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Liu BY, Jhu JS, Syu ML, Hwang DF. Effects of Arsenic-induced Diabetic Vascular Diseases through Mitogen-activated Protein Kinase Signaling Pathway: In vitro and In vivo Studies. JOURNAL OF PHYSIOLOGICAL INVESTIGATION 2025:02275668-990000000-00035. [PMID: 40298380 DOI: 10.4103/ejpi.ejpi-d-24-00097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 02/02/2025] [Indexed: 04/30/2025]
Abstract
ABSTRACT Arsenic (As) is an environmental pollutant that causes endocrine disruption. Diabetes increases the risk of Blackfoot disease, which is a peripheral artery disease caused by chronic exposure to As through drinking water in Taiwan and Bangladesh; however, the mechanism underlying this increased risk remains unclear. Therefore, in this study, we aimed to investigate the mechanisms underlying vascular damage in hyperglycemic conditions caused by As exposure using in vivo and in vitro studies. We utilized an animal model of streptozotocin-induced diabetes that was exposed to As through drinking water for 8 weeks. Subsequently, blood and organ samples of the animals were collected for follow-up analysis. Further, we cultured endothelial cells that were treated with As treatment in glucose condition and detected their biomarkers. The findings revealed that both the diabetes and diabetes + As groups exhibited insulin resistance, weight gain, and increased plasma triglyceride and total cholesterol levels. The diabetes + As group had lower antioxidant activity, which caused the arteries to exhibit prominent luminal narrowing with increased thickness. In vivo study revealed that glucose + As group-induced cell cycle arrest, a 98.80% increase in reactive oxygen species (ROS) levels, and decreased cell viability and mitochondrial membrane potential (MMP). However, in glucose + As group, treatment with SP600125 and U10126 treatment decreased ROS production by 80.5% and 84%, respectively, and restored MMP and cell viability. The glucose-regulated protein 78 level increased in the As as well as glucose + As groups. Our findings demonstrate that As exacerbates vascular damage in individuals with diabetes and its associated complications through the activation of the mitogen-activated protein kinase signaling pathway.
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Affiliation(s)
- Bi-Yu Liu
- Department of Nursing, University of Kang Ning, Taipei, Taiwan
| | - Jhih-Syuan Jhu
- Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan
| | - Man-Lun Syu
- Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan
| | - Deng-Fwu Hwang
- Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan
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2
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Chumroenvidhayakul S, Thilavech T, Abeywardena MY, Conlon M, Dallimore J, Adams M, Muhlhausler B, Adisakwattana S. Dragon Fruit Peel ( Hylocereus undatus) Modulates Hepatic Lipid Metabolism and Inflammation in a Rat Model of High-Fat, High-Fructose-Induced Metabolic Dysfunction. Antioxidants (Basel) 2025; 14:319. [PMID: 40227294 PMCID: PMC11939235 DOI: 10.3390/antiox14030319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Revised: 02/28/2025] [Accepted: 03/04/2025] [Indexed: 04/15/2025] Open
Abstract
Metabolic dysfunction and hepatic abnormalities, such as those associated with high-fat, high-fructose (HFHFr) diets, are major contributors to obesity-related health issues. The growing interest in sustainable dietary interventions has highlighted the potential of plant-based byproducts. Dragon fruit (Hylocereus undatus) peel waste, rich in bioactive compounds such as dietary fibers, phenolics, and betacyanins, represents a promising functional ingredient for managing these disorders. This study investigated the effects of dragon fruit peel powder (DFP) on metabolic dysfunction and hepatic abnormalities induced by a HFHFr diet in rats. Over 12 weeks, the rats were fed a standard AIN-93M diet (control or C), C with 5% (w/w) DFP (C + DFP), a HFHFr diet, or a HFHFr diet with 5% (w/w) DFP (HFHFr + DFP). DFP supplementation significantly reduced HFHFr-induced body weight gain, visceral adiposity, insulin resistance, and dyslipidemia while also lowering systolic blood pressure and systemic oxidative stress markers. In the liver, DFP supplementation attenuated fat accumulation and lipid peroxidation, reduced glycogen storage abnormalities, and modulated the expression of lipid metabolism and inflammatory genes. These findings suggest that DFP may serve as a functional dietary supplement for preventing and managing metabolic disorders and liver abnormalities associated with excessive fat and fructose consumption.
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Affiliation(s)
- Siriwan Chumroenvidhayakul
- Center of Excellence in Phytochemical and Functional Food for Clinical Nutrition, Department of Nutrition and Dietetics, Faculty of Allied Health Science, Chulalongkorn University, Bangkok 10330, Thailand;
- School of Food Industry, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand
| | - Thavaree Thilavech
- Department of Food Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand
| | | | - Michael Conlon
- CSIRO Health & Biosecurity, Kintore Avenue, Adelaide, SA 5000, Australia
| | - Julie Dallimore
- CSIRO Health & Biosecurity, Kintore Avenue, Adelaide, SA 5000, Australia
| | - Michael Adams
- CSIRO Health & Biosecurity, Kintore Avenue, Adelaide, SA 5000, Australia
| | | | - Sirichai Adisakwattana
- Center of Excellence in Phytochemical and Functional Food for Clinical Nutrition, Department of Nutrition and Dietetics, Faculty of Allied Health Science, Chulalongkorn University, Bangkok 10330, Thailand;
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Li X, Ding X, He Y, Yi W, Zhu Y, Han W, Liao B, Han X, Bai D. Ultrasound Tissue Engineering Technology for Regulating Immune Microenvironment. ADVANCED FUNCTIONAL MATERIALS 2024; 34. [DOI: 10.1002/adfm.202400656] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Indexed: 01/06/2025]
Abstract
AbstractThe immune microenvironment is critical for the occurrence, progression, and treatment of diseases. Ultrasound tissue engineering technology utilizes ultrasound and the principles of tissue engineering to repair, regenerate, and functionally reconstruct biological tissues. Ultrasound therapy is a non‐invasive treatment modality that regulates the immune microenvironment and maintains homeostasis through various characteristic effects. Ultrasound‐responsive biomaterials utilize biological properties or drug/gene delivery to regulate the immune microenvironment under ultrasound stimulation for targeted and purposeful treatment. This article comprehensively and systematically reviews advancements in ultrasound tissue engineering technology for regulating the immune microenvironment. First, the changes in the immune microenvironment at different stages of the disease is briefly illustrated. It is then reviewed the regulation of the immune microenvironment by ultrasound and ultrasound‐responsive biomaterials in five types of diseases: tumor, cardiovascular system diseases, nervous system diseases, musculoskeletal diseases, and wound. Finally, the prospects of the ultrasound tissue engineering technology for regulating the immune microenvironment is summarized.
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Affiliation(s)
- Xinhe Li
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
| | - Xiaoqian Ding
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
| | - Yi He
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
| | - Weiwei Yi
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
| | - Ying Zhu
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
| | - Wang Han
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
| | - Bo Liao
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
| | - Xiaoyu Han
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
| | - Dingqun Bai
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China
- State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University Chongqing 400016 P. R. China
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Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression. Int J Mol Sci 2022; 23:ijms232415856. [PMID: 36555498 PMCID: PMC9781739 DOI: 10.3390/ijms232415856] [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: 11/15/2022] [Revised: 12/11/2022] [Accepted: 12/12/2022] [Indexed: 12/15/2022] Open
Abstract
The current investigation assessed the effect of the eudesmanolid, Vulgarin (VGN), obtained from Artemisia judaica (A. judaica), on the antidiabetic potential of glibenclamide (GLB) using streptozotocin (STZ) to induce diabetes. Seven groups of rats were used in the study; the first group received the vehicle and served as normal control. The diabetic rats of the second to the fifth groups were treated with the vehicle (negative control), GLB at 5 mg/kg (positive control), VGN at 10 mg/kg (VGN-10) and VGN at 20 mg/kg (VGN-20), respectively. The diabetic rats of the sixth and seventh groups were administered combinations of GLB plus VGN-10 and GLB plus VGN-20, respectively. The diabetic rats treated with GLB plus VGN-20 combination showed marked improvement in the fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c), as well as the lipid profile, compared with those treated with GLB alone. Further, the pancreatic tissues of the diabetic rats that received the GLB+VGN-20 combination showed superior improvements in lipid peroxidation and antioxidant parameters than those of GLB monotherapy. The insulin content of the β-cells was restored in all treatments, while the levels of glucagon and somatostatin of the α- and δ-endocrine cells were reduced in the pancreatic islets. In addition, the concurrent administration of GLB+VGN-20 was the most effective in restoring PEPCK and G6Pase mRNA expression in the liver. In conclusion, the results demonstrated that the GLB+VGN-20 combination led to greater glycemic improvement in diabetic rats compared with GLB monotherapy through its antioxidant effect and capability to modulate PEPCK and G6Pase gene expression in their livers.
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Anticancer Activities of Biogenic Silver Nanoparticles Targeting Apoptosis and Inflammatory Pathways in Colon Cancer Cells. J CLUST SCI 2021. [DOI: 10.1007/s10876-021-02143-z] [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]
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Jafari F, Ramezani M, Nomani H, Amiri MS, Moghadam AT, Sahebkar A, Emami SA, Mohammadpour AH. Therapeutic Effect, Chemical Composition, Ethnobotanical Profile of Eucalyptus globulus: A Review. LETT ORG CHEM 2021. [DOI: 10.2174/1570178617999200807213043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The composition of essential oil (EO) of E. globulus is so different all over the world. The
main component of essential oil is 1,8-cineole (Compound 64), macrocarpal C (Compound 22), terpenes
(Compound 23-92), oleanolic acid (Compound 21), and tannins (Compound 93-99). We
searched in vitro and in vivo articles and reviewed botanical aspects, therapeutic activity, chemical
composition and mechanism of action of E. globulus. Essential oils and extracts of leaves, stump,
wood, root and fruits of E. globulus represented many various medicinal effects including antibacterial,
antifungal, antidiabetic, anticancer, anthelmintic, antiviral, antioxidant, anti-inflammatory, protection
against UV-B, wound healing effect and stimulating the immune response. Also, the leaf extract of eucalyptus
is used as a food additive in the industry. Eucalyptus has so many different therapeutic effects
and some of these effects were confirmed by pharmacological and clinical studies. More clinical studies
are recommended to confirm the useful pharmacological activity of E. globulus.
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Affiliation(s)
- Fatemeh Jafari
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad,Iran
| | - Mahin Ramezani
- Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad,Iran
| | - Homa Nomani
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad,Iran
| | | | | | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad,Iran
| | - Seyed Ahmad Emami
- Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad,Iran
| | - Amir Hooshang Mohammadpour
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad,Iran
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Balta V, Đikić D, Crnić I, Odeh D, Orsolic N, Kmetič I, Murati T, Dragović Uzelac V, Landeka Jurčević I. Effects of Four-Week Intake of Blackthorn Flower Extract on Mice Tissue Antioxidant Status and Phenolic Content. POL J FOOD NUTR SCI 2020. [DOI: 10.31883/pjfns/128132] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
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Mousa AA, Elweza AE, Elbaz HT, Tahoun EAEA, Shoghy KM, Elsayed I, Hassan EB. Eucalyptus Globulus protects against diclofenac sodium induced hepatorenal and testicular toxicity in male rats. J Tradit Complement Med 2020; 10:521-528. [PMID: 33134128 PMCID: PMC7588335 DOI: 10.1016/j.jtcme.2019.11.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 10/01/2019] [Accepted: 11/23/2019] [Indexed: 12/11/2022] Open
Abstract
The current study was conducted to investigate the protective properties of Eucalyptus globulus leaves methanolic extract (EGLME) against diclofenac sodium (DS) induced hepatorenal and testicular toxicity in male rats. A total of 40 rats were equally divided into 4 groups, Control, Diclofenac sodium (DS), EGLME and DS + EGLME groups, respectively. DS and EGLME were administered orally at dose rate 2.5 and 100 mg/kg BW, 4 times/week for 8 weeks, respectively. Administration of DS distorted hepatorenal functions manifested by alteration of serum levels of ALT, AST, total protein and albumin, creatinine and urea with changes of histological architectures. DS caused reproductive toxicity represented by minimized sperm count, individual sperm motility and viability; depleted concentration of reduced glutathione (GSH) in testicular tissue; and decreased testosterone level with alteration in testicular histological features. In contrast, co-treatment of DS intoxicated rats with EGLME protected rats against the adverse effects of DS revealing enhancing properties of EGLME on rats' liver, kidney and testes. In conclusion, we demonstrated that EGLME had a potent protecting property against DS induced hepatic, renal and testicular toxicity in male rats, with special concern to testicular tissue via modulation of GSH as an oxidant marker. TAXONOMY (classification by EVISE): Diclofenac sodium toxicity (hepatorenal and testicular toxicity), co-treatment with natural herbal extract, blood biochemical assays, tissue anti-oxidants assay, histopathology and reproductive indices analyses.
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Affiliation(s)
- Ahmed Abdelmoniem Mousa
- Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, 32897, Menoufia, Egypt
| | - Ahmed Essam Elweza
- Department of Theriogenology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, 32897, Menoufia, Egypt
| | - Hamed Talaat Elbaz
- Department of Theriogenology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, 32897, Menoufia, Egypt
| | - Enas Abd El-aziz Tahoun
- Department of Pathology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, 32897, Menoufia, Egypt
| | - Khaled Mohamed Shoghy
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, University of Sadat City, Sadat, City, 32897, Menoufia, Egypt
| | - Islam Elsayed
- Department of Sustainable Bioproducts, Mississippi State University, Box 9820, Mississippi State, MS, 39762, United States
| | - El Barbary Hassan
- Department of Sustainable Bioproducts, Mississippi State University, Box 9820, Mississippi State, MS, 39762, United States
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9
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Tahara A, Takasu T. SGLT2 inhibitor ipragliflozin alone and combined with pioglitazone prevents progression of nonalcoholic steatohepatitis in a type 2 diabetes rodent model. Physiol Rep 2020; 7:e14286. [PMID: 31782258 PMCID: PMC6883099 DOI: 10.14814/phy2.14286] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic steatohepatitis (NASH) has become the most common cause of chronic liver disease worldwide in recent years. The pathogenesis of NASH is closely linked to metabolic diseases such as insulin resistance, obesity, dyslipidemia, and type 2 diabetes. However, there is currently no pharmacological agent for preventing the progression of NASH. Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion by inhibiting renal glucose reabsorption, and improve various pathological conditions of type 2 diabetes, including insulin resistance. In the present study, we examined the effects of ipragliflozin, a SGLT2-selective inhibitor, alone and in combination with pioglitazone on NASH in high-fat diet-fed KK/Ay type 2 diabetic mice. Type 2 diabetic mice with NASH exhibited steatosis, inflammation, and fibrosis in the liver as well as hyperglycemia, insulin resistance, and obesity, features that are observed in human NASH. Four-week repeated administration of ipragliflozin (0.1-3 mg/kg) led to significant improvements in hyperglycemia, insulin resistance, and obesity in addition to hyperlipidemia and liver injury including hepatic steatosis and fibrosis. Moreover, ipragliflozin reduced inflammation and oxidative stress in the liver. Repeated administration of pioglitazone (3-30 mg/kg) also significantly improved various parameters of diabetes and NASH, excluding obesity. Furthermore, combined treatment comprising ipragliflozin (1 mg/kg) and pioglitazone (10 mg/kg) additively improved these parameters. These findings indicate that the SGLT2-selective inhibitor ipragliflozin improves hyperglycemia as well as NASH in type 2 diabetic mice. Therefore, treatment with ipragliflozin monotherapy or coadministered with pioglitazone is expected to be a potential therapeutic option for the treatment of type 2 diabetes with NASH.
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Affiliation(s)
- Atsuo Tahara
- Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan
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Kondo M, Tahara A, Hayashi K, Inami H, Ishikawa T, Tomura Y. Therapeutic effects of interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 on diabetic nephropathy in type 2 diabetic mice. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2020; 393:1197-1209. [PMID: 31974740 DOI: 10.1007/s00210-020-01816-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 01/08/2020] [Indexed: 02/06/2023]
Abstract
Renal inflammation is a final common pathway of chronic kidney disease including diabetic nephropathy, which is the leading cause of end-stage renal disease and is associated with high cardiovascular risk and significant morbidity and mortality. Interleukin-1 (IL-1) receptor-associated kinase 4 (IRAK-4) is a pivotal molecule for IL-1 receptor- and Toll-like receptor-induced activation of proinflammatory mediators. In this study, we investigated the renoprotective properties of IRAK-4 inhibitor AS2444697 in KK/Ay type 2 diabetic mice. Four-week repeated administration of AS2444697 dose-dependently and significantly improved albuminuria; hyperfiltration, as measured by creatinine clearance; renal injury, including glomerulosclerosis; tubular injury markers, including urinary N-acetyl-β-D-glucosaminidase activity; and glomerular podocyte injury markers, including urinary nephrin excretion. In addition, AS2444697 attenuated plasma levels of proinflammatory cytokines, including IL-6; plasma levels of endothelial dysfunction markers, including intercellular adhesion molecule-1; and plasma levels and renal contents of oxidative stress markers. In contrast, AS2444697 did not significantly affect food intake or blood glucose levels. These results suggest that AS2444697 attenuates the progression of diabetic nephropathy mainly via anti-inflammatory mechanisms through inhibition of IRAK-4 activity under diabetic conditions and may represent a promising therapeutic option for the treatment of type 2 diabetic nephropathy.
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Affiliation(s)
- Mitsuhiro Kondo
- Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan
| | - Atsuo Tahara
- Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan.
| | - Kazumi Hayashi
- Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan
| | - Hiroshi Inami
- Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan
| | - Takeshi Ishikawa
- Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan
| | - Yuichi Tomura
- Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan
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11
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Influence of Corymbia citriodora leaf extract on growth performance, ruminal fermentation, nutrient digestibility, plasma antioxidant activity and faecal bacteria in young calves. Anim Feed Sci Technol 2020. [DOI: 10.1016/j.anifeedsci.2020.114394] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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12
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Abstract
Background and aim: Sodium-glucose cotransporter (SGLT) 2 is responsible for most of the glucose reabsorption in the kidneys and has been proposed as a novel therapeutic target for the treatment of type 2 diabetes. In recent years, nonalcoholic steatohepatitis (NASH), the pathogenesis of which is strongly associated with insulin resistance, obesity, and type 2 diabetes, has become a considerable healthcare burden worldwide. However, there is currently no established pharmacotherapy for NASH. Here, we investigated the therapeutic effects of the SGLT2 selective inhibitor ipragliflozin alone and in combination with metformin on NASH in high fat and cholesterol diet-fed KK/Ay type 2 diabetic mice.Results: This diabetic model had hyperglycemia, insulin resistance, and obesity, and also exhibited steatosis, inflammation, and fibrosis in the liver, pathological features resembling those in human NASH. Four-week repeated administration of ipragliflozin significantly improved not only hyperglycemia, insulin resistance, and obesity but also hyperlipidemia and NASH-associated symptoms including hepatic steatosis and fibrosis. In addition, ipragliflozin attenuated inflammation and oxidative stress in the liver. Repeated administration of metformin also significantly improved symptoms of type 2 diabetes with NASH to a comparable degree to that by ipragliflozin. In addition, combination treatment with ipragliflozin and metformin additively improved these symptoms.Conclusions: These results demonstrate that the SGLT2 selective inhibitor ipragliflozin improves not only hyperglycemia but also NASH in type 2 diabetic mice, suggesting that treatment with ipragliflozin alone and in combination with metformin may be effective for treating type 2 diabetes with NASH.
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Affiliation(s)
- Atsuo Tahara
- Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan
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Abdel-Kader MS, Soliman GA, Abdel-Rahman RF, Saeedan AS, Abd-Elsalam RM, Ogaly HA. Effect of olive leaves extract on the antidiabetic effect of glyburide for possible herb-drug interaction. Saudi Pharm J 2019; 27:1182-1195. [PMID: 31885478 PMCID: PMC6921200 DOI: 10.1016/j.jsps.2019.10.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 10/02/2019] [Indexed: 02/02/2023] Open
Abstract
The concomitant use of olive leaves (OL) and glyburide (GLB) is a possible therapy for diabetic patients. However, there is no report about the effect of OL on the antidiabetic effect of GLB till now. In the current study, the possible interaction of olive leaves extract (OLE) with GLB was assessed to determine if there was any pharmacological benefit over GLB alone. Seven groups of male Sprague Dawley rats were used. Normal rats of the 1st group treated with 2 mL/kg of 3% Tween 80 (vehicle). The 2nd–5th groups were diabetic rats received vehicle, GLB (5 mg/kg), OLE low dose and OLE high dose respectively, while the 6th–7th groups administered combinations of GLB plus OLE low dose and GLB plus OLE high dose, respectively. All treatments were administered orally once daily for 8 weeks. The use of GLB+OLE-500 obviously improved fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c) in diabetic rats (95.5 ± 5.55 mg/dL, 6.8 ± 0.16 mg/dL and 6.1 ± 0.29%, respectively) compared to those treated with GLB monotherapy (140.0 ± 6.36 mg/dL, 5.4 ± 0.19 mg/dL and 7.0 ± 0.20%, respectively). The lipid profile [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] was significantly improved in diabetic rats exposed to GLB+OLE-500 (35.6 ± 1.51 mg/dL, 48.5 ± 2.74 mg/dL, 25.1 ± 1.21 mg/dL and 17.0 ± 0.82 mg/dL, respectively) in comparison with diabetic group exposed to GLB alone (43.2 ± 2.15 mg/dL, 56.8 ± 2.14 mg/dL, 18.6 ± 0.96 mg/dL, 23.0 ± 1.26 mg/dL, respectively). Additionally, the benefit impacts of GLB+OLE-500GLB+OLE-500 therapy on the antioxidant and lipid peroxidation parameters in the pancreatic tissues of diabetic rats were higher than those of GLB monotherapy. Moreover, GLB plus OLE-500 combination had the greatest effect on restoration of the insulin content of Beta (β) cells and reduction of the glucagon and somatostatin of Alpha (α) and Delta (δ) endocrine cells in the pancreatic islets among the different treatment. The current study suggests that OL and GLB combination could cause herb-drug interactions through modulation of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes expression in the liver of diabetic rats.
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Affiliation(s)
- Maged S Abdel-Kader
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia.,Department of Pharmacognosy, College of Pharmacy, Alexandria University, Alexandria 21215, Egypt
| | - Gamal A Soliman
- Department of Pharmacology, College of Pharmacy, Prince Sattam bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia.,Department of Pharmacology, College of Veterinary Medicine, Cairo University, Giza, Egypt
| | | | - Abdulaziz S Saeedan
- Department of Pharmacology, College of Pharmacy, Prince Sattam bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia
| | - Reham M Abd-Elsalam
- Department of Pathology, College of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Hanan A Ogaly
- Department of Chemistry, College of Science, King Khalid University, Abha, Saudi Arabia.,Department of Biochemistry, College of Veterinary Medicine, Cairo University, Giza, Egypt
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Ghareeb MA, Sobeh M, El-Maadawy WH, Mohammed HS, Khalil H, Botros S, Wink M. Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato-Renal Protective Potential Against Cyclophosphamide Induced Toxicity in Mice. Antioxidants (Basel) 2019; 8:E415. [PMID: 31546777 PMCID: PMC6769961 DOI: 10.3390/antiox8090415] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 08/17/2019] [Accepted: 08/19/2019] [Indexed: 12/23/2022] Open
Abstract
Cyclophosphamide (CP) is a potent anti-neoplastic and immunosuppressive agent; however, it causes multi-organ toxicity. We elucidated the protective activities of Eucalyptus globulus (EG) leaf extract against CP-induced hepato-renal toxicity. Mice were treated with EG for 15 days plus CP on day 12 and 13 of the experiment. Using HPLC-DAD-ESI-MS/MS, 26 secondary metabolites were identified in EG leaf extract. Out of them, 4 polyphenolic compounds were isolated: (1) 4-(O-β-d-xylopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (2) 4-(O-α-l-rhamnopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (3) gallic acid, and (4) methyl gallate. Effects of EG extract on biochemical parameters, gene expression, and immune-histopathological changes were assessed in comparison to mesna positive control. Results showed that EG improved CP-increased serum ALT, AST, creatinine, and blood urea nitrogen levels. The hepatic and renal tissue levels of MDA, nitric oxide, protein carbonyl, TNF-α, IL-6, and immunohistochemical expression of nuclear factor kappa-B (NF-kB) and caspase-3 were reduced. Also, hepatic and renal GSH contents, and nuclear factor E2-related factor 2 (NRf2)/ hemoxygenase-1 (HO-1) signaling levels were increased. Histopathological findings supported our findings where hepatic and renal architecture were almost restored. Results revealed the protective effects of EG against CP-induced hepato-renal toxicity. These effects may be related to EG antioxidant, anti-inflammatory, and anti-apoptotic properties coupled with activation of Nrf2/HO-1 signaling.
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Affiliation(s)
- Mosad A Ghareeb
- Medicinal Chemistry Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt.
| | - Mansour Sobeh
- Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 44883-2462 Heidelberg, Germany.
- AgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660-Hay MoulayRachid, 43150 Ben-Guerir, Morocco.
| | - Walaa H El-Maadawy
- Pharmacology Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt.
| | - Hala Sh Mohammed
- Department of Pharmacognosy, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11311, Egypt.
| | - Heba Khalil
- Pathology Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt.
| | - Sanaa Botros
- Pharmacology Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt.
| | - Michael Wink
- Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 44883-2462 Heidelberg, Germany.
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15
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Abdel-Rahman RF, Soliman GA, Saeedan AS, Ogaly HA, Abd-Elsalam RM, Alqasoumi SI, Abdel-Kader MS. Molecular and biochemical monitoring of the possible herb-drug interaction between Momordica charantia extract and glibenclamide in diabetic rats. Saudi Pharm J 2019; 27:803-816. [PMID: 31516323 PMCID: PMC6733788 DOI: 10.1016/j.jsps.2019.05.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 05/13/2019] [Indexed: 12/14/2022] Open
Abstract
Momordica charantia is used in folk medicine to manage diabetes mellitus. In this study, we investigated the possible herb-drug interaction between M. charantia fruit extract (MCFE) and glibenclamide (GLB) in streptozotocin-diabetic rats. Rats were divided into 7 groups. The 1st group received 3% Tween 80. The 2nd–5th groups were diabetic rats received vehicle, GLB (5 mg/kg), MCFE (250 and 500 mg/kg), respectively. The 6th–7th groups administered GLB plus MCFE (250 and 500 mg/kg), respectively. After 8 weeks, fasting blood glucose (FBG), insulin and glycosylated hemoglobin (HbA1c) levels were assessed. Histopathological and immunohistochemical examinations of the pancreases were done. Quantitative RT-PCR was used to analyze hepatic mRNA expression of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes. All medicaments greatly reduced FBG in diabetic rats when compared with diabetic control group. GLB plus MCFE combination was better than GLB alone in improving levels of insulin and HbA1c. All medicaments restored insulin content of pancreatic β-cells and reduced glucagon and somatostatin of alpha and delta endocrine cells. Moreover, GLB plus MCFE-500 was the most efficient in restoring INR, Slc2a2 and PPAR-α mRNA expression to their normal levels. In conclusion, MCFE in combination with GLB gives greater glycemic improvement than GLB monotherapy.
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Affiliation(s)
| | - Gamal A Soliman
- Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.,Department of Pharmacology, College of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Abdulaziz S Saeedan
- Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Hanan A Ogaly
- Department of Chemistry, College of Science, King Khalid University, Abha, Saudi Arabia.,Department of Biochemistry, College of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Reham M Abd-Elsalam
- Department of Pathology, College of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Saleh I Alqasoumi
- Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Maged S Abdel-Kader
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.,Department of Pharmacognosy, College of Pharmacy, Alexandria University, Alexandria 21215, Egypt
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16
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Maqbool F, Bahadar H, Hassani S, Niaz K, Baeeri M, Rahimifard M, Ghasemi-Niri SF, Abdollahi M. Biochemical evidence on the potential role of methyl mercury in hepatic glucose metabolism through inflammatory signaling and free radical pathways. J Cell Biochem 2019; 120:16195-16205. [PMID: 31081130 DOI: 10.1002/jcb.28899] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Revised: 03/12/2019] [Accepted: 03/22/2019] [Indexed: 12/18/2022]
Abstract
Methylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6-phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators' cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8-deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals.
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Affiliation(s)
- Faheem Maqbool
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Haji Bahadar
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
| | - Shokoufeh Hassani
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Kamal Niaz
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Baeeri
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahban Rahimifard
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Farnaz Ghasemi-Niri
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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17
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Baeeri M, Bahadar H, Rahimifard M, Navaei-Nigjeh M, Khorasani R, Rezvanfar MA, Gholami M, Abdollahi M. α-Lipoic acid prevents senescence, cell cycle arrest, and inflammatory cues in fibroblasts by inhibiting oxidative stress. Pharmacol Res 2019; 141:214-223. [PMID: 30611855 DOI: 10.1016/j.phrs.2019.01.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 12/31/2018] [Accepted: 01/02/2019] [Indexed: 01/24/2023]
Abstract
Senescence is a process characterized by an irreversible growth arrest in cells and induced by oxidative stress. In the current study, anti-aging potential of a well-known antioxidant, α-lipoic acid (α-LA), in rat embryonic fibroblast (REF) cells was assessed. In this regard, oxidative stress, inflammation, and apoptosis pathways were investigated on REF cells exposed to H2O2 as a senescence inducer and α-LA as a protective compound. In cells treated with α-LA and H2O2, level of β-galactosidase, as an aging marker, and oxidative stress biomarkers, were significantly lower than those exposed to H2O2 only. Furthermore, flow cytometry assay showed that α-LA caused a significant reduction in the number of apoptotic cells via the caspase-dependent pathway. In addition, it could neutralize the inflammatory effects of H2O2 and attenuated the concentration of inflammatory cytokines. In comparison to H2O2 group, a significant increase in G0/G1 arrest was observed during cell cycle analysis in cells exposed to H2O2 and α-LA. The results of this study show that α-LA has beneficial effects on H2O2-induced cellular senescence. α-LA works by attenuating the reactive oxygen species, subsiding inflammation, and affecting cell division.
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Affiliation(s)
- Maryam Baeeri
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Haji Bahadar
- Institute of Paramedical Sciences, Khyber Medical University, Peshawar, Pakistan
| | - Mahban Rahimifard
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Mona Navaei-Nigjeh
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Khorasani
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Amin Rezvanfar
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdi Gholami
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
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18
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Biochemical Effects of Oleuropein in Streptozotocin Induced Diabetic Male Rat. MACEDONIAN VETERINARY REVIEW 2018. [DOI: 10.2478/macvetrev-2018-0021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Abstract
Diabetes is a chronic disease characterized by a disorder in the metabolism of proteins, fats, and carbohydrates. The liver as a non-insulin dependent organ plays an important role in the regulation of blood fat and glucose. Most blood glucose lowering drugs that are introduced for treatment have side effects in long-term consumption. Therefore, to control diabetes and its complications, the use of herbal drugs is widely considered nowadays. The present study investigates the biochemical effects of oleuropein in diabetic male rats. In this study, 30 adult male Wistar rats with a weight range of 190±30 gr were equally divided into 3 groups randomly: 1) control group or intact animals, 2) diabetic animals, and 3) treatment group, which received 60 mg/kg oleuropein for 30 days by gastric gavage. Diabetes was induced in diabetic and treatment groups by injection of streptozotocin (60 mg/kg) intraperitoneally. At the end of the treatment, the levels of triglyceride, cholesterol, LDL, HDL, VLDL, blood glucose, HbA1C, and activity of AST and ALT were determined. The results showed that the serum lipid profile and blood glucose increased significantly in the diabetic group compared with the control group (p<0.05). Also, HbA1C and atherogenic index decreased significantly in the treatment group compared with the diabetic group (p<0.05). This study showed that oral administration of oleuropein has hypoglycemic effects, which can reduce the serum levels of the lipids profile and the atherogenic index in streptozotocin-induced diabetic male rats.
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González-Burgos E, Liaudanskas M, Viškelis J, Žvikas V, Janulis V, Gómez-Serranillos MP. Antioxidant activity, neuroprotective properties and bioactive constituents analysis of varying polarity extracts from Eucalyptus globulus leaves. J Food Drug Anal 2018; 26:1293-1302. [PMID: 30249328 PMCID: PMC9298563 DOI: 10.1016/j.jfda.2018.05.010] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 05/11/2018] [Accepted: 05/22/2018] [Indexed: 11/20/2022] Open
Abstract
Eucalyptus globulus is employed as herbal tea and therapeutical purposes. In this work, it is investigated for first time the neuroprotective activities, based on antioxidant properties, of varying polarity extracts (acetone, ethanol and methanol) from E. globulus leaves and elucidate their main bioactive constituents. Methanol and acetone extracts contained the highest phenolic compounds amount and chlorogenic acid was the major compound identified by UPLC-ESI-MS/MS. Moreover, the three tested extracts showed significant antioxidant properties, varying their potency depending on the in vitro technique used. Furthermore, E. globulus extracts were effective in ameliorating H2O2-induced oxidative stress by increasing cell viability, GSH levels and antioxidant enzymes activity and, by decreasing ROS production and lipid peroxidation levels in SH-SY5Y cells. Taken together, E. globulus leaves extracts could be used as raw material for food and pharmaceutical supplements for their high content in antioxidant compounds with health benefits properties against oxidative stress.
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Affiliation(s)
- Elena González-Burgos
- Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, University Complutense Madrid, Madrid,
Spain
- Corresponding author. E-mail address: (E. González-Burgos)
| | - Mindaugas Liaudanskas
- Institute of Pharmaceutical Technologies of the Faculty of Pharmacy of Lithuanian University of Health Sciences, Kaunas,
Lithuania
- Institute of Horticulture, Lithuanian Research Centre for Agriculture and Forestry, Kaunas,
Lithuania
| | - Jonas Viškelis
- Institute of Horticulture, Lithuanian Research Centre for Agriculture and Forestry, Kaunas,
Lithuania
| | - Vaidotas Žvikas
- Department of Pharmacognosy, Faculty of Pharmacy, Lithuanian University of Health Sciences, Kaunas,
Lithuania
| | - Valdimaras Janulis
- Department of Pharmacognosy, Faculty of Pharmacy, Lithuanian University of Health Sciences, Kaunas,
Lithuania
| | - M. Pilar Gómez-Serranillos
- Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, University Complutense Madrid, Madrid,
Spain
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20
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Sarkar P, Bhowmick A, Banu S. Comparative analysis of different dietary antioxidants on oxidative stress pathway genes in L6 myotubes under oxidative stress. Cytotechnology 2018. [PMID: 29541961 DOI: 10.1007/s10616-018-0209-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Enhanced oxidative stress plays an important role in the progression and onset of diabetes and its complications. Strategies or efforts meant to reduce the oxidative stress are needed which may mitigate these pathogenic processes. The present study aims to investigate the in vitro ameliorative potential of nine antioxidant molecules in L6 myotubes under oxidative stress condition induced by 4-hydroxy-2-nonenal and also to comprehend the gene expression patterns of oxidative stress genes upon the supplementation of different antioxidants in induced stress condition. The study results demonstrated a marked increase in the level of malondialdehyde and protein carbonyl content with a subsequent increase in the free radicals that was reversed by the pretreatment of different dietary antioxidant. From the expression analysis of the oxidative stress genes, it is evident that the expression of these genes is modulated by the presence of antioxidants. The highest expression was found in the cells treated with Insulin in conjugation with an antioxidant. Resveratrol is the most potent modulator followed by Mangiferin, Estragole, and Capsaicin. This comparative analysis ascertains the potency of Resveratrol along with Insulin in scavenging the reactive oxygen species (ROS) generated under induced stress conditions through antioxidant defense mechanism against excessive ROS production, contributing to the prevention of oxidative damage in L6 myotubes.
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Affiliation(s)
- Purabi Sarkar
- Department of Bioengineering and Technology, GUIST, Gauhati University, Guwahati, Assam, 781014, India
| | - Ananya Bhowmick
- Department of Bioengineering and Technology, GUIST, Gauhati University, Guwahati, Assam, 781014, India
| | - Sofia Banu
- Department of Bioengineering and Technology, GUIST, Gauhati University, Guwahati, Assam, 781014, India.
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21
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Sakina MY, Ahmed IY. Traditional medicinal plants used for the treatment of diabetes in the Sudan: A review. ACTA ACUST UNITED AC 2018. [DOI: 10.5897/ajpp2017.4878] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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22
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Antioxidant and Synergistic Antidiabetic Activities of a Three-Plant Preparation Used in Cameroon Folk Medicine. INTERNATIONAL SCHOLARLY RESEARCH NOTICES 2017; 2017:9501675. [PMID: 28529969 PMCID: PMC5424193 DOI: 10.1155/2017/9501675] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Revised: 02/17/2017] [Accepted: 03/02/2017] [Indexed: 01/24/2023]
Abstract
Introduction. Several plant preparations like a mixture of aqueous extracts of Spilanthes africana; Portulaca oleracea; and Sida rhombifolia are currently utilized in Foumban (West Cameroon) to manage diabetes. The aim of this study is to investigate the antidiabetic property of the aqueous mixture of three plant extracts (1 : 1 : 1) on streptozotocin induced diabetes rats. Methods. Diabetes was induced to rats by intraperitoneal (i.p.) injection of streptozotocin (STZ) at a dose of 50 mg/kg b.w. The diabetic rats received different dosages of the mixture of extracts for 21 days and glibenclamide 6.5 mg/kg b.w. as positive control. Results. The results showed that the mixture of extracts significantly (p < 0.05) decreased the level of the glycaemia, the total cholesterol, triglyceride, and LDL-cholesterol as well as MDA, AST, ALT, and creatinine levels. It also increased significantly the concentration of HDL-cholesterol, glutathione, and TAOS. A great reduction of the atherogenic indexes CT/HDL and LDL/HDL of the treated groups was observed. Each extract and the mixture demonstrated significant scavenging property on DPPH and OH radicals and present a good antioxidant property. Conclusion. The mixture of plant extracts has hypoglycemic, antioxidant, and hypolipidemic properties and can be used for the management of diabetes mellitus.
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The Role of Metformin in Controlling Oxidative Stress in Muscle of Diabetic Rats. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:6978625. [PMID: 27579154 PMCID: PMC4989083 DOI: 10.1155/2016/6978625] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 06/15/2016] [Accepted: 07/04/2016] [Indexed: 12/24/2022]
Abstract
Metformin can act in muscle, inhibiting the complex I of the electron transport chain and decreasing mitochondrial reactive oxygen species. Our hypothesis is that the inhibition of complex I can minimize damage oxidative in muscles of hypoinsulinemic rats. The present study investigated the effects of insulin and/or metformin treatment on oxidative stress levels in the gastrocnemius muscle of diabetic rats. Rats were rendered diabetic (D) with an injection of streptozotocin and were submitted to treatment with insulin (D+I), metformin (D+M), or insulin plus metformin (D+I+M) for 7 days. The body weight, glycemic control, and insulin resistance were evaluated. Then, oxidative stress levels, glutathione antioxidant defense system, and antioxidant status were analyzed in the gastrocnemius muscle of hypoinsulinemic rats. The body weight decreased in D+M compared to ND rats. D+I and D+I+M rats decreased the glycemia and D+I+M rats increased the insulin sensitivity compared to D rats. D+I+M reduced the oxidative stress levels and the activity of catalase and superoxide dismutase in skeletal muscle when compared to D+I rats. In conclusion, our results reveal that dual therapy with metformin and insulin promotes more benefits to oxidative stress control in muscle of hypoinsulinemic rats than insulinotherapy alone.
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24
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Effects of methyl mercury on the activity and gene expression of mouse Langerhans islets and glucose metabolism. Food Chem Toxicol 2016; 93:119-28. [DOI: 10.1016/j.fct.2016.05.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 04/29/2016] [Accepted: 05/06/2016] [Indexed: 01/01/2023]
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25
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Aqueous leaf extract of Passiflora alata Curtis promotes antioxidant and anti-inflammatory effects and consequently preservation of NOD mice beta cells (non-obese diabetic). Int Immunopharmacol 2016; 35:127-136. [DOI: 10.1016/j.intimp.2016.03.031] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 03/22/2016] [Accepted: 03/23/2016] [Indexed: 11/23/2022]
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26
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Rezaei A, Farzadfard A, Amirahmadi A, Alemi M, Khademi M. Diabetes mellitus and its management with medicinal plants: A perspective based on Iranian research. JOURNAL OF ETHNOPHARMACOLOGY 2015; 175:567-616. [PMID: 26283471 DOI: 10.1016/j.jep.2015.08.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 08/10/2015] [Accepted: 08/11/2015] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Complementary and alternative medicine has been increasingly used to treat chronic illnesses, such as diabetes mellitus. However, various limitations in terms of their application and efficacies exist. Furthermore, there is still much to be done to discover the right herbal medicine for diabetes. AIM OF THE STUDY This paper aims to evaluate previous herbal studies on the management of diabetes mellitus, to address their strengths and weaknesses and propose a general framework for future studies. APPROACH AND METHODS Data sources such as PubMed, ScienceDirect, Scopus, SpringerLink, and Wiley were searched, limited to Iran, using 36 search terms such as herbal, traditional, medicine, and phytopharmacy in combination with diabetes and related complications. Reviewed articles were evaluated regarding the use of botanical nomenclature and included information on (1) identity of plants and plant parts used, (2) the processing procedure, and (3) the extraction process. The main outcomes were extracted and then surveyed in terms of the efficacies of herbs in the management of diabetes mellitus. Then a comparative study was performed between Iranian and non-Iranian studies with respect to herbs best studied in Iran. RESULTS Of the 82 herbs studied in Iran, only six herbs were endemic and 19 were studied in detail. Although most of the reviewed herbs were found to decrease the level of blood glucose (BG) and/or glycated hemoglobin (HbA1C) in both Iranian and non-Iranian studies, information on their pharmacological mechanisms is scarce. However, the level of HbA1C was measured in a limited number of clinical trials or animal studies. Available information on both short- and long-term use of studied herbs on diabetes related complications and functions of involved organs as well as comorbid depression and/or simultaneous changes in lifestyle is also insufficient. Furthermore, little or no information on their phytochemical, toxicological, and herb-drug interaction properties is available. It is worth noting that the efficacy of the reviewed herbs has been studied scarcely in both humans and animals regarding both Iranian and non-Iranian studies. A significant number of reviewed articles failed to cite the scientific name of herbs and include information on the processing procedure and the extraction process. CONCLUSIONS Treatment of diabetes mellitus as a multifactorial disease using herbal medicines requires a comprehensive approach. In order to discover the right herbal medicine for the management of diabetes many other important factors than the levels of BG, HbA1C and insulin should be considered. According to our criteria, all the reviewed herbs suffered from inadequate investigation in human, animal and in vitro models in this respect, whereas they are worth investigating further. However, more research on endemic plants and the traditional history of herbal medicine is warranted. In our opinion, the pharmacological, toxicological, and phytochemical information should be obtained before clinical trials. Furthermore, information such as botanical scientific nomenclature, side effects, and toxicity will improve the quality and validity of publications in herbal research. In particular, designing a database covering all valid information about herbs and/or diseases will decrease unnecessary costs and increase the efficiency of research.
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Affiliation(s)
- Arezou Rezaei
- School of Biology, Damghan University, Damghan, Iran; Institute of Biological Sciences, Damghan University, Damghan, Iran.
| | - Azad Farzadfard
- School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Atefe Amirahmadi
- School of Biology, Damghan University, Damghan, Iran; Institute of Biological Sciences, Damghan University, Damghan, Iran
| | - Maasoomeh Alemi
- School of Biology, Damghan University, Damghan, Iran; Institute of Biological Sciences, Damghan University, Damghan, Iran
| | - Mitra Khademi
- Institute for Advanced Studies in Basic Sciences, Zanjan, Iran
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Simon Gonzalez Schumacher N, Colomeu TC, de Figueiredo D, Carvalho VDC, Baú Betim Cazarin C, Prado MA, Molina Meletti LM, de Lima Zollner R. Identification and Antioxidant Activity of the Extracts of Eugenia uniflora Leaves. Characterization of the Anti-Inflammatory Properties of Aqueous Extract on Diabetes Expression in an Experimental Model of Spontaneous Type 1 Diabetes (NOD Mice). Antioxidants (Basel) 2015; 4:662-80. [PMID: 26783951 PMCID: PMC4712943 DOI: 10.3390/antiox4040662] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 09/04/2015] [Accepted: 09/08/2015] [Indexed: 11/16/2022] Open
Abstract
Medical and folklore reports suggest that Eugenia uniflora (E. uniflora) is a functional food that contains numerous compounds in its composition, with anti-inflammatory, antioxidant and anti-diabetic effects. In the present study, we investigated the best solvents (water, ethanol and methanol/acetone) for extracting bioactive compounds of E. uniflora leaves, assessing total phenols and the antioxidant activity of the extracts by 2,2-Diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and Oxygen Radical Absorbance Capacity (ORAC) assays, identifying hydrolysable tannins and three phenolic compounds (ellagic acid, gallic acid and rutin) present in the leaves. In addition, we evaluated the incidence of diabetes, degree of insulitis, serum insulin, hepatic glutathione and tolerance test glucose in non-obese diabetic (NOD) mice. Our results suggest that the aqueous extract presents antioxidant activity and high total phenols, which were used as a type 1 diabetes mellitus (DM-1) treatment in NOD mice. We verified that the chronic consumption of aqueous extract reduces the inflammatory infiltrate index in pancreatic islets, maintaining serum insulin levels and hepatic glutathione, and reducing serum lipid peroxidation as well as the risk for diabetes.
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Affiliation(s)
- Nayara Simon Gonzalez Schumacher
- Laboratory of Translational Immunology, Faculty of Medical Sciences, University of Campinas, Rua Vital Brazil, 300, Cidade Universitária Zeferino Vaz, 13083-888 Campinas-SP, Brazil; E-Mails: (N.S.G.S.); (T.C.C.); (D.F.); (V.C.C.)
| | - Talita Cristina Colomeu
- Laboratory of Translational Immunology, Faculty of Medical Sciences, University of Campinas, Rua Vital Brazil, 300, Cidade Universitária Zeferino Vaz, 13083-888 Campinas-SP, Brazil; E-Mails: (N.S.G.S.); (T.C.C.); (D.F.); (V.C.C.)
| | - Daniella de Figueiredo
- Laboratory of Translational Immunology, Faculty of Medical Sciences, University of Campinas, Rua Vital Brazil, 300, Cidade Universitária Zeferino Vaz, 13083-888 Campinas-SP, Brazil; E-Mails: (N.S.G.S.); (T.C.C.); (D.F.); (V.C.C.)
| | - Virginia de Campos Carvalho
- Laboratory of Translational Immunology, Faculty of Medical Sciences, University of Campinas, Rua Vital Brazil, 300, Cidade Universitária Zeferino Vaz, 13083-888 Campinas-SP, Brazil; E-Mails: (N.S.G.S.); (T.C.C.); (D.F.); (V.C.C.)
| | - Cinthia Baú Betim Cazarin
- Department of Food and Nutrition, School of Food Engineering, University of Campinas (FEA-Unicamp), Rua Monteiro Lobato, 80, Cidade Universitária Zeferino Vaz, 13083-862 Campinas-SP, Brazil; E-Mails: (C.B.B.C.); (M.A.P.)
| | - Marcelo Alexandre Prado
- Department of Food and Nutrition, School of Food Engineering, University of Campinas (FEA-Unicamp), Rua Monteiro Lobato, 80, Cidade Universitária Zeferino Vaz, 13083-862 Campinas-SP, Brazil; E-Mails: (C.B.B.C.); (M.A.P.)
| | - Laura Maria Molina Meletti
- Agronomic Institute of Campinas, Theodureto de Almeida Camargo, 1500, Vila Nova, 13012-970 Campinas-SP, Brazil; E-Mail:
| | - Ricardo de Lima Zollner
- Laboratory of Translational Immunology, Faculty of Medical Sciences, University of Campinas, Rua Vital Brazil, 300, Cidade Universitária Zeferino Vaz, 13083-888 Campinas-SP, Brazil; E-Mails: (N.S.G.S.); (T.C.C.); (D.F.); (V.C.C.)
- Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887 Campinas-SP, Brazil
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +55-19-3289-3709; Fax: +55-19-3521-8925
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Aldahmash BA, El-Nagar DM, Ibrahim KE. Attenuation of hepatotoxicity and oxidative stress in diabetes STZ-induced type 1 by biotin in Swiss albino mice. Saudi J Biol Sci 2015; 23:311-7. [PMID: 26981014 PMCID: PMC4778583 DOI: 10.1016/j.sjbs.2015.09.027] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 09/13/2015] [Accepted: 09/18/2015] [Indexed: 11/19/2022] Open
Abstract
Diabetes mellitus is one of the major health problems. This study was designed to investigate the effect of biotin to regulate blood glucose level, reduced toxicity and oxidative stress in liver of diabetic mice STZ-induced type 1. Male mice were divided into three groups, the first one served as the control group, the second and the third groups received single ip dose of 150 mg/kg of STZ, the second group served as the untreated diabetic group, the third group received daily oral dose of 15 mg/kg of biotin, livers and liver index showed insignificant difference among groups. Blood glucose level showed a significant decrease in treated diabetic mice compared to untreated diabetic mice. Biochemical analysis showed a significant decrease in liver enzymes AST and ALT compared to the control group. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and moderate to severe histopathological score, whereas, treated diabetic mice with biotin showed reduction in hepatotoxicity represented by appearance of relative healthy hepatocytes and normal histopathological score. Immunohistochemistry of acrolein showed intense immunoreactions in liver section of untreated diabetic mice and faint immunoreactions in treated diabetic mice with biotin as evidence to oxidative stress reduction.
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Affiliation(s)
| | - Doaa Mohamed El-Nagar
- Zoology Department, College of Girls for Arts, Science and Education, Ain Shams University, Cairo, Egypt; Faculty of Science and Humanity Studies, Satam University, Hotat Bani Tamim, Saudi Arabia
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Antihyperglycemic Activity of Eucalyptus tereticornis in Insulin-Resistant Cells and a Nutritional Model of Diabetic Mice. Adv Pharmacol Sci 2015; 2015:418673. [PMID: 26366171 PMCID: PMC4558436 DOI: 10.1155/2015/418673] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 07/21/2015] [Indexed: 12/12/2022] Open
Abstract
Eucalyptus tereticornis is a plant used in traditional medicine to control diabetes, but this effect has not been proved scientifically. Here, we demonstrated through in vitro assays that E. tereticornis extracts increase glucose uptake and inhibit their production in insulin-resistant C2C12 and HepG2 cells, respectively. Furthermore, in a nutritional model using diabetic mice, the administration of ethyl acetate extract of E. tereticornis reduced fasting glycaemia, improved tolerance to glucose, and reduced resistance to insulin. Likewise, this extract had anti-inflammatory effects in adipose tissue when compared to control diabetic mice. Via bioguided assays and sequential purification of the crude extract, a triterpenoid-rich fraction from ethyl acetate extracts was shown to be responsible for the biological activity. Similarly, we identified the main compound responsible for the antihyperglycemic activity in this extract. This study shows that triterpenes found in E. tereticornis extracts act as hypoglycemic/antidiabetic compounds and contribute to the understanding of their use in traditional medicine.
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Fluorimetric screening assay for protein carbonyl evaluation in biological samples. Anal Biochem 2015; 482:55-61. [DOI: 10.1016/j.ab.2015.04.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 04/20/2015] [Accepted: 04/22/2015] [Indexed: 11/18/2022]
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Bahadar H, Maqbool F, Mostafalou S, Baeeri M, Gholami M, Ghafour-Boroujerdi E, Abdollahi M. The molecular mechanisms of liver and islets of Langerhans toxicity by benzene and its metabolite hydroquinone in vivo and in vitro. Toxicol Mech Methods 2015; 25:628-36. [PMID: 26056850 DOI: 10.3109/15376516.2015.1053650] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Revised: 04/21/2015] [Accepted: 05/03/2015] [Indexed: 02/06/2023]
Abstract
Benzene (C6H6) is one of the most commonly used industrial chemicals causing environmental pollution. This study aimed to examine the effect of benzene and its metabolite hydroquinone on glucose regulating organs, liver and pancreas, and to reveal the involved toxic mechanisms, in rats. In the in vivo part, benzene was dissolved in corn oil and administered through intragastric route at doses of 200, 400 and 800 mg/kg/day, for 4 weeks. And, in the in vitro part, toxic mechanisms responsible for weakening the antioxidant system in islets of Langerhans by hydroquinone at different concentrations (0.25, 0.5 and 1 mM), were revealed. Benzene exposure raised the activity of phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase) enzymes and increased fasting blood sugar (FBS) in comparison to control animals. Also, the activity of hepatic glucokinase (GK) was decreased significantly. Along with, a significant increase was observed in hepatic tumor necrosis factor (TNF-α) and plasma insulin in benzene treated rats. Moreover, benzene caused a significant rise in hepatic lipid peroxidation, DNA damage and oxidation of proteins. In islets of Langerhans, hydroquinone was found to decrease the capability of antioxidant system to fight free radicals. Also, the level of death proteases (caspase 3 and caspase 9) was found higher in hydroquinone exposed islets. The current study demonstrated that benzene and hydroquinone causes toxic effects on liver and pancreatic islets by causing oxidative impairment.
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Affiliation(s)
- Haji Bahadar
- a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran
| | - Faheem Maqbool
- a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran
| | - Sara Mostafalou
- b School of Pharmacy, Ardabil University of Medical Sciences , Ardabil , Iran , and
| | - Maryam Baeeri
- a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran
| | - Mahdi Gholami
- a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran
| | - Elmira Ghafour-Boroujerdi
- a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran
| | - Mohammad Abdollahi
- a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran
- c Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences , Tehran , Iran
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Dhibi S, Mbarki S, Elfeki A, Hfaiedh N. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat. Bosn J Basic Med Sci 2015; 14:99-104. [PMID: 24856382 DOI: 10.17305/bjbms.2014.2272] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Plants have historically been used in treating many diseases. Eucalyptus globules, a rich source of bioactive compounds, and have been shown to possess antioxidative properties. The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon acetaminophen-induced damages in kidney. Our study is realized in the Department of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were divided into 4 batches: a control group (n=8), a group of rats treated with acetaminophen (900 mg/kg) by intraperitoneal injection during 4 days (n=8), a group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in drinking water during 42 days after 2 hours of acetaminophen administration (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days. After 6 weeks, animals from each group were rapidly sacrificed by decapitation. Blood serum was obtained by centrifugation. Under our experimental conditions, acetaminophen poisoning resulted in an oxidative stress evidenced by statistically significant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in renal tissue of acetaminophen-treated group compared with the control group. Acetaminophen also caused kidney damage as evident by statistically significant (p<0.05) increase in levels of creatinine and urea and decreased levels of uric acid and proteins in blood. Histological analysis demonstrated alteration of proximal tubules, atrophy of the glomerule and dilatation of urinary space. Previous administration of plant extract is found to alleviate this acetaminophen-induced damage.
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Affiliation(s)
- Sabah Dhibi
- Laboratory Animal Eco Physiology, Faculty of Science Sfax, Road Soukra km 3.5 - PB n 1171-3000, Sfax ,Tunisia
| | - Sakhria Mbarki
- Laboratory Animal Eco Physiology, Faculty of Science Sfax, Road Soukra km 3.5 - PB n 1171-3000, Sfax ,Tunisia
| | - Abdelfettah Elfeki
- Laboratory Animal Eco Physiology, Faculty of Science Sfax, Road Soukra km 3.5 - PB n 1171-3000, Sfax ,Tunisia
| | - Najla Hfaiedh
- Laboratory Animal Eco Physiology, Faculty of Science Sfax, Road Soukra km 3.5 - PB n 1171-3000, Sfax ,Tunisia
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Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats. VETERINARY RESEARCH FORUM : AN INTERNATIONAL QUARTERLY JOURNAL 2015; 6:119-24. [PMID: 26261706 PMCID: PMC4522524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Accepted: 06/09/2014] [Indexed: 11/24/2022]
Abstract
Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg(-1) body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes.
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Dey B, Mitra A, Katakam P, Singla RK. Exploration of natural enzyme inhibitors with hypoglycemic potentials amongst Eucalyptus Spp. by in vitro assays. World J Diabetes 2014. [PMID: 24748933 DOI: 10.4239/wjd.v5i2.209] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the presence and potency of natural enzyme inhibitors with hypoglycemic potentials amongst Eucalyptus Spp. by in vitro assays. METHODS The leaf extracts of the three different Eucalyptus species [E. globulus (EG), E. citriodora (EC), E. camaldulensis (ECA)] were subjected to in vitro assay procedures to explore the prevalence of natural enzyme inhibitors (NEIs) after preliminary qualitative and quantitative phytochemical evaluations, to study their inhibitory actions against the enzymes like α-amylase, α-glucosidase, aldose reductase, angiotensin converting enzyme and dipeptidyl peptidase 4 playing pathogenic roles in type 2 diabetes. The antioxidant potential and total antioxidant capacity of the species were also evaluated. RESULTS Major bioactive compounds like polyphenols (341.75 ± 3.63 to 496.85 ± 3.98) and flavonoids (4.89 ± 0.01 to 7.15 ± 0.02) were found in appreciable quantity in three species. Based on the IC50 values of the extracts under investigation, in all assays the effectivity was in the order of EG > ECA > EC. The results of the ferric reducing antioxidant power assay showed that the reducing ability of the species was also in the order of EG > ECA > EC. A strong correlation (R(2) = 0.81-0.99) was found between the phenolic contents and the inhibitory potentials of the extracts against the targeted enzymes. CONCLUSION These results show immense hypoglycemic potentiality of the Eucalyptus Spp. and a remarkable source of NEIs for a future phytotherapeutic approach in Type 2 diabetes.
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Affiliation(s)
- Baishakhi Dey
- Baishakhi Dey, Analava Mitra, School of Medical Science and Technology, IIT Kharaghpur 721302, India
| | - Analava Mitra
- Baishakhi Dey, Analava Mitra, School of Medical Science and Technology, IIT Kharaghpur 721302, India
| | - Prakash Katakam
- Baishakhi Dey, Analava Mitra, School of Medical Science and Technology, IIT Kharaghpur 721302, India
| | - Rajeev K Singla
- Baishakhi Dey, Analava Mitra, School of Medical Science and Technology, IIT Kharaghpur 721302, India
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Dey B, Mitra A, Katakam P, Singla RK. Exploration of natural enzyme inhibitors with hypoglycemic potentials amongst Eucalyptus Spp. by in vitro assays. World J Diabetes 2014; 5:209-18. [PMID: 24748933 PMCID: PMC3990318 DOI: 10.4239/wjd.v5.i2.209] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Revised: 12/27/2013] [Accepted: 01/17/2014] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the presence and potency of natural enzyme inhibitors with hypoglycemic potentials amongst Eucalyptus Spp. by in vitro assays. METHODS The leaf extracts of the three different Eucalyptus species [E. globulus (EG), E. citriodora (EC), E. camaldulensis (ECA)] were subjected to in vitro assay procedures to explore the prevalence of natural enzyme inhibitors (NEIs) after preliminary qualitative and quantitative phytochemical evaluations, to study their inhibitory actions against the enzymes like α-amylase, α-glucosidase, aldose reductase, angiotensin converting enzyme and dipeptidyl peptidase 4 playing pathogenic roles in type 2 diabetes. The antioxidant potential and total antioxidant capacity of the species were also evaluated. RESULTS Major bioactive compounds like polyphenols (341.75 ± 3.63 to 496.85 ± 3.98) and flavonoids (4.89 ± 0.01 to 7.15 ± 0.02) were found in appreciable quantity in three species. Based on the IC50 values of the extracts under investigation, in all assays the effectivity was in the order of EG > ECA > EC. The results of the ferric reducing antioxidant power assay showed that the reducing ability of the species was also in the order of EG > ECA > EC. A strong correlation (R(2) = 0.81-0.99) was found between the phenolic contents and the inhibitory potentials of the extracts against the targeted enzymes. CONCLUSION These results show immense hypoglycemic potentiality of the Eucalyptus Spp. and a remarkable source of NEIs for a future phytotherapeutic approach in Type 2 diabetes.
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Liu CT, Hsu TW, Chen KM, Tan YP, Lii CK, Sheen LY. The Antidiabetic Effect of Garlic Oil is Associated with Ameliorated Oxidative Stress but Not Ameliorated Level of Pro-inflammatory Cytokines in Skeletal Muscle of Streptozotocin-induced Diabetic Rats. J Tradit Complement Med 2014; 2:135-44. [PMID: 24716126 PMCID: PMC3942916 DOI: 10.1016/s2225-4110(16)30087-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress and inflammatory condition has been broadly accepted being associated with the progression of diabetes. On the other hand, garlic (大蒜 dà suàn, bulb of Allium sativum) has been shown to possess both antioxidant and anti-inflammatory action in several clinical conditions. Our previous study demonstrated that treatment with garlic oil improves oral glucose tolerance and insulin tolerance and improves the insulin-stimulated utilization of glucose to synthesize glycogen in skeletal muscle in streptozotocin (STZ)-induced diabetes, in vivo and ex vivo, respectively. The aim of the present study is to investigate the antioxidant and anti-inflammatory effects of garlic oil (GO) in the skeletal muscle of diabetic rats. Rats with STZ-induced diabetes received GO (10, 50, or 100 mg/kg body weight) or corn oil by gavage every other day for 3 weeks. Control rats received corn oil only. GO dose-dependently improved insulin sensitivity, as assessed by the insulin tolerance test, and oral glucose tolerance. GO significantly elevated total glutathione and glutathione peroxidase activity and lowered the nitrate/nitrite content in skeletal muscle at 50 and 100 mg/kg and significantly elevated glutathione reductase activity and lowered lipid peroxidation at 100 mg/kg. By contrast, GO did not reverse diabetes-induced elevation of IL-1β and TNF-α in skeletal muscle at any tested dose. On the other hand, GO elevated the expression of GLUT4 in skeletal muscle along with glycogen content as observed with PAS staining. In conclusion, the antidiabetic effect of garlic oil is associated with ameliorated oxidative stress in skeletal muscle.
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Affiliation(s)
- Cheng-Tzu Liu
- School of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan ; Department of Nutrition, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Tien-Wei Hsu
- School of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan
| | - Ke-Ming Chen
- Department of Parasitology, Chung Shan Medical University, Taichung 402, Taiwan
| | - Ya-Ping Tan
- School of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan
| | - Chong-Kuei Lii
- Department of Nutrition, China Medical University, Taichung 404, Taiwan
| | - Lee-Yan Sheen
- Graduate Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
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Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M. Effects of sodium-glucose cotransporter 2 selective inhibitor ipragliflozin on hyperglycaemia, oxidative stress, inflammation and liver injury in streptozotocin-induced type 1 diabetic rats. J Pharm Pharmacol 2014; 66:975-87. [PMID: 24533859 DOI: 10.1111/jphp.12223] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Accepted: 01/01/2013] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Sodium-glucose cotransporter (SGLT) 2 plays an important role in renal glucose reabsorption and has been highlighted as a therapeutic target for the treatment of diabetes. Here, we investigated the therapeutic effects of SGLT2 selective inhibitor ipragliflozin in type 1 diabetic rats. METHODS Type 1 diabetic rats were prepared by intravenous administration of streptozotocin (STZ). Ipragliflozin was acutely or chronically administered, and therapeutic effects were investigated. KEY FINDINGS Single administration of ipragliflozin significantly increased urinary glucose excretion, and its effect lasted over 12 h. In addition, ipragliflozin improved glucose tolerance and sustainably reduced hyperglycaemia. Repeated administration of ipragliflozin to diabetic rats for 4 weeks significantly improved not only hyperglycaemia, but also hyperlipidaemia and hepatic steatosis with concomitant increases in urinary glucose excretion. In addition, ipragliflozin ameliorates renal glomerular hyperfiltration and albuminuria. Further, ipragliflozin reduced liver levels of oxidative stress biomarkers and plasma levels of inflammatory markers, and improved liver injury as assessed by plasma levels of aminotransferases. CONCLUSION These results suggest that SGLT2 selective inhibitor ipragliflozin exerts a beneficial effect on glycaemic control and ameliorates diabetes-associated metabolic abnormalities and complications in STZ-induced diabetic rats, and would be a potential agent for the treatment of type 1 diabetes.
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Affiliation(s)
- Atsuo Tahara
- Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan
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Kumar V, Bhandari U, Tripathi CD, Khanna G. Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats. Indian J Pharm Sci 2014; 76:315-22. [PMID: 25284929 PMCID: PMC4171868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Revised: 06/07/2014] [Accepted: 06/15/2014] [Indexed: 11/07/2022] Open
Abstract
Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na(+)/K(+) ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na(+)/K(+) ATPase activity and DNA laddering, visceral fat pad and organ's weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus.
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Affiliation(s)
- V. Kumar
- Department of Pharmacology, KIET School of Pharmacy, Ghaziabad-201 206, India,Address for correspondence E-mail:
| | - Uma Bhandari
- Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi-110 062, India
| | - C. D. Tripathi
- Department of Pharmacology, Vardhman Mahavir Medical College, Safdarjung Hospital, New Delhi-110 029, India
| | - Geetika Khanna
- Department of Pathology, Vardhman Mahavir Medical College, Safdarjung Hospital, New Delhi-110 029, India
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Dey B, Mitra A. Chemo-profiling of eucalyptus and study of its hypoglycemic potential. World J Diabetes 2013; 4:170-6. [PMID: 24147201 PMCID: PMC3797882 DOI: 10.4239/wjd.v4.i5.170] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Revised: 05/17/2013] [Accepted: 07/23/2013] [Indexed: 02/05/2023] Open
Abstract
Constant escalations in the number of diabetics world-wide and the failure of conventional therapy to restore normoglycemia without adverse effects, in spite of tremendous strides in modern medicine, calls for naturopathy and alternative medicine. Because diabetes is multi-factorial and has secondary complications, prevention of hyperglycemia is the central dogma for its management. To date, no oral hypoglycemic exists which can achieve tight glycemic control without side effects. Dietary adjuncts, lifestyle interventions and a resurgence of interest in phyto-therapy have consequently gained ground. Natural hypoglycemics have attracted attention due to ease of incorporation in everyday diet, affordability, less adverse effects, and long term safety. Ethno botanical literature reports more than 800 anti-diabetic plants species. Eucalyptus is well represented in the Aboriginal Pharmacopoeias for its various pharmacological activities. Its hot aqueous decoction has been used as a hypoglycemic in various regions of world. This editorial attempts to summarize the data on the hypoglycemic potential of the different eucalyptus species, highlight the value of its natural biomolecules for the prophylaxis and treatment of type 2 diabetes, describe their mechanistic actions, shed light on the posology and safety aspects of eucalyptus and assess its applicability as a reinforcement to currently used therapy.
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Zhu K, Nie S, Li C, Huang J, Hu X, Li W, Gong D, Xie M. Antidiabetic and pancreas-protective effects of zinc threoninate chelate in diabetic rats may be associated with its antioxidative stress ability. Biol Trace Elem Res 2013; 153:291-8. [PMID: 23625696 DOI: 10.1007/s12011-013-9675-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Accepted: 04/15/2013] [Indexed: 01/25/2023]
Abstract
Zinc exerts a wide range of important biological roles. The present study was carried out to investigate the effects of zinc threoninate chelate in blood glucose levels, lipid peroxidation, activities of antioxidant defense systems and nitrite concentration, and histology of the pancreas in diabetic rats. Wistar rats were intravenously injected with a single dose of streptozotocin to induce diabetes. Then, diabetic rats were administrated orally with zinc threoninate chelate (3, 6, and 9 mg/kg body weight) once daily for 7 weeks. Fasting blood glucose was monitored weekly. At the end of the experimental period, the diabetic rats were killed, and levels of serum insulin, malondialdehyde, and nitric oxide, activities of glutathione peroxidase, total superoxide dismutase, copper/zinc-superoxide dismutase, and nitric oxide synthase were determined; pancreas was examined histopathologically as well. Zinc threoninate chelate significantly reduced the blood glucose levels and significantly increased the serum insulin levels in diabetic rats. In addition, zinc threoninate chelate caused a significant increase in activities of antioxidant enzymes and significant decrease in nitrite concentration and malondialdehyde formation in the pancreas and serum of diabetic rats. These biochemical observations were supplemented by histopathological examination of the pancreas. These results suggested that the antidiabetic effect of zinc threoninate chelate may be related to its antioxidative stress ability in diabetic rats.
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Affiliation(s)
- Kexue Zhu
- State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
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Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 2013; 715:246-55. [PMID: 23707905 DOI: 10.1016/j.ejphar.2013.05.014] [Citation(s) in RCA: 244] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 03/25/2013] [Accepted: 05/11/2013] [Indexed: 12/25/2022]
Abstract
The sodium-glucose cotransporter 2 (SGLT2) is responsible for most glucose reabsorption in the kidney and has been proposed as a novel therapeutic target for the treatment of type 2 diabetes. In the present study, the therapeutic effects of SGLT2 selective inhibitor ipragliflozin were examined in high-fat diet and streptozotocin-nicotinamide-induced type 2 diabetic mice which exhibit impaired insulin secretion, insulin resistance, hyperlipidemia, hepatic steatosis, and obesity. Single administration of ipragliflozin dose-dependently increased urinary glucose excretion, reduced blood glucose and plasma insulin levels, and improved glucose intolerance. Four-week repeated administration of ipragliflozin improved not only glucose tolerance, hyperglycemia, and hyperinsulinemia but also impaired insulin secretion, hyperlipidemia, hepatic steatosis, and obesity with a concomitant increase in urinary glucose excretion. In addition, ipragliflozin reduced plasma and liver levels of oxidative stress biomarkers (thiobarbituric acid reactive substances and protein carbonyl) and inflammatory markers (interleukin 6, tumor necrosis factor α, monocyte chemotactic protein-1, and c-reactive protein), and improved liver injury as assessed by plasma levels of aminotransferases. These results demonstrate that SGLT2 selective inhibitor ipragliflozin improves not only hyperglycemia but also diabetes/obesity-associated metabolic abnormalities in type 2 diabetic mice and suggest that ipragliflozin may be useful in treating type 2 diabetes with metabolic syndrome.
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Belviranli M, Gökbel H, Okudan N, Büyükbaş S. Oxidative stress and anti-oxidant status in diabetic rat liver: effect of plant polyphenols. Arch Physiol Biochem 2012; 118:237-43. [PMID: 22803804 DOI: 10.3109/13813455.2012.702775] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Increased evidence in role of oxidative stress and grape seed extract (GSE) in diabetes and its complication led us to investigate the changes of oxidative stress and anti-oxidant defence in liver tissue of diabetic rats and possible effects of GSE. Diabetes was induced by a single intraperitoneal injection of streptozotocin. Seven days after STZ injection four groups were formed: Control, GSE-supplemented control, diabetic and GSE-supplemented diabetic and GSE was given for 6 weeks. Malondialdehyde levels and xanthine oxidase activities were not different among the groups. However, nitric oxide (NO) levels were higher in diabetic and GSE supplemented groups compared with non-diabetic and non-supplemented groups, respectively. Total anti-oxidant activity (TAA) was lower in diabetic groups compared with their non-diabetic controls and it was not affected by GSE. In conclusion, GSE supplementation has limited protective effect in liver tissue of diabetic rats via affecting NO levels and was not affecting TAA.
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Affiliation(s)
- Muaz Belviranli
- Department of Physiology, Meram Faculty of Medicine, Selcuk University, Konya, Turkey.
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Kumar R, Pate DK, Prasad SK, Sairam K, Hemalatha S. Antidiabetic activity of alcoholic leaves extract of Alangium lamarckii Thwaites on streptozotocin-nicotinamide induced type 2 diabetic rats. ASIAN PAC J TROP MED 2012; 4:904-9. [PMID: 22078954 DOI: 10.1016/s1995-7645(11)60216-2] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2011] [Revised: 08/15/2011] [Accepted: 10/15/2011] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE To investigate antidiabetic potential of alcoholic leaves extract of Alangium lamarckii (A. lamarckii) on streptozotocin-nicotinamide induced type 2 diabetic rats. METHODS Oral glucose tolerance test was done by inducing hyperglycemic state via administration of glucose in water (2g/kg). Single dose of alcoholic leaves extract of A. lamarckii (250 and 500 mg/kg, p.o.) were administered to normoglycemic, hyperglycemic rats. Type 2 diabetes was induced by single intraperitoneal injection of nicotinamide (110 mg/kg) followed by streptozotocin (65mg/kg). The study also included estimations of blood plasma glucose, lipid profile, liver glycogen, body weight and antioxidant status in normal and diabetic rats. RESULTS Admistration of alcoholic extract of A. lamarckii at two dosage 250 and 500 mg/kg, p.o. did not showed any significant change in blood glucose level of normoglycemic rats (P>0.05), whereas, oral glucose tolerance test depicted reduction in blood glucose level (P<0.05). The streptozotocin-nicotinamide induced diabetic rats, significantly decreased the blood plasma glucose level (P<0.001) comparable to glibenclamide (10 mg/kg), restored the lipid profile and showed improvement in liver glycogen, body weight and antioxidant status in diabetic rats. CONCLUSIONS Present finding demonstrated the significant antidiabetic activity of alcoholic leaves extract of A. lamarckii.
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Affiliation(s)
- Rajesh Kumar
- Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi-221005, India
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Role of antioxidants in phytomedicine with special reference to antidiabetic herbs. ASIAN PACIFIC JOURNAL OF TROPICAL DISEASE 2012. [DOI: 10.1016/s2222-1808(12)60303-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Bokaeian M, Nakhaee A, Moodi B, Ali Khazaei H. Eucalyptus globulus (eucalyptus) treatment of candidiasis in normal and diabetic rats. IRANIAN BIOMEDICAL JOURNAL 2010; 14:121-126. [PMID: 21079663 PMCID: PMC3904063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 02/07/2010] [Revised: 07/06/2010] [Accepted: 08/01/2010] [Indexed: 05/30/2023]
Abstract
BACKGROUND The leaves of Eucalyptus globulus (eucalyptus) are used for treatment of diabetes mellitus in traditional medicine. The aim of this study was to evaluate the effects of eucalyptus in treatment of established systemic infection with Candida albicans in normal and streptozotocin-induced diabetic rats. METHODS Sixty normoglycemic male Wistar rats, weighing 200-250 g, were selected and randomly divided into six groups (n= 10): normal control, control + C. albicans, control + eucalyptus + C. albicans, diabetic control, diabetic + C. albicans, diabetic + eucalyptus + C. albicans. Diabetes was induced after a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and eucalyptus was added to the diet (62.5 g/kg) and drinking water (2.5 g/L) of treated animals for 4 weeks. The concerned groups were inoculated with C. albicans 15 days after diabetes induction. At the end of one month experiment, fasted rats were killed by cervical decapitation. Blood was collected from neck vein for estimation of glucose. C. albicans concentrations were estimated in liver and kidneys using serial dilution culture of tissue homogenates. RESULTS Eucalyptus administration significantly improved the hyperglycemia, polydipsia, polyphagia, and it also compensated weight loss of diabetic rats (P less than 0.05). Moreover, eucalyptus caused a significant reduction in C. albicans concentration in liver and kidney homogenates (P less than 0.01). CONCLUSION The results revealed that eucalyptus improves Candidia infection in normal and diabetic rats that in some ways validates the traditional use of this plant in treatment of diabetic patients.
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Affiliation(s)
- Mohammad Bokaeian
- *Corresponding Author; Tel. (+98-541) 3414 558; Fax: (+98-541) 3414 567; E-mail:
| | | | - Bita Moodi
- Research Center for Cellular and Molecular Biology, School of Medicine, Zahedan University of Medical Sciences, Zahedan;
| | - Hossein Ali Khazaei
- Dept. of Immunology and Hematology, School of Medicine, Zahedan University of Medical
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