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Kavita, Adiani V, Sharma D, Mishra BB. Effect of gamma irradiation on different components of onion (Allium cepa) skin waste and enhancement of bioactive potentials. Food Chem 2025; 484:144395. [PMID: 40286711 DOI: 10.1016/j.foodchem.2025.144395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 04/15/2025] [Accepted: 04/16/2025] [Indexed: 04/29/2025]
Abstract
The current study was aimed to use gamma irradiation (10-25 kGy) as pre-treatment technique for improved extraction of phenolics and oil from onion dry skin powder (OSP) which was evaluated by TLC, FT/IR and GC/MS methods. Gamma irradiation (10 kGy) enhanced the extractability of oil and phenolics by 80 % and 50 %, respectively. The ethyl acetate extract (EAE) of irradiated (10 kGy) OSP showed significant anti-cancer activity by inhibiting proliferation, migration and inducing apoptosis in mice breast cancer cell line (4T1) at lower concentration of 0.01 % in comparison with pure quercetin. In addition, compositional changes in oil showed oleic, linoleic and palmitic acids as major among eight identified fatty acids. The surface morphology of isolated MCC was also characterized using SEM. These findings demonstrated the valorization of OSP in a zero waste approach using gamma irradiation (10 kGy) which concomitantly improved yield and bioactivities of phenolic constituents for various health applications.
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Affiliation(s)
- Kavita
- Food Technology Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India
| | - Vanshika Adiani
- Food Technology Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India
| | - Deepak Sharma
- Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India
| | - Bibhuti Bhusan Mishra
- Food Technology Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India.
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Nile A, Nile SH, Cespedes-Acuña CL, Oh JW. Spiraeoside extracted from red onion skin ameliorates apoptosis and exerts potent antitumor, antioxidant and enzyme inhibitory effects. Food Chem Toxicol 2021; 154:112327. [PMID: 34116102 DOI: 10.1016/j.fct.2021.112327] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/18/2021] [Accepted: 06/04/2021] [Indexed: 12/11/2022]
Abstract
Red onion skin waste (ROSW) was analyzed for extraction of naturally occurring 4'-O-glucoside of quercetin, spiraeoside (SPI) with promising biological activities. Reversed-phase high-performance liquid chromatography was used to determine the SPI content in three different solvent extracts of ROSW: water (12.2 mg/g), methanol (27.6 mg/g), and ethanol (32.5 mg/g). The ethanol extract and SPI showed significant radical-scavenging and anti-inflammatory activities. In addition, the anti-cancer effects of SPI on a HeLa cells was investigated. The results indicated that SPI treatment significantly inhibited cell growth, and the dose of 50 μg/mL exhibited the highest anti-cancer activity. SPI inhibited the expression of B-cell lymphoma 2 and BH3-interacting domain-death agonist and promoted apoptosis by activating caspase-9/-3 expression. Notably, SPI inhibited the expression of mu-2-related death-inducing gene, a molecule involved in death receptor-mediated apoptotic signaling. Cyclin-dependent kinase 2-cyclin-E expression was also inhibited after SPI treatment, particularly at the G2/M checkpoint. Our findings provide novel insights into the apoptotic potential with promising anticancer and enzyme inhibitory effects of ROSW SPI.
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Affiliation(s)
- Arti Nile
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Shivraj Hariram Nile
- Laboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China.
| | - Carlos L Cespedes-Acuña
- Laboratory of Phytochemistry and Eco-toxicology, Research Group in Chemistry and Biotechnology of Bioactive Natural Products, Department of Basic Sciences, Faculty of Sciences, University of Bio-Bío, Andrés Bello Avenue # 720, Chillan, Chile
| | - Jae-Wook Oh
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
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Silva Dos Santos J, Gonçalves Cirino JP, de Oliveira Carvalho P, Ortega MM. The Pharmacological Action of Kaempferol in Central Nervous System Diseases: A Review. Front Pharmacol 2021; 11:565700. [PMID: 33519431 PMCID: PMC7838523 DOI: 10.3389/fphar.2020.565700] [Citation(s) in RCA: 111] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 11/20/2020] [Indexed: 01/01/2023] Open
Abstract
Kaempferol (KPF) is a flavonoid antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary KPF in reducing the risk of chronic diseases, especially cancer. Nevertheless, little is known about the cellular and molecular mechanisms underlying KPF actions in the central nervous system (CNS). Also, the relationship between KPF structural properties and their glycosylation and the biological benefits of these compounds is unclear. The aim of this study was to review studies published in the PubMed database during the last 10 years (2010–2020), considering only experimental articles that addressed the isolated cell effect of KPF (C15H10O6) and its derivatives in neurological diseases such as Alzheimer's disease, Parkinson, ischemia stroke, epilepsy, major depressive disorder, anxiety disorders, neuropathic pain, and glioblastoma. 27 publications were included in the present review, which presented recent advances in the effects of KPF on the nervous system. KPF has presented a multipotential neuroprotective action through the modulation of several proinflammatory signaling pathways such as the nuclear factor kappa B (NF-kB), p38 mitogen-activated protein kinases (p38MAPK), serine/threonine kinase (AKT), and β-catenin cascade. In addition, there are different biological benefits and pharmacokinetic behaviors between KPF aglycone and its glycosides. The antioxidant nature of KPF was observed in all neurological diseases through MMP2, MMP3, and MMP9 metalloproteinase inhibition; reactive oxygen species generation inhibition; endogenous antioxidants modulation as superoxide dismutase and glutathione; formation and aggregation of beta-amyloid (β-A) protein inhibition; and brain protective action through the modulation of brain-derived neurotrophic factor (BDNF), important for neural plasticity. In conclusion, we suggest that KPF and some glycosylated derivatives (KPF-3-O-rhamnoside, KPF-3-O-glucoside, KPF-7-O-rutinoside, and KPF-4′-methyl ether) have a multipotential neuroprotective action in CNS diseases, and further studies may make the KPF effect mechanisms in those pathologies clearer. Future in vivo studies are needed to clarify the mechanism of KPF action in CNS diseases as well as the impact of glycosylation on KPF bioactivity.
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Affiliation(s)
- Jéssica Silva Dos Santos
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, Post Graduate Program in Health Science, São Francisco University (USF), Bragança Paulista, Brazil
| | - João Pedro Gonçalves Cirino
- Laboratory of Multidisciplinary Research, Post Graduate Program in Health Science, São Francisco University (USF), Bragança Paulista, Brazil
| | - Patrícia de Oliveira Carvalho
- Laboratory of Multidisciplinary Research, Post Graduate Program in Health Science, São Francisco University (USF), Bragança Paulista, Brazil
| | - Manoela Marques Ortega
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, Post Graduate Program in Health Science, São Francisco University (USF), Bragança Paulista, Brazil
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Liu H, Zhang Z, Zhang L, Yao X, Zhong X, Cheng G, Wang L, Wan Q. Spiraeoside protects human cardiomyocytes against high glucose-induced injury, oxidative stress, and apoptosis by activation of PI3K/Akt/Nrf2 pathway. J Biochem Mol Toxicol 2020; 34:e22548. [PMID: 32602595 DOI: 10.1002/jbt.22548] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 04/26/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023]
Abstract
The present study aimed to explore the effect of spiraeoside, an active quercetin glucoside, on diabetic cardiomyopathy in vitro. Our results showed that spiraeoside attenuated high glucose (HG)-induced reduction of cell viability and increased myocardial enzymes lactate dehydrogenase and aspartate aminotransferase in AC16 cells. Spiraeoside exerted antioxidant activity in HG-induced AC16 cells as spiraeoside inhibited reactive oxygen species and malondialdehyde production and increased activities of superoxide dismutase, glutathione peroxidase, and catalase. Spiraeoside prevented HG-induced apoptosis of AC16 cells. HG stimulation-caused the decrease in the expression levels of p-Akt, nuclear Nrf2, and HO-1 was elevated after spiraeoside treatment in AC16 cells. However, the effects of spiraeoside were reversed by LY294002. In conclusion, spiraeoside protected AC16 cells against HG-induced oxidative stress, cell injury, and apoptosis. The protective effect of spiraeoside was regulated by the PI3K/Akt/Nrf2 signaling pathway.
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Affiliation(s)
- Hongyang Liu
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Zhiyong Zhang
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Lei Zhang
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Xinliang Yao
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Xiaoming Zhong
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Guanchang Cheng
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Lefeng Wang
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Qilin Wan
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, China
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5
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A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity. Bioorg Med Chem 2019; 27:2923-2934. [DOI: 10.1016/j.bmc.2019.05.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 04/25/2019] [Accepted: 05/16/2019] [Indexed: 01/26/2023]
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Seo JY, Pandey RP, Lee J, Sohng JK, Namkung W, Park YI. Quercetin 3-O-xyloside ameliorates acute pancreatitis in vitro via the reduction of ER stress and enhancement of apoptosis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 55:40-49. [PMID: 30668442 DOI: 10.1016/j.phymed.2018.07.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 07/01/2018] [Accepted: 07/16/2018] [Indexed: 06/09/2023]
Abstract
BACKGROUND AND PURPOSE Glycosylation of phenolic compounds has been reported to increase water-solubility, reduce toxicity, and sometimes give improved or novel pharmacological activities. Present study was aimed to evaluate and compare the beneficial effects of quercetin aglycone (Quer) and its glycosylated derivative, quercetin 3-O-xyloside (Quer-Xyl), against acute pancreatitis (AP). METHODS The cellular acute pancreatitis model was established by treating the rat pancreatic acinar cells (AR42J) with lipopolysaccharide (10 µg/ml) and cerulein (10-7 M). The cytotoxicity of Quer or Quer-Xyl on AR42J cells was assessed by MTT assay. Calcium and ROS levels were fluorometrically determined. The ER stress levels (PERK, GRP78), expression levels of amylase and lipase, and apoptotic markers (caspase-3 and -9) were measured by RT-PCR, western blotting, or fluorometric assay. RESULTS While Quer increased the mRNA expressions of AP marker enzymes, amylase and lipase, Quer-Xyl dose-dependently reversed their expressions. Quer-Xyl suppressed intracellular ROS production and both mRNA and protein levels of GRP78 and PERK, which were significantly elevated in cerulein and LPS-treated AR42J cells. Further, RT-PCR and fluorescence assay revealed that Quer-Xyl dose-dependently augmented the mRNA expressions and activities of caspase-3 and -9. CONCLUSION These results showed that Quer-Xyl, but not Quer, has a significant anti-pancreatitis activity through attenuating intracellular ROS production and ER stress response and enhancing apoptotic cell death, suggesting that it might be useful as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat AP.
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Affiliation(s)
- Jeong Yeon Seo
- Department of Biotechnology, Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea
| | - Ramesh Prasad Pandey
- Department of BT-Convergent Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University, Asan, Chungnam 31460, Republic of Korea
| | - Jisun Lee
- Department of Biotechnology, Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea
| | - Jae Kyung Sohng
- Department of BT-Convergent Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University, Asan, Chungnam 31460, Republic of Korea
| | - Wan Namkung
- Department of Integrated OMICS for Biomedical Science, Graduate School, Yonsei University, Seoul 21983, Republic of Korea
| | - Yong Il Park
- Department of Biotechnology, Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea.
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Brazilian insulin plant as a bifunctional food: Dual high-resolution PTP1B and α-glucosidase inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of antidiabetic compounds in Myrcia rubella Cambess. J Funct Foods 2018. [DOI: 10.1016/j.jff.2018.04.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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Prasain JK, Rajbhandari R, Keeton AB, Piazza GA, Barnes S. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells. Food Funct 2018; 7:4012-4019. [PMID: 27711848 DOI: 10.1039/c6fo00499g] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 μM. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.
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Affiliation(s)
- Jeevan K Prasain
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
| | - Rajani Rajbhandari
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
| | - Adam B Keeton
- Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Suite 3029, Mobile AL 36604-1405, USA
| | - Gary A Piazza
- Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Suite 3029, Mobile AL 36604-1405, USA
| | - Stephen Barnes
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
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Elsayed HE, Ebrahim HY, Mohyeldin MM, Siddique AB, Kamal AM, Haggag EG, El Sayed KA. Rutin as A Novel c-Met Inhibitory Lead for The Control of Triple Negative Breast Malignancies. Nutr Cancer 2017; 69:1256-1271. [PMID: 29083228 DOI: 10.1080/01635581.2017.1367936] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Triple negative breast cancer (TNBC) has high metastatic and mortality potential and lacks effective and selective therapeutic options. Aberrant dysregulation of the receptor tyrosine kinase c-Met promotes TNBC progression, motility and survival and therefore considered a valid therapeutic target. Among various identified anticancer agents, plant polyphenols (PPs) including flavonoids, have been shown to be safe and proven for their antitumor activity through modulating diverse macromolecular targets. This study reports the bioassay-guided identification of the common flavonol glycoside rutin as breast cancer cell proliferation, migration and invasion inhibitor. The cell free Z'-LYTE kinase assay, Western blot and in silico docking experiments uncovered, for the first time, c-Met kinase as a potential mechanistic target for rutin-mediated anticancer effects on TNBC cell lines. Likewise, the intraperitoneal injection of rutin at 30 mg/kg, 3X/week, significantly reduced the growth of the TNBC MDA-MB-231/GFP orthotopic xenograft in nude mouse model. These results clearly designate the functional dietary flavonoid rutin as a potential lead for the prevention and control of c-Met-dependent breast malignancies.
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Affiliation(s)
- Heba E Elsayed
- a Department of Basic Pharmaceutical Sciences, School of Pharmacy , University of Louisiana at Monroe , Monroe , Louisiana.,b Department of Pharmacognosy, Faculty of Pharmacy , Helwan University , Helwan , Cairo , Egypt
| | - Hassan Y Ebrahim
- a Department of Basic Pharmaceutical Sciences, School of Pharmacy , University of Louisiana at Monroe , Monroe , Louisiana
| | - Mohamed M Mohyeldin
- a Department of Basic Pharmaceutical Sciences, School of Pharmacy , University of Louisiana at Monroe , Monroe , Louisiana
| | - Abu Bakar Siddique
- a Department of Basic Pharmaceutical Sciences, School of Pharmacy , University of Louisiana at Monroe , Monroe , Louisiana
| | - Amel M Kamal
- b Department of Pharmacognosy, Faculty of Pharmacy , Helwan University , Helwan , Cairo , Egypt
| | - Eman G Haggag
- b Department of Pharmacognosy, Faculty of Pharmacy , Helwan University , Helwan , Cairo , Egypt
| | - Khalid A El Sayed
- a Department of Basic Pharmaceutical Sciences, School of Pharmacy , University of Louisiana at Monroe , Monroe , Louisiana
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Xu JQ, Fan N, Yu BY, Wang QQ, Zhang J. Biotransformation of quercetin by Gliocladium deliquescens NRRL 1086. Chin J Nat Med 2017; 15:615-624. [PMID: 28939024 DOI: 10.1016/s1875-5364(17)30089-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Indexed: 01/08/2023]
Abstract
With an attempt to synthesize high-value isoquercitrin (quercetin-3-O-β-D-glucopyranoside), we carried out the biotransformation of quercetin (1) by Gliocladium deliquescens NRRL 1086. Along with the aimed product quercetin 3-O-β-D-glycoside (2), three additional metabolites, 2-protocatechuoyl-phlorogucinol carboxylic acid (3), 2,4,6-trihydroxybenzoic acid (4), and protocatechuic acid (5), were also isolated. The time-course experiments revealed that there were two metabolic routes, regio-selectivity glycosylation and quercetin 2,3-dioxygenation, co-existing in the culture. Both glycosylation and oxidative cleavage rapidly took place after quercetin feeding; about 98% quercetin were consumed within the initial 8 h and the oxdized product (2-protocatechuoyl-phlorogucinol carboxylic acid) was hydrolyzed into two phenolic compounds (2,4,6-trihydroxybenzoic acid and protocatechuic acid). We also investigated the impact of glucose content and metal ions on the two reactions and found that high concentrations of glucose significantly inhibited the oxidative cleavage and improved the yield of isoquercitrin and that Ca2+, Fe2+, Mn2+, Mg2+, and Zn2+ inhibited glycosylation. To test the promiscuity of this culture, we selected other four flavonols as substrates; the results demonstrated its high regio-selectivity glycosylation ability towards flavonols at C-3 hydroxyl. In conclusion, our findings indicated that the versatile microbe of G. deliquescens NRRL 1086 maitained abundant enzymes, deserving further research.
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Affiliation(s)
- Jia-Qi Xu
- Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 210009, China
| | - Ni Fan
- Institute of Biotechnology for TCM Research, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 211198, China
| | - Bo-Yang Yu
- Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 210009, China.
| | - Qian-Qian Wang
- Institute of Biotechnology for TCM Research, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 211198, China
| | - Jian Zhang
- Institute of Biotechnology for TCM Research, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 211198, China.
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Zang Y, Zhang D, Yu C, Jin C, Igarashi K. Antioxidant and hepatoprotective activity of kaempferol 3- O-β-d- (2,6-di- O-α-l-rhamnopyranosyl)galactopyronoside against carbon tetrachloride-induced liver injury in mice. Food Sci Biotechnol 2017; 26:1071-1076. [PMID: 30263638 PMCID: PMC6049529 DOI: 10.1007/s10068-017-0170-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 04/26/2017] [Accepted: 05/02/2017] [Indexed: 10/19/2022] Open
Abstract
This study aims to investigate the antioxidant and hepatoprotective effects of kaempferol 3-O-β-d- (2,6-di-O-α-l-rhamnopyranosyl)galactopyronoside (KG) isolated from unripe soybean leaves. Carbon tetrachloride (CCl4)-induced hepatotoxic ddY mice were used in the study. The mice were divided into three groups, namely the control group, the CCl4 group (CCl4, CCl4 injected), and the KG group (KG, CCl4 injected with KG administration). Hepatic injury markers of serum and liver were analyzed. The results show that serum ALT, AST activities, hepatic glutathione, superoxide dismutase, catalase, and glutathione peroxidase activities were normalized in mice pretreated with KG. Furthermore, the liver thiobarbituric acid reactive substances levels were found to be improved by pretreatment with KG, indicating that KG is available to alleviate liver injury, this may be due to its antioxidant properties. This study suggests that unripe soy leaves could be used as functional food materials.
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Affiliation(s)
- Yanqing Zang
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, 163319 Heilongjiang China
| | - Dongjie Zhang
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, 163319 Heilongjiang China
| | - Changqing Yu
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, 163319 Heilongjiang China
| | - Chenghao Jin
- College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, 163319 Heilongjiang China
| | - Kiharu Igarashi
- Department of Bioresource Engineering, Faculty of Agriculture, Yamagata University, Tsuruoka, 997-8555 Japan
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12
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Xiao J. Dietary flavonoid aglycones and their glycosides: Which show better biological significance? Crit Rev Food Sci Nutr 2017; 57:1874-1905. [PMID: 26176651 DOI: 10.1080/10408398.2015.1032400] [Citation(s) in RCA: 188] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. The natural flavonoids almost all exist as their O-glycoside or C-glycoside forms in plants. In this review, we summarized the existing knowledge on the different biological benefits and pharmacokinetic behaviors between flavonoid aglycones and their glycosides. Due to various conclusions from different flavonoid types and health/disease conditions, it is very difficult to draw general or universally applicable comments regarding the impact of glycosylation on the biological benefits of flavonoids. It seems as though O-glycosylation generally reduces the bioactivity of these compounds - this has been observed for diverse properties including antioxidant activity, antidiabetes activity, anti-inflammation activity, antibacterial, antifungal activity, antitumor activity, anticoagulant activity, antiplatelet activity, antidegranulating activity, antitrypanosomal activity, influenza virus neuraminidase inhibition, aldehyde oxidase inhibition, immunomodulatory, and antitubercular activity. However, O-glycosylation can enhance certain types of biological benefits including anti-HIV activity, tyrosinase inhibition, antirotavirus activity, antistress activity, antiobesity activity, anticholinesterase potential, antiadipogenic activity, and antiallergic activity. However, there is a lack of data for most flavonoids, and their structures vary widely. There is also a profound lack of data on the impact of C-glycosylation on flavonoid biological benefits, although it has been demonstrated that in at least some cases C-glycosylation has positive effects on properties that may be useful in human healthcare such as antioxidant and antidiabetes activity. Furthermore, there is a lack of in vivo data that would make it possible to make broad generalizations concerning the influence of glycosylation on the benefits of flavonoids for human health. It is possible that the effects of glycosylation on flavonoid bioactivity in vitro may differ from that seen in vivo. With in vivo (oral) treatment, flavonoid glycosides showed similar or even higher antidiabetes, anti-inflammatory, antidegranulating, antistress, and antiallergic activity than their flavonoid aglycones. Flavonoid glycosides keep higher plasma levels and have a longer mean residence time than those of aglycones. We should pay more attention to in vivo benefits of flavonoid glycosides, especially C-glycosides.
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Affiliation(s)
- Jianbo Xiao
- a Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau , Taipa , Macau
- b Institut für Pharmazie und Lebensmittelchemie, Universität Würzburg , Am Hubland , Würzburg , Germany
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Kim YS, Jeong HY, Kim AR, Kim WH, Cho H, Um J, Seo Y, Kang WS, Jin SW, Kim MC, Kim YC, Jung DW, Williams DR, Ahn Y. Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment. Sci Rep 2016; 6:30726. [PMID: 27510556 PMCID: PMC4980696 DOI: 10.1038/srep30726] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 07/07/2016] [Indexed: 02/06/2023] Open
Abstract
The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2′Z,3′E)-6-Bromoindirubin-3′-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI.
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Affiliation(s)
- Yong Sook Kim
- Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea
| | - Hye-Yun Jeong
- Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea
| | - Ah Ra Kim
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - Woong-Hee Kim
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - Haaglim Cho
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - JungIn Um
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - Youngha Seo
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - Wan Seok Kang
- Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea
| | - Suk-Won Jin
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - Min Chul Kim
- Department of Cardiology, Chonnam National University Hospital, Gwangju 61469, Republic of Korea
| | - Yong-Chul Kim
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - Da-Woon Jung
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - Darren R Williams
- School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Republic of Korea
| | - Youngkeun Ahn
- Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea.,Department of Cardiology, Chonnam National University Hospital, Gwangju 61469, Republic of Korea
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Orfali GDC, Duarte AC, Bonadio V, Martinez NP, de Araújo MEMB, Priviero FBM, Carvalho PO, Priolli DG. Review of anticancer mechanisms of isoquercitin. World J Clin Oncol 2016; 7:189-199. [PMID: 27081641 PMCID: PMC4826964 DOI: 10.5306/wjco.v7.i2.189] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 10/19/2015] [Accepted: 02/16/2016] [Indexed: 02/06/2023] Open
Abstract
This review was based on a literature search of PubMed and Scielo databases using the keywords “quercetin, rutin, isoquercitrin, isoquercitin (IQ), quercetin-3-glucoside, bioavailability, flavonols and favonoids, and cancer” and combinations of all the words. We collected relevant scientific publications from 1990 to 2015 about the absorption, bioavailability, chemoprevention activity, and treatment effects as well as the underlying anticancer mechanisms of isoquercitin. Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom. The subclass of flavonols receives special attention owing to their health benefits. The main components of this class are quercetin, rutin, and IQ, which is a flavonoid and although mostly found as a glycoside, is an aglycone (lacks a glycoside side chain). This compound presents similar therapeutic profiles to quercetin but with superior bioavailability, resulting in increased efficacy compared to the aglycone form. IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant, antiproliferative, anti-inflammatory, anti-hypertensive, and anti-diabetic. The protective effects of IQ in cancer may be due to actions on lipid peroxidation. In addition, the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway, mixed-lineage protein kinase 3, mitogen-activated protein kinase, apoptotic pathways, as well proinflammatory protein signaling. This review contributed to clarifying the mechanisms of absorption, metabolism, and actions of IQ and isoquercitrin in cancer.
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Quercetin-6-C-β-d-glucopyranoside, natural analog of quercetin exhibits anti-prostate cancer activity by inhibiting Akt-mTOR pathway via aryl hydrocarbon receptor. Biochimie 2015; 119:68-79. [DOI: 10.1016/j.biochi.2015.10.012] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 10/12/2015] [Indexed: 12/16/2022]
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Tabassum N, Tai H, Jung DW, Williams DR. Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2015; 2015:287847. [PMID: 26681965 PMCID: PMC4670909 DOI: 10.1155/2015/287847] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 10/28/2015] [Indexed: 12/14/2022]
Abstract
Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.
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Affiliation(s)
- Nadia Tabassum
- New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea
| | - Hongmei Tai
- Department of Endocrinology, Yanji Hospital, Jilin 133000, China
| | - Da-Woon Jung
- New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea
| | - Darren R. Williams
- New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea
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Shimoda K, Kubota N, Uesugi D, Hamada H, Tanigawa M, Hamada H. Synthesis and pharmacological evaluation of glycosides of resveratrol, pterostilbene, and piceatannol. Ann N Y Acad Sci 2015; 1348:141-9. [DOI: 10.1111/nyas.12836] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Kei Shimoda
- Department of Chemistry; Faculty of Medicine; Oita University; Oita Japan
| | - Naoji Kubota
- Department of Chemistry; Faculty of Medicine; Oita University; Oita Japan
| | - Daisuke Uesugi
- Department of Life Science; Faculty of Science; Okayama University of Science; Okayama Japan
| | | | - Masato Tanigawa
- Department of Physics; Faculty of Medicine; Oita University; Oita Japan
| | - Hiroki Hamada
- Department of Life Science; Faculty of Science; Okayama University of Science; Okayama Japan
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