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Baghel M, Baghel I, Kumari P, Bharkatiya M, Joshi G, Sakure K, Badwaik H. Nano-delivery Systems and Therapeutic Applications of Phytodrug Mangiferin. Appl Biochem Biotechnol 2024; 196:7429-7463. [PMID: 38526662 DOI: 10.1007/s12010-024-04906-6] [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] [Accepted: 03/04/2024] [Indexed: 03/27/2024]
Abstract
In order to cure a range of ailments, scientists have investigated a number of bioactive antioxidant compounds produced from natural sources. Mangiferin, a C-glycosyl xanthone-structured yellow polyphenol, is abundant in mangoes and other dietary sources. In-depth examinations found that it is effective in the treatment of a variety of disorders due to its antiviral, anti-inflammatory, antiproliferative, antigenotoxic, antiatherogenic, radioprotective, nephroprotective, antihyperlipidemic, and antidiabetic properties. However, it is recognised that mangiferin's poor bioavailability, volatility, and limited solubility restrict its therapeutic usefulness. Over time, effective solutions to these problems have arisen in the shape of effective delivery methods. The current articles present a summary of the several researches that have updated Mangiferin's biopharmaceutical characteristics. Additionally, strategies for enhancing the bioavailability, stability, and solubility of this phytodrug have been discussed. This review provides detailed information on the development of innovative Mangiferin delivery methods such as nanoparticles, liposomes, micelles, niosomes, microspheres, metal nanoparticles, and complexation, as well as its therapeutic applications in a variety of sectors. This article provides effective guidance for researchers who desire to work on the formulation and development of an effective delivery method for improved magniferin therapeutic effectiveness.
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Affiliation(s)
- Madhuri Baghel
- Apollo College of Pharmacy, Anjora, Durg, 491001, Chhattisgarh, India
| | - Ishita Baghel
- Foothill High School, 4375, Foothill Road, Pleasanton, CA, 94588, USA
| | | | - Meenakshi Bharkatiya
- Bhupal Nobles' Institute of Pharmaceutical Sciences, Bhupal Nobles' University, Udaipur, 313001, India
| | - Garvita Joshi
- Mahakal Institute of Pharmaceutical Studies, Ujjain, India
| | - Kalyani Sakure
- Rungta College of Pharmaceutical Sciences and Research, Bhilai, 490023, CG, India
| | - Hemant Badwaik
- Shri Shankaracharya Institute of Pharmaceutical Sciences and Research, Junwani, Bhilai, 490020, Chhattisgarh, India.
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Kong C, Wang K, Sun L, Zhao H, Wang T, Zhou W, Wu D, Xu F. Novel Carbon Dots Derived from Moutan Cortex Significantly Improve the Solubility and Bioavailability of Mangiferin. Int J Nanomedicine 2024; 19:3611-3622. [PMID: 38660022 PMCID: PMC11041979 DOI: 10.2147/ijn.s456053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/14/2024] [Indexed: 04/26/2024] Open
Abstract
Background Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics. Methods In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo. Results The results indicated that MC-CDs with a uniform spherical particle size of 1-5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg. Conclusion Moutan Cortex-derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs.
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Affiliation(s)
- Chuihao Kong
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China
- Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China
| | - Kaidi Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China
- Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China
| | - Lei Sun
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China
- Zhejiang CONBA Pharmaceutical Co. LTD, Hangzhou, 310052, People’s Republic of China
| | - Hongsu Zhao
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China
- Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China
| | - Tongsheng Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China
| | - Wuxi Zhou
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China
| | - Deling Wu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China
- Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China
| | - Fengqing Xu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China
- Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China
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Gálvez-Rodríguez A, Ferino-Pérez A, Rodríguez-Riera Z, Guerra IR, Jáuregui-Haza UJ. In silico evaluation of new mangiferin-based Positron Emission Tomography radiopharmaceuticals through the inhibition of metalloproteinase-9. J Mol Graph Model 2023; 124:108569. [PMID: 37487370 DOI: 10.1016/j.jmgm.2023.108569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 07/16/2023] [Accepted: 07/17/2023] [Indexed: 07/26/2023]
Abstract
Metalloproteinase-9 (MMP-9) is a key protein in cancer advancement and metastasis owing to its ability to degrade some extracellular matrix components. Mangiferin, a natural polyphenolic compound, has demonstrated through experimental and theoretical studies to be a great anticancer agent for the selective inhibition of MMP-9. This work aimed to evaluate the utility of several fluorinated compounds obtained from MF as possible Positron Emission Tomography (PET) radiopharmaceuticals oriented to MMP-9. Density Functional Theory calculations of MF were made to obtain the most active sites toward electrophilic and nucleophilic reactions and propose a synthetic route to produce its fluorinated derivatives. The reactivity study allowed us to propose a late-stage synthetic route based on click chemistry to obtain three fluorinated MF-based derivatives. Molecular docking calculations suggested that the derivative F-propyl-MF could be suitable as PET radiopharmaceutical owing to the establishment of a five-coordinated complex with the catalytic Zn atom belonging to the active site of MMP-9, crucial factor in the inhibition of MMP-9.
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Affiliation(s)
- Andy Gálvez-Rodríguez
- Instituto Superior de Tecnologías y Ciencias Aplicadas (InSTEC), Universidad de La Habana, La Habana, CP 10600, Cuba
| | - Anthuan Ferino-Pérez
- Department of Chemistry, KU Leuven Chem&Tech, Celestijnenlaan 200F, Bus 2404, 3001, Louvain, Belgium
| | - Zalua Rodríguez-Riera
- Instituto Superior de Tecnologías y Ciencias Aplicadas (InSTEC), Universidad de La Habana, La Habana, CP 10600, Cuba
| | - Idania Rodeiro Guerra
- Departamento de Farmacología, Instituto de Ciencias del Mar, Loma 14, Alturas del Vedado, Plaza de la Revolución, La Habana, CP 10600, Cuba
| | - Ulises J Jáuregui-Haza
- Instituto Tecnológico de Santo Domingo (INTEC), Avenida de los Próceres #49, Los Jardines del Norte, 10602, Santo Domingo, Dominican Republic.
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Maenpuen S, Mee-Udorn P, Pinthong C, Athipornchai A, Phiwkaow K, Watchasit S, Pimviriyakul P, Rungrotmongkol T, Tinikul R, Leartsakulpanich U, Chitnumsub P. Mangiferin is a new potential antimalarial and anticancer drug for targeting serine hydroxymethyltransferase. Arch Biochem Biophys 2023; 745:109712. [PMID: 37543353 DOI: 10.1016/j.abb.2023.109712] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/02/2023] [Accepted: 08/02/2023] [Indexed: 08/07/2023]
Abstract
Mangiferin, a polyphenolic xanthone glycoside found in various botanical sources, including mango (Mangifera indica L.) leaves, can exhibit a variety of bioactivities. Although mangiferin has been reported to inhibit many targets, none of the studies have investigated the inhibition of serine hydroxymethyltransferase (SHMT), an attractive target for antimalarial and anticancer drugs. SHMT, one of the key enzymes in the deoxythymidylate synthesis cycle, catalyzes the reversible conversion of l-serine and (6S)-tetrahydrofolate (THF) into glycine and 5,10-methylene THF. Here, in vitro and in silico studies were used to probe how mangiferin isolated from mango leaves inhibits Plasmodium falciparum and human cytosolic SHMTs. The inhibition kinetics at pH 7.5 revealed that mangiferin is a competitive inhibitor against THF for enzymes from both organisms. Molecular docking and molecular dynamic (MD) simulations demonstrated the inhibitory effects of the deprotonated forms of mangiferin, specifically the C6-O- species and its resonance C9-O- species appearing at pH 7.5, combined with two docked poses, either a xanthone or glucose moiety, placed inside the THF-binding pocket. The MD analysis revealed that both C6-O- and its resonance-stabilized C9-O- species can favorably bind to SHMT in a similar fashion to THF, supporting the THF competitive inhibition of mangiferin. In addition, characterization of the proton dissociation equilibria of isolated mangiferin revealed that only three hydroxy groups of the xanthone moiety, C6-OH, C3-OH, and C7-OH, underwent varying degrees of deprotonation with pKa values of 6.38 ± 0.11, 8.21 ± 0.35, and 12.37 ± 0.30, respectively, while C1-OH remained protonated. Altogether, our findings demonstrate a new bioactivity of mangiferin and provide the basis for the future development of mangiferin as a potent antimalarial and anticancer drug.
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Affiliation(s)
- Somchart Maenpuen
- Department of Biochemistry, Faculty of Science, Burapha University, Chonburi, 20131, Thailand.
| | - Pitchayathida Mee-Udorn
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Phahonyothin road, Khlong Nueng, Khlong Luang, Pathum Thani, 12120, Thailand
| | - Chatchadaporn Pinthong
- Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, 10110, Thailand
| | - Anan Athipornchai
- The Research Unit in Synthetic Compounds and Synthetic Analogues from Natural Product for Drug Discovery, Center of Excellence for Innovation in Chemistry and Department of Chemistry, Faculty of Science, Burapha University, Chonburi, 20131, Thailand
| | - Kochakorn Phiwkaow
- Department of Biochemistry, Faculty of Science, Burapha University, Chonburi, 20131, Thailand
| | - Sarayut Watchasit
- Nuclear Magnetic Resonance Spectroscopic Laboratory, Science Innovation Facility, Faculty of Science, Burapha University, Chonburi, 20131, Thailand
| | - Panu Pimviriyakul
- Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand
| | - Thanyada Rungrotmongkol
- Center of Excellence in Biocatalyst and Sustainable Biotechnology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Ruchanok Tinikul
- Department of Biochemistry and Center for Excellence in Protein and Enzyme Technology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
| | - Ubolsree Leartsakulpanich
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Phahonyothin road, Khlong Nueng, Khlong Luang, Pathum Thani, 12120, Thailand
| | - Penchit Chitnumsub
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Phahonyothin road, Khlong Nueng, Khlong Luang, Pathum Thani, 12120, Thailand
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Sarfraz M, Khan A, Batiha GES, Akhtar MF, Saleem A, Ajiboye BO, Kamal M, Ali A, Alotaibi NM, Aaghaz S, Siddique MI, Imran M. Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy. Cancers (Basel) 2023; 15:4194. [PMID: 37627222 PMCID: PMC10453289 DOI: 10.3390/cancers15164194] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/22/2023] [Accepted: 07/25/2023] [Indexed: 08/27/2023] Open
Abstract
Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.
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Affiliation(s)
- Muhammad Sarfraz
- College of Pharmacy, Al Ain University, Al Ain P.O. Box 64141, United Arab Emirates
| | - Abida Khan
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia;
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt
| | - Muhammad Furqan Akhtar
- Riphah Institute of Pharmaceutical Sciences, Riphah International University Lahore, Lahore 54000, Pakistan
| | - Ammara Saleem
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad 38000, Pakistan
| | - Basiru Olaitan Ajiboye
- Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Oye 371104, Ekiti State, Nigeria;
| | - Mehnaz Kamal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Abuzer Ali
- Department of Pharmacognosy, College of Pharmacy, Taif University, Taif 21944, Saudi Arabia
| | - Nawaf M. Alotaibi
- Department of Clinical Pharmacy, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Shams Aaghaz
- Department of Pharmacy, School of Medical & Allied Sciences, Galgotias University, Greater Noida 203201, India
| | - Muhammad Irfan Siddique
- Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Mohd Imran
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia;
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Balogun TA, Iqbal MN, Saibu OA, Akintubosun MO, Lateef OM, Nneka UC, Abdullateef OT, Omoboyowa DA. Discovery of potential HER2 inhibitors from Mangifera indica for the treatment of HER2-Positive breast cancer: an integrated computational approach. J Biomol Struct Dyn 2022; 40:12772-12784. [PMID: 34514973 DOI: 10.1080/07391102.2021.1975570] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Human epidermal growth factor receptor 2 (HER2) is a member of epidermal growth factor receptors with tyrosine kinase functionality. The dimerization of HER2 leads to the autophosphorylation of tyrosine residues within its cytoplasmic domain, resulting in hyperactivation of several downstream signal transduction pathways that play an important role in tumorigenesis, cancer aggressiveness and cell proliferation. Amplification or overexpression of HER2 has been found in approximately 15-30% of breast cancers. Hence, HER2 serve as a therapeutic biomarker in breast cancer. Herein, we applied structural bioinformatics techniques via molecular docking, molecular dynamics simulations, Molecular mechanics/generalized Born surface area (MM/GBSA) calculations and pharmacokinetic models to identify putative HER2 inhibitors. Application of stringent molecular docking results in the identification of bioactive compounds from Mangifera indica as selective, potent inhibitors of HER2. However, only the top three compounds with the highest negative docking score (< -9kcal/mol) was considered in reference to neratinib (-8.601 kcal/mol) for computational analysis. The molecular dynamics simulations and post-simulation analysis of docked HER2-ligand complexes unveil the substantial stability for M. indica ligands over the 100 ns simulation period. Additionally, MM/GBSA binding free energy calculation supports the inhibitory potential for the docked ligands, which exclusively revealed the highest binding energy for selected M. indica ligands than the reference compound (neratinib). The pharmacokinetic model showed that M. indica ligands are promising therapeutic agents. Conclusively, bioactive compounds from M. indica may serve as lead molecules that could be developed into potent and effective HER2 inhibitors for breast cancer treatment.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
| | - Muhammad Nasir Iqbal
- Department of Biosciences, COMSATS University Islamabad, Islamabad, ICT, Pakistan
| | - Oluwatosin Abideen Saibu
- Department of Environmental Toxicology, Universitat Duisburg-Essen, NorthRhine-Westphalia, Germany
| | | | | | - Uche Catherine Nneka
- Department of Quality Assurance, Loving Gaze-SHOPS Plus Tuberculosis USAID Project, Nsukka, Nigeria
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Aboyewa JA, Sibuyi NRS, Goboza M, Murtz LA, Oguntibeju OO, Meyer M. Co-Treatment of Caco-2 Cells with Doxorubicin and Gold Nanoparticles Produced from Cyclopia intermedia Extracts or Mangiferin Enhances Drug Effects. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:3918. [PMID: 36364694 PMCID: PMC9654788 DOI: 10.3390/nano12213918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/01/2022] [Accepted: 11/03/2022] [Indexed: 06/16/2023]
Abstract
Mangiferin (MGF) is a natural and valuable polyphenol found in significant levels in many plant species, including Cyclopia intermedia (C. intermedia). In a previous study, we synthesized gold nanoparticles (AuNPs) using MGF and a water extract of C. intermedia and reported that these AuNPs have very low cytotoxicity toward a human colon cancer (Caco-2) cell line. Although the study also showed that these biogenic AuNPs in combination with doxorubic (DOX) significantly augmented the cytotoxic effects of DOX in Caco-2 cells, the mechanism of the enhanced effect was not fully understood, and it was also not known if other cell lines would be sensitive to this co-treatment. In the present study, we examined the cytotoxicity of the co-treatment in Caski, HeLa, HT-29, KMST-6 and MDA-321 cell lines. Additionally, we investigated the mechanistic effects of this co-treatment in Caco-2 cells using several assays, including the adenosine triphosphate (ATP), the oxidative stress, the mitochondrial depolarization, the colony formation, the APOPercentage and the DNA fragmentation assays. We also assessed the intracellular uptake of the biogenic AuNPs. The study showed that the biogenic AuNPs were effectively taken up by the cancer cells, which, in turn, may have enhanced the sensitivity of Caco-2 cells to DOX. Moreover, the combination of the biogenic AuNPs and DOX caused a rapid depletion of ATP levels, increased mitochondrial depolarization, induced apoptosis, reduced the production of reactive oxygen species (ROS) and inhibited the long-term survival of Caco-2 cells. Although the study provided some insight into the mechanism of cytotoxicity induced by the co-treatment, further mechanistic and molecular studies are required to fully elucidate the enhanced anticancer effect of the co-treatment.
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Affiliation(s)
- Jumoke A. Aboyewa
- Phytomedicine and Phytochemistry Group, Oxidative Stress Research Centre, Department of Biomedical Sciences, Cape Peninsula University of Technology, Bellville 7535, South Africa
- DSI/Mintek Nanotechnology Innovation Centre, Biolabels Node, Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa
| | - Nicole R. S. Sibuyi
- DSI/Mintek Nanotechnology Innovation Centre, Biolabels Node, Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa
| | - Mediline Goboza
- DSI/Mintek Nanotechnology Innovation Centre, Biolabels Node, Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa
| | - Lee-Ann Murtz
- DSI/Mintek Nanotechnology Innovation Centre, Biolabels Node, Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa
| | - Oluwafemi O. Oguntibeju
- Phytomedicine and Phytochemistry Group, Oxidative Stress Research Centre, Department of Biomedical Sciences, Cape Peninsula University of Technology, Bellville 7535, South Africa
| | - Mervin Meyer
- DSI/Mintek Nanotechnology Innovation Centre, Biolabels Node, Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa
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Hassanein EHM, Mohamed WR, Ahmed OS, Abdel-Daim MM, Sayed AM. The role of inflammation in cadmium nephrotoxicity: NF-κB comes into view. Life Sci 2022; 308:120971. [PMID: 36130617 DOI: 10.1016/j.lfs.2022.120971] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/06/2022] [Accepted: 09/13/2022] [Indexed: 11/29/2022]
Abstract
Kidney diseases are major health problem and understanding the underlined mechanisms that lead to kidney diseases are critical research points with a marked potential impact on health. Cadmium (Cd) is a heavy metal that occurs naturally and can be found in contaminated food. Kidneys are the most susceptible organ to heavy metal intoxication as it is the main route of waste excretion. The harmful effects of Cd were previously well proved. Cd induces inflammatory responses, oxidative injury, mitochondrial dysfunction and disturbs Ca2+ homeostasis. The nuclear factor-kappa B (NF-κB) is a cellular transcription factor that regulates inflammation and controls the expression of many inflammatory cytokines. Therefore, great therapeutic benefits can be attained from NF-κB inhibition. In this review we focused on certain compounds including cytochalasin D, mangiferin, N-acetylcysteine, pyrrolidine dithiocarbamate, roflumilast, rosmarinic acid, sildenafil, sinapic acid, telmisartan and wogonin and certain plants as Astragalus Polysaccharide, Ginkgo Biloba and Thymus serrulatus that potently inhibit NF-κB and effectively counteracted Cd-associated renal intoxication. In conclusion, the proposed NF-κB involvement in Cd-renal intoxication clarified the underlined inflammation associated with Cd-nephropathy and the beneficial effects of NF-κB inhibitors that make them the potential to substantially optimize treatment protocols for Cd-renal intoxication.
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Affiliation(s)
- Emad H M Hassanein
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Wafaa R Mohamed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt
| | - Osama S Ahmed
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Mohamed M Abdel-Daim
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia; Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, 41522 Ismailia, Egypt
| | - Ahmed M Sayed
- Biochemistry Laboratory, Chemistry Department, Faculty of Science, Assiut University, Egypt.
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Explaining the interaction of mangiferin with MMP-9 and NF-ƙβ: a computational study. J Mol Model 2022; 28:266. [DOI: 10.1007/s00894-022-05260-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 08/05/2022] [Indexed: 10/15/2022]
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Chaparro-Hernández I, Rodríguez-Ramírez J, Barriada-Bernal LG, Méndez-Lagunas L. Tree ferns (Cyatheaceae) as a source of phenolic compounds – A review. J Herb Med 2022. [DOI: 10.1016/j.hermed.2022.100587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Keathley J, de Toro-Martín J, Kearney M, Garneau V, Pilon G, Couture P, Marette A, Vohl MC, Couillard C. Gene expression signatures and cardiometabolic outcomes following 8-week mango consumption in individuals with overweight/obesity. Front Nutr 2022; 9:918844. [PMID: 36034894 PMCID: PMC9407242 DOI: 10.3389/fnut.2022.918844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 07/18/2022] [Indexed: 11/29/2022] Open
Abstract
Background Little is known about the impact of mango consumption on metabolic pathways assessed by changes in gene expression. Methods In this single-arm clinical trial, cardiometabolic outcomes and gene expression levels in whole blood samples from 26 men and women were examined at baseline and after 8 weeks of mango consumption and differential gene expression changes were determined. Based on changes in gene expression profiles, partial least squares discriminant analysis followed by hierarchical clustering were used to classify participants into subgroups of response and differences in gene expression changes and in cardiometabolic clinical outcomes following the intervention were tested. Results Two subgroups of participants were separated based on the resemblance of gene expression profiles in response to the intervention and as responders (n = 8) and non-responders (n = 18). A total of 280 transcripts were significantly up-regulated and 603 transcripts down-regulated following the intervention in responders, as compared to non-responders. Several metabolic pathways, mainly related to oxygen and carbon dioxide transport as well as oxidative stress, were found to be significantly enriched with differentially expressed genes. In addition, significantly beneficial changes in hip and waist circumference, c-reactive protein, HOMA-IR and QUICKI indices were observed in responders vs. non-responders, following the intervention. Conclusion The impact of mango consumption on cardiometabolic health appears to largely rely on interindividual variability. The novel transcriptomic-based clustering analysis used herein can provide insights for future research focused on unveiling the origins of heterogeneous responses to dietary interventions. Clinical Trial Registration [clinicaltrials.gov], identifier [NCT03825276].
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Affiliation(s)
- Justine Keathley
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,School of Nutrition, Université Laval, Québec, QC, Canada
| | - Juan de Toro-Martín
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,School of Nutrition, Université Laval, Québec, QC, Canada
| | - Michèle Kearney
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,School of Nutrition, Université Laval, Québec, QC, Canada
| | - Véronique Garneau
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,School of Nutrition, Université Laval, Québec, QC, Canada
| | - Geneviève Pilon
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,Quebec Heart and Lung Institute (IUCPQ) Research Center, Québec, QC, Canada
| | - Patrick Couture
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,Endocrinology and Nephrology Unit, CHU de Quebec Research Center, Québec, QC, Canada
| | - André Marette
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,Quebec Heart and Lung Institute (IUCPQ) Research Center, Québec, QC, Canada
| | - Marie-Claude Vohl
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,School of Nutrition, Université Laval, Québec, QC, Canada
| | - Charles Couillard
- Center Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC, Canada.,School of Nutrition, Université Laval, Québec, QC, Canada
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12
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Islam F, Bepary S, Nafady MH, Islam MR, Emran TB, Sultana S, Huq MA, Mitra S, Chopra H, Sharma R, Sweilam SH, Khandaker MU, Idris AM. Polyphenols Targeting Oxidative Stress in Spinal Cord Injury: Current Status and Future Vision. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:8741787. [PMID: 36046682 PMCID: PMC9423984 DOI: 10.1155/2022/8741787] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/03/2022] [Accepted: 08/03/2022] [Indexed: 02/07/2023]
Abstract
A spinal cord injury (SCI) occurs when the spinal cord is deteriorated or traumatized, leading to motor and sensory functions lost even totally or partially. An imbalance within the generation of reactive oxygen species and antioxidant defense levels results in oxidative stress (OS) and neuroinflammation. After SCI, OS and occurring pathways of inflammations are significant strenuous drivers of cross-linked dysregulated pathways. It emphasizes the significance of multitarget therapy in combating SCI consequences. Polyphenols, which are secondary metabolites originating from plants, have the promise to be used as alternative therapeutic agents to treat SCI. Secondary metabolites have activity on neuroinflammatory, neuronal OS, and extrinsic axonal dysregulated pathways during the early stages of SCI. Experimental and clinical investigations have noted the possible importance of phenolic compounds as important phytochemicals in moderating upstream dysregulated OS/inflammatory signaling mediators and axonal regeneration's extrinsic pathways after the SCI probable significance of phenolic compounds as important phytochemicals in mediating upstream dysregulated OS/inflammatory signaling mediators. Furthermore, combining polyphenols could be a way to lessen the effects of SCI.
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Affiliation(s)
- Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Sristy Bepary
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Mohamed H. Nafady
- Faculty of Applied Health Science Technology, Misr University for Science and Technology, Giza, Egypt
| | - Md. Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
| | - Sharifa Sultana
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Md. Amdadul Huq
- Department of Food and Nutrition, Chung Ang University, Anseong-Si, Gyeonggi-Do 17546, Republic of Korea
| | - Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Rohit Sharma
- Department of Rasashastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
| | - Sherouk Hussein Sweilam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Egyptian Russian University, Cairo-Suez Road, Badr City 11829, Egypt
| | - Mayeen Uddin Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, 47500 Bandar Sunway, Selangor, Malaysia
| | - Abubakr M. Idris
- Department of Chemistry, College of Science, King Khalid University, Abha 62529, Saudi Arabia
- Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha 62529, Saudi Arabia
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13
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Attia SH, Elshazly SM, Abdelaal MM, Soliman E. Reno-protective effect of mangiferin against methotrexate-induced kidney damage in male rats: PPARγ-mediated antioxidant activity. Saudi Pharm J 2022; 30:1252-1261. [PMID: 36249937 PMCID: PMC9561181 DOI: 10.1016/j.jsps.2022.06.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 06/24/2022] [Indexed: 11/30/2022] Open
Abstract
Methotrexate (MTX) is an immunosuppressant used for the treatment of cancer and autoimmune diseases. MTX has a major adverse effect, acute kidney injury, which limits its use. Mangiferin (MF) is a natural bioactive xanthonoid used as a traditional herbal supplement to boost the immune system due to its potent anti-inflammatory and antioxidant activity. The present study evaluates the protective effect of MF against MTX-induced kidney damage. Male Wistar rats received MTX to induce nephrotoxicity or were pretreated with MF for 10 constitutive days before MTX administration. MF dose-dependently improved renal functions of MTX-treated rats and this activity was correlated with increased renal expression of PPARγ, a well-known transcriptional regulator of the immune response. Pretreating rats with PPARγ inhibitor, BADGE, reduced the reno-protective activity of MF. Furthermore, MF treatment significantly reduced MTX-induced upregulation of the pro-inflammatory (NFκB, interleukin-1ß, TNF-α, and COX-2), oxidative stress (Nrf-2, hemoxygenase-1, glutathione, and malondialdehyde), and nitrosative stress (nitric oxide and iNOS) markers in the kidney. Importantly, BADGE treatment significantly reduced the anti-inflammatory and antioxidant activity of MF. Therefore, our data suggest that the reno-protective effect of MF against MTX-induced nephrotoxicity is due to inhibition of inflammation and oxidative stress in a PPAR-γ-dependent manner.
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Affiliation(s)
- Seba Hassan Attia
- Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Egypt
| | | | | | - Eman Soliman
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Zagazig University, Egypt
- Corresponding author.
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14
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Keathley J, Kearney M, Garneau V, Toro-Martín JD, Varin TV, Pilon G, Couture P, Marette A, Vohl MC, Couillard C. Changes in systolic blood pressure, postprandial glucose, and gut microbial composition following mango consumption in individuals with overweight and obesity. Appl Physiol Nutr Metab 2022; 47:565-574. [PMID: 35506190 DOI: 10.1139/apnm-2021-0637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
This study aimed to explore the impact of daily mango consumption (Mangifera indica) on cardiometabolic health and gut microbiota in individuals with overweight and obesity. Changes in cardiometabolic variables, gut microbiota diversity and composition, physical activity habits, and dietary intakes were assessed in 8 males and 19 females with overweight and obesity who consumed 280 g/day of mango pulp for 8 weeks. There were no significant changes in body weight, waist circumference, or plasma lipid levels. However, after consuming mangos for 8 weeks, participants showed a 3.5% reduction in systolic blood pressure (-4 ± 6 mm Hg, p = 0.011) as well as a 10.5% reduction in 2-hour plasma glucose concentration after a 75-g oral glucose tolerance test (-0.58 ± 1.03 mmol/L, p = 0.008). These beneficial cardiometabolic outcomes were accompanied with enhanced gut microbiota diversity and with changes in the abundance of specific gut bacterial species. Mango consumption may have beneficial effects on both blood pressure and glucose homeostasis in individuals with overweight and obesity. Further studies are warranted to determine the impact of long-term and regular mango intake on cardiometabolic risk factors of individuals with overweight and obesity, and the potential mechanisms linking gut microbial changes to those health benefits. This study was registered with clinicaltrials.gov as NCT03825276. Novelty: A 3.5% reduction in systolic blood pressure is noted after consuming mangos for 8 weeks. A 10.5% reduction in 2-hour plasma glucose concentration of an oral glucose tolerance test is observed after consuming mangos for 8 weeks. Mango consumption for 8 weeks may enhance gut microbial diversity and abundance of specific bacterial species.
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Affiliation(s)
- Justine Keathley
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.,School of Nutrition, Université Laval, Québec, QC G1V 0A6, Canada
| | - Michèle Kearney
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.,School of Nutrition, Université Laval, Québec, QC G1V 0A6, Canada
| | - Véronique Garneau
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.,School of Nutrition, Université Laval, Québec, QC G1V 0A6, Canada
| | - Juan de Toro-Martín
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.,School of Nutrition, Université Laval, Québec, QC G1V 0A6, Canada
| | - Thibault V Varin
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada
| | - Geneviève Pilon
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.,Québec Heart and Lung Institute (IUCPQ) Research Centre, Québec, QC G1V 4G5, Canada
| | - Patrick Couture
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada
| | - André Marette
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.,Québec Heart and Lung Institute (IUCPQ) Research Centre, Québec, QC G1V 4G5, Canada
| | - Marie-Claude Vohl
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.,School of Nutrition, Université Laval, Québec, QC G1V 0A6, Canada
| | - Charles Couillard
- Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.,School of Nutrition, Université Laval, Québec, QC G1V 0A6, Canada
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15
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Fakhri S, Abbaszadeh F, Moradi SZ, Cao H, Khan H, Xiao J. Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:8100195. [PMID: 35035667 PMCID: PMC8759836 DOI: 10.1155/2022/8100195] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/11/2021] [Indexed: 02/05/2023]
Abstract
Despite the progression in targeting the complex pathophysiological mechanisms of neurodegenerative diseases (NDDs) and spinal cord injury (SCI), there is a lack of effective treatments. Moreover, conventional therapies suffer from associated side effects and low efficacy, raising the need for finding potential alternative therapies. In this regard, a comprehensive review was done regarding revealing the main neurological dysregulated pathways and providing alternative therapeutic agents following SCI. From the mechanistic point, oxidative stress and inflammatory pathways are major upstream orchestras of cross-linked dysregulated pathways (e.g., apoptosis, autophagy, and extrinsic mechanisms) following SCI. It urges the need for developing multitarget therapies against SCI complications. Polyphenols, as plant-derived secondary metabolites, have the potential of being introduced as alternative therapeutic agents to pave the way for treating SCI. Such secondary metabolites presented modulatory effects on neuronal oxidative stress, neuroinflammatory, and extrinsic axonal dysregulated pathways in the onset and progression of SCI. In the present review, the potential role of phenolic compounds as critical phytochemicals has also been revealed in regulating upstream dysregulated oxidative stress/inflammatory signaling mediators and extrinsic mechanisms of axonal regeneration after SCI in preclinical and clinical studies. Additionally, the coadministration of polyphenols and stem cells has shown a promising strategy for improving post-SCI complications.
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Affiliation(s)
- Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Fatemeh Abbaszadeh
- Department of Neuroscience, Faculty of Advanced Technologies in Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
- Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Zachariah Moradi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Hui Cao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, E-32004 Ourense, Spain
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, E-32004 Ourense, Spain
- Institute of Food Safety and Nutrition, Jinan University, Guangzhou 510632, China
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16
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Gul S, Aslam K, Pirzada Q, Rauf A, Khalil AA, Semwal P, Bawazeer S, Al-Awthan YS, Bahattab OS, Al Duais MA, Thiruvengadam M. Xanthones: A Class of Heterocyclic Compounds with Anticancer Potential. Curr Top Med Chem 2022; 22:1930-1949. [PMID: 36056870 DOI: 10.2174/1568026622666220901145002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/09/2022] [Accepted: 07/18/2022] [Indexed: 11/22/2022]
Abstract
Xanthones (9H xanthen-9-one) are an important class of heterocyclic compounds containing oxygen and a moiety of gamma-pirone, dense with a two-benzene ring structure, distributed widely in nature. Naturally occurring xanthones are found in micro-organisms and higher plants as secondary metabolites in fungi and lichens. Compounds of the family Caryophyllaceae, Guttiferae and Gentianaceae, are the most common natural source of xanthones. The structure of the xanthones nucleus, coupled with its biogenetic source, imposes that the carbons are numbered according to the biosynthetic pact. The characteristics oxygenation pattern of xanthones earlier is mixed shikimateacetate biogenesis. The major class of xanthones includes simple oxygenated, non-oxygenated, xanthonolignoids, bisxanthones, prenylated and related xanthones, miscellaneous xanthones. Their great pharmacological importance and interesting scaffolds were highly encouraged by scientists to investigate either the synthesis design or natural products for cancer treatment. Because currently used antitumor drugs possess high toxicity and low selectivity, efficacious treatment may be compromised. This review is limited to the antitumor activity of xanthones and the chemistry of xanthone core, which may help provide fundamental knowledge to the medicinal chemist for new and advanced research in drug development.
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Affiliation(s)
- Somia Gul
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jinnah University for Women, Karachi, 74600, Pakistan
| | - Khadija Aslam
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jinnah University for Women, Karachi, 74600, Pakistan
| | - Quratulain Pirzada
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jinnah University for Women, Karachi, 74600, Pakistan
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar, 23430, Khyber Pakhtunkhwa (KP), Pakistan
| | - Anees Ahmed Khalil
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Prabhakar Semwal
- Department of Life Sciences, Graphic Era Deemed to be University, Dehradun, Uttarakhand, India
| | - Sami Bawazeer
- Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Yahya Saleh Al-Awthan
- Department of Biology, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
- Department of Biology, Faculty of Science, Ibb University, Ibb, Yemen
| | - Omar Salem Bahattab
- Department of Biology, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Mohammed Ali Al Duais
- Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
- Biochemistry Unit, Chemistry Department, Faculty of Science, Ibb University, Ibb, Yemen
| | - Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea
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17
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Rodriguez-Gonzalez JC, Hernández-Balmaseda I, Declerck K, Pérez-Novo C, Logie E, Theys C, Jakubek P, Quiñones-Maza OL, Dantas-Cassali G, Carlos Dos Reis D, Van Camp G, Lopes Paz MT, Rodeiro-Guerra I, Delgado-Hernández R, Vanden Berghe W. Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism. Front Pharmacol 2021; 12:670167. [PMID: 34924998 PMCID: PMC8678272 DOI: 10.3389/fphar.2021.670167] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 11/03/2021] [Indexed: 12/24/2022] Open
Abstract
In spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one of the greatest challenges in long-term management of CRC and urges need for new leads of anticancer drugs. We demonstrate that CRC treatment with the phytopharmaceutical mangiferin (MGF), a glucosylxanthone present in Mango tree stem bark and leaves (Mangifera Indica L.), induces dose-dependent tumor regression and decreases lung metastasis in a syngeneic immunocompetent allograft mouse model of murine CT26 colon carcinoma, which increases overall survival of mice. Antimetastatic and antiangiogenic MGF effects could be further validated in a wound healing in vitro model in human HT29 cells and in a matrigel plug implant mouse model. Interestingly, transcriptome pathway enrichment analysis demonstrates that MGF inhibits tumor growth, metastasis and angiogenesis by multi-targeting of mitochondrial oxidoreductase and fatty acid β-oxidation metabolism, PPAR, SIRT, NFκB, Stat3, HIF, Wnt and GP6 signaling pathways. MGF effects on fatty acid β-oxidation metabolism and carnitine palmitoyltransferase 1 (CPT1) protein expression could be further confirmed in vitro in human HT29 colon cells. In conclusion, antitumor, antiangiogenic and antimetastatic effects of MGF treatment hold promise to reduce adverse toxicity and to mitigate therapeutic outcome of colorectal cancer treatment by targeting mitochondrial energy metabolism in the tumor microenvironment.
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Affiliation(s)
| | | | - Ken Declerck
- Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium
| | - Claudina Pérez-Novo
- Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium
| | - Emilie Logie
- Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium
| | - Claudia Theys
- Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium
| | - Patrycja Jakubek
- Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium.,Department of Food Chemistry, Technology and Biotechnology, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland
| | | | - Geovanni Dantas-Cassali
- Departamento de Farmacología, Instituto de Ciencias Biológicas (ICB), Universidad Federal de Minas Gerais (UFMG), Horizonte, Brazil
| | - Diego Carlos Dos Reis
- Departamento de Farmacología, Instituto de Ciencias Biológicas (ICB), Universidad Federal de Minas Gerais (UFMG), Horizonte, Brazil
| | - Guy Van Camp
- Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
| | - Miriam Teresa Lopes Paz
- Departamento de Farmacología, Instituto de Ciencias Biológicas (ICB), Universidad Federal de Minas Gerais (UFMG), Horizonte, Brazil
| | - Idania Rodeiro-Guerra
- Laboratorio de Farmacología, Instituto de Ciencias del Mar (ICIMAR), CITMA, La Habana, Cuba
| | - René Delgado-Hernández
- Centro de Estudios para las Investigaciones y Evaluaciones Biológicas (CEIEB), Instituto de Farmacia y Alimentos (IFAL), Universidad de La Habana, La Habana, Cuba.,Facultad de Ciencias Naturales y Agropecuarias, Universidat de Santander (UDES), Bucaramanga, Colombia
| | - Wim Vanden Berghe
- Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Antwerp, Belgium
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18
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Mei S, Perumal M, Battino M, Kitts DD, Xiao J, Ma H, Chen X. Mangiferin: a review of dietary sources, absorption, metabolism, bioavailability, and safety. Crit Rev Food Sci Nutr 2021; 63:3046-3064. [PMID: 34606395 DOI: 10.1080/10408398.2021.1983767] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Mangiferin is a potential candidate for use in nutraceutical and functional food applications due to its numerous bioactivities. However, the low bioavailability of mangiferin is a major limitation for establishing efficacy for use. This review describes current information on known food sources and factors that influence mangiferin contents, absorption, and metabolism features, and recent progress that has come from research efforts to increase the bioavailability of mangiferin. We also list patents that targeted to enhance mangiferin bioavailability. Mangifera indica L. is the major dietary source for mangiferin, a xanthone that varies widely in different parts of the plant and is influenced by many factors that involve plant propagation and post-harvest processing. Mangiferin absorption occurs mostly in the small intestine by passive diffusion with varying absorption capacities in different segments of the gastrointestinal tract. Recent research has led to the development of novel technologies to encapsulate mangiferin in nano/microparticle carrier systems as well as generate mangiferin derivatives to improve solubility and bioavailability. Preclinical studies reported that mangiferin < 2000 mg/kg is generally nontoxic. The safety and the increase in bioavailability are key limiting factors for developing successful applications for mangiferin as a nutritional dietary supplement or nutraceutical.Supplemental data for this article is available online at.
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Affiliation(s)
- Suhuan Mei
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
- Institute of Food Physical Processing, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
| | - Manivel Perumal
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
- Institute of Food Physical Processing, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
| | - Maurizio Battino
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China
- Department of Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy
| | - David D Kitts
- Food, Nutrition, and Health, University of British Columbia, Vancouver, BC, Canada
| | - Jianbo Xiao
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China
- Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo, Vigo, Spain
| | - Haile Ma
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
- Institute of Food Physical Processing, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
| | - Xiumin Chen
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
- Institute of Food Physical Processing, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China
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19
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Sicurella M, Sguizzato M, Cortesi R, Huang N, Simelière F, Montesi L, Marconi P, Esposito E. Mangiferin-Loaded Smart Gels for HSV-1 Treatment. Pharmaceutics 2021; 13:pharmaceutics13091323. [PMID: 34575399 PMCID: PMC8465222 DOI: 10.3390/pharmaceutics13091323] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/10/2021] [Accepted: 08/18/2021] [Indexed: 11/16/2022] Open
Abstract
Infections due to HSV-1 affect many people all over the world. To counteract this pathology, usually characterized by perioral sores or by less frequent serious symptoms including keratitis, synthetic antiviral drugs are employed, such as acyclovir, often resulting in resistant viral strains under long-term use. Many plant-derived compounds, such as mangiferin and quercetin, have demonstrated antiviral potentials. In this study, smart semisolid forms based on phosphatidylcholine and Pluronic were investigated as delivery systems to administer mangiferin on skin and mucosae affected by HSV-1 infection. Particularly, lecithin organogels, Pluronic gel, and Pluronic lecithin organogels were formulated and characterized. After the selection of gel compositions, physical aspects, such as rheological behavior, spreadability, leakage, and adhesion were evaluated, suggesting a scarce suitability of the lecithin organogel for topical administration. Mangiferin was efficiently included in all type of gels. An in vitro study based on the Franz cell enabled us to find evidence of the gel capability to control drug diffusion, especially in the case of Pluronic organogel, while an in vivo study conducted on human volunteers demonstrated the safeness of all of the gels after cutaneous administration. Furthermore, a plaque reduction assay demonstrated the virucidal effect of mangiferin loaded in a Pluronic gel and a Pluronic lecithin organogel against the HSV-1 KOS strain.
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Affiliation(s)
- Mariaconcetta Sicurella
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy; (M.S.); (M.S.); (R.C.)
| | - Maddalena Sguizzato
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy; (M.S.); (M.S.); (R.C.)
| | - Rita Cortesi
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy; (M.S.); (M.S.); (R.C.)
| | - Nicolas Huang
- CNRS, Institut Galien Paris-Saclay, Université Paris-Saclay, 92296 Châtenay-Malabry, France; (N.H.); (F.S.)
| | - Fanny Simelière
- CNRS, Institut Galien Paris-Saclay, Université Paris-Saclay, 92296 Châtenay-Malabry, France; (N.H.); (F.S.)
| | - Leda Montesi
- Cosmetology Center, University of Ferrara, I-44121 Ferrara, Italy;
| | - Peggy Marconi
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy; (M.S.); (M.S.); (R.C.)
- Correspondence: (P.M.); (E.E.)
| | - Elisabetta Esposito
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy; (M.S.); (M.S.); (R.C.)
- Correspondence: (P.M.); (E.E.)
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Sguizzato M, Ferrara F, Mariani P, Pepe A, Cortesi R, Huang N, Simelière F, Boldrini P, Baldisserotto A, Valacchi G, Esposito E. "Plurethosome" as Vesicular System for Cutaneous Administration of Mangiferin: Formulative Study and 3D Skin Tissue Evaluation. Pharmaceutics 2021; 13:1124. [PMID: 34452085 PMCID: PMC8398752 DOI: 10.3390/pharmaceutics13081124] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/18/2021] [Accepted: 07/21/2021] [Indexed: 12/21/2022] Open
Abstract
Human skin is dramatically exposed to toxic pollutants such as ozone. To counteract the skin disorders induced by the air pollution, natural antioxidants such as mangiferin could be employed. A formulative study for the development of vesicular systems for mangiferin based on phosphatidylcholine and the block copolymer pluronic is described. Plurethosomes were designed for mangiferin transdermal administration and compared to ethosome and transethosome. Particularly, the effect of vesicle composition was investigated on size distribution, inner and outer morphology by photon correlation spectroscopy, small angle X-ray diffraction, and transmission electron microscopy. The potential of selected formulations as vehicles for mangiferin was studied, evaluating encapsulation efficiency and in vitro diffusion parameters by Franz cells. The mangiferin antioxidant capacity was verified by the 2,2-diphenyl-1-picrylhydrazyl assay. Vesicle size spanned between 200 and 550 nm, being influenced by phosphatidylcholine concentration and by the presence of polysorbate or pluronic. The vesicle supramolecular structure was multilamellar in the case of ethosome or plurethosome and unilamellar in the case of transethosome. A linear diffusion of mangiferin in the case of ethosome and transethosomes and a biphasic profile in the case of plurethosomes indicated the capability of multilamellar vesicles to retain the drug more efficaciously than the unilamellar ones. The antioxidant and anti-inflammatory potential effect of mangiferin against pollutants was evaluated on 3D human skin models exposed to O3. The protective effect exerted by plurethosomes and transethosomes suggests their possible application to enhance the cutaneous antioxidant defense status.
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Affiliation(s)
- Maddalena Sguizzato
- Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy; (M.S.); (R.C.)
| | - Francesca Ferrara
- Department of Neurosciences and Rehabilitation, University of Ferrara, I-44121 Ferrara, Italy;
| | - Paolo Mariani
- Department of Life and Environmental Sciences, Polytechnic University of Marche, I-60131 Ancona, Italy; (P.M.); (A.P.)
| | - Alessia Pepe
- Department of Life and Environmental Sciences, Polytechnic University of Marche, I-60131 Ancona, Italy; (P.M.); (A.P.)
| | - Rita Cortesi
- Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy; (M.S.); (R.C.)
| | - Nicolas Huang
- Institut Galien Paris-Saclay, CNRS, Université Paris-Saclay, 92296 Châtenay-Malabry, France; (N.H.); (F.S.)
| | - Fanny Simelière
- Institut Galien Paris-Saclay, CNRS, Université Paris-Saclay, 92296 Châtenay-Malabry, France; (N.H.); (F.S.)
| | - Paola Boldrini
- Center of Electron Microscopy, University of Ferrara, I-44121 Ferrara, Italy;
| | - Anna Baldisserotto
- Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy;
| | - Giuseppe Valacchi
- Department of Neurosciences and Rehabilitation, University of Ferrara, I-44121 Ferrara, Italy;
- Animal Science Department, NC Research Campus, Plants for Human Health Institute, NC State University, Kannapolis, NC 28081, USA
- Department of Food and Nutrition, Kyung Hee University, Seoul 02447, Korea
| | - Elisabetta Esposito
- Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy; (M.S.); (R.C.)
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Qin ZZ, Ruan J, Lee MR, Sun K, Chen P, Chen Y, Hong M, Xia LH, Fang J, Tang H. Mangiferin Promotes Bregs Level, Activates Nrf2 Antioxidant Signaling, and Inhibits Proinflammatory Cytokine Expression in Murine Splenic Mononuclear Cells In Vitro. Curr Med Sci 2021; 41:454-464. [PMID: 34129203 DOI: 10.1007/s11596-021-2371-9] [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: 03/30/2021] [Accepted: 05/26/2021] [Indexed: 01/16/2023]
Abstract
Recent studies indicated that regulatory B cells (Bregs) and nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant signaling pathway play important roles in the pathogenesis of chronic graft-versus-host disease (cGVHD). Mangiferin (MA), a polyphenol compound, has been reported to activate Nrf2/antioxidant-responsive element (ARE) signaling pathway. This study was aimed to investigate the effects of MA on Bregs and Nrf2 antioxidant signaling in murine splenic mononuclear cells (MNCs) in vitro. Our results revealed that MA could increase the Bregs level in murine splenic MNCs. Moreover, MA up-regulated the expression of Bregs-associated immunosuppressive factor interleukin-10 (IL-10) by activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) signaling in murine splenic MNCs. Meanwhile, MA inhibited the proinflammatory cytokines IL-2 and interferon-γ (INF-γ) at both mRNA and protein levels. MA also enhanced the transcription and protein expression of Nrf2 and NADPH quinine oxidoreductase 1 (NQO1), whereas decreased that of Kelch-like ECH-associated protein 1 (Keap1) in murine splenic MNCs. Moreover, MA promoted the proliferation and inhibited the apoptosis of murine splenic MNCs. These results suggested that MA exerts immunosuppressive effects by upregulating the Bregs level, activating the Nrf2 antioxidant pathway, and inhibiting the expression of pro-immunoinflammatory factors. MA, as a natural immunomodulatory and anti-inflammatory agent, may have a potential role in the prophylaxis and treatment of cGVHD.
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Affiliation(s)
- Zhi-Zhi Qin
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, 475000, China
| | - Jun Ruan
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Department of Gastroenterology, Wuhan Resources & Wisco General Hospital, Wuhan, 430080, China
| | - Meng-Ran Lee
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kang Sun
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ping Chen
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yan Chen
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Mei Hong
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215000, China
| | - Ling-Hui Xia
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jun Fang
- Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Hao Tang
- Department of Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.
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Ethosomes and Transethosomes for Mangiferin Transdermal Delivery. Antioxidants (Basel) 2021; 10:antiox10050768. [PMID: 34066018 PMCID: PMC8150765 DOI: 10.3390/antiox10050768] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/08/2021] [Accepted: 05/09/2021] [Indexed: 12/13/2022] Open
Abstract
Mangiferin is a natural glucosyl xanthone with antioxidant and anti-inflammatory activity, making it suitable for protection against cutaneous diseases. In this study ethosomes and transethosomes were designed as topical delivery systems for mangiferin. A preformulation study was conducted using different surfactants in association with phosphatidylcholine. Vesicle dimensional distribution was monitored by photon correlation spectroscopy, while antioxidant capacity and cytotoxicity were respectively assessed by free radical scavenging analysis and MTT on HaCaT keratinocytes. Selected nanosystems were further investigated by cryogenic transmission electron microscopy, while mangiferin entrapment capacity was evaluated by ultracentrifugation and HPLC. The diffusion kinetics of mangiferin from ethosomes and transethosomes evaluated by Franz cell was faster in the case of transethosomes. The suitability of mangiferin-containing nanovesicles in the treatment of skin disorders related to pollutants was investigated, evaluating, in vitro, the antioxidant and anti-inflammatory effect of ethosomes and transethosomes on human keratinocytes exposed to cigarette smoke as an oxidative and inflammatory challenger. The ability to induce an antioxidant response (HO-1) and anti-inflammatory status (IL-6 and NF-kB) was determined by RT-PCR and immunofluorescence. The data demonstrated the effectiveness of mangiferin loaded in nanosystems to protect cells from damage. Finally, to gain insight into the keratinocytes’ uptake of ethosome and transethosome, transmission electron microscopy analyses were conducted, showing that both nanosystems were able to pass intact within the cells.
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Ohiagu FO, Chikezie PC, Chikezie CM, Enyoh CE. Anticancer activity of Nigerian medicinal plants: a review. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2021. [DOI: 10.1186/s43094-021-00222-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Cancer is currently the leading cause of death globally and the number of deaths from cancer is on the rise daily. Medicinal plants have been in continuous use over the years for the management of cancer, particularly, in most developing countries of the world including Nigeria. The use of synthetic drugs for the treatment of cancer is often accompanied by toxic side effects. Thus, the alternative use of readily available and inexpensive medicinal plants is the panacea to the toxic side effects associated with synthetic drugs.
Main body
The present review summarized the anticancer activity of 51 medicinal plants that are widespread in all regions of Nigeria. Furthermore, the proposed anticancer pharmacological actions as well as the anticancer bioactive compounds, the type of cancer cell inhibited, the plant parts responsible for the anticancer activity, and the nature of the extracts used for the studies were discussed in this review. The 51 Nigerian medicinal plants were reported to exhibit anticancer activities of the prostate, cervices, lung, skin, colon, esophagus, blood, ovary, central nervous system/brain, breast, stomach, pancreas, larynx, and kidney. The major classes of bioactive compounds indicated to be responsible for the anticancer activity include the polyphenols, flavonoids, alkaloids, saponins, triterpenes, tannins, and quinones. The major anticancer pharmacological actions of these bioactive compounds were antiproliferative, cytotoxic, cytostatic, antimetastatic, apoptotic, and antioxidative as well as provoked cell cycle arrest, inhibition of angiogenesis and reduction of cancer cell viability.
Conclusion
The Nigerian medicinal plants can be harnessed to provide for readily available and inexpensive anticancer drugs in the future because the plants reported in this review showed promising anticancer activity.
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Padervand M, Naseri S, Hajiahmadi S. Preferential solvation and solvation shell composition of sunitinib malate, an anti-tumor compound, in some binary mixed solvents at 298.15 K. CHEMICAL PAPERS 2021. [DOI: 10.1007/s11696-020-01367-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Abstract
Advanced metastatic melanoma, one of the most aggressive skin malignancies, is currently without reliable therapy. The process of angiogenesis is crucial for progression and metastasis of the majority of solid tumors including melanomas. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone which exerts many pharmacological activities against cancer-inflammation. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we demonstrate that mangiferin interferes with inflammation, lipid and calcium signaling which selectively inhibits multiple NFkB target genes including interleukin-6, tumor necrosis factor, interferon gamma, vascular endothelial growth factor receptor 2, plasminogen activator urokinase, matrix metalloprotease 19, C-C Motif Chemokine Ligand 2 and placental growth factor. This abrogates angiogenic and invasive processes and capillary tube formation of metastatic melanoma cells as well as human placental blood vessel explants in-vitro and blocks angiogenesis characteristic of the chicken egg chorioallantoic membrane assay and in melanoma syngeneic studies in vivo. The results obtained in this research illustrate promising anti-angiogenic effects of the natural glucosylxanthone mangiferin for further (pre)clinical studies in melanoma cancer patients.
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Mirza B, Croley CR, Ahmad M, Pumarol J, Das N, Sethi G, Bishayee A. Mango ( Mangifera indica L.): a magnificent plant with cancer preventive and anticancer therapeutic potential. Crit Rev Food Sci Nutr 2020; 61:2125-2151. [PMID: 32506936 DOI: 10.1080/10408398.2020.1771678] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Mangifera indica L. (mango), a long-living evergreen plant belonging to the Anacardiaceae family, has been cultivated for thousands of years in the Indian subcontinent for its excellent fruits which represent a rich source of fiber, vitamin A and C, essential amino acids, and a plethora of phytochemicals. M. indica is extensively used in various traditional systems of medicine to prevent and treat several diseases. The health-promoting and disease-preventing effects of M. indica are attributed to a number of bioactive phytochemicals, including polyphenols, terpenoids, carotenoid and phytosterols, found in the leaf, bark, edible flesh, peel, and seed. M. indica has been shown to exhibit various biological and pharmacological activities, such as antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antidiabetic, antiobesity, and anticancer effects. There are a few studies conducted that have indicated the nontoxic nature of mango constituents. However, while there are numerous individual studies investigating anticancer effects of various constituents from the mango tree, an up-to-date, comprehensive and critical review of available research data has not been performed according to our knowledge. The purpose of this review is to present a comprehensive and critical evaluation of cancer preventive and anticancer therapeutic potential of M. indica and its phytochemicals with special focus on the cellular and molecular mechanisms of action. The bioavailability, pharmacokinetics, and safety profile of individual phytocomponents of M. indica as well as current limitations, challenges, and future directions of research have also been discussed.
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Affiliation(s)
- Bilal Mirza
- Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | | | - Maha Ahmad
- Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Joshua Pumarol
- Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Niranjan Das
- Department of Chemistry, Iswar Chandra Vidyasagar College, Belonia, Tripura, India
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
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Ahmad R, Khan MA, Srivastava A, Gupta A, Srivastava A, Jafri TR, Siddiqui Z, Chaubey S, Khan T, Srivastava AK. Anticancer Potential of Dietary Natural Products: A Comprehensive Review. Anticancer Agents Med Chem 2020; 20:122-236. [DOI: 10.2174/1871520619666191015103712] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 06/21/2019] [Accepted: 07/02/2019] [Indexed: 02/07/2023]
Abstract
Nature is a rich source of natural drug-like compounds with minimal side effects. Phytochemicals
better known as “Natural Products” are found abundantly in a number of plants. Since time immemorial, spices
have been widely used in Indian cuisine as flavoring and coloring agents. Most of these spices and condiments
are derived from various biodiversity hotspots in India (which contribute 75% of global spice production) and
form the crux of India’s multidiverse and multicultural cuisine. Apart from their aroma, flavor and taste, these
spices and condiments are known to possess several medicinal properties also. Most of these spices are mentioned
in the Ayurveda, the indigenous system of medicine. The antimicrobial, antioxidant, antiproliferative,
antihypertensive and antidiabetic properties of several of these natural products are well documented in
Ayurveda. These phytoconstituemts are known to act as functional immunoboosters, immunomodulators as well
as anti-inflammatory agents. As anticancer agents, their mechanistic action involves cancer cell death via induction
of apoptosis, necrosis and autophagy. The present review provides a comprehensive and collective update
on the potential of 66 commonly used spices as well as their bioactive constituents as anticancer agents. The
review also provides an in-depth update of all major in vitro, in vivo, clinical and pharmacological studies done
on these spices with special emphasis on the potential of these spices and their bioactive constituents as potential
functional foods for prevention, treatment and management of cancer.
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Affiliation(s)
- Rumana Ahmad
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Mohsin A. Khan
- Chancellor, Era University, Sarfarazganj, Hardoi Road, Lucknow-226003, UP, India
| | - A.N. Srivastava
- Department of Pathology, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Anamika Gupta
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Aditi Srivastava
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Tanvir R. Jafri
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Zainab Siddiqui
- Department of Pathology, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Sunaina Chaubey
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Tahmeena Khan
- Department of Chemistry, Integral University, Dasauli, P.O. Bas-ha, Kursi Road, Lucknow 226026, UP, India
| | - Arvind K. Srivastava
- Department of Food and Nutrition, Era University, Sarfarazganj, Lucknow-226003, UP, India
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Adewole KE. Nigerian antimalarial plants and their anticancer potential: A review. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2020; 18:92-113. [DOI: 10.1016/j.joim.2020.01.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 10/09/2019] [Indexed: 02/07/2023]
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Klein-Júnior LC, Campos A, Niero R, Corrêa R, Vander Heyden Y, Filho VC. Xanthones and Cancer: from Natural Sources to Mechanisms of Action. Chem Biodivers 2020; 17:e1900499. [PMID: 31794156 DOI: 10.1002/cbdv.201900499] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 12/03/2019] [Indexed: 12/19/2022]
Abstract
Xanthones are a class of heterocyclic natural products that have been widely studied for their pharmacological potential. In fact, they have been serving as scaffolds for the design of derivatives focusing on drug development. One of the main study targets of xanthones is their anticancer activity. Several compounds belonging to this class have already demonstrated cytotoxic and antitumor effects, making it a promising group for further exploration. This review therefore focuses on recently published studies, emphasizing their natural and synthetic sources and describing the main mechanisms of action responsible for the anticancer effect of promising xanthones.
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Affiliation(s)
- Luiz C Klein-Júnior
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, 88302-901, Itajaí, Brazil
| | - Adriana Campos
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, 88302-901, Itajaí, Brazil
| | - Rivaldo Niero
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, 88302-901, Itajaí, Brazil
| | - Rogério Corrêa
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, 88302-901, Itajaí, Brazil
| | - Yvan Vander Heyden
- Department of Analytical Chemistry, Applied Chemometrics and Molecular Modelling, Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel - VUB, B-1090, Brussels, Belgium
| | - Valdir Cechinel Filho
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, 88302-901, Itajaí, Brazil
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Li HW, Lan TJ, Yun CX, Yang KD, Du ZC, Luo XF, Hao EW, Deng JG. Mangiferin exerts neuroprotective activity against lead-induced toxicity and oxidative stress via Nrf2 pathway. CHINESE HERBAL MEDICINES 2020; 12:36-46. [PMID: 36117559 PMCID: PMC9476390 DOI: 10.1016/j.chmed.2019.12.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 07/26/2019] [Accepted: 07/31/2019] [Indexed: 12/12/2022] Open
Affiliation(s)
- Hao-wen Li
- Community Health Services Management center, University of Chinese Academy of Sciences – Shenzhen Hospital, Shenzhen 518106, China
- MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, China
| | - Tai-jin Lan
- School of Basic Medical Science, Guangxi University of Chinese Medicine, Nanning 530200, China
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, China
| | - Chen-xia Yun
- School of Basic Medical Science, Guangxi University of Chinese Medicine, Nanning 530200, China
| | - Ke-di Yang
- MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Zheng-cai Du
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, China
| | - Xue-fei Luo
- Department of Clinical Laboratory, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, China
| | - Er-wei Hao
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, China
| | - Jia-gang Deng
- Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, China
- Corresponding author.
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Ballesteros-Vivas D, Alvarez-Rivera G, García Ocampo AF, Morantes SJ, Sánchez Camargo ADP, Cifuentes A, Parada-Alfonso F, Ibánez E. Supercritical antisolvent fractionation as a tool for enhancing antiproliferative activity of mango seed kernel extracts against colon cancer cells. J Supercrit Fluids 2019. [DOI: 10.1016/j.supflu.2019.104563] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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Polyphenolic Characterization, Antioxidant, and Cytotoxic Activities of Mangifera indica Cultivars from Costa Rica. Foods 2019; 8:foods8090384. [PMID: 31480721 PMCID: PMC6769667 DOI: 10.3390/foods8090384] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/10/2019] [Accepted: 08/20/2019] [Indexed: 12/13/2022] Open
Abstract
The phenolic profile of skin and flesh from Manifera indica main commercial cultivars (Keitt and Tommy Atkins) in Costa Rica was studied using ultra performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-ESI-MS) on enriched phenolic extracts. A total of 71 different compounds were identified, including 32 gallates and gallotannins (of different polymerization degree, from galloyl hexose monomer up to decagalloyl hexoses and undecagalloyl hexoses); seven hydroxybenzophenone (maclurin and iriflophenone) derivatives, six xanthonoids (including isomangiferin and mangiferin derivatives); 11 phenolic acids (hydroxybenzoic and hydroxycinnamic acid derivatives); and eight flavonoids (rhamnetin and quercetin derivatives). The findings for T. Atkins skin constitute the first report of such a high number and diversity of compounds. Also, it is the first time that the presence of gallotannin decamers and undecamers are reported in the skin and flesh of Keitt cultivar and in T. Atkins skins. In addition, total phenolic content (TPC) was measured with high values especially for fruits' skins, with a TPC of 698.65 and 644.17 mg gallic acid equivalents/g extract, respectively, for Keitt and T. Atkins cultivars. Antioxidant potential using 2,2-diphenyl-1-picrylhidrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods were evaluated, with T. Atkins skin showing the best values for both DPPH (IC50 = 9.97 µg/mL) and ORAC (11.02 mmol TE/g extract). A significant negative correlation was found for samples between TPC and DPPH antioxidant values (r = -0.960, p < 0.05), as well as a significant positive correlation between TPC and ORAC (r = 0.910, p < 0.05) and between DPPH and ORAC antioxidant methods (r = 0.989, p < 0.05). Also, cytotoxicity was evaluated in gastric adenocarcinoma (AGS), hepatocarcinoma (HepG2), and colon adenocarcinoma (SW620), with T. Atkins skin showing the best results (IC50 = 138-175 µg/mL). Finally, for AGS and SW 620 cell lines particularly, a high significant negative correlation was found between cytotoxic activity and gallotannins (r = -0.977 and r = -0.940, respectively) while for the HepG2 cell line, the highest significant negative correlation was found with xanthonoids compounds (r = -0.921).
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Ballesteros-Vivas D, Álvarez-Rivera G, Morantes SJ, Sánchez-Camargo ADP, Ibáñez E, Parada-Alfonso F, Cifuentes A. An integrated approach for the valorization of mango seed kernel: Efficient extraction solvent selection, phytochemical profiling and antiproliferative activity assessment. Food Res Int 2019; 126:108616. [PMID: 31732074 DOI: 10.1016/j.foodres.2019.108616] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 08/06/2019] [Accepted: 08/11/2019] [Indexed: 01/19/2023]
Abstract
A novel valorization strategy is proposed in this work for the sustainable utilization of a major mango processing waste (i.e. mango seed kernel, MSK), integrating green pressurized-liquid extraction (PLE), bioactive assays and comprehensive HRMS-based phytochemical characterization to obtain bioactive-rich fractions with high antioxidant capacity and antiproliferative activity against human colon cancer cells. Thus, a two steps PLE procedure was proposed to recover first the non-polar fraction (fatty acids and lipids) and second the polar fraction (polyphenols). Efficient selection of the most suitable solvent for the second PLE step (ethanol/ethyl acetate mixture) was based on the Hansen solubility parameters (HSP) approach. A comprehensive GC- and LC-Q-TOF-MS/MS profiling analysis allowed the complete characterization of the lipidic and phenolic fractions obtained under optimal condition (100% EtOH at 150 °C), demonstrating the abundance of oleic and stearic acids, as well as bioactive xanthones, phenolic acids, flavonoids, gallate derivatives and gallotannins. The obtained MSK-extract exhibited higher antiproliferative activity against human colon adenocarcinoma cell line HT-29 compared to traditional extraction procedures described in literature for MSK utilization (e.g. Soxhlet), demonstrating the great potential of the proposed valorization strategy as a valuable opportunity for mango processing industry to deliver a value-added product to the market with health promoting properties.
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Affiliation(s)
- Diego Ballesteros-Vivas
- High Pressure Laboratory, Department of Chemistry, Faculty of Science, Universidad Nacional de Colombia, Carrera 30 #45-03, Bogotá D.C. 111321, Colombia; Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain
| | - Gerardo Álvarez-Rivera
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain
| | - Sandra Johanna Morantes
- Unit of Basic Oral Investigation (UIBO), School of Dentistry, Universidad El Bosque, Av. Carrera 9 #131 A-02, Bogotá D.C. 110121, Colombia
| | - Andrea Del Pilar Sánchez-Camargo
- High Pressure Laboratory, Department of Chemistry, Faculty of Science, Universidad Nacional de Colombia, Carrera 30 #45-03, Bogotá D.C. 111321, Colombia
| | - Elena Ibáñez
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain
| | - Fabián Parada-Alfonso
- High Pressure Laboratory, Department of Chemistry, Faculty of Science, Universidad Nacional de Colombia, Carrera 30 #45-03, Bogotá D.C. 111321, Colombia
| | - Alejandro Cifuentes
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain.
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Deepak M, Sulaiman C, Balachandran I, Chandran KPS. Isolation characterization and high-performance thin-layer chromatographic quantification of active xanthonoid mangiferin from Canscora perfoliata. JPC-J PLANAR CHROMAT 2019. [DOI: 10.1556/1006.2019.32.3.8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Mundengara Deepak
- Research & Development Centre, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India
| | | | - Indira Balachandran
- Centre for Medicinal Plants Research, Kottakkal Arya Vaida Sala, Kerala, India
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Quadri F, Telang M, Mandhare A. Therapeutic and cosmetic applications of mangiferin: an updated patent review (patents published after 2013). Expert Opin Ther Pat 2019; 29:463-479. [DOI: 10.1080/13543776.2019.1620205] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Farha Quadri
- CSIR Unit for Research and Development of Information Products (CSIR-URDIP), Pune, India
| | - Manasi Telang
- CSIR Unit for Research and Development of Information Products (CSIR-URDIP), Pune, India
| | - Anita Mandhare
- CSIR Unit for Research and Development of Information Products (CSIR-URDIP), Pune, India
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Castro-Vargas HI, Ballesteros Vivas D, Ortega Barbosa J, Morantes Medina SJ, Aristizabal Gutiérrez F, Parada-Alfonso F. Bioactive Phenolic Compounds from the Agroindustrial Waste of Colombian Mango Cultivars 'Sugar Mango' and 'Tommy Atkins'-An Alternative for Their Use and Valorization. Antioxidants (Basel) 2019; 8:E41. [PMID: 30781395 PMCID: PMC6406469 DOI: 10.3390/antiox8020041] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 02/06/2019] [Accepted: 02/13/2019] [Indexed: 12/15/2022] Open
Abstract
The aim of this study was to explore the potential of the agroindustrial waste from two Colombian mango cultivars as sources of bioactive phenolic compounds. Phenolic extracts from mango waste (peels, seed coats, and seed kernels) of 'sugar mango' and 'Tommy Atkins' cultivars were obtained. The bioactive properties of the phenolic extracts were accessed by measuring their free radical scavenging activity and antioxidant effects against lipid oxidation in food products; moreover, their antiproliferative effects against some cell lines of human cancer were explored. It is observed that the agroindustrial waste studied provides promising sources of bioactive phenolics. 'Sugar mango' waste provided extracts with the highest antioxidant effect in food products and antiproliferative activity; these extracts reduced lipid oxidation and cell growth by more than 57% and 75%, respectively. The seed kernel from 'sugar mango' supplied the extract with the best bioactive qualities; in addition, some recognized bioactive phenolics (such as mangiferin and several galloyl glucosides) were observed in this extract and related with its properties. The results obtained suggest that 'sugar mango' waste may be considered a source of bioactive phenolics, with promising uses in food and pharmaceutical products. Thus, a suitable alternative for the use and valorization of agroindustrial waste from Colombian mango cultivars is presented.
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Affiliation(s)
- Henry I Castro-Vargas
- Faculty of Engineering, Universidad Libre, Seccional Bogotá, Carrera 70 No 53-40, Bogotá D.C. 111071, Colombia.
- Department of Chemistry, Faculty of Sciences, Universidad Nacional de Colombia, Carrera 30 No 45-03, Bogotá D.C. 111321, Colombia.
| | - Diego Ballesteros Vivas
- Department of Chemistry, Faculty of Sciences, Universidad Nacional de Colombia, Carrera 30 No 45-03, Bogotá D.C. 111321, Colombia.
| | - Jenny Ortega Barbosa
- Department of Chemistry, Faculty of Sciences, Universidad Nacional de Colombia, Carrera 30 No 45-03, Bogotá D.C. 111321, Colombia.
| | - Sandra Johanna Morantes Medina
- Unit of Basic Oral Investigation (UIBO), School of Dentistry, Universidad El Bosque, Av. Cra 9 No. 131 A-02, Bogotá D.C. 110121, Colombia.
| | - Fabio Aristizabal Gutiérrez
- Department of Farmacy, Faculty of Sciences, Universidad Nacional de Colombia, Carrera 30 No 45-03, Bogotá D.C. 111321, Colombia.
| | - Fabián Parada-Alfonso
- Department of Chemistry, Faculty of Sciences, Universidad Nacional de Colombia, Carrera 30 No 45-03, Bogotá D.C. 111321, Colombia.
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Nurcahyanti AR. Mangifera and Impatiens from Sumatra: Phylogenetic positions and their modes of action as anticancer agents. Pharmacogn Rev 2019. [DOI: 10.4103/phrev.phrev_26_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Ayatollahi A, Rahmati J, Salimi A, Pourahmad J. A Comparison of Cytotoxic Effects of Mangifera Indica L. and Juglans RegiaAqueous Extract on Human Chronic Lymphocytic Leukemia. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2019; 18:1843-1853. [PMID: 32184851 PMCID: PMC7059048 DOI: 10.22037/ijpr.2019.111977.13462] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Natural products isolated from plant sources are well known for their pharmacological potential in diversity of disease treatments such as inflammatory or cancer conditions. Mango (Mangifera indica L.) and Juglans regia are thought to be rich of functional phytochemicals. To clarify the anticancer activity, aqueous extracts of Juglans regia (JR) nut and Mangifera indica L (MI) fruit were exanimated on chronic lymphocytic leukemia (CLL) B lymphocytes and their mitochondria and the results were compared with those of normal B lymphocytes. Cellular parameters such as viability and caspase 3 activity, and mitochondrial parameters such as reactive oxygen species (ROS), mitochondria membrane potential (MMP), mitochondrial swelling, and cytochrome c release were evaluated. Our results demonstrated that the extract of Mangifera indica L increased cytotoxicity and caspase 3 activation through mitochondria pathway only in CLL B lymphocytes and also the extract of Juglans regia did not show cytotoxicity and caspase 3 activation on CLL and healthy B lymphocytes. Our in-vitro findings on isolated mitochondria indicated that mitochondrial ROS formation, MMP collapse, and mitochondrial swelling and cytochrome c release were significantly (p < 0.05) increased after addition of Mangifera indica only in cancerous mitochondria. These results demonstrated that Mangifera indica can act as a promising source for anti-cancer drug candidates by directly and selectively targeting mitochondria and inducing selective mitochondria mediated apoptosis on CLL B lymphocytes.
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Affiliation(s)
- Abdollmajid Ayatollahi
- School of Pharmacy, Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Jalil Rahmati
- Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ahmad Salimi
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
| | - Jalal Pourahmad
- Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Improving the biopharmaceutical attributes of mangiferin using vitamin E-TPGS co-loaded self-assembled phosholipidic nano-mixed micellar systems. Drug Deliv Transl Res 2018; 8:617-632. [PMID: 29637488 PMCID: PMC5937873 DOI: 10.1007/s13346-018-0498-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The current research work encompasses the development, characterization, and evaluation of self-assembled phospholipidic nano-mixed miceller system (SPNMS) of a poorly soluble BCS Class IV xanthone bioactive, mangiferin (Mgf) functionalized with co-delivery of vitamin E TPGS. Systematic optimization using I-optimal design yielded self-assembled phospholipidic nano-micelles with a particle size of < 60 nm and > 80% of drug release in 15 min. The cytotoxicity and cellular uptake studies performed using MCF-7 and MDA-MB-231 cell lines demonstrated greater kill and faster cellular uptake. The ex vivo intestinal permeability revealed higher lymphatic uptake, while in situ perfusion and in vivo pharmacokinetic studies indicated nearly 6.6- and 3.0-folds augmentation in permeability and bioavailability of Mgf. In a nutshell, vitamin E functionalized SPNMS of Mgf improved the biopharmaceutical performance of Mgf in rats for enhanced anticancer potency.
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Aung HM, Huangteerakul C, Panvongsa W, Jensen AN, Chairoungdua A, Sukrong S, Jensen LT. Interrogation of ethnomedicinal plants for synthetic lethality effects in combination with deficiency in the DNA repair endonuclease RAD1 using a yeast cell-based assay. JOURNAL OF ETHNOPHARMACOLOGY 2018; 223:10-21. [PMID: 29777901 DOI: 10.1016/j.jep.2018.05.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 05/10/2018] [Accepted: 05/11/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Plant materials used in this study were selected based on the ethnobotanical literature. Plants have either been utilized by Thai practitioners as alternative treatments for cancer or identified to exhibit anti-cancer properties. AIM OF THE STUDY To screen ethnomedicinal plants using a yeast cell-based assay for synthetic lethal interactions with cells deleted for RAD1, the yeast homologue of human ERCC4 (XPF) MATERIALS AND METHODS: Ethanolic extracts from thirty-two species of medicinal plants utilized in Thai traditional medicine were screened for synthetic lethal/sick interactions using a yeast cell-based assay. Cell growth was compared between the parental strain and rad1∆ yeast following exposure to select for specific toxicity of plant extracts. Candidate extracts were further examined for the mode of action using genetic and biochemical approaches. RESULTS Screening a library of ethanolic extracts from medicinal plants identified Bacopa monnieri and Colubrina asiatica as having synthetic lethal effects in the rad1∆ cells but not the parental strain. Synthetic lethal effects for B. monneiri extracts were more apparent and this plant was examined further. Genetic analysis indicates that pro-oxidant activities and defective excision repair pathways do not significantly contribute to enhanced sensitivity to B. monneiri extracts. Exposure to B. monneiri extracts resulted in nuclear fragmentation and elevated levels of ethidium bromide staining in rad1∆ yeast suggesting promotion of an apoptosis-like event. Growth inhibition also observed in the human Caco-2 cell line suggesting the effects of B. monnieri extracts on both yeast and human cells may be similar. CONCLUSIONS B. monneiri extracts may have utility in treatment of colorectal cancers that exhibit deficiency in ERCC4 (XPF).
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Affiliation(s)
- Hsu Mon Aung
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok Thailand
| | | | - Wittaya Panvongsa
- Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand; Excellent Center for Drug Discovery (ECDD), Mahidol University, Bangkok, Thailand
| | - Amornrat N Jensen
- Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Arthit Chairoungdua
- Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand; Excellent Center for Drug Discovery (ECDD), Mahidol University, Bangkok, Thailand; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
| | - Suchada Sukrong
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Laran T Jensen
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok Thailand.
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Wisutthathum S, Kamkaew N, Inchan A, Chatturong U, Paracha TU, Ingkaninan K, Wongwad E, Chootip K. Extract of Aquilaria crassna leaves and mangiferin are vasodilators while showing no cytotoxicity. J Tradit Complement Med 2018; 9:237-242. [PMID: 31453117 PMCID: PMC6701956 DOI: 10.1016/j.jtcme.2018.09.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Revised: 08/19/2018] [Accepted: 09/11/2018] [Indexed: 12/19/2022] Open
Abstract
The leaves of Aquilaria spp. promote “physiological balance”, and are “cardiotonic and provide blood nourishment”. In Asia, these leaves are increasingly consumed as tea and claimed to provide benefits to cardiovascular function, albeit without any scientific proof. Therefore, this study sought to evaluate the action of Aquilaria crassna leaf aqueous extract (AE) on vascular function and vascular smooth muscle cytotoxicity. AE and a main constituent, mangiferin were investigated for their vasorelaxation of rat mesenteric arteries and aortae in vitro. Acute cytotoxicity of AE (0.1–1000 μg/ml) and mangiferin (0.1–100 μM) on rat enzymatically isolated vascular smooth muscle cells was assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. AE dilated rat mesenteric arteries (EC50∼107 μg/ml, Emax∼95%) more than aorta (EC50∼265 μg/ml, Emax∼76%, p < 0.05). AE-induced vasodilation in mesenteric artery was reduced by endothelial removal (EC50∼202 μg/ml, p < 0.05), incubation with endothelial nitric oxide synthase (eNOS) (100 μM, L-NAME) (EC50∼309 μg/ml, p < 0.05), and partly reduced by L-type Ca2+ channel blockade at higher concentrations. Likewise, mangiferin (1–100 μM) dilated the mesenteric artery more potently than the aorta. However, its maximum relaxation was less than with AE (41% in the mesenteric artery and <10% in the aorta). Isolated vascular smooth muscle cells incubated in AE or mangiferin for 1 h showed no cytotoxicity. Thus, AE is a vasorelaxant while being free of acute cytotoxicity towards vascular smooth muscle, thus potentially ameliorating human vascular dysfunction.
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Affiliation(s)
- Sutthinee Wisutthathum
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
| | - Natakorn Kamkaew
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand.,School of Medical Sciences, University of Phayao, Phayao, 56000, Thailand
| | - Anjaree Inchan
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
| | - Usana Chatturong
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
| | - Tamkeen Urooj Paracha
- Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand
| | - Kornkanok Ingkaninan
- Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand
| | - Eakkaluk Wongwad
- Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand
| | - Krongkarn Chootip
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
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Mangiferin attenuates cisplatin-induced acute kidney injury in rats mediating modulation of MAPK pathway. Mol Cell Biochem 2018; 452:141-152. [DOI: 10.1007/s11010-018-3420-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Accepted: 07/28/2018] [Indexed: 02/08/2023]
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Anoop NV, Jacob R, Paulson JM, Dineshkumar B, Narayana CR. Mango leaf extract synthesized silver nanorods exert anticancer activity on breast cancer and colorectal carcinoma cells. J Drug Deliv Sci Technol 2018. [DOI: 10.1016/j.jddst.2017.11.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Velderrain-Rodríguez GR, Torres-Moreno H, Villegas-Ochoa MA, Ayala-Zavala JF, Robles-Zepeda RE, Wall-Medrano A, González-Aguilar GA. Gallic Acid Content and an Antioxidant Mechanism Are Responsible for the Antiproliferative Activity of 'Ataulfo' Mango Peel on LS180 Cells. Molecules 2018; 23:molecules23030695. [PMID: 29562699 PMCID: PMC6017175 DOI: 10.3390/molecules23030695] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 03/02/2018] [Accepted: 03/04/2018] [Indexed: 12/20/2022] Open
Abstract
Mango “Ataulfo” peel is a rich source of polyphenols (PP), with antioxidant and anti-cancer properties; however, it is unknown whether such antiproliferative activity is related to PP’s antioxidant activity. The content (HPLC-DAD), antioxidant (DPPH, FRAP, ORAC), and antiproliferative activities (MTT) of free (FP) and chemically-released PP from mango ‘Ataulfo’ peel after alkaline (AKP) and acid (AP) hydrolysis, were evaluated. AKP fraction was higher (µg/g DW) in gallic acid (GA; 23,816 ± 284) than AP (5610 ± 8) of FR (not detected) fractions. AKP fraction and GA showed the highest antioxidant activity (DPPH/FRAP/ORAC) and GA’s antioxidant activity follows a single electron transfer (SET) mechanism. AKP and GA also showed the best antiproliferative activity against human colon adenocarcinoma cells (LS180; IC50 (µg/mL) 138.2 ± 2.5 and 45.7 ± 5.2) and mouse connective cells (L929; 93.5 ± 7.7 and 65.3 ± 1.2); Cheminformatics confirmed the hydrophilic nature (LogP, 0.6) and a good absorption capacity (75%) for GA. Data suggests that GA’s antiproliferative activity appears to be related to its antioxidant mechanism, although other mechanisms after its absorption could also be involved.
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Affiliation(s)
- Gustavo R Velderrain-Rodríguez
- Coordination of Food Technology of Plant Origin, Center for Research in Food and Development, A.C. (CIAD), Carretera a la Victoria Km 0.6. C.P., Hermosillo 83304, Mexico.
| | - Heriberto Torres-Moreno
- Department of Biological Chemistry., Universidad de Sonora, Blvd. Luis Encinas y Rosales S/N Col. Centro, C.P., Hermosillo 83000, Mexico.
| | - Mónica A Villegas-Ochoa
- Coordination of Food Technology of Plant Origin, Center for Research in Food and Development, A.C. (CIAD), Carretera a la Victoria Km 0.6. C.P., Hermosillo 83304, Mexico.
| | - J Fernando Ayala-Zavala
- Coordination of Food Technology of Plant Origin, Center for Research in Food and Development, A.C. (CIAD), Carretera a la Victoria Km 0.6. C.P., Hermosillo 83304, Mexico.
| | - Ramón E Robles-Zepeda
- Department of Biological Chemistry., Universidad de Sonora, Blvd. Luis Encinas y Rosales S/N Col. Centro, C.P., Hermosillo 83000, Mexico.
| | - Abraham Wall-Medrano
- Biomedical Sciences Institute, Autonomous University of Ciudad Juarez, Anillo Envolvente del Pronaf y Estocolmo S/N, Ciudad Juárez 32310, Chihuahua, Mexico.
| | - Gustavo A González-Aguilar
- Coordination of Food Technology of Plant Origin, Center for Research in Food and Development, A.C. (CIAD), Carretera a la Victoria Km 0.6. C.P., Hermosillo 83304, Mexico.
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Burton-Freeman BM, Sandhu AK, Edirisinghe I. Mangos and their bioactive components: adding variety to the fruit plate for health. Food Funct 2018; 8:3010-3032. [PMID: 28612853 DOI: 10.1039/c7fo00190h] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The diet is an essential factor affecting the risk for development and progression of modern day chronic diseases, particularly those with pathophysiological roots in inflammation and oxidative stress-induced damage. The potential impact of certain foods and their bioactive compounds to reverse or prevent destructive dysregulated processes leading to disease has attracted intense research attention. The mango (Mangifera indica Linn.) is a tropical fruit with distinctive nutritional and phytochemical composition. Notably, the mango contains several essential water- and lipid-soluble micronutrients along with the distinguishing phytochemicals gallotannins and mangiferin. In vitro and in vivo studies reveal various mechanisms through which mangos or their associated compounds reduce risk or reverse metabolic- and inflammation-associated diseases. Health benefits of isolated individual mango compounds and extracts from mango by-products are well described in the literature with less attention devoted to the whole fruit. Here, we review and summarize the available literature assessing the health promoting potential of mango flesh, the edible portion contributing to dietary fruit intake, focusing specifically on modern day health issues of obesity and the risk factors and diseases it precipitates, including diabetes and cardiovascular disease. Additionally, this review explores new insights on the benefits of mango for brain, skin and intestinal health. Overall, the foundation of research supporting the potential role of mangos in reducing risk for inflammation- and metabolically-based chronic diseases is growing.
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Affiliation(s)
- Britt M Burton-Freeman
- Center for Nutrition Research, Institute for Food Safety and Health, Illinois Institute of Technology, IL, USA.
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Lauricella M, Emanuele S, Calvaruso G, Giuliano M, D'Anneo A. Multifaceted Health Benefits of Mangifera indica L. (Mango): The Inestimable Value of Orchards Recently Planted in Sicilian Rural Areas. Nutrients 2017; 9:E525. [PMID: 28531110 PMCID: PMC5452255 DOI: 10.3390/nu9050525] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 03/16/2017] [Accepted: 03/17/2017] [Indexed: 02/05/2023] Open
Abstract
Historically, Mangifera indica L. cultivations have been widely planted in tropical areas of India, Africa, Asia, and Central America. However, at least 20 years ago its spreading allowed the development of some cultivars in Sicily, an island to the south of Italy, where the favourable subtropical climate and adapted soils represent the perfect field to create new sources of production for the Sicilian agricultural supply chain. Currently, cultivations of Kensington Pride, Keitt, Glenn, Maya, and Tommy Atkins varieties are active in Sicily and their products meet the requirements of local and European markets. Mango plants produce fleshy stone fruits rich in phytochemicals with an undisputed nutritional value for its high content of polyphenolics and vitamins. This review provides an overview of the antioxidant, anti-inflammatory, and anticancer properties of mango, a fruit that should be included in everyone's diet for its multifaceted biochemical actions and health-enhancing properties.
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Affiliation(s)
- Marianna Lauricella
- Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Biochemistry, University of Palermo, via del Vespro 129, 90127 Palermo, Italy.
| | - Sonia Emanuele
- Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Biochemistry, University of Palermo, via del Vespro 129, 90127 Palermo, Italy.
| | - Giuseppe Calvaruso
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, via del Vespro 129, 90127 Palermo, Italy.
| | - Michela Giuliano
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, via del Vespro 129, 90127 Palermo, Italy.
| | - Antonella D'Anneo
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, via del Vespro 129, 90127 Palermo, Italy.
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Khurana RK, Kaur S, Kaur J, Singh B. Elucidation of stress-induced degradation products of mangiferin: Method development and validation. Biomed Chromatogr 2017; 31. [DOI: 10.1002/bmc.3935] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Revised: 12/22/2016] [Accepted: 01/10/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Rajneet Kaur Khurana
- University Institute of Pharmaceutical Sciences; Panjab University; Chandigarh India
| | | | | | - Bhupinder Singh
- University Institute of Pharmaceutical Sciences; Panjab University; Chandigarh India
- UGC Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences); Panjab University; Chandigarh India
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Exploring and validating physicochemical properties of mangiferin through GastroPlus ® software. Future Sci OA 2017; 3:FSO167. [PMID: 28344830 PMCID: PMC5351510 DOI: 10.4155/fsoa-2016-0055] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 11/01/2016] [Indexed: 01/01/2023] Open
Abstract
AIM Mangiferin (Mgf), a promising therapeutic polyphenol, exhibits poor oral bioavailability. Hence, apt delivery systems are required to facilitate its gastrointestinal absorption. The requisite details on its physicochemical properties have not yet been well documented in literature. Accordingly, in order to have explicit insight into its physicochemical characteristics, the present work was undertaken using GastroPlus™ software. RESULTS Aqueous solubility (0.38 mg/ml), log P (-0.65), Peff (0.16 × 10-4 cm/s) and ability to act as P-gp substrate were defined. Potency to act as a P-gp substrate was verified through Caco-2 cells, while Peff was estimated through single pass intestinal perfusion studies. Characterization of Mgf through transmission electron microscopy, differential scanning calorimetry, infrared spectroscopy and powder x-ray diffraction has also been reported. CONCLUSION The values of physicochemical properties for Mgf reported in the current manuscript would certainly enable the researchers to develop newer delivery systems for Mgf.
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Niu ZS, Niu XJ, Wang WH. Genetic alterations in hepatocellular carcinoma: An update. World J Gastroenterol 2016; 22:9069-9095. [PMID: 27895396 PMCID: PMC5107590 DOI: 10.3748/wjg.v22.i41.9069] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 09/20/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.
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MESH Headings
- Animals
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/pathology
- Cell Transformation, Neoplastic/genetics
- Cell Transformation, Neoplastic/metabolism
- Cell Transformation, Neoplastic/pathology
- Gene Expression Regulation, Neoplastic
- Genetic Predisposition to Disease
- Genomic Instability
- Humans
- Liver Neoplasms/drug therapy
- Liver Neoplasms/genetics
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Molecular Diagnostic Techniques
- Molecular Targeted Therapy
- Mutation
- Patient Selection
- Phenotype
- Polymorphism, Single Nucleotide
- Precision Medicine
- Predictive Value of Tests
- Signal Transduction
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Dhananjaya BL, Sudarshan S, Dongol Y, More SS. The standard aqueous stem bark extract of Mangifera indica L. inhibits toxic PLA2 - NN-XIb-PLA2 of Indian cobra venom. Saudi Pharm J 2016; 24:371-8. [PMID: 27275129 PMCID: PMC4881193 DOI: 10.1016/j.jsps.2016.04.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
The aqueous extract of Mangifera indica is known to possess diverse medicinal properties, which also includes anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic snake venom phospholipases A2s are still unknown. Therefore, the objective of this study was to evaluate the modulatory effect of standard aqueous bark extract of M. indica on NN-XIb-PLA2 of Indian cobra venom. The in vitro sPLA2, in situ hemolytic and in vivo edema inhibition effect were carried out as described. Also the effect of substrate and calcium concentration was carried out. M. indica extract dose dependently inhibited the GIA sPLA2 (NN-XIb-PLA2) activity with an IC50 value of 7.6 μg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ∼40 μg/ml concentration. Further, M. indica extract (0–50 μg/ml) inhibited the edema formed in a dose dependent manner. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect of M. indica extract on the NN-XIb-PLA2. Further, the inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inhibiting activities of M. indica. As the inhibition is independent of substrate and calcium and was irreversible, it can be concluded that M. indica extract mode of inhibition could be due to direct interaction of components present in the extract with the PLA2 enzyme. The aqueous extract of M. indica effectively inhibits svPLA2 enzymatic and its associated toxic activities, which substantiate their anti-snake venom properties. Further in-depth studies on the role and mechanism of the principal constituents present in the extract, responsible for the anti-PLA2 activity will be interesting to develop them into potent antisnake component and also as an anti-inflammatory agent.
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Affiliation(s)
- Bhadrapura Lakkappa Dhananjaya
- Venom Research Unit, Adichunchanagiri Biotechnology and Cancer Research Institute (ABCRI), Balagangadharanatha Nagara, Mandya District, Karnataka 571 448, India; Toxinology/Toxicology and Drug Discovery Unit, Center for Emerging Technologies, Jain Global Campus, Jain University, Kanakapura Taluk, Ramanagara 562112, Karnataka, India
| | - Shivalingaiah Sudarshan
- Venom Research Unit, Adichunchanagiri Biotechnology and Cancer Research Institute (ABCRI), Balagangadharanatha Nagara, Mandya District, Karnataka 571 448, India
| | - Yashad Dongol
- Department of Biochemistry, KIST Medical College, Lalitpur, Kathmandu, Nepal
| | - Sunil S More
- School of Basic and Applied Sciences, Dayananda Sagar University, K.S. Layout, SM Hills, Bangalore 560078, India
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