R3B 2G3, Canada.
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Sáez V, Pastene E, Vergara C, Mardones C, Hermosín-Gutiérrez I, Gómez-Alonso S, Gómez MV, Theoduloz C, Riquelme S, von Baer D. Oligostilbenoids in Vitis vinifera L. Pinot Noir grape cane extract: Isolation, characterization, in vitro antioxidant capacity and anti-proliferative effect on cancer cells. Food Chem 2018; 265:101-110. [PMID: 29884360 DOI: 10.1016/j.foodchem.2018.05.050] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 04/21/2018] [Accepted: 05/08/2018] [Indexed: 11/28/2022]
Abstract
The following oligostilbenoids were isolated from extracts of Vitis vinifera L. Pinot Noir grape canes produced at a pilot-plant scale: (E)-ε-viniferin, (E)-resveratrol, (E)-piceatannol, ampelopsin A, vitisin B, pallidol, (E)-δ-viniferin, (E)-ω-viniferin, (E)-trans-cis-miyabenol C, isorhapontigenin, scirpusin A, and a new isomer named isoscirpusin A. The antioxidant capacity of the isolated stilbenoids was studied by three different assays, and their 50% inhibition concentration (IC50) against cancer cells was determined by MTT reduction assay. Besides (E)-resveratrol, stilbenoids have outstanding antioxidant capacity in the ORAC-FL assay. The strongest antiproliferative effect was observed for (E)-piceatannol and ampelopsin A against the bladder cancer cell line J82. (E)-Piceatannol has inhibitory effect on human lung cancer SK-MES-1 cells. Moreover, the whole extract has antiproliferative effect on all tested cell lines. In conclusion, beside (E)-resveratrol, grape cane extract contains oligostilbenoids with potential health benefits. This underexploited viticultural residue has the potential to produce valuable phytochemicals or ingredients in functional foods.
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Affiliation(s)
- Vania Sáez
- Departamento de Análisis Instrumental, Facultad de Farmacia, Universidad de Concepción, P.O. Box 160-C, Concepción, Chile
| | - Edgar Pastene
- Laboratorio de Farmacognosia, Facultad de Farmacia, Universidad de Concepción, P.O. Box 160-C, 4070386 Concepción, Chile
| | - Carola Vergara
- Departamento de Análisis Instrumental, Facultad de Farmacia, Universidad de Concepción, P.O. Box 160-C, Concepción, Chile
| | - Claudia Mardones
- Departamento de Análisis Instrumental, Facultad de Farmacia, Universidad de Concepción, P.O. Box 160-C, Concepción, Chile
| | - Isidro Hermosín-Gutiérrez
- Instituto Regional de Investigación Científica Aplicada, Universidad de Castilla-La Mancha, Campus Universitario s/n 13071, Ciudad Real, Spain
| | - Sergio Gómez-Alonso
- Instituto Regional de Investigación Científica Aplicada, Universidad de Castilla-La Mancha, Campus Universitario s/n 13071, Ciudad Real, Spain
| | - M Victoria Gómez
- Instituto Regional de Investigación Científica Aplicada, Universidad de Castilla-La Mancha, Campus Universitario s/n 13071, Ciudad Real, Spain
| | - Cristina Theoduloz
- Laboratorio de Cultivo Celular, Facultad de Ciencias de la Salud, Universidad de Talca, P.O. Box 747, 3460000 Talca, Chile
| | - Sebastián Riquelme
- Unidad de Desarrollo Tecnológico (UDT), Universidad de Concepción, Coronel, Chile
| | - Dietrich von Baer
- Departamento de Análisis Instrumental, Facultad de Farmacia, Universidad de Concepción, P.O. Box 160-C, Concepción, Chile.
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Cancian M, Loreto ELS. A Mos1 transposase in vivo assay to screen new HIV-1 integrase inhibitors. Genetica 2018; 146:243-247. [PMID: 29352755 DOI: 10.1007/s10709-018-0007-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 01/11/2018] [Indexed: 11/27/2022]
Abstract
The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28-32% when treated with dolutegravir. The gene expression of the mariner transposase gene, estimated by qPCR, is similar among treated and control flies. The results suggest that in vivo assays using Drosophila can be used as a primary screening of inhibitory drugs for transposase and retroviral integrase. The advantages of this assay are that it is easy, quick, cheap and is an in vivo test, meaning that the tested substance has to have been taken in by cells and has arrived at the target site, which is not the case when in vitro assays are applied.
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Affiliation(s)
- Mariana Cancian
- Curso Ciências Biológicas, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil
| | - Elgion L S Loreto
- Department of Biochemistry and Molecular Biology, CCNE, Federal University of Santa Maria (UFSM), Av. Roraima 1000, Camobi, Santa Maria, RS, 97105-900, Brazil.
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Espinoza JL, Inaoka PT. Gnetin-C and other resveratrol oligomers with cancer chemopreventive potential. Ann N Y Acad Sci 2017; 1403:5-14. [PMID: 28856688 DOI: 10.1111/nyas.13450] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 07/11/2017] [Accepted: 07/18/2017] [Indexed: 02/06/2023]
Abstract
Resveratrol has been extensively studied to investigate its biological effects, including its chemopreventive potential against cancer. Over the past decade, various resveratrol oligomers, both naturally occurring and synthetic, have been described. These resveratrol oligomers result from the polymerization of two or more resveratrol units to form dimers, trimers, tetramers, or even more complex derivatives. Some oligomers appear to have antitumor activities that are similar or superior to monomeric resveratrol. In this review, we discuss resveratrol oligomers with anticancer potential, with emphasis on well-characterized compounds, such as the dimer gnetin-C and other oligomers from Gnetum gnemon, whose safety, pharmacokinetic, and biological activities have been studied in humans.
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Affiliation(s)
- J Luis Espinoza
- Department of Hematology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Pleiades T Inaoka
- Department of Physical Therapy, School of Health Sciences, Kanazawa University, Kanazawa, Japan
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22
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Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene. Antimicrob Agents Chemother 2017; 61:AAC.00408-17. [PMID: 28652233 DOI: 10.1128/aac.00408-17] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 06/20/2017] [Indexed: 12/12/2022] Open
Abstract
HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health-promoting benefits. Resveratrol has been shown to inhibit the replication of several viruses, including herpes simplex viruses 1 and 2, papillomaviruses, severe acute respiratory syndrome virus, and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at a low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, an HIV-1 and simian immunodeficiency virus protein that increases deoxynucleoside triphosphate (dNTP) levels. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. This study supports the potential use of resveratrol, pterostilbene, or related compounds as adjuvants in anti-HIV preexposure prophylaxis (PrEP) formulations.
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Anti-Inflammatory Effects of Vitisinol A and Four Other Oligostilbenes from Ampelopsis brevipedunculata var. Hancei. Molecules 2017; 22:molecules22071195. [PMID: 28714918 PMCID: PMC6152071 DOI: 10.3390/molecules22071195] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 07/14/2017] [Accepted: 07/14/2017] [Indexed: 12/17/2022] Open
Abstract
In this study, the cytotoxicities and anti-inflammatory activities of five resveratrol derivatives-vitisinol A, (+)-ε-viniferin, (+)-vitisin A, (-)-vitisin B, and (+)-hopeaphenol-isolated from Ampelopsis brevipedunculata var. hancei were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lipopolysaccharide (LPS)-stimulated RAW264.7 cells, respectively. The result from MTT assay analysis indicated that vitisinol A has lower cytotoxicity than the other four well-known oligostilbenes. In the presence of vitisinol A (5 μM), the significant reduction of inflammation product (nitric oxide, NO) in LPS-induced RAW264.7 cells was measured using Griess reaction assay. In addition, the under-expressed inflammation factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-induced RAW264.7 cells monitored by Western blotting simultaneously suggested that vitisinol A has higher anti-inflammatory effect compared with other resveratrol derivatives. Finally, the anti-inflammatory effect of vitisinol A was further demonstrated on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. As a preliminary functional evaluation of natural product, the anti-inflammatory effect of vitisinol A is the first to be examined and reported by this study.
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Ye XL, Lu LQ, Li W, Lou Q, Guo HG, Shi QJ. Oral administration of ampelopsin protects against acute brain injury in rats following focal cerebral ischemia. Exp Ther Med 2017; 13:1725-1734. [PMID: 28565759 PMCID: PMC5443315 DOI: 10.3892/etm.2017.4197] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 12/19/2016] [Indexed: 12/14/2022] Open
Abstract
Ampelopsin (AMP) is isolated from the Chinese medicinal herb Ampelopsis grossedentata (Hand-Mazz) and has been associated with numerous biological and pharmacological activities. However, it is not clear whether AMP has a direct protective effect on cerebral ischemia reperfusion injury. Therefore, the present study investigated its role in acute brain injury following focal cerebral ischemia in rats. The current study induced transient focal cerebral ischemia by performing middle cerebral artery occlusion (MCAO) for 60 min, followed by 24 h of reperfusion. Rats were exposed to 40, 80 and 160 mg/kg AMP by oral administration 30 min prior to MCAO and the cysteinyl leukotriene receptor 1-antagonist, pranlukast (0.1 mg/kg, i.p.) was used as a positive control. Neurological deficit scores were observed and an inclined board test was used to assess behavioral dysfunction. The coronal slices were stained with 3,5-triphenyltetrazolium chloride to determine the infarct volume and brain edema. Neuronal morphology was assessed in brain sections stained with cresyl violet and degenerating neurons were identified using Fluoro-Jade B staining. Blood-brain barrier permeability was determined with immunoglobulin (Ig)G immunohistochemistry. Interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) in serum and cerebrospinal fluid were measured using ELISA kits. AMP at 80 and 160 mg/kg attenuated neurological deficits, reduced infarct volume, brain edema, IgG exudation and neuron degeneration and loss. Similar to pranlukast, AMP also inhibited the MCAO-induced IL-1β and TNF-α release. Thus, AMP has a neuroprotective effect on acute brain injury following focal cerebral ischemia in rats at an effective oral dose of 80-160 mg/kg. The results of the current study indicate a therapeutic role for AMP in the treatment of ischemic stroke.
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Affiliation(s)
- Xiao-Li Ye
- Department of Pharmacy, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China
| | - Ling-Qun Lu
- Experimental Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China
| | - Wei Li
- Experimental Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China
| | - Qi Lou
- Experimental Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China
| | - Hong-Gang Guo
- Experimental Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China
| | - Qiao-Juan Shi
- Experimental Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China
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25
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Lee S, Yoon KD, Lee M, Cho Y, Choi G, Jang H, Kim B, Jung D, Oh J, Kim G, Oh J, Jeong Y, Kwon HJ, Bae SK, Min D, Windisch MP, Heo T, Lee C. Identification of a resveratrol tetramer as a potent inhibitor of hepatitis C virus helicase. Br J Pharmacol 2016; 173:191-211. [PMID: 26445091 PMCID: PMC4813382 DOI: 10.1111/bph.13358] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 09/16/2015] [Accepted: 10/02/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND PURPOSE Hepatitis C virus (HCV) infection is responsible for various chronic inflammatory liver diseases. Here, we have identified a naturally occurring compound with anti-HCV activity and have elucidated its mode of antiviral action. EXPERIMENTAL APPROACH Luciferase reporter and real-time RT-PCR assays were used to measure HCV replication. Western blot, fluorescence-labelled HCV replicons and infectious clones were employed to quantitate expression levels of viral proteins. Resistant HCV mutant mapping, in vitro NS3 protease, helicase, NS5B polymerase and drug affinity responsive target stability assays were also used to study the antiviral mechanism. KEY RESULTS A resveratrol tetramer, vitisin B from grapevine root extract showed high potency against HCV replication (EC50 = 6 nM) with relatively low cytotoxicity (EC50 >10 μM). Combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B-resistant HCV variants suggested an NS3 helicase as its potential target. We confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. Vitisin B was a potent inhibitor of a HCV NS3 helicase (IC50 = 3 nM). In vivo, Finally, we observed a preferred tissue distribution of vitisin B in the liver after i.p. injection in rats, at clinically attainable concentrations. Conclusion and Implications Vitisin B is one of the most potent HCV helicase inhibitors identified so far. Vitisin B is thus a prime candidate to be developed as the first HCV drug derived from natural products.
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Affiliation(s)
- Sungjin Lee
- College of PharmacyDongguk UniversityGoyangKorea
| | - Kee Dong Yoon
- College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of KoreaBucheonKorea
| | - Myungeun Lee
- Hepatitis Research LaboratoryInstitut Pasteur KoreaSeongnamKorea
| | - Yoojin Cho
- Hepatitis Research LaboratoryInstitut Pasteur KoreaSeongnamKorea
| | - Gahee Choi
- Hepatitis Research LaboratoryInstitut Pasteur KoreaSeongnamKorea
| | - Hongje Jang
- Department of ChemistrySeoul National UniversitySeoulKorea
| | - BeomSeok Kim
- Translational Research Center for Protein Function Control, Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeoulKorea
| | - Da‐Hee Jung
- Department of Bio and Nano ChemistryKookmin UniversitySeoulKorea
| | - Jin‐Gyo Oh
- College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of KoreaBucheonKorea
| | - Geon‐Woo Kim
- Department of BiotechnologyYonsei UniversitySeoulKorea
| | - Jong‐Won Oh
- Department of BiotechnologyYonsei UniversitySeoulKorea
| | - Yong‐Joo Jeong
- Department of Bio and Nano ChemistryKookmin UniversitySeoulKorea
| | - Ho Jeong Kwon
- Translational Research Center for Protein Function Control, Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeoulKorea
| | - Soo Kyung Bae
- College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of KoreaBucheonKorea
| | - Dal‐Hee Min
- Department of ChemistrySeoul National UniversitySeoulKorea
| | - Marc P Windisch
- Hepatitis Research LaboratoryInstitut Pasteur KoreaSeongnamKorea
| | - Tae‐Hwe Heo
- College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of KoreaBucheonKorea
| | - Choongho Lee
- College of PharmacyDongguk UniversityGoyangKorea
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Thierry S, Benleulmi MS, Sinzelle L, Thierry E, Calmels C, Chaignepain S, Waffo-Teguo P, Merillon JM, Budke B, Pasquet JM, Litvak S, Ciuffi A, Sung P, Connell P, Hauber I, Hauber J, Andreola ML, Delelis O, Parissi V. Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration. ACTA ACUST UNITED AC 2015; 22:712-23. [PMID: 26051216 DOI: 10.1016/j.chembiol.2015.04.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Revised: 03/31/2015] [Accepted: 04/22/2015] [Indexed: 12/24/2022]
Abstract
The cellular DNA repair hRAD51 protein has been shown to restrict HIV-1 integration both in vitro and in vivo. To investigate its regulatory functions, we performed a pharmacological analysis of the retroviral integration modulation by hRAD51. We found that, in vitro, chemical activation of hRAD51 stimulates its integration inhibitory properties, whereas inhibition of hRAD51 decreases the integration restriction, indicating that the modulation of HIV-1 integration depends on the hRAD51 recombinase activity. Cellular analyses demonstrated that cells exhibiting high hRAD51 levels prior to de novo infection are more resistant to integration. On the other hand, when hRAD51 was activated during integration, cells were more permissive. Altogether, these data establish the functional link between hRAD51 activity and HIV-1 integration. Our results highlight the multiple and opposite effects of the recombinase during integration and provide new insights into the cellular regulation of HIV-1 replication.
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Affiliation(s)
| | | | - Ludivine Sinzelle
- MFP, UMR5234, CNRS-Université de Bordeaux, SFR Transbiomed, 33076 Bordeaux, France
| | | | - Christina Calmels
- MFP, UMR5234, CNRS-Université de Bordeaux, SFR Transbiomed, 33076 Bordeaux, France
| | | | - Pierre Waffo-Teguo
- GESVAB, EA 3675 - UFR Pharmacie, Université de Bordeaux, ISVV, 33076 Bordeaux, France
| | - Jean-Michel Merillon
- GESVAB, EA 3675 - UFR Pharmacie, Université de Bordeaux, ISVV, 33076 Bordeaux, France
| | - Brian Budke
- Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA
| | - Jean-Max Pasquet
- Laboratoire Biothérapies des Maladies Génétiques et Cancers, INSERM U1035, Université de Bordeaux, 33076 Bordeaux, France
| | - Simon Litvak
- MFP, UMR5234, CNRS-Université de Bordeaux, SFR Transbiomed, 33076 Bordeaux, France
| | - Angela Ciuffi
- Institute of Microbiology (IMUL), Lausanne University Hospital, 1011 Lausanne, Switzerland
| | - Patrick Sung
- Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06320-8024, USA
| | - Philip Connell
- Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA
| | - Ilona Hauber
- HPI, Leibniz Institute for Experimental Virology, German Center for Infection Research (DZIF), 20251 Hamburg, Germany
| | - Joachim Hauber
- HPI, Leibniz Institute for Experimental Virology, German Center for Infection Research (DZIF), 20251 Hamburg, Germany
| | - Marie-Line Andreola
- MFP, UMR5234, CNRS-Université de Bordeaux, SFR Transbiomed, 33076 Bordeaux, France
| | | | - Vincent Parissi
- MFP, UMR5234, CNRS-Université de Bordeaux, SFR Transbiomed, 33076 Bordeaux, France.
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27
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Keylor MH, Matsuura BS, Stephenson CRJ. Chemistry and Biology of Resveratrol-Derived Natural Products. Chem Rev 2015; 115:8976-9027. [PMID: 25835567 PMCID: PMC4566929 DOI: 10.1021/cr500689b] [Citation(s) in RCA: 245] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Mitchell H Keylor
- Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109, United States
| | - Bryan S Matsuura
- Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109, United States
| | - Corey R J Stephenson
- Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109, United States
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