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Atasagun B, Uysal A, Fathallah N, Eldahshan O, Singab AN, Cetiz MV, Zengin G. Exploring the Utility of Prunus mahaleb Extracts as a Source of Natural Bioactive Compounds for Functional Applications. Food Sci Nutr 2025; 13:e70121. [PMID: 40161410 PMCID: PMC11953010 DOI: 10.1002/fsn3.70121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 04/02/2025] Open
Abstract
Prunus mahaleb has garnered attention as a potent medicinal agent and functional component. We aimed to detect the chemical composition and biological activities of several parts (fruit, leaves, and twigs) of P. mahaleb. Biological activities were assessed for antioxidant properties, enzyme inhibition, mutagenic/antimutagenic effects, and antibacterial efficacy. Antioxidant capabilities were evaluated using various assays, including DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelating. The chemical constituents of the extracts were identified and quantified using the HPLC-ESI-MS/MS method. The effects of enzyme inhibition were examined on some enzymes, including AChE, BChE, tyrosinase, amylase, and glucosidase. The Ames test was used to evaluate the mutagenic and antimutagenic properties of the plant extracts. Furthermore, a broth microdilution assay was employed to evaluate the possible antibacterial effects of the extracts against microorganisms. The methanol extract of twigs showed superior antioxidant capabilities (DPPH: 388.39 mg TE/g; ABTS: 701.50 mg TE/g; CUPRAC: 459.05 mg TE/g; FRAP: 264.99 mg TE/g). The methanol extract of twigs demonstrated the highest tyrosinase inhibitory activity (61.91 mg KAE/g). A total of 40 metabolites, mainly flavonoids, were detected through HPLC-ESI-MS/MS analysis, revealing that ferulic acid, naringenin, and herniarin were the predominant compounds. In the Ames test, the tested extracts exhibited no mutagenic potential. The antimutagenicity assay demonstrated that methanol and ethyl acetate extracts from twigs and leaves were particularly efficient against frameshift and base pair substitution mutations induced by recognized mutagens. The metabolic activation system amplified these strong activities to inhibition rates ranging from 85% to 98%. The results from the antibacterial assay indicated antibacterial effectiveness at dosages between 6.25 and 0.195 mg/mL, particularly effective against Sarcina lutea, Bacillus cereus, Candida albicans, and Staphylococcus aureus. Our findings indicate that P. mahaleb can serve as a versatile raw material for the development of health-promoting applications, including medicines, cosmeceuticals, and nutraceuticals.
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Affiliation(s)
- Bayram Atasagun
- Department of Medical Services and TechniquesVocational School of Health Services, Selcuk UniversityKonyaTürkiye
| | - Ahmet Uysal
- Department of Medical Services and TechniquesVocational School of Health Services, Selcuk UniversityKonyaTürkiye
| | - Noha Fathallah
- Department of Pharmacognosy and Medicinal Plants, Faculty of PharmacyFuture University in EgyptCairoEgypt
| | - Omayma Eldahshan
- Department of Pharmacognosy, Faculty of PharmacyAin Shams UniversityCairoEgypt
- Faculty of Pharmacy, Center for Drug Discovery Research and DevelopmentAin Shams UniversityCairoEgypt
| | - Abdel Nasser Singab
- Department of Pharmacognosy, Faculty of PharmacyAin Shams UniversityCairoEgypt
- Faculty of Pharmacy, Center for Drug Discovery Research and DevelopmentAin Shams UniversityCairoEgypt
| | - Mehmet Veyis Cetiz
- Department of Medical Biochemistry, Faculty of MedicineHarran UniversitySanliurfaTurkey
| | - Gokhan Zengin
- Department of Biology, Science FacultySelcuk UniversityKonyaTurkey
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Shetty M, Shenoy S, Amuthan A, Devi V, Kumar N, Kiran A, Shenoy G, Chinta DR, Prasada K S, Shetty A, Rao K G M. Kadukkai maathirai (Indian herbal drug) prevents hepatocellular cancer progression by enhancing GSTM1 expression and modulating β catenin transcription: in-silico and in-vivo study. F1000Res 2024; 13:639. [PMID: 39916986 PMCID: PMC11800331 DOI: 10.12688/f1000research.145961.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2024] [Indexed: 02/09/2025] Open
Abstract
Background Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor clinical outcomes. Hence cost-effective drugs with fewer side effects as a standard supportive therapy might yield substantial advantages in efficacy and safety. Kadukkai maathirai (KM) is being used as a supplement in hepatocellular carcinoma. We evaluated whether KM has any preventive action on cancer progression in diethyl nitrosamine (DEN) - induced HCC in rats. Methods DEN was injected to produce HCC in rats, which was confirmed after 16 weeks. All the rats were orally administered KM for 4 weeks. Hepatoprotective potential (serum AST, ALT, ALP, Bilirubin) and anticancer efficacy (body weight, nodule count, tumor progression by histopathology, expression of GSTM1 by Liquid chromatography-mass spectrometry (LC-MS), and In-silico analysis of phytoconstituents against β catenin and LRP analysis were evaluated. Results KM prevented cancer progression against DEN-induced HCC by an increase in GSTM1, a phase II detoxifying enzyme. It significantly reversed altered nodule count, relative liver weight, body weight, and histopathological features of HCC. In silico analysis of phytoconstituents of KM showed that they modulate the intracellular transcription process by inhibiting the armadillo repeat region of β catenin. Conclusions Our results elucidate the potential of KM as a supplement in HCC by reducing nodule count, protecting the liver from further damage, GSTM1 expression, and inhibiting armadillo repeat region of β catenin.
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Affiliation(s)
- Manjunath Shetty
- Centre Of Excellence, Ocular Nanoscience, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
- Division of Pharmacology, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Smita Shenoy
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Arul Amuthan
- Division of Pharmacology, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Vasudha Devi
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Nitesh Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Vaishali, Bihar, 844102, India
| | - Amruth Kiran
- Division of Pharmacology, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Ganesh Shenoy
- Division of Pharmacology, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Diya Rajasekhar Chinta
- Department of Pharmacology, Manipal University College Malaysia, Bukit Baru, Melaka, 75150, Malaysia
| | - Shama Prasada K
- Department of Cell and Molecular Biology, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Manipal, Karnataka, 576104, India
| | - Akshatha Shetty
- Department of Research and Development, Muniyal Institute of Ayurveda and Medical Sciences, Manipal, Manipal, Karnataka, 576104, India
| | - Mohandas Rao K G
- Division of Anatomy, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
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Gao J, Shi X, Sun Y, Liu X, Zhang F, Shi C, Yu X, Yan Z, Liu L, Yu S, Zhang J, Zhang X, Zhang S, Guo W. Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase (G6PD) by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis. SCIENCE CHINA. LIFE SCIENCES 2024; 67:1648-1665. [PMID: 38679670 DOI: 10.1007/s11427-023-2481-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 10/11/2023] [Indexed: 05/01/2024]
Abstract
Betaine-homocysteine methyltransferase (BHMT) regulates protein methylation and is correlated with tumorigenesis; however, the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored. Here, we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma (HCC) using tissue samples from 198 patients. BHMT was to be frequently found (86.6%) expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC. Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo, whereas complete knockout of Bhmt (Bhmt-/-) produced the opposite effect. We combined proteomics, metabolomics, and molecular biological strategies and detected that Bhmt-/- promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models. In contrast, restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis. Additionally, coimmunoprecipitation identified monomethylated modifications of the G6PD, and BHMT regulated the methylation of G6PD. Protein sequence analysis, generation and application of specific antibodies, and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246. Furthermore, we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD, thereby inhibiting G6PD activity, which in turn suppressed hepatocarcinogenesis. Taken together, this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency, suggesting a potential therapeutic strategy for HCC treatment.
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Affiliation(s)
- Jie Gao
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Xiaoyi Shi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Yaohui Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Xudong Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Feng Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Chengcheng Shi
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Xiao Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Zhiping Yan
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Long Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Shizhe Yu
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China
- Cancer Metastasis Institute, Fudan University, Shanghai, 200040, China
| | - Jiacheng Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Xiaodan Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China.
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China.
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China.
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Henan Diagnosis & Treatment League for Hepatopathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Henan Innovative Research Group for Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation, Zhengzhou, 450052, China.
- Henan Organ Transplantation Quality Control Centre, Zhengzhou, 450052, China.
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, 450052, China.
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Chen GQ, Nan Y, Huang SC, Ning N, Du YH, Lu DD, Yang YT, Meng FD, Yuan L. Research progress of ginger in the treatment of gastrointestinal tumors. World J Gastrointest Oncol 2023; 15:1835-1851. [DOI: 10.4251/wjgo.v15.i11.1835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 09/15/2023] [Accepted: 09/27/2023] [Indexed: 11/15/2023] Open
Abstract
Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors.
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Affiliation(s)
- Guo-Qing Chen
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yi Nan
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Shi-Cong Huang
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Na Ning
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yu-Hua Du
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Dou-Dou Lu
- School of Clinical Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Ya-Ting Yang
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Fan-Di Meng
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Ling Yuan
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
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Zieschang AD, Hoffseth KF, Dugas TR, Astete CE, Boldor D. Method for assessing coating uniformity of angioplasty balloons coated with poly(lactic-co-glycolic acid) nanoparticles loaded with quercetin. PARTICULATE SCIENCE AND TECHNOLOGY 2023; 42:601-611. [PMID: 38966520 PMCID: PMC11221576 DOI: 10.1080/02726351.2023.2269881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/06/2024]
Abstract
In this study, we aim to quantify coating uniformity and correlate fluorescence intensity to drug loading for drug-coated angioplasty balloons (DCB) coated with 5, 10, 15, or 20 layers of poly(lactic-co-glycolic acid) nanoparticles (NPs) entrapped with quercetin. Uniformity was quantified from histograms and horizontal line profiles of microscopic fluorescent images acquired with sample specific parameters, and cracks in the coating were measured and counted. The fluorescence of images acquired with global parameters was correlated with quercetin loading measured via gravimetric/HPLC analysis. More layers on DCBs may be associated with less uniform coatings, as indicated by differences in histogram standard deviations. The line profile percent deviation from average for each sample was <20%. Cracks were present on all balloons, but their length was not significantly different between samples. The 5-layer DCBs had the fewest cracks, whereas the 15-layer DCBs had the most cracks. A strong positive correlation (R = 0.896) was identified between fluorescence intensity and drug loading. A relationship between the number of layers and coating uniformity seems to exist, but further investigations are required for confirmation. Fluorescence intensity appears to strongly predict drug loading, demonstrating that fluorescent imaging may be a viable alternative to drug release studies.
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Affiliation(s)
- Allison D. Zieschang
- Louisiana State University and the LSU AgCenter, Department of Biological and Agricultural Engineering, Baton Rouge, Louisiana, United States of America
| | - Kevin F. Hoffseth
- Louisiana State University and the LSU AgCenter, Department of Biological and Agricultural Engineering, Baton Rouge, Louisiana, United States of America
| | - Tammy R. Dugas
- Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Baton Rouge, Louisiana, United States of America
| | - Carlos E. Astete
- Louisiana State University and the LSU AgCenter, Department of Biological and Agricultural Engineering, Baton Rouge, Louisiana, United States of America
| | - Dorin Boldor
- Louisiana State University and the LSU AgCenter, Department of Biological and Agricultural Engineering, Baton Rouge, Louisiana, United States of America
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Owumi SE, Olugbami JO, Akinnifesi AO, Odunola OA. Leaf paste of Telfairia occidentalis favourably modulates deleterious effects associated with exposure to diethylnitrosamine in male Wistar rats. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2023; 20:590-596. [PMID: 34674412 DOI: 10.1515/jcim-2021-0151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 09/29/2021] [Indexed: 01/14/2023]
Abstract
OBJECTIVES Diethylnitrosamine (DEN) is found in workplaces, processed meats, tobacco smoke, whiskey, etc. It is capable of forming DNA-adducts. Fluted pumpkin (Telfairia occidentalis [To]) is a medicinal plant, and its herbal preparations have been employed variously in ethnomedicine. Furthermore, it has been reported to possess anti-oxidant, anti-cancer, anti-inflammatory properties. We investigated the possible mitigating effect of the leaf paste of To on DEN-induced deleterious effects in male Wistar rats. METHODS Forty-five rats weighing between 100 and 150 g were equally divided into nine groups and treated thus: Group 1 (negative control), Group 2 (0.05 mg/kg carboxymethyl cellulose [CMC] daily), Group 3 (positive control, 25 mg/kg bw DEN administered intraperitoneally thrice per week), Group 4 (25 mg/kg bw quercetin [QUE] daily alone), Groups 5 and 6 (100 and 200 mg/kg bw To daily, respectively), Group 7 (25 mg/kg bw DEN and QUE), Groups 8 and 9 (25 mg/kg bw DEN with 100 and 200 mg/kg bw To, respectively). Blood glucose levels, liver damage biomarkers (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyltransferase [γ-GT]), frequency of micronucleated polychromatic erythrocyte (mPCEs), and liver histology were assessed. RESULTS DEN significantly (p<0.05) increased blood glucose levels, activities of ALT, AST and γ-GT, and frequency of mPCEs. Histologically, DEN caused a severe architectural anarchy. However, the intervention groups demonstrated the remarkable protective properties of To by ameliorating the adverse effects caused by DEN. CONCLUSIONS Taken together, the leaf paste of To is capable of mitigating DEN-induced hepatotoxicity and clastogenicity in male Wistar rats.
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Affiliation(s)
- Solomon E Owumi
- Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Jeremiah O Olugbami
- Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Andrew O Akinnifesi
- Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Oyeronke A Odunola
- Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
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A Double-Edged Sword: Focusing on Potential Drug-to-Drug Interactions of Quercetin. REVISTA BRASILEIRA DE FARMACOGNOSIA 2022. [DOI: 10.1007/s43450-022-00347-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Altındağ F, Boğokşayan S, Bayram S. Eumelanin protects the liver against diethylnitrosamine-induced liver injury. Toxicology 2022; 480:153311. [PMID: 36113623 DOI: 10.1016/j.tox.2022.153311] [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: 08/17/2022] [Revised: 08/30/2022] [Accepted: 09/02/2022] [Indexed: 11/26/2022]
Abstract
This study aims to evaluate in vivo protective effects of eumelanin (EU) on diethylnitrosamine (DEN)-induced liver injury. Wistar albino male rats were divided into 6 groups (n = 6), Control, DMSO, DEN, DEN + EU10, DEN + EU15, and DEN + EU20. Animals in the DEN group were injected i.p a single dose of 200 mg/kg DEN, DEN + EU10 group was given 10 mg/kg EU, DEN + EU15 group was given 15 mg/kg, DEN + EU20 group was given 20 mg/kg EU for a week. The results showed that there was no significant difference in vessel volume density between the groups. Inflammatory cell infiltration, hydropic degeneration, and necrotic cells were observed in the DEN group, and these histopathological changes were significantly reduced in all treatment groups. Although there was a low intensity of PAS-positive staining in the DEN groups, moderate staining was observed in the treatment groups. While Caspase-3, PCNA, TNF-α, and IL-6 expressions increased in the DEN group, their expressions decreased in the EU-treated groups. DEN increased AST, ALT, and MDA levels and decreased CAT levels. In particular, the EU10 dose significantly improved these parameters. The present study revealed that eumelanin has protective effects against DEN-induced liver injury.
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Affiliation(s)
- Fikret Altındağ
- Department of Histology and Embryology, Van Yüzüncü Yıl University Faculty of Medicine, Van, Turkey.
| | - Seda Boğokşayan
- Department of Histology and Embryology, Van Yüzüncü Yıl University Faculty of Medicine, Van, Turkey
| | - Sinan Bayram
- Department of Medical Services and Techniques, Vocational School of Health Services, Bayburt University, Bayburt, Turkey
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Sawong S, Pekthong D, Suknoppakit P, Winitchaikul T, Kaewkong W, Somran J, Intapa C, Parhira S, Srisawang P. Calotropis gigantea stem bark extracts inhibit liver cancer induced by diethylnitrosamine. Sci Rep 2022; 12:12151. [PMID: 35840761 PMCID: PMC9287404 DOI: 10.1038/s41598-022-16321-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 07/08/2022] [Indexed: 11/09/2022] Open
Abstract
Several fractions of Calotropis gigantea extracts have been proposed to have potential anticancer activity in many cancer models. The present study evaluated the anticancer activity of C. gigantea stem bark extracts in liver cancer HepG2 cells and diethylnitrosamine (DEN)-induced primary liver cancer in rats. The carcinogenesis model induced by DEN administration has been widely used to study pathophysiological features and responses in rats that are comparable to those seen in cancer patients. The dichloromethane (CGDCM), ethyl acetate, and water fractions obtained from partitioning crude ethanolic extract were quantitatively analyzed for several groups of secondary metabolites and calactin contents. A combination of C. gigantea stem bark extracts with doxorubicin (DOX) was assessed in this study to demonstrate the enhanced cytotoxic effect to cancer compared to the single administration. The combination of DOX and CGDCM, which had the most potential cytotoxic effect in HepG2 cells when compared to the other three fractions, significantly increased cytotoxicity through the apoptotic effect with increased caspase-3 expression. This combination treatment also reduced ATP levels, implying a correlation between ATP and apoptosis induction. In a rat model of DEN-induced liver cancer, treatment with DOX, C. gigantea at low (CGDCM-L) and high (CGDCM-H) doses, and DOX + CGDCM-H for 4 weeks decreased the progression of liver cancer by lowering the liver weight/body weight ratio and the occurrence of liver hyperplastic nodules, fibrosis, and proliferative cells. The therapeutic applications lowered TNF-α, IL-6, TGF-β, and α-SMA inflammatory cytokines in a similar way, implying that CGDCM had a curative effect against the inflammation-induced liver carcinogenesis produced by DEN exposure. Furthermore, CGDCM and DOX therapy decreased ATP and fatty acid synthesis in rat liver cancer, which was correlated with apoptosis inhibition. CGDCM reduced cleaved caspase-3 expression in liver cancer rats when used alone or in combination with DOX, implying that apoptosis-inducing hepatic carcinogenesis was suppressed. Our results also verified the low toxicity of CGDCM injection on the internal organs of rats. Thus, this research clearly demonstrated a promising, novel anticancer approach that could be applied in future clinical studies of CGDCM and combination therapy.
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Affiliation(s)
- Suphunwadee Sawong
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
| | - Dumrongsak Pekthong
- Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand
| | - Pennapha Suknoppakit
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
| | - Thanwarat Winitchaikul
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
| | - Worasak Kaewkong
- Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
| | - Julintorn Somran
- Department of Pathology, Faculty of Medicine, Naresuan University, Phitsanulok, 65000, Thailand
| | - Chaidan Intapa
- Department of Oral Diagnosis, Faculty of Dentistry, Naresuan University, Phitsanulok, 65000, Thailand
| | - Supawadee Parhira
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand.
| | - Piyarat Srisawang
- Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand.
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10
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Đorđević MM, Tolić A, Rajić J, Mihailović M, Arambašić Jovanović J, Uskoković A, Grdović N, Đorđević MB, Mišić D, Šiler B, Vidaković M, Dinić S. Centaurium erythraea methanol extract improves the functionality of diabetic liver and kidney by mitigating hyperglycemia-induced oxidative stress. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.104975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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11
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Sakr MA, Al-Azzawi MA, Anis A, Abd El-Aziz AA, Ebeid ME, Shokeer MA, fayed A. The correlation between P53 and COX-2 expression and the pathological alteration in hepatocellular carcinoma. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022. [DOI: 10.1186/s43042-022-00230-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is among the highest life-threatening malignancies. On both a molecular and histological level, HCC is a highly heterogeneous malignancy. This study was aimed to study the correlation between the molecular expression of some molecular biomarkers (P53 and Cox-2) and the histopathological alterations in the chemically induced HCC by Diethylnitrosamine (DEN) in Adult female Rats. The liver tumor induction was done by injection of DEN intraperitoneally one, two and three times/week for 2 months by the dose of 50 mg/kg Bw. The histopathological analysis was done and expression level of P53 and cox-2 was detected by quantitative polymerase chain reaction (qRT-PCR) at the end of the experiment.
Results
In this study, Grossly, livers of the groups administered with DEN showed multiple grayish-white macronodules on the outer surface which is dose dependent. Histopathologically, DEN induce multifocal micronodules of hepatocellular carcinoma which characterized by nuclear atypia, clear cell, mitotic figures and necrosis of hepatocytes. P53 mRNA expression to GAPDH, revealed that, there was a statistically significant decrease in HCC groups compared to healthy control group, while Cox-2 mRNA expression was significantly increased in HCC groups than healthy control group.
Conclusions
HCC staging can be achieved by detection the expression of P53, and Cox-2 as molecular markers as it considers noninvasive, rapid and easy method than the histopathological analysis. Finally, Cox-2 could be a therapeutic candidate for HCC due to the higher expression of Cox-2 in HCC lesions.
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12
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Hosny KM, Alhakamy NA, Al Nahyah KS. The relevance of nanotechnology, hepato-protective agents in reducing the toxicity and augmenting the bioavailability of isotretinoin. Drug Deliv 2021; 28:123-133. [PMID: 33355019 PMCID: PMC7758053 DOI: 10.1080/10717544.2020.1862365] [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] [Indexed: 11/30/2022] Open
Abstract
Acne Vulgaris is one of the most common chronic inflammatory skin disorders that affect majority of teen-agers worldwide. Isotretinoin (ITT) is the drug of choice in the management of acne, but, it suffers from serious side-effects including hepatotoxicity, and some psychological disturbances following its oral intake. The objective of this study was to develop and optimize ITT loaded nanoemulsions (ITT-SNEDDS) and to incorporate resveratrol (RSV)in optimum formulation to decrease ITT side effects The ITT solubility was first tested in various essential oils, surfactants, and co-surfactants to select the essential nanoemulsion ingredients. Mixture design was applied to study the effect of independent variables and their interactions on the selected dependent responses. The developed ITT-SNEDDS were characterized for their globule size and ex vivo permeation. The optimized batch was further loaded with RSV and evaluated for in vitro and ex vivo permeation and for in vivo hepatotoxicity. The developed ITT-SNEDDS exhibited globule size below 300 nm, up to 272.27 ± 7.12 mcg/cm2.h and 61.27 ± 2.83% of steady-state flux (JSS) and permeability % respectively. Optimum formulation consisted of 0.15 g oil mixture, 0.6 g of surfactant (Labrasol), and 0.250 g co-surfactant (Transcutol). Permeability studies confirmed the enhanced permeation percentage of ITT (40.77 ± 1.18%), and RSV (29.94 ± 2.02%) from optimized formulation, with enhanced steady-state flux (JSS). In vivo studies demonstrated the superior hepatoprotective activity of optimized formulation compared to a different drug formulations and marketed product. Therefore, RVS loaded ITT-SNEDDS might be a successful strategy for acne management with improved action, and minimum side effects.
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Affiliation(s)
- Khaled M Hosny
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.,Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nabil A Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.,Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Khalid S Al Nahyah
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
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13
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Su X, Xian C, Gao M, Liu G, Wu J. Edible Materials in Tissue Regeneration. Macromol Biosci 2021; 21:e2100114. [PMID: 34117831 DOI: 10.1002/mabi.202100114] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/28/2021] [Indexed: 11/07/2022]
Abstract
Edible materials have attracted increasing attention because of their excellent properties including availability, biocompatibility, biological activity, and biodegradability. Natural polysaccharides, phenolic compounds, and proteins are widely used in tissue regeneration. To better characterize their healing effect, this review article describes the applications of edible materials in tissue regeneration including wound healing and bone tissue regeneration. As an introduction to the topic, their sources and main bioactive properties are discussed. Then, the mechanism by which they facilitate wound healing based on their hemostasis, antibacterial, anti-inflammatory, and antioxidant properties is systematically investigated. Moreover, a more comprehensive discussion is presented on the approaches by which edible materials can be used as scaffolds or agents for the provision of the components of natural bones for regulating the level of osteogenesis-related cytokines to enhance bone repair. Finally, the prospects of edible materials for tissue regeneration are discussed.
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Affiliation(s)
- Xiaohan Su
- School of Biomedical Engineering, Sun Yat-sen University, Shenzhen, 518057, China
| | - Caihong Xian
- School of Biomedical Engineering, Sun Yat-sen University, Shenzhen, 518057, China
| | - Ming Gao
- Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Guiting Liu
- The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu, 610065, China
| | - Jun Wu
- School of Biomedical Engineering, Sun Yat-sen University, Shenzhen, 518057, China
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14
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Pal LC, Prateeksha, Singh BN, Pande V, Rao CV. Phenolics-Enriched Fraction of Pterospermum Lanceifolium Roxb. efficiently Reverses the Hepatocellular Carcinoma in NDEA-Induced HCC Rats. Nutr Cancer 2021; 74:1106-1121. [PMID: 34018459 DOI: 10.1080/01635581.2021.1922716] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Hepatocellular Carcinoma is one of the most frequently diagnosed cancer and highly refractory for chemotherapeutics agents. Therefore, the study aims to explore the new therapeutic agents for HCC. Phenolics rich fraction of leaves of P. lanceifolium was studied against hepatic cancer cell lines (HepG2) and NDEA-induced HCC rat model system. The obtained results showed that PLE induces reactive oxygen species (ROS) generation and chromatin condensation in nucleus and, alters the mitochondrial membrane potential (MMP) in HepG2 cell lines. The acridine orange/propidium iodide analysis and annexin-V FITC/PI analysis confirms that PLE induces apoptosis-mediated cell death in HepG2-cell lines. In In Vivo analysis, the administration of PLE in NDEA-induced rats declined the elevated biochemicals markers (ALT, AST, ALP, and GGT), interleukins, TNF-α, α-fetoprotein, carcinoembryonic antigen, and total bilirubin. PLE reinstated the level of antioxidant enzyme (GSH, GST, catalase, SOD, and GPX) and the expression of pro-apoptotic (p53, caspase-3, caspase-9, and Bax) and anti-apoptotic (Bcl-2) genes in a dose-dependent manner. The GC-MS analysis of Pterospermum lanceifolium fraction (PLE) represents the presence of palmitic acid, myristic acid, β-sitosterol, and catechin as major bioactive phytocompounds. The study discloses the new lead for HCC that can be further useful for development of new chemopreventive agent.
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Affiliation(s)
- Lal Chand Pal
- Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow, India.,Department of Biotechnology, Kumaun University, Nainital, India
| | - Prateeksha
- Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow, India
| | - Brahma Nand Singh
- Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow, India
| | - Veena Pande
- Department of Biotechnology, Kumaun University, Nainital, India
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15
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Sanjay S, Girish C, Toi PC, Bobby Z. Quercetin modulates NRF2 and NF-κB/TLR-4 pathways to protect against isoniazid- and rifampicin-induced hepatotoxicity in vivo. Can J Physiol Pharmacol 2021; 99:952-963. [PMID: 33617360 DOI: 10.1139/cjpp-2021-0008] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Isoniazid and rifampicin are crucial for treating tuberculosis (TB); however, they can cause severe hepatotoxicity leading to liver failure. Therapeutic options are limited and ineffective. We hypothesized that prophylaxis with quercetin attenuates isoniazid- and rifampicin-induced liver injury. We randomly divided Wistar rats into seven groups (n = 6). The animals received isoniazid and rifampicin or were co-treated with quercetin or silymarin for 28 days. The protective effect of quercetin was assessed using liver function tests and liver histology. Nuclear factor erythroid 2-related factor 2 (NRF2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways were explored to elucidate the mechanism of action. Quercetin co-administration prevented the elevation of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and bilirubin compared with isoniazid and rifampicin treatment alone. In the histological analysis, we observed that quercetin prophylaxis lessened the severity of hepatic necrosis and inflammation compared with the anti-TB drug-treated group. Quercetin attenuated anti-TB drug-induced oxidative stress by increasing NRF2 activation and expression, boosting endogenous antioxidant levels. Additionally, quercetin blocked inflammatory mediators high mobility group box-1 (HMGB-1) and interferon γ (IFN-γ), inhibiting activation of the NF-κB/ toll like receptor 4 (TLR-4) axis. Quercetin protects against anti-TB liver injury by activating NRF2 and blocking NF-κB/TLR-4.
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Affiliation(s)
| | | | - Pampa Ch Toi
- Department of Pathology, JIPMER, Puducherry, India
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16
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Hassanen EI, Korany RMS, Bakeer AM. Cisplatin-conjugated gold nanoparticles-based drug delivery system for targeting hepatic tumors. J Biochem Mol Toxicol 2021; 35:e22722. [PMID: 33484050 DOI: 10.1002/jbt.22722] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 12/01/2020] [Accepted: 01/09/2021] [Indexed: 01/19/2023]
Abstract
Cisplatin is a highly cytotoxic anticarcinogenic drug used to treat several kinds of solid tumors such as liver tumors. With the increase in the incidences associated with hepatic tumors and a lack of selectivity of cisplatin to cancer cells, it is important to explore new therapeutic strategies against them. The present study was designed to verify the ability of gold nanoparticles (GNPs) to improve the hepatotherapeutic effect of cisplatin against DENA-induced hepatic tumors and to declare its ability to reduce the renal toxicity induced by cisplatin. Forty male Wistar rats were divided into two groups (n = 20): Group (A)-negative control and group (B)-model of hepatocellular tumor induction. After 4 months, each group was subdivided into four subgroups as the following: Group (1) received normal saline, Group (2) was treated by cisplatin, Group (3) was treated by GNPs, Group (4) was treated by GNPs-cisplatin conjugates. Our results revealed a marked elevation in liver and kidney function tests and oxidant levels with a reduction in antioxidant levels in the DENA-administrated group. Remarkable histopathological alterations in the liver and kidney tissue sections were observed and confirmed by the overexpression of the immunohistochemical staining of placental glutathione S-transferase, Hep Par 1, and proliferating cell nuclear antigen. Noticeable improvements in all the measurable toxicological parameters were recorded in the group treated with either GNPs or GNPs-cisplatin conjugate not observed in the group treated with cisplatin. We can conclude that GNPs not only improve the distribution of cisplatin, targeting it to the site of tumors, but it also reduces the renal toxicity induced by cisplatin, which are the primary concerns in cancer therapy.
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Affiliation(s)
| | | | - Adel M Bakeer
- Department of Pathology, Cairo University, Giza, Egypt
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17
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Alsahli MA, Almatroodi SA, Almatroudi A, Khan AA, Anwar S, Almutary AG, Alrumaihi F, Rahmani AH. 6-Gingerol, a Major Ingredient of Ginger Attenuates Diethylnitrosamine-Induced Liver Injury in Rats through the Modulation of Oxidative Stress and Anti-Inflammatory Activity. Mediators Inflamm 2021; 2021:6661937. [PMID: 33531877 PMCID: PMC7837795 DOI: 10.1155/2021/6661937] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/19/2020] [Accepted: 01/02/2021] [Indexed: 12/24/2022] Open
Abstract
Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-α, IL-6, and ICAM1), haematoxylin and eosin staining, Sirius red staining, immunohistochemistry, and electron microscopy were performed. The results showed a significant increase in liver function enzymes, oxidative stress, and inflammatory markers in the DEN-treated group as compared to the control group. Besides this, altered architecture of hepatocytes (infiltration of inflammatory cells, congestion, blood vessel dilation, and edema), abundant collagen fiber and organelle structures like distorted shaped and swollen mitochondria, and broken endoplasmic reticulum were noticed. The administration of 6-gingerol significantly ameliorated the biochemical and histopathological changes. The increased expression of TNF-α protein was noticed in the DEN-treated group whereas the administration of 6-gingerol significantly decreased the expression of this protein. Based on these findings, it can be suggested that 6-gingerol may be an alternative therapy for the prevention and treatment of liver diseases.
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Affiliation(s)
- Mohammed A. Alsahli
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Saleh A. Almatroodi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Ahmad Almatroudi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Amjad Ali Khan
- Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Shehwaz Anwar
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Abdulmajeed G. Almutary
- Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Faris Alrumaihi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Arshad Husain Rahmani
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
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18
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Hosny KM, Al Nahyah KS, Alhakamy NA. Self-Nanoemulsion Loaded with a Combination of Isotretinoin, an Anti-Acne Drug, and Quercetin: Preparation, Optimization, and In Vivo Assessment. Pharmaceutics 2020; 13:pharmaceutics13010046. [PMID: 33396942 PMCID: PMC7823934 DOI: 10.3390/pharmaceutics13010046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/22/2020] [Accepted: 12/28/2020] [Indexed: 11/20/2022] Open
Abstract
Acne vulgaris is a common skin disease that affects everybody at least once in their lives. The treatment is challenging because the stratum corneum contains rigid corneocytes surrounded by intercellular lamellae that are difficult to bypass. In the present study, we intended to formulate an effective nanoemulsion that could deliver isotretinoin (ITT) with enhanced solubility, permeability, and bioavailability across the skin. ITT can have a serious hepatotoxic effect if given too frequently or erratically. Therefore, to overcome the aforesaid limitation, quercetin (QRS), a hepatoprotective agent, was incorporated into the formulation. Initially, the ITT solubility was determined in various surfactants and cosurfactants to select the essential ingredients to be used in the formulation and to optimize a nanoemulsion that could enhance the solubility and permeability of ITT and its antimicrobial activity against Staphyloccocus aureus, which is the main microorganism responsible for acne vulgaris. The mixture design was applied to study the interactions and optimize the independent variables that could match the prerequisites of selected dependent responses. A formulation containing 0.25 g of rosehip oil, 0.45 g of surfactant (Lauroglycol-90), and 0.3 g of cosurfactant (propylene glycol) was chosen as an optimized desirable formulation. The optimized batch was loaded with QRS and evaluated for in vitro and ex vivo permeation. The in vivo hepatotoxicity was assessed through topical administration. Permeability studies confirmed the enhanced permeation percentage of ITT (52.11 ± 2.85%) and QRS (25.44 ± 3.18%) of the optimized formulation, with an enhanced steady-state flux (Jss). The in vivo studies conducted on experimental animals demonstrated superior hepatoprotective activity of the prepared optimized formulation compared with other formulations of drugs and commercially marketed products. We anticipate that this optimized ITT formulation, followed up with good clinical evaluations, can be a breakthrough in the safe treatment of acne vulgaris.
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Affiliation(s)
- Khaled M. Hosny
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (K.S.A.N.); (N.A.A.)
- Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Correspondence: ; Tel.: +966-5-9272-2634
| | - Khalid S. Al Nahyah
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (K.S.A.N.); (N.A.A.)
| | - Nabil A. Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (K.S.A.N.); (N.A.A.)
- Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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19
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Akhtar MF, Saleem A, Rasul A, Faran Ashraf Baig MM, Bin-Jumah M, Abdel Daim MM. Anticancer natural medicines: An overview of cell signaling and other targets of anticancer phytochemicals. Eur J Pharmacol 2020; 888:173488. [PMID: 32805253 DOI: 10.1016/j.ejphar.2020.173488] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 07/23/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023]
Abstract
Therapies of cancer are as diverse as multifaceted the cancer is. Anticancer drugs include, but not limited to synthetic, semisynthetic and natural drugs and monoclonal antibodies. A recent decline in new drug development has led to the rebirth of herbal therapeutics in the form of dietary supplements and botanical preparations. Medicinal plants comprise of complex phytochemicals due to vast biosynthetic capacity. A wide array of phytochemicals has been pharmacologically evaluated for their chemo-preventive and chemotherapeutic potential for several decades. These phytochemicals target cancer at diverse sites such as apoptotic pathways, genetic and epigenetic mutations, damage to deoxyribonucleic acid, production of reactive oxygen species, autophagy, invasion and metastasis of cancer cells, and modulation of cell signaling through Janus-activated kinase/Signal transducer and activator of transcription, Notch, mitogen-activated protein kinase/Extracellular signal-regulated kinase, phosphatidylinositol 3-kinase/Protein kinase B/mammalian target of rapamycin, Nuclear factor kappa B, Wingless-related integration site and Transforming growth factor β pathways. This review focuses on the therapeutic targets of anticancer and chemo-preventive phytochemicals and their mode of action.
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Affiliation(s)
- Muhammad Furqan Akhtar
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Pakistan.
| | - Ammara Saleem
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Azhar Rasul
- Department of Zoology, Government College University Faisalabad, Faisalabad, Pakistan
| | | | - May Bin-Jumah
- Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Mohamed M Abdel Daim
- Department of Zoology, College of Science, King Saud University, 2455, Riyadh, 11451, Saudi Arabia; Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt
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20
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Ali S, Ejaz M, Dar KK, Nasreen S, Ashraf N, Gillani SF, Shafi N, Safeer S, Khan MA, Andleeb S, Akhtar N, Mughal TA. Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice. BRAZ J BIOL 2020; 80:484-496. [DOI: 10.1590/1519-6984.185979] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Accepted: 02/26/2019] [Indexed: 11/22/2022] Open
Abstract
Abstract The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.
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Affiliation(s)
- S. Ali
- Government College University, Pakistan
| | - M. Ejaz
- University of Azad Jammu and Kashmir, Pakistan
| | - K. K. Dar
- University of Azad Jammu and Kashmir, Pakistan
| | - S. Nasreen
- University of Azad Jammu and Kashmir, Pakistan
| | - N. Ashraf
- University of Azad Jammu and Kashmir, Pakistan
| | | | - N. Shafi
- University of Azad Jammu and Kashmir, Pakistan
| | - S. Safeer
- University of Azad Jammu and Kashmir, Pakistan
| | - M. A. Khan
- University of Azad Jammu and Kashmir, Pakistan
| | - S. Andleeb
- University of Azad Jammu and Kashmir, Pakistan
| | - N. Akhtar
- University of Azad Jammu and Kashmir, Pakistan
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Saha P, Talukdar AD, Nath R, Sarker SD, Nahar L, Sahu J, Choudhury MD. Role of Natural Phenolics in Hepatoprotection: A Mechanistic Review and Analysis of Regulatory Network of Associated Genes. Front Pharmacol 2019; 10:509. [PMID: 31178720 PMCID: PMC6543890 DOI: 10.3389/fphar.2019.00509] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 04/24/2019] [Indexed: 12/11/2022] Open
Abstract
The liver is not only involved in metabolism and detoxification, but also participate in innate immune function and thus exposed to frequent target Thus, they are the frequent target of physical injury. Interestingly, liver has the unique ability to regenerate and completely recoup from most acute, non-iterative situation. However, multiple conditions, including viral hepatitis, non-alcoholic fatty liver disease, long term alcohol abuse and chronic use of medications can cause persistent injury in which regenerative capacity eventually becomes dysfunctional resulting in hepatic scaring and cirrhosis. Despite the recent therapeutic advances and significant development of modern medicine, hepatic diseases remain a health problem worldwide. Thus, the search for the new therapeutic agents to treat liver disease is still in demand. Many synthetic drugs have been demonstrated to be strong radical scavengers, but they are also carcinogenic and cause liver damage. Present day various hepatic problems are encountered with number of synthetic and plant based drugs. Nexavar (sorafenib) is a chemotherapeutic medication used to treat advanced renal cell carcinoma associated with several side effects. There are a few effective varieties of herbal preparation like Liv-52, silymarin and Stronger neomin phages (SNMC) against hepatic complications. Plants are the huge repository of bioactive secondary metabolites viz; phenol, flavonoid, alkaloid etc. In this review we will try to present exclusive study on phenolics with its mode of action mitigating liver associated complications. And also its future prospects as new drug lead.
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Affiliation(s)
- Priyanka Saha
- Department of Life Science & Bioinformatics, Assam University, Silchar, India
| | - Anupam Das Talukdar
- Department of Life Science & Bioinformatics, Assam University, Silchar, India
| | - Rajat Nath
- Department of Life Science & Bioinformatics, Assam University, Silchar, India
| | - Satyajit D. Sarker
- Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Lutfun Nahar
- Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Jagajjit Sahu
- Department of Mycology and Plant Pathology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, India
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Şengelen A, Önay-Uçar E. Rosmarinic acid and siRNA combined therapy represses Hsp27 (HSPB1) expression and induces apoptosis in human glioma cells. Cell Stress Chaperones 2018; 23:885-896. [PMID: 29627902 PMCID: PMC6111096 DOI: 10.1007/s12192-018-0896-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 02/10/2018] [Accepted: 03/24/2018] [Indexed: 12/11/2022] Open
Abstract
High expression of Hsp27 in glioma cells has been closely associated with tumor cell proliferation and apoptosis inhibition. The aim of the present study was to asses the effects of rosmarinic acid (RA) on Hsp27 expression and apoptosis in non-transfected and transfected human U-87 MG cells. The effect of rosmarinic acid was compared to quercetin, which is known to be a good Hsp27 inhibitor. In order to block the expression of Hsp27 gene (HSPB1), transfection with specific siRNAs was performed. Western blotting technique was used to assess the Hsp27 expression, and caspase-3 colorimetric activity assay was performed to determine apoptosis induction. According to the results, it was found that RA and quercetin effectively silenced Hsp27 and both agents induced apoptosis by activating the caspase-3 pathway. Eighty and 215 μM RA decreased the level of Hsp27 by 28.8 and 46.7% and induced apoptosis by 30 and 54%, respectively. For the first time, we reported that rosmarinic acid has the ability to trigger caspase-3 induced apoptosis in human glioma cells. As a result of siRNA transfection, the Hsp27 gene was silenced by ~ 50% but did not cause a statistically significant change in caspase-3 activation. It was also observed that apoptosis was induced at a higher level as a result of Hsp27 siRNA and subsequent quercetin or RA treatment. siRNA transfection and 215 μM RA treatment suppressed Hsp27 expression level by 90.5% and increased caspase-3 activity by 58%. Herein, we demonstrated that RA administered with siRNA seems to be a potent combination for glioblastoma therapy.
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Affiliation(s)
- Aslıhan Şengelen
- Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Vezneciler, 34134, Istanbul, Turkey.
| | - Evren Önay-Uçar
- Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Vezneciler, 34134, Istanbul, Turkey
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23
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Ibitoye OB, Olofinsan KA, Teralı K, Ghali UM, Ajiboye TO. Bioactivity-guided isolation of antidiabetic principles from the methanolic leaf extract ofBryophyllum pinnatum. J Food Biochem 2018. [DOI: 10.1111/jfbc.12627] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- O. B. Ibitoye
- Department of Biological Sciences; Al-Hikmah University; Ilorin Nigeria
| | - K. A. Olofinsan
- Faculty of Natural and Applied Sciences, Department of Biological Sciences; Nile University of Nigeria; Abuja Nigeria
| | - K. Teralı
- Faculty of Medicine, Department of Medical Biochemistry; Near East University; Nicosia Cyprus
| | - U. M. Ghali
- Faculty of Medicine, Department of Medical Biochemistry; Near East University; Nicosia Cyprus
| | - T. O. Ajiboye
- Antioxidants, Redox Biology and Toxicology Research Group, Department of Medical Biochemistry; College of Health Sciences, Nile University of Nigeria; Abuja Nigeria
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Al-Asmari AK, Khan HA, Manthiri RA, Al-Khlaiwi AA, Al-Asmari BA, Ibrahim KE. Protective effects of a natural herbal compound quercetin against snake venom-induced hepatic and renal toxicities in rats. Food Chem Toxicol 2018; 118:105-110. [PMID: 29751071 DOI: 10.1016/j.fct.2018.05.016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 04/18/2018] [Accepted: 05/07/2018] [Indexed: 02/08/2023]
Abstract
Echis pyramidum is a highly poisonous viper snake. Previous studies have shown acute phase hepatic and renal toxicities of Echis pyramidum venom (EPV) in rats. This study reports the protective effects of a natural herbal compound quercetin (QRC) on EPV-induced hepatic and renal toxicities in rats. A singly injection of EPV (4.76 mg/kg) caused significant increase in serum biomarkers of liver and kidney function. Pre-treatment of QRC (10 mg/kg) significantly reduced the toxic effects of EPV on functional impairment in liver and kidneys of rats. Administration of QRC also reversed EPV-induced increase in lipid peroxidation and decrease in total thiols. The histopathology of liver showed fat accumulation, focal degeneration and cytoplasmic vacuolation of hepatocytes in EPV treated rats. EPV also caused renal tubular dilation and focal atrophy of glomerular tufts in rat kidneys. Administration of QRC prevented EPV-induced structural tissue damage in liver and kidneys of rats. In conclusion, QRC significantly inhibited the acute phase toxic effects of EPV on liver and kidneys of rats by preventing the oxidative stress in these organs. QRC is also known for its anti-inflammatory, anti-edema, anti-hemorrhagic and PLA2-inhibitory properties and therefore may be regarded as a multi-action antidote against snake venom toxicity.
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Affiliation(s)
- Abdulrahman K Al-Asmari
- Scientific Research Center, Medical Services Department, Ministry of Defense, Riyadh 11159, Saudi Arabia.
| | - Haseeb A Khan
- Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Rajamohamed A Manthiri
- Scientific Research Center, Medical Services Department, Ministry of Defense, Riyadh 11159, Saudi Arabia
| | - Ahmad A Al-Khlaiwi
- Scientific Research Center, Medical Services Department, Ministry of Defense, Riyadh 11159, Saudi Arabia
| | - Bayan A Al-Asmari
- Dental Department, Dental Public Health, Ministry of Health, Riyadh 11176, Saudi Arabia
| | - Khalid E Ibrahim
- Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
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Ziyatdinova G, Kozlova E, Budnikov H. Poly(gallic acid)/MWNT-modified electrode for the selective and sensitive voltammetric determination of quercetin in medicinal herbs. J Electroanal Chem (Lausanne) 2018. [DOI: 10.1016/j.jelechem.2017.12.071] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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26
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Önay Uçar E, Şengelen A, Mertoğlu E, Pekmez M, Arda N. Suppression of HSP70 Expression by Quercetin and Its Therapeutic Potential Against Cancer. HSP70 IN HUMAN DISEASES AND DISORDERS 2018. [DOI: 10.1007/978-3-319-89551-2_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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27
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Usmani A, Mishra A, Ahmad M. Nanomedicines: a theranostic approach for hepatocellular carcinoma. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2017; 46:680-690. [DOI: 10.1080/21691401.2017.1374282] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Afreen Usmani
- Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Anuradha Mishra
- Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Mohd Ahmad
- Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, India
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Tzankova V, Aluani D, Kondeva-Burdina M, Yordanov Y, Odzhakov F, Apostolov A, Yoncheva K. Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity. Biomed Pharmacother 2017; 92:569-579. [DOI: 10.1016/j.biopha.2017.05.008] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 04/25/2017] [Accepted: 05/02/2017] [Indexed: 01/01/2023] Open
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Radwan RR, Zaher NH, El-Gazzar MG. Novel 1,2,4-triazole derivatives as antitumor agents against hepatocellular carcinoma. Chem Biol Interact 2017; 274:68-79. [DOI: 10.1016/j.cbi.2017.07.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 06/19/2017] [Accepted: 07/07/2017] [Indexed: 01/03/2023]
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Sherif AA, Abdelhalim SZ, Salim EI. Immunohistochemical and biochemical alterations following administration of proanthocyanidin extract in rats hepatocellular carcinoma. Biomed Pharmacother 2017; 93:1310-1319. [PMID: 28747012 DOI: 10.1016/j.biopha.2017.07.039] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 06/26/2017] [Accepted: 07/06/2017] [Indexed: 12/15/2022] Open
Abstract
Grape seed proanthocyanidin extract (GSPE) is known to be effective on broad spectrum of biological pathways in living organisms including oxidative stress. The present study aimed to investigate the effects of proanthocyanidin on preneoplastic lesions and liver cancer induced in rats by Diethylnitrosamine (DEN). 7-8 Week old male Sprague Dawley (S.D.) rats were divided into six groups: The 1st group received no treatment and were -ve controls, the 2nd were treated with a single dose of DEN 200mg/kg intraperitoneally (i.p.) and served as +ve control group. The 3rd and 4th groups were injected with the same dose of DEN as in group 2 and then post treated with 300 or 150mg/kg/b.wt./day GSPE by intrgastroluminal gavage (i.g.) respectively until the end after the 22 weeks. Groups 5 and 6 were treated with the same doses of GSPE as in groups 3 and 4 respectively without DEN administration. The results showed that the immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling indexes (PCNA LI%) were significantly inhibited in liver tissues and tumors by both treatments of GSPE. Furthermore, treatment with GSPE has modified the liver tissue oxidative stress markers levels of SOD, CAT, GSH, GST, GPx, GR and MDA changed by DEN. In conclusion, GSPE has a sufficient therapeutic effect against liver carcinogenesis through their free radical scavenging, inhibition of cellular proliferation.
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Affiliation(s)
- Aya A Sherif
- Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt.
| | - Somaia Z Abdelhalim
- Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Elsayed I Salim
- Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt
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31
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Nagpal I, Abraham SK. Ameliorative effects of gallic acid, quercetin and limonene on urethane-induced genotoxicity and oxidative stress in Drosophila melanogaster. Toxicol Mech Methods 2017; 27:286-292. [PMID: 28043195 DOI: 10.1080/15376516.2016.1278294] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The main objective of our present work was to ascertain the efficacy of Drosophila melanogaster model for assessing antigenotoxic and antioxidant effects of dietary phytochemicals gallic acid (GA), quercetin (QC) and limonene (Lim) against urethane (URE), a genotoxic environmental carcinogen. Oregon-K (ORK) adult male flies were fed GA, QC and Lim in combination with URE (20 mM) in 10% sucrose for 72 h. Third instar larvae were fed instant medium containing the above phytochemicals and URE for 24 h. Sex-linked recessive lethal (SLRL) test and assays for estimating glutathione content (GSH), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content) were performed. Adult feeding experiments demonstrated that co-treatment of flies with URE and the test phytochemicals has significantly decreased the frequencies of SLRL mutations in all the germ cell stages when compared to that with URE alone. Larval feeding experiments also showed a similar pattern. The above results correlate well with antioxidative potentials of the test agents where we observed the elevated enzymatic levels with a significant reduction in MDA level in Drosophila larvae. The results further suggest that the dietary phytochemicals have an antioxidant and antimutagenic property which can be assessed using D. melanogaster.
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Affiliation(s)
- Isha Nagpal
- a School of Life Sciences , Jawaharlal Nehru University , New Delhi , India
| | - Suresh K Abraham
- a School of Life Sciences , Jawaharlal Nehru University , New Delhi , India
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32
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Polyphenols and DNA Damage: A Mixed Blessing. Nutrients 2016; 8:nu8120785. [PMID: 27918471 PMCID: PMC5188440 DOI: 10.3390/nu8120785] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 11/15/2016] [Accepted: 11/23/2016] [Indexed: 12/26/2022] Open
Abstract
Polyphenols are a very broad group of chemicals, widely distributed in plant foods, and endowed with antioxidant activity by virtue of their numerous phenol groups. They are widely studied as putative cancer-protective agents, potentially contributing to the cancer preventive properties of fruits and vegetables. We review recent publications relating to human trials, animal experiments and cell culture, grouping them according to whether polyphenols are investigated in whole foods and drinks, in plant extracts, or as individual compounds. A variety of assays are in use to study genetic damage endpoints. Human trials, of which there are rather few, tend to show decreases in endogenous DNA damage and protection against DNA damage induced ex vivo in blood cells. Most animal experiments have investigated the effects of polyphenols (often at high doses) in combination with known DNA-damaging agents, and generally they show protection. High concentrations can themselves induce DNA damage, as demonstrated in numerous cell culture experiments; low concentrations, on the other hand, tend to decrease DNA damage.
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Matloub AA, Aglan HA, Mohamed El Souda SS, Aboutabl ME, Maghraby AS, Ahmed HH. Influence of bioactive sulfated polysaccharide-protein complexes on hepatocarcinogenesis, angiogenesis and immunomodulatory activities. ASIAN PAC J TROP MED 2016; 9:1200-1211. [DOI: 10.1016/j.apjtm.2016.11.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 08/21/2016] [Accepted: 09/20/2016] [Indexed: 12/09/2022] Open
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Ye L, He M, Huang Y, Zhao G, Lei Y, Zhou Y, Chen X. Tree shrew as a new animal model for the study of lung cancer. Oncol Lett 2016; 11:2091-2095. [PMID: 26998127 PMCID: PMC4774532 DOI: 10.3892/ol.2016.4156] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 01/27/2016] [Indexed: 01/21/2023] Open
Abstract
Animal models play a key role in identifying treatments for various types of cancer, including lung cancer. The aim of the present study was to develop a new animal model for lung cancer induction using tree shrews from the Yunnan region in China. Tree shrews are suitable for a full simulation of human disease because their structure, function and metabolism are adequately close to human. This animal may offer a new experimental animal model to be used in the study of lung cancer. In the present study, 80 healthy tree shrews were distributed in experimental and control groups. Animals in the experimental group received different concentrations of iodized oil suspension of 3-methylcholanthrene (3-MC) and diethylnitrosamine (DEN) while animals in the control groups received saline or lipiodol solvent via endotracheal instillation. In the 3rd, 5th, 7th, 9th and 11th weeks the body weights of the animals were measured and chest X-ray examinations were conducted. Pathological studies on the lung tissues were also performed and the pathological changes occurring in bronchial epithelium in all the groups were examined. Animals in the experimental group gradually lost their body weight. For tree shrews in the blank control and solvent control groups the survival rates were 100 and 80%, respectively while the survival rate for the experimental group was 0%. Results from the chest X-ray conducted on animals in the blank control and solvent control groups revealed no obvious abnormalities while in the experimental group high-density shadow spots within the perfusion sites were observed. Pathological studies performed on these high-density areas confirmed changes in the bronchial epithelium. In the experimental groups we also detected bronchial epithelial atypical hyperplasia, and apparent changes in carcinoma in situ. In conclusion, lung cancer was successfully induced in tree shrews by a one-time endotracheal introduction of iodized oil suspension of 3-MC and DEN.
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Affiliation(s)
- Lianhua Ye
- Department of Thoracic Surgery of the Third Affiliated Hospital to Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, P.R. China
| | - Meng He
- Department of Thoracic Surgery of the Third Affiliated Hospital to Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, P.R. China
| | - Yunchao Huang
- Department of Thoracic Surgery of the Third Affiliated Hospital to Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, P.R. China
| | - Guangqiang Zhao
- Department of Thoracic Surgery of the Third Affiliated Hospital to Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, P.R. China
| | - Yujie Lei
- Department of Thoracic Surgery of the Third Affiliated Hospital to Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, P.R. China
| | - Yongchun Zhou
- Department of Thoracic Surgery of the Third Affiliated Hospital to Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, P.R. China
| | - Xiaobo Chen
- Department of Thoracic Surgery of the Third Affiliated Hospital to Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, P.R. China
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Ganeshkumar M, Ponrasu T, Subamekala MK, Janani M, Suguna L. Curcumin loaded on pullulan acetate nanoparticles protects the liver from damage induced by DEN. RSC Adv 2016. [DOI: 10.1039/c5ra18989f] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Curcumin loaded nanoparticles protect liver from damage induced by DEN.
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Affiliation(s)
- Moorthy Ganeshkumar
- Department of Biochemistry
- CSIR-Central Leather Research Institute
- Council of Scientific and Industrial Research
- Chennai 600020
- India
| | - Thangavel Ponrasu
- Department of Biochemistry
- CSIR-Central Leather Research Institute
- Council of Scientific and Industrial Research
- Chennai 600020
- India
| | | | - Murthy Janani
- Department of Biopharmaceutics
- Anna University
- Chennai
- India
| | - Lonchin Suguna
- Department of Biochemistry
- CSIR-Central Leather Research Institute
- Council of Scientific and Industrial Research
- Chennai 600020
- India
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Oldenlandia diffusa Promotes Antiproliferative and Apoptotic Effects in a Rat Hepatocellular Carcinoma with Liver Cirrhosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:501508. [PMID: 25852766 PMCID: PMC4379430 DOI: 10.1155/2015/501508] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 02/09/2015] [Accepted: 02/11/2015] [Indexed: 01/11/2023]
Abstract
Oldenlandia diffusa (OD) is commonly used with various diseases such as cancer, arthritis, and autoimmune disease. Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). Here, we show that the therapeutic effect of OD, which was investigated both in vitro and chemically, induced HCC model. OD significantly enhanced apoptosis and antiproliferative activity and reduced migration ability of HCC cells. In vivo, OD was treated twice a day for 28 days after confirmed HCC model through 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) imaging. The survival in OD treated groups was shown to have a greater therapeutic effect than the control group. 28 days after OD treatment, OD treated groups resulted in a significant reduction in tumor number, size, 18F-FDG uptake, and serum levels such as alanine transaminase, aspartate transaminase, and alkaline phosphate compared to the control group. Also, proliferated cells in tumor sites by OD were reduced compared to the control group. Furthermore, several rats in OD treated group survived over 60 days and liver morphology of these rats showed the difference between tumor mass and normal tissue. These results suggest that OD may have antiproliferative activity, inhibition of metastasis, and apoptotic effects in chemically induced HCC model and can have the potential use for clinical application as anticancer drug of the herbal extract.
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Aceituno-Medina M, Mendoza S, Rodríguez BA, Lagaron JM, López-Rubio A. Improved antioxidant capacity of quercetin and ferulic acid during in-vitro digestion through encapsulation within food-grade electrospun fibers. J Funct Foods 2015. [DOI: 10.1016/j.jff.2014.11.028] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
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38
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Souda SSEDE, Mohammed RS, Marzouk MM, Fahmy MA, Hassan ZM, Farghaly AA. Antimutagenicity and phytoconstituents of Egyptian Plantago albicans L. ASIAN PACIFIC JOURNAL OF TROPICAL DISEASE 2014. [DOI: 10.1016/s2222-1808(14)60764-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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39
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Schwingel TE, Klein CP, Nicoletti NF, Dora CL, Hadrich G, Bica CG, Lopes TG, da Silva VD, Morrone FB. Effects of the compounds resveratrol, rutin, quercetin, and quercetin nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice. Naunyn Schmiedebergs Arch Pharmacol 2014; 387:837-48. [PMID: 24908156 DOI: 10.1007/s00210-014-0994-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Accepted: 05/16/2014] [Indexed: 02/06/2023]
Abstract
Oxaliplatin (OXA) is a platinum compound widely used in the treatment of some solid tumors, especially colorectal cancer. Despite its usefulness, oxaliplatin-associated neurotoxicity represents the main dose-limiting factor of this drug, and until now, there is no suitable treatment. Chemotherapy with oxaliplatin also increases the rate of developing hepatic damages with inflammatory activity, termed chemotherapy-associated steatohepatitis (CASH). In the present study, we aimed to compare the effects of a series of antioxidant compounds on simultaneous development of oxaliplatin-induced hepato- and neurotoxicity in mice. Mice BALB/c were treated with oxaliplatin for 6 weeks, 10 mg/kg, intraperitoneally, resulting in mechanical allodynia and hepatic steatosis. We administered the following antioxidant compounds--rutin (RT) (20 mg/kg), resveratrol (RVS) (100 mg/kg), quercetin (QT) (20 mg/kg), and quercetin nanoemulsion (NQT) (20 mg/kg)--daily by gavage to BALB/c, and N-acetylcysteine (NAC) was used as positive control. Treatments with RSV, RUT, or NQT were able to prevent mechanical allodynia when compared to the OXA group, and this effect was associated with decreased c-Fos immunopositivity in the lumbar spinal cord. Regarding the effects on steatohepatitis, RVS, QT, and NQT almost completely reversed the mean liver weight increase induced by OXA. In accordance with these previous data, histological evaluation indicated attenuation of all features of hepatic steatosis evaluated in RSV, RUT, QT, and NQT groups. These compounds were able to reduce the immunopositivity for the apoptosis marker caspase-3. On the other hand, only QT and NQT treatments were able to reduce neutrophil migration measured by myeloperoxidase (MPO) activity. These results suggest that the compounds tested, RSV, RUT, QT, and NQT, would be useful for the clinical treatment of neuro- and hepatoxicity induced by oxaliplatin.
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Affiliation(s)
- Tania E Schwingel
- Programa de Pós Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Ahmed OA, Badr-Eldin SM, Tawfik MK, Ahmed TA, El-Say KM, Badr JM. Design and Optimization of Self-Nanoemulsifying Delivery System to Enhance Quercetin Hepatoprotective Activity in Paracetamol-Induced Hepatotoxicity. J Pharm Sci 2014; 103:602-12. [DOI: 10.1002/jps.23834] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 12/04/2013] [Accepted: 12/06/2013] [Indexed: 12/14/2022]
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Sharmila G, Athirai T, Kiruthiga B, Senthilkumar K, Elumalai P, Arunkumar R, Arunakaran J. Chemopreventive effect of quercetin in MNU and testosterone induced prostate cancer of Sprague-Dawley rats. Nutr Cancer 2013; 66:38-46. [PMID: 24320139 DOI: 10.1080/01635581.2014.847967] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Prostate cancer becomes an ideal target for chemoprevention because of its high incidence and extended natural history. The consumption of quercetin (plant flavonoid) in diet is associated with decreased risk of disease and many cancers but then this was not elucidated in prostate malignancy. Hence, a study in which the male Sprague-Dawley rats were induced prostate cancer by hormone (testosterone) and carcinogen (MNU) and simultaneously supplemented with quercetin (200 mg/Kg body weight) thrice a week, was conducted. After the treatment period, rats were killed; ventral and dorsolateral lobes of the prostate were dissected. Histology and oxidative stress markers LPO, H2O2, and antioxidant GSH level were measured in both lobes. The lipid peroxidation, H2O2, in (MNU+T) treated rats were increased and GSH level was decreased, whereas simultaneous quercetin-treated rats reverted back to normal level in both ventral and dorsolateral regions. The different patterns of PIN were observed with associated hyperplasia and dysplasia; changes in these regions and the occurrence of this lesion were reduced in simultaneous quercetin-treated rats. The study concluded that dietary quercetin prevented MNU + T-induced prostate carcinogenesis on both ventral and dorsolateral lobes of Sprague-Dawley rats.
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Affiliation(s)
- Govindaraj Sharmila
- a Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences , University of Madras , Chennai , India
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Jain AK, Thanki K, Jain S. Solidified Self-Nanoemulsifying Formulation for Oral Delivery of Combinatorial Therapeutic Regimen: Part I. Formulation Development, Statistical Optimization, and In Vitro Characterization. Pharm Res 2013; 31:923-45. [DOI: 10.1007/s11095-013-1213-2] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2013] [Accepted: 09/18/2013] [Indexed: 01/14/2023]
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Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen: part II in vivo pharmacokinetics, antitumor efficacy and hepatotoxicity. Pharm Res 2013; 31:946-58. [PMID: 24135934 DOI: 10.1007/s11095-013-1214-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2013] [Accepted: 09/18/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE The present work focuses on the in vivo evaluation of tamoxifen and quercetin combination loaded into solid self-nanoemulsifying drug delivery system (s-Tmx-QT-SNEDDS). METHODS Lyophilization was employed to prepare s-Tmx-QT-SNEDDS using Aerosil 200 as carrier. The developed formulation was evaluated for in vitro cell cytotoxicity, in vivo pharmacokinetics, antitumor efficacy and toxicity studies. RESULTS In vivo pharmacokinetics revealed ~8-fold and ~4-fold increase in oral bioavailability of tamoxifen and quercetin, respectively as compared to free counterparts. s-Tmx-QT-SNEDDS exhibited significantly higher cell cytotoxicity, as compared to free drug combination revealing ~32-fold and ~22-fold higher dose reduction index for tamoxifen and quercetin, respectively estimated using median effect dose analysis. s-Tmx-QT-SNEDDS could suppress tumor growth in DMBA induced tumor bearing animals by ~80% in contrast to ~35% observed with tamoxifen citrate. The significant appreciation in antitumor efficacy was further supported by normalized levels of tumor angiogenesis markers (MMP-2 and MMP-9). Finally, complete obliteration in tamoxifen induced hepatotoxicity was observed upon administration of developed formulation in contrast to that of clinically available tamoxifen citrate when measured as function of hepatotoxicity markers and histopathological changes. CONCLUSIONS In nutshell, co-encapsulation of quercetin with tamoxifen in solid SNEDDS poses great potential in improving the therapeutic efficacy and safety of tamoxifen.
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Ajiboye TO, Abdussalam FA, Adeleye AO, Iliasu GA, Ariyo FA, Adediran ZA, Raji KO, Raji HO. Bridelia ferrugineaPromotes Reactive Oxygen Species Detoxification in N-Nitrosodiethylamine-Treated Rats. J Diet Suppl 2013; 10:210-28. [DOI: 10.3109/19390211.2013.822451] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Polyphenolic extract of Sorghum bicolor grains enhances reactive oxygen species detoxification in N-nitrosodiethylamine-treated rats. FOOD SCIENCE AND HUMAN WELLNESS 2013. [DOI: 10.1016/j.fshw.2013.02.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Vásquez-Garzón VR, Macias-Pérez JR, Jiménez-García MN, Villegas V, Fattel-Fazenta S, Villa-Treviño S. The chemopreventive capacity of quercetin to induce programmed cell death in hepatocarcinogenesis. Toxicol Pathol 2012. [PMID: 23197198 DOI: 10.1177/0192623312467522] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In this study of chemoprevention in the rat modified resistant hepatocyte model, preneoplastic cells were diminished by >60% with quercetin pretreatment compared with those rats treated with N-Diethylnitrosamine (DEN) to induce liver cancer. This decrease occurred associated with an abolished DEN-induced lipid peroxidation as well as activation of caspase 9 and increased caspase 3, as determined by increased expression of cleaved caspase 3 and 9, but not cleaved caspase 8 and increased fragmentation of Poly (ADP-ribose) polymerase (PARP) inducing apoptosis of presumed genetically injured cells, when quercetin was administered before the initiation agent.
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Effects of Viscum album L. extract and quercetin on methotrexate-induced cyto-genotoxicity in mouse bone-marrow cells. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2012; 746:56-9. [DOI: 10.1016/j.mrgentox.2012.02.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Revised: 10/22/2011] [Accepted: 02/22/2012] [Indexed: 01/26/2023]
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Ghosh D, Choudhury ST, Ghosh S, Mandal AK, Sarkar S, Ghosh A, Saha KD, Das N. Nanocapsulated curcumin: Oral chemopreventive formulation against diethylnitrosamine induced hepatocellular carcinoma in rat. Chem Biol Interact 2012; 195:206-14. [DOI: 10.1016/j.cbi.2011.12.004] [Citation(s) in RCA: 110] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2011] [Revised: 11/16/2011] [Accepted: 12/08/2011] [Indexed: 12/15/2022]
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El Mesallamy HO, Metwally NS, Soliman MS, Ahmed KA, Abdel Moaty MM. The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats. Cancer Cell Int 2011; 11:38. [PMID: 22040519 PMCID: PMC3225333 DOI: 10.1186/1475-2867-11-38] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 10/31/2011] [Indexed: 02/08/2023] Open
Abstract
Background/objective This study was designed to evaluate the potential chemopreventive activities of Ginkgo biloba extract (EGb) and Silybum marianum extract (silymarin) against hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in rats. Methods Rats were divided into 6 groups. Group 1 served as normal control rats. Group 2 animals were intragastrically administrated NDEA at a dose of 10 mg/kg five times a week for 12 weeks to induce hepatocellular carcinoma (HCC). Groups 3 and 4 animals were pretreated with silymarin and EGb respectively. Groups 5 and 6 animals were posttreated with silymarin and EGb respectively. The investigated parameters in serum are alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and vascular endothelial growth factor (VEGF). The investigated parameters in liver tissue are malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and comet assay parameters. Results In NDEA group, MDA level was elevated with subsequent decrease in GSH level and SOD, GPx and GR activities. In addition, NDEA group revealed a significant increase in serum ALT, AST and GGT activities and VEGF level. Furthermore, NDEA administrated animals showed a marked increase in comet assay parameters. These biochemical alterations induced by NDEA were confirmed by the histopathological examination of rat livers intoxicated with NDEA that showed an obvious cellular damage and well differentiated HCC. In contrast, silymarin+NDEA treated groups (3&5) and EGb+NDEA treated groups (4&6) showed a significant decrease in MDA level and a significant increase in GSH content and SOD, GPx and GR activities compared to NDEA group. Silymarin and EGb also beneficially down-regulated the increase in serum ALT, AST, GGT activities and VEGF level induced by NDEA. In addition, silymarin and EGb significantly decreased comet assay parameters. Histopathological examination of rat livers treated with either silymarin or EGb exhibited an improvement in the liver architecture compared to NDEA group. Conclusions The obtained findings suggested that silymarin and EGb may have beneficial chemopreventive roles against hepatocarcinogenesis through their antioxidant, antiangiogenic and antigenotoxic activities.
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Affiliation(s)
- Hala O El Mesallamy
- Therapeutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Tahrir st,, Dokki, Giza, Egypt.
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Barcelos GRM, Angeli JPF, Serpeloni JM, Grotto D, Rocha BA, Bastos JK, Knasmüller S, Júnior FB. Quercetin protects human-derived liver cells against mercury-induced DNA-damage and alterations of the redox status. Mutat Res 2011; 726:109-15. [PMID: 21820078 DOI: 10.1016/j.mrgentox.2011.05.011] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2010] [Revised: 04/20/2011] [Accepted: 05/23/2011] [Indexed: 02/05/2023]
Abstract
Aim of this study was to investigate the cytotoxic and genotoxic properties of inorganic and organic mercury compounds, i.e., HgCl(2) and methylmercury (MeHg). In addition, the DNA-protective and antioxidant effects of the flavonoid quercetin (QC) were studied. All experiments were conducted with human-derived liver cells (HepG2), which possess antioxidant and drug-metabolizing enzymes in an inducible form. 8-Hydroxydeoxyguanosine (8-OHdG) and comet formation were monitored as endpoints of DNA damage. The impact of the metal compounds on the redox status was also investigated, since it is assumed that their toxic effects are due to oxidative damage. A number of biochemical parameters related to oxidative stress, namely glutathione, malondialdehyde, protein carbonyl and formation of reactive oxygen species (ROS) were measured after treatment of the cells with the mercury compounds in the presence and absence of quercetin. To elucidate the mechanisms that underlie the effects of QC, three protocols (pre-, simultaneous and post-treatment) were used. Both mercury compounds (range 0.1-5.0μM) caused induction of DNA migration and formation of 8-OHdG. In combination with the flavonoid (range 0.1-5.0μM), DNA-protective effects of QC were observed after pre- and simultaneous treatment but not when the flavonoid was added after treatment with the metal compounds. Exposure to the metal compounds led also to substantial changes of all parameters of the redox status and co-treatment experiments with QC showed that these alterations are reversed by the flavonoid. Taken together, the results of our experiments indicate that these two mercury compounds cause DNA damage and oxidative stress in human-derived liver cells and that the flavonoid reduces these effects. Since the concentrations of the metals and of the flavonoids used in the present work reflect human exposure, our findings can be taken as an indication that QC may protect humans against the adverse effects caused by the metal.
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