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Elsayed HM, Abdel-Aziz HO, Ahmed GM, Adly MA, Mohammed SA. The Possible Ameliorative Effect of Echinacea, Ginger, and Their Combination on Experimentally Induced Diabetic Nephropathy in a Rat Model: Histological and Immunohistochemical Study. J Microsc Ultrastruct 2024; 12:199-210. [PMID: 39811596 PMCID: PMC11729022 DOI: 10.4103/jmau.jmau_62_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 09/30/2022] [Accepted: 10/06/2022] [Indexed: 01/16/2025] Open
Abstract
Background Diabetes represents a chronic disease characterized by hyperglycemia. Several changes in the renal functions had been detected in diabetic patients. Aim of the Work This study was conducted to compare the possible ameliorative role of both ginger and Echinacea either alone or in combination upon experimentally induced diabetic nephropathy. Materials and Methods Sixty adult male albino rats were used in this study. Rats were divided into three groups. Control (group I) included 20 rats. Diabetic group (group II) included 10 rats. Group III included 30 rats subdivided into three subgroups 10 animals each: Subgroup IIIa diabetic treated with 100 mg/kg Echinacea for 30 days. Subgroup IIIb diabetic treated with 400 mg/kg ginger for 30 days orally. Subgroup IIIc diabetic treated with both 100 mg/kg Echinacea and 400 mg/kg ginger for 30 days orally. Hemotoxylin and eosin staining, Periodic acid Schiff and Masson trichrome were done. Ultrastructural examination was done. Immunohistochemical markers used were caspase-3 for apoptosis and CD68 for macrophages. Morphometric and statistical analyses were done. Results Diabetes caused a significant increase in collagen fibers in the renal cortex, the caspase-3 expression as well as the number of macrophages. Ultrastructurally, there was an irregularly thickened glomerular basement membrane and effacement of podocytes. Ginger treatment alone or in combination with Echinacea exhibited more pronounced improvement of diabetes-induced degenerative changes and a significant decrease in collagen fibers, the caspase-3 expression as well as the number of macrophages compared to Echinacea alone. Conclusion Ginger treatment alone or in combination with Echinacea exhibited more pronounced improvement in diabetes nephropathy.
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Affiliation(s)
- Hoda M. Elsayed
- Department of Histology, Faculty of Medicine, Sohag University, Sohag, Egypt
| | | | | | - Mohamed Arafa Adly
- Department of Zoology, Faculty of Science, Sohag University, Sohag, Egypt
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Guan X, Santos RR, Koopmans SJ, Molist F. Effects of the Inclusion of Dietary Bitter Gourd ( Momordica charantia) on the Performance and Carcass Characteristics of Pigs: Potential Application in the Feed Chain. Animals (Basel) 2023; 13:2159. [PMID: 37443956 DOI: 10.3390/ani13132159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 06/02/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
The objective of this study was to determine the effect of bitter gourd (BG) leftovers (stems and leaves) as an alternative dietary ingredient on pig performance, carcass characteristics, serum parameters (urea, insulin, and leptin levels), and faecal consistency. Healthy Tempo × Great Yorkshire and Landrace pigs (N = 240; 120 gilts and 120 boars) weighing 25.8 kg (9-10 weeks of age) were randomly assigned to three treatments (eight pens per treatment; each pen with five gilts and five boars). The three treatments consisted of a non-supplemented commercial diet (control; CON) and a CON diet supplemented with 6.5 g/kg BG (BG1) or 13 g/kg BG (BG2). Pigs were fed the experimental diets until slaughter (120 kg body weight; BW). Feed intake was recorded daily and calculated for each experimental phase (i.e., days 0-36, days 36-66, days 66-98, and the overall experimental period). Average daily feed intake (ADFI), average daily gain (ADG), and feed conversion ratio (FCR) were calculated. The frequencies of visiting the feed station and of feeding were recorded daily. Faecal scores (FS) for consistency were measured per pen twice weekly. On the day of slaughter, two pigs per pen (one male and one female) were randomly selected for the measurement of muscle thickness and blood collection. At the slaughterhouse, carcass weight, dressing percentage, back fat thickness, muscle depth, and lean meat percentage were recorded. Data were analysed using ANOVA, with the pen as the experimental unit. Diets BG1 or BG2 did not affect the performance of the pigs, except for a significant decrease in the ADG of the pigs fed the BG2 diet in the feeding period of 50-80 kg. However, no differences in performance were observed in the overall experimental period. Faecal scores, carcass quality, and serum levels of urea, insulin, and leptin were also not affected by the diet. In summary, leftovers (stems and leaves) of BG can be successfully added to the diet of growing-finishing pigs without interfering with performance and carcass characteristics.
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Affiliation(s)
- Xiaonan Guan
- Department of Research & Development, Schothorst Feed Research, 8200 AM Lelystad, The Netherlands
| | - Regiane R Santos
- Department of Research & Development, Schothorst Feed Research, 8200 AM Lelystad, The Netherlands
| | - Sietse J Koopmans
- Wageningen Livestock Research, Wageningen University & Research, 6700 AH Wageningen, The Netherlands
| | - Francesc Molist
- Department of Research & Development, Schothorst Feed Research, 8200 AM Lelystad, The Netherlands
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Rahman MM, Dhar PS, Sumaia, Anika F, Ahmed L, Islam MR, Sultana NA, Cavalu S, Pop O, Rauf A. Exploring the plant-derived bioactive substances as antidiabetic agent: An extensive review. Biomed Pharmacother 2022; 152:113217. [PMID: 35679719 DOI: 10.1016/j.biopha.2022.113217] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 11/24/2022] Open
Abstract
Diabetes mellitus (DM) is a metabolic syndrome. Diabetes has become more common in recent years. Chemically generated drugs are used to lessen the effects of DM and its following repercussions due to unpleasant side effects such as weight gain, gastrointestinal issues, and heart failure. On the other hand, medicinal plants could be a good source of anti-diabetic medications. This article aims to determine any plant matrix's positive potential. Food restriction, physical activity, and the use of antidiabetic plant-derived chemicals are all being promoted as effective ways to manage diabetes because they are less expensive and have fewer or no side effects. This review focuses on antidiabetic plants, along with their bioactive constituent, chemically characterization, and plant-based diets for diabetes management. There is minimal scientific data about the mechanism of action of the plant-based product has been found. The purpose of this article is to highlight anti-diabetic plants and plant-derived bioactive compounds that have anti-diabetic properties. It also provides researchers with data that may be used to build future strategies, such as identifying promising bioactive molecules to make diabetes management easier.
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Affiliation(s)
- Md Mominur Rahman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Puja Sutro Dhar
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Sumaia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Fazilatunnesa Anika
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Limon Ahmed
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Nazneen Ahmeda Sultana
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410087 Oradea, Romania
| | - Ovidiu Pop
- Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410087 Oradea, Romania.
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, Swabi, KPK, Pakistan.
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4
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V G, Das M, Zarei M, Vp M, Harohally NV, G SK. Studies on the partial characterization of extracted glycosaminoglycans from fish waste and its potentiality in modulating obesity through in-vitro and in-vivo. Glycoconj J 2022; 39:525-542. [PMID: 35913650 DOI: 10.1007/s10719-022-10077-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 07/14/2022] [Accepted: 07/19/2022] [Indexed: 11/26/2022]
Abstract
Glycosaminoglycans (GAGs) are bioactive polysaccharides or glycoconjugates found in the fish waste having significant health impacts. In the present study it has been attempted to extract GAGs from mackerel fish waste through chemical and enzymatic methods. Further, the extracted GAGs (e-GAGs) were analyzed for their composition (uronic acid, total sugar & sulfate), chemical characterization was carried out through techniques of scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) & Proton NMR. Further, probable major GAGs present was identified by enzymatic digestion. The biological potential of the extracted glycoconjugate was assessed further through in-vitro and in-vivo studies. In-vitro biological activity showed good lipase inhibition (IC50, 2.6 mg/mL) and bile acid binding properties (dose-dependent). Lipid accumulation lowered in the e-GAGs differentiated 3T3L1 preadipocyte cells have also been observed. The high fat fed animal (in-vivo) study showed ameliorative effect via reducing blood sugar∼1.28↓, lipid profile↓, plasma insulin∼3.5↓, improved glucose tolerance, and homeostatic model assessment for insulin resistance (HOMA-IR, ∼3.0↓). Furthermore, elimination of bile acid (BA) due to GAG-BA binding properties resultant in removal of elevated fecal triglyceride and cholesterol suggesting its lipid lowering activity. Regulation of various proteins linked to carbohydrate and lipid metabolism including fatty acid synthase (FAS), low density lipoproteins receptor (LDL-R), 7α-hydroxylase, glucose transporter-4 (GLUT4) and Peroxisome proliferator- activated receptor gamma (PPAR-γ) were significant (p < 0.05) with e-GAGs treatment when compared to HFD group. Thus, the e-GAGs showed potential hypolipidemic activity through elimination of bile acid binding property together with regulating the specific protein related to obesity and its associated complications.
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Affiliation(s)
- Geetha V
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, 570 020, Mysore, India
| | - Moumita Das
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, 570 020, Mysore, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Mehrdad Zarei
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, 570 020, Mysore, India
| | - Mayookha Vp
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, 570 020, Mysore, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Nanishankar V Harohally
- Department of Spices and Flavour Sciences, CSIR-Central Food Technological Research Institute, 570 020, Mysore, India
| | - Suresh Kumar G
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, 570 020, Mysore, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
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Liao PY, Lo HY, Liu IC, Lo LC, Hsiang CY, Ho TY. A gastro-resistant peptide from Momordica charantia improves diabetic nephropathy in db/ db mice via its novel reno-protective and anti-inflammatory activities. Food Funct 2022; 13:1822-1833. [PMID: 35083999 DOI: 10.1039/d1fo02788c] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Diabetic nephropathy (DN), a principal diabetic microvascular complication, is a chronic inflammatory immune disorder. A gastro-resistant peptide mcIRBP-9 from Momordica charantia has shown modulation of blood glucose homeostasis in diabetic mice. Here we conducted a long-term experiment to evaluate the therapeutic effects and mechanisms of mcIRBP-9 on DN. Type 2 diabetic mice (db/db mice) were orally given mcIRBP-9 once daily for 12 consecutive weeks. The amelioration of DN was evaluated by renal function indexes, vascular leakage, and pathological lesions. Possible effective mechanisms of mcIRBP-9 on DN were analyzed by gene expression profiles. A pharmacokinetic study in rats was carried out to evaluate the oral bioavailability of mcIRBP-9. Our data showed that mcIRBP-9 was able to enter systemic circulation in rats after oral administration. In comparison with mock, long-term administration of mcIRBP-9 significantly decreased blood glucose (572.25 ± 1.55 mg dL-1vs. 213.50 ± 163.39 mg dL-1) and HbA1c levels (13.58 ± 0.30% vs. 8.23 ± 2.98%) and improved the survival rate (85.7% vs. 100%) in diabetic mice. mcIRBP-9 ameliorated DN by reducing renal vascular leakage and histopathological changes. mcIRBP-9 altered the pathways involved in inflammatory and immune responses, and the nuclear factor-κB played a central role in the regulation of mcIRBP-9-affected pathways. Moreover, mcIRBP-9 improved the inflammatory characteristic of DN in diabetic and non-diabetic mice. In conclusion, mcIRBP-9 displayed a novel anti-inflammatory activity and exhibited a reno-protective ability in addition to controlling the blood glucose and HbA1c levels. These findings suggested the role of mcIRBP-9 from M. charantia as a nutraceutical agent for diabetes and subsequent DN.
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Affiliation(s)
- Pei-Yung Liao
- Graduate Institute of Chinese Medicine, China Medical University, Taichung 404333, Taiwan. .,Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500209, Taiwan
| | - Hsin-Yi Lo
- Graduate Institute of Chinese Medicine, China Medical University, Taichung 404333, Taiwan.
| | - I-Chen Liu
- Graduate Institute of Chinese Medicine, China Medical University, Taichung 404333, Taiwan.
| | - Lun-Chien Lo
- School of Chinese Medicine, China Medical University, Taichung 404333, Taiwan
| | - Chien-Yun Hsiang
- Department of Microbiology and Immunology, China Medical University, Taichung 404333, Taiwan.
| | - Tin-Yun Ho
- Graduate Institute of Chinese Medicine, China Medical University, Taichung 404333, Taiwan. .,Department of Health and Nutrition Biotechnology, Asia University, Taichung 413305, Taiwan
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6
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Liu Z, Gong J, Huang W, Lu F, Dong H. The Effect of Momordica charantia in the Treatment of Diabetes Mellitus: A Review. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:3796265. [PMID: 33510802 PMCID: PMC7826218 DOI: 10.1155/2021/3796265] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 12/02/2020] [Accepted: 12/18/2020] [Indexed: 12/29/2022]
Abstract
In recent years, many studies of Momordica charantia (MC) in the treatment of diabetes mellitus (DM) and its complications have been reported. This article reviewed the effect and mechanism of MC against diabetes, including the results from in vitro and in vivo experiments and clinical trials. The common side effects of MC were also summarized. We hope that it might open up new ideas for further mechanism exploration and clinical application as well as provide a scientific theoretical basis for the development of drugs or foods derived from MC.
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Affiliation(s)
- Zhuo Liu
- Grade 2016 of Integrated Traditional Chinese and Western Clinical Medicine, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Gong
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenya Huang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fuer Lu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Dong
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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7
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Konda PY, Marella S, Natava R, Chippada A. Diabetes affects hepatic and renal glycoproteins: effect of Boswellia ovalifoliolata on glycoproteins proportions in diabetes induced hepatic and renal injury. J Diabetes Metab Disord 2020; 19:153-162. [PMID: 32550165 DOI: 10.1007/s40200-020-00487-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 01/02/2020] [Indexed: 11/24/2022]
Abstract
Purpose Chronic hyperglycemia and deficiency of insulin are peculiar features of diabetes mellitus alters glycoprotein levels in various tissues leads to impaired metabolism of glycoproteins which play a major role in the pathogenesis of diabetic complications. Boswellia ovalifoliolata is a medicinal plant known for its many medicinal properties including diabetes. In this background our study was aimed to evaluate the effect of aqueous extract of stem bark of Boswellia ovalifoliolata (AESBBO) on antidiabetic and glycoprotein metabolism. Methods Diabetes was induced in rats by intraperitoneal administration of streptozotocin at a dose of 50 mg/kg bw. After induction of diabetes rats were treated with AESBBO at dosage of 200 mg/kg for a long term treatment of 40 days. Finally, by the end of study all the rats were dissected blood, liver, and kidney tissue samples were collected to investigate the long term effects of AESBBO on diabetes and glycoprotein metabolism. Results Treatment with AESBBO significantly reduced the fasting blood glucose levels whereas the levels of insulin and hemoglobin were increased with decreased levels of glycosylated hemoglobin. The long term treatment of AESBBO significantly decreased the levels of plasma, liver and kidney tissue glycoproteins such as fucose, hexose, hexosamine and sialic acid. Conclusions This study concludes that the aqueous extract of stem bark of Boswellia ovalifoliolata possesses a protective role on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.
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Affiliation(s)
| | - Saritha Marella
- Department of Bio-Chemistry, Sri Venkateswara University, Tirupati-517 502, India
| | - Rajesh Natava
- Department of Bio-Chemistry, Sri Venkateswara University, Tirupati-517 502, India
| | - AppaRao Chippada
- Department of Bio-Chemistry, Sri Venkateswara University, Tirupati-517 502, India
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8
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Kalaska B, Miklosz J, Kamiński K, Musielak B, Yusa SI, Pawlak D, Nowakowska M, Szczubiałka K, Mogielnicki A. The neutralization of heparan sulfate by heparin-binding copolymer as a potential therapeutic target. RSC Adv 2019; 9:3020-3029. [PMID: 35518950 PMCID: PMC9059929 DOI: 10.1039/c8ra09724k] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 01/15/2019] [Indexed: 12/12/2022] Open
Abstract
Besides regulating ligand–receptor and cell–cell interactions, heparan sulfate (HS) may participate in the development of many diseases, such as cancer, bacterial or viral infections, and their complications, like bleeding or inflammation. In these cases, the neutralization of HS could be a potential therapeutic target. The heparin-binding copolymer (HBC, PEG41-PMAPTAC53) was previously reported by us as a fully synthetic compound for efficient and safe neutralization of heparins and synthetic anticoagulants. In a search for molecular antagonists of HS, we examined the activity of HBC as an HS inhibitor both in vitro and in vivo and characterized HBC/HS complexes. Using a colorimetric Azure A method, isothermal titration calorimetry and dynamic light scattering techniques we found that HBC binds HS by forming complexes below 200 nm with less than 1 : 1 stoichiometry. We confirmed the HBC inhibitory effect in rats by measuring activated partial thromboplastin time, prothrombin time, anti-factor Xa activity, anti-factor IIa activity, and platelet aggregation. HBC reversed the enhancement of all tested parameters caused by HS demonstrating that cationic synthetic block copolymers may have a therapeutic value in various disorders involving overproduction of HS. The neutralization of heparan sulfate (HS) by a heparin-binding copolymer (HBC) could be a promising treating option for bacterial or viral infections or bleeding related to overproduction of HS in cancer or other diseases.![]()
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Affiliation(s)
- Bartlomiej Kalaska
- Department of Pharmacodynamics
- Medical University of Bialystok
- 15-089 Bialystok
- Poland
| | - Joanna Miklosz
- Department of Pharmacodynamics
- Medical University of Bialystok
- 15-089 Bialystok
- Poland
| | - Kamil Kamiński
- Faculty of Chemistry
- Jagiellonian University
- 30-387 Krakow
- Poland
| | - Bogdan Musielak
- Faculty of Chemistry
- Jagiellonian University
- 30-387 Krakow
- Poland
| | - Shin-Ichi Yusa
- Department of Applied Chemistry
- Graduate School of Engineering
- University of Hyogo
- Himeji
- Japan
| | - Dariusz Pawlak
- Department of Pharmacodynamics
- Medical University of Bialystok
- 15-089 Bialystok
- Poland
| | | | | | - Andrzej Mogielnicki
- Department of Pharmacodynamics
- Medical University of Bialystok
- 15-089 Bialystok
- Poland
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9
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Saeed F, Afzaal M, Niaz B, Arshad MU, Tufail T, Hussain MB, Javed A. Bitter melon (Momordica charantia): a natural healthy vegetable. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2018. [DOI: 10.1080/10942912.2018.1446023] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Farhan Saeed
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Afzaal
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Bushra Niaz
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Umair Arshad
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Tabussam Tufail
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Bilal Hussain
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Ahsan Javed
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
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10
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Gonzalez-Calero L, Martínez PJ, Martin-Lorenzo M, Baldan-Martin M, Ruiz-Hurtado G, de la Cuesta F, Calvo E, Segura J, Lopez JA, Vázquez J, Barderas MG, Ruilope LM, Vivanco F, Alvarez-Llamas G. Urinary exosomes reveal protein signatures in hypertensive patients with albuminuria. Oncotarget 2018; 8:44217-44231. [PMID: 28562335 PMCID: PMC5546475 DOI: 10.18632/oncotarget.17787] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 04/20/2017] [Indexed: 01/05/2023] Open
Abstract
Albuminuria is an indicator of cardiovascular risk and renal damage in hypertensive individuals. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control and prevents development of new-onset-albuminuria. A significant number of patients, however, develop albuminuria despite chronic RAS blockade, and the physiopathological mechanisms are underexplored. Urinary exosomes reflect pathological changes taking place in the kidney. The objective of this work was to examine exosomal protein alterations in hypertensive patients with albuminuria in the presence of chronic RAS suppression, to find novel clues underlying its development. Patients were followed-up for three years and were classified as: a) patients with persistent normoalbuminuria; b) patients developing de novo albuminuria; and c) patients with maintained albuminuria. Exosomal protein alterations between groups were identified by isobaric tag quantitation (iTRAQ). Confirmation was approached by target analysis (SRM). In total, 487 proteins were identified with high confidence. Specifically, 48 proteins showed an altered pattern in response to hypertension and/or albuminuria. Out of them, 21 proteins interact together in three main functional clusters: glycosaminoglycan degradation, coagulation and complement system, and oxidative stress. The identified proteins constitute potential targets for drug development and may help to define therapeutic strategies to evade albuminuria progression in hypertensive patients chronically treated.
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Affiliation(s)
| | - Paula J Martínez
- Department of Immunology, IIS-Fundacion Jimenez Diaz, REDinREN, Madrid, Spain
| | | | | | - Gema Ruiz-Hurtado
- Hypertension Unit, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Fernando de la Cuesta
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain
| | | | - Julian Segura
- Hypertension Unit, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | - Jesús Vázquez
- Laboratory of Cardiovascular Proteomics CNIC, Madrid, Spain
| | - Maria G Barderas
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain
| | - Luis M Ruilope
- Hypertension Unit, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Fernando Vivanco
- Department of Immunology, IIS-Fundacion Jimenez Diaz, REDinREN, Madrid, Spain.,Department of Biochemistry and Molecular Biology I, Universidad Complutense, Madrid, Spain
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11
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Hu X, Liu C, Wang X, Jia D, Lu W, Sun X, Liu Y, Yuan L. Hpyerglycemic and anti-diabetic nephritis activities of polysaccharides separated from Auricularia auricular in diet-streptozotocin-induced diabetic rats. Exp Ther Med 2016; 13:352-358. [PMID: 28123514 DOI: 10.3892/etm.2016.3943] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 10/21/2016] [Indexed: 01/02/2023] Open
Abstract
Due to substantial morbidity and complications including nephropathy, a search for alternative treatment of diabetes mellitus is urgently required. The present study aimed to investigate the hypoglycemic and anti-diabetic nephropathy activities of polysaccharides separated from Auricularia auricular (AAP). Diet streptozotocin (STZ)-induced diabetic Sprague-Dawley rats were orally treated with metformin (100 mg/kg; positive control) and AAP (100 and 400 mg/kg) for four weeks, and parameters in the serum and liver associated with blood glucose, free radicals and nephropathy were determined. Similar to metformin, AAP treatment strongly reduced blood glucose levels by promoting glucose metabolism. The anti-oxidative activity of AAP, which was indicated by the modulation of superoxide dismutase, glutathione peroxidase, reactive oxygen species and methane dicarboxylic aldehyde levels in serum, was observed in diabetic rats. Furthermore, the regulatory effects of AAP on blood urea nitrogen, creatinine, uric protein and inflammatory-related factors revealed its protection against diabetic nephropathy. The present data suggests that AAP-mediated anti-diabetic and anti-nephritic effects are partially associated with their modulations on the anti-oxidative system and nuclear factor kappa B-related signaling pathway. In conclusion, AAP has potential to be a novel source of treatments for diabetes.
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Affiliation(s)
- Xinyu Hu
- Faculty of Medicine, Changchun Medical College, Changchun, Jilin 130013, P.R. China
| | - Chungang Liu
- School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China
| | - Xue Wang
- School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China
| | - Dongxu Jia
- School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China
| | - Wenqian Lu
- School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China
| | - Xiaoqi Sun
- Faculty of Medicine, Changchun Medical College, Changchun, Jilin 130013, P.R. China
| | - Yang Liu
- Engineering Research Center of the Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, Jilin 130118, P.R. China
| | - Lijia Yuan
- Center for Drug Evaluation of China, Beijing 100038, P.R. China
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Gowd V, Gurukar A, Chilkunda ND. Glycosaminoglycan remodeling during diabetes and the role of dietary factors in their modulation. World J Diabetes 2016; 7:67-73. [PMID: 26962410 PMCID: PMC4766247 DOI: 10.4239/wjd.v7.i4.67] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2015] [Revised: 11/23/2015] [Accepted: 01/04/2016] [Indexed: 02/06/2023] Open
Abstract
Glycosaminoglycans (GAGs) play a significant role in various aspects of cell physiology. These are complex polymeric molecules characterized by disaccharides comprising of uronic acid and amino sugar. Compounded to the heterogeneity, these are variously sulfated and epimerized depending on the class of GAG. Among the various classes of GAG, namely, chondroitin/dermatan sulfate, heparin/heparan sulfate, keratan sulfate and hyaluronic acid (HA), only HA is non-sulfated. GAGs are known to undergo remodeling in various tissues during various pathophysiological conditions, diabetes mellitus being one among them. These changes will likely affect their structure thereby impinging on their functionality. Till date, diabetes has been shown to affect GAGs in organs such as kidney, liver, aorta, skin, erythrocytes, etc. to name a few, with deleterious consequences. One of the mainstays in the treatment of diabetes is though dietary means. Various dietary factors are known to play a significant role in regulating glucose homeostasis. Furthermore, in recent years, there has been a keen interest to decipher the role of dietary factors on GAG metabolism. This review focuses on the remodeling of GAGs in various organs during diabetes and their modulation by dietary factors. While effect of diabetes on GAG metabolism has been worked out quite a bit, studies on the role of dietary factors in their modulation has been few and far between. We have tried our best to give the latest reports available on this subject.
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Studies on the antidiabetic activities of Cordyceps militaris extract in diet-streptozotocin-induced diabetic Sprague-Dawley rats. BIOMED RESEARCH INTERNATIONAL 2014; 2014:160980. [PMID: 24738047 PMCID: PMC3967809 DOI: 10.1155/2014/160980] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 01/29/2014] [Accepted: 01/30/2014] [Indexed: 01/08/2023]
Abstract
Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities of Cordyceps militaris on diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin, Cordyceps militaris extracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum. Cordyceps militaris extracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection of Cordyceps militaris extracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively, Cordyceps militaris extract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment.
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Abstract
BACKGROUND Momordica charantia (bitter gourd) is not only a nutritious vegetable but it is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control. OBJECTIVES To assess the effects of mormodica charantia for type 2 diabetes mellitus. SEARCH METHODS Several electronic databases were searched, among these were The Cochrane Library (Issue 1, 2012), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to February 2012), combined with handsearches. No language restriction was used. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared momordica charantia with placebo or a control intervention, with or without pharmacological or non-pharmacological interventions. DATA COLLECTION AND ANALYSIS Two authors independently extracted data. Risk of bias of the trials was evaluated using the parameters of randomisation, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in the interventions (no similar preparation was tested twice). MAIN RESULTS Four randomised controlled trials with up to three months duration and investigating 479 participants met the inclusion criteria. Risk of bias of these trials (only two studies were published as a full peer-reviewed publication) was generally high. Two RCTs compared the effects of preparations from different parts of the momordica charantia plant with placebo on glycaemic control in type 2 diabetes mellitus. There was no statistically significant difference in the glycaemic control with momordica charantia preparations compared to placebo. When momordica charantia was compared to metformin or glibenclamide, there was also no significant change in reliable parameters of glycaemic control. No serious adverse effects were reported in any trial. No trial investigated death from any cause, morbidity, health-related quality of life or costs. AUTHORS' CONCLUSIONS There is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.
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Affiliation(s)
- Cheow Peng Ooi
- Endocrine Unit, Department of Medicine, Universiti Putra Malaysia, Serdang, Malaysia.
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Joladarashi D, Chilkunda ND, Salimath PV. Tinospora cordifolia consumption ameliorates changes in kidney chondroitin sulphate/dermatan sulphate in diabetic rats. J Nutr Sci 2012; 1:e7. [PMID: 25191554 PMCID: PMC4153103 DOI: 10.1017/jns.2012.6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2011] [Revised: 04/25/2012] [Accepted: 05/28/2012] [Indexed: 12/11/2022] Open
Abstract
Diabetes is known to alter kidney extracellular matrix (ECM) components. Chondroitin sulphate (CS)/dermatan sulphate (DS), an ECM component, which plays an essential role in kidney is altered during diabetes. The focus of this study has been to examine the effect of Tinospora cordifolia (TC) consumption, a potent plant widely used to treat diabetes, on kidney CS/DS. Experimentally induced diabetic rats were fed with diet containing TC at 2·5 and 5 % levels and the effect of it on kidney CS/DS was examined. The CS/DS content and CS:heparan sulphate ratio which was decreased during diabetic condition were ameliorated in TC-fed groups. Disaccharide composition analysis of CS/DS by HPLC showed that decreases in 'E' units and degree of sulphation were modulated in 5 % TC-fed groups. Apparent molecular weight of purified CS/DS from the control rat kidney was found to be 38 kDa which was decreased to 29 kDa in diabetic rat kidney. Rats in 5 % TC-fed groups showed chain length of 38 kDa akin to control rats. Expression of chondroitin 4-O-sulfotransferase-1, dermatan 4-O-sulfotransferase-1 and N-acetylgalactosamine 4 sulphate 6-O-sulfotransferase, enzymes involved in the synthesis of 'E' units which was reduced during diabetic condition, was significantly contained in the 5 % TC-fed group. Purified CS/DS from 5 % TC-fed group was able to bind higher amounts of ECM components, namely type IV collagen and laminin, when compared with untreated diabetic rats. The present results demonstrate that consumption of a diet containing TC at the 5 % level modulates changes in kidney CS/DS which were due to diabetes.
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Key Words
- 2AB 2-aminobenzamide
- AIN, American Institute of Nutrition
- CS, chondroitin sulphate
- Chondroitin sulphate/dermatan sulphate
- DMMB, 1,9-dimethylmethylene blue
- DS, dermatan sulphate
- Diabetes
- ECM, extracellular matrix
- GAG, glycosaminoglycan
- GFR, glomerular filtration rate
- GalNAc, N-acetyl-d-galactosamine
- Glycosaminoglycans
- HS, heparan sulphate
- HexUA, hexuronic acid
- IdoA-l-iduronic acid
- Kidneys
- SFC, starch-fed control
- SFD, starch-fed diabetic
- STZ, streptozotocin
- TC, Tinospora cordifolia
- TFD, TC-fed diabetic.
- Tinospora cordifolia
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Affiliation(s)
- Darukeshwara Joladarashi
- Department of Biochemistry and Nutrition, Central Food Technological Research
Institute, Mysore 570 020, Karnataka, India
| | - Nandini D. Chilkunda
- Department of Biochemistry and Nutrition, Central Food Technological Research
Institute, Mysore 570 020, Karnataka, India
| | - Paramahans V. Salimath
- Department of Biochemistry and Nutrition, Central Food Technological Research
Institute, Mysore 570 020, Karnataka, India
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Thakur G, Pal K, Mitra A, Mukherjee S, Basak A, Rousseau D. Some Common Antidiabetic Plants of the Indian Subcontinent. FOOD REVIEWS INTERNATIONAL 2010. [DOI: 10.1080/87559129.2010.496024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Abstract
BACKGROUND Momordica charantia is not only a nutritious vegetable, but is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control. OBJECTIVES To assess the effects of mormodica charantia for type 2 diabetes mellitus. SEARCH STRATEGY Several electronic databases were searched, among these The Cochrane Library (issue 4, 2009), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to November 2009), combined with handsearches. No language restriction was used. SELECTION CRITERIA Randomized controlled trials that compared momordica charantia with a placebo or a control intervention with or without pharmacological or non-pharmacological interventions were included. DATA COLLECTION AND ANALYSIS Two authors independently extracted the data. Risk of bias of trials was evaluated using the parameters of randomization, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in interventions (no similar preparation was tested twice). MAIN RESULTS Three randomised controlled trials with up to three months duration and investigating 350 participants met the inclusion criteria. Risk of bias of these trials (only one study was published as a full peer-reviewed publication) was generally high. Two RCTs compared the effect of preparations from different parts of the momordica charantia plants and placebo on the glycemic control in type 2 diabetes mellitus. There was no statistically significant difference compared to placebo. The effects of preparation from the leaves of the plant and glibenclamide were comparable in the third trial. No serious adverse effects were reported in all the trials. There were no documentations of death from any cause, morbidity, (health-related) quality of life and costs. AUTHORS' CONCLUSIONS There is insufficient evidence to recommend momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.
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Affiliation(s)
- Cheow Peng Ooi
- Institute of Gerontology, University Putra Malaysia, 3rd floor, Faculty of Medicine and Health Sciences, Serdang, Selangor Darul Ehsan, Malaysia, 43400
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Mapanga RF, Musabayane CT. The Renal Effects of Blood Glucose-Lowering Plant-Derived Extracts in Diabetes Mellitus—an Overview. Ren Fail 2010; 32:132-8. [DOI: 10.3109/08860220903367585] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- R. F. Mapanga
- Discipline of Human Physiology, Faculty of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa
| | - C. T. Musabayane
- Discipline of Human Physiology, Faculty of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa
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Mapanga RF, Tufts MA, Shode FO, Musabayane CT. Renal effects of plant-derived oleanolic acid in streptozotocin-induced diabetic rats. Ren Fail 2010; 31:481-91. [PMID: 19839826 DOI: 10.1080/08860220902963558] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Previous studies from our laboratories indicate that the anti-diabetic effects of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract in streptozotocin-induced diabetic rats may be attributed in part to mixtures of triterpenes, oleanolic acid (3ss-hydroxy-olea-12-en-28-oic acid, OA) and ursolic acid (3ss -hydroxyl-urs-12-en-28-oic acid, UA). For the bioactive compounds to have potential in diabetes management, they should alleviate or prevent complications of diabetes mellitus, kidney function, and cardiovascular disorders. This study was, therefore, designed to assess whether S. cordatum leaf derived OA influenced renal function evaluated by the ability to increase urinary Na(+) outputs parameters and creatinine clearance (Ccr) of streptozotocin (STZ)-induced diabetic rats. Extraction and fractionation of S. cordatum powdered leaf ethyl acetate-solubles (EAS) yielded mixtures of OA/UA and methyl maslinate/methyl corosolate. Recrystallization of OA/UA mixture using ethanol afforded OA, the structure of which was confirmed by NMR spectroscopy ((1)H & (13)C). Acute effects of OA on kidney function and mean arterial blood pressure (MAP) were investigated in anesthetized rats challenged with hypotonic saline after a 3.5-h equilibration for 4h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. OA was added to the infusate during the treatment period. Chronic effects of OA were studied in individually caged rats treated twice daily with OA (60 mg/kg, p.o.) for five weeks. By comparison with respective control animals administration, OA significantly increased Na(+) excretion rates of non-diabetic and STZ-induced diabetic rats without affecting urine flow, K(+) and Cl(-) rates. At the end of five weeks, OA treatment significantly (p < 0.05) increased Ccr in non-diabetic (2.88 +/- 0.14 vs. 3.71 +/- 0.30 ml/min) and STZ-diabetic rats (1.81 +/- 0.32 vs. 3.07 +/- 0.16 ml/min) with concomitant reduction of plasma creatinine concentration (n = 6 in all groups). OA also caused significant decreases in MAP in non-diabetic and STZ-induced diabetic rats. These findings suggest that OA may have beneficial effects on some processes associated with renal derangement of STZ-induced diabetic rats.
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Affiliation(s)
- R F Mapanga
- Disciplines of Human Physiology, Faculty of Health Sciences, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban, South Africa
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Ooi CP, Yassin Z, Hamid TA. Momordica charantia for type 2 diabetes mellitus. Cochrane Database Syst Rev 2009. [DOI: 10.1002/14651858.cd007845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Pavana P, Sethupathy S, Manoharan S. Protective Role of Tephrosia purpurea Ethanolic Seed Extract on Glycoprotein Components in Streptozotocin Induced Diabetic Rats. INT J PHARMACOL 2008. [DOI: 10.3923/ijp.2008.114.119] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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