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1.
Molecules ; 23(12)2018 Dec 05.
Article in English | MEDLINE | ID: mdl-30563087

ABSTRACT

Diabetes mellitus is a metabolic disease that can lead to high morbidity, mortality and long-term complications. Available treatment strategies, which are mainly based on treating hyperglycemia, with insulin and other pharmacological agents are not completely efficient and can even lead to development of unwanted side effects. Scientific evidence suggests that bioactive compounds from teas and other plant-based foods, which are known source of natural antioxidants, could be an attractive strategy to preferentially treat and manage type 2 diabetes mellitus (T2DM) and thus, have significant therapeutic implications. In this review, we attempt an in-depth analysis and discussion of the current progress in our understanding of the antidiabetic potential of two commercialized South Africa herbal tisanes-Rooibos and Honeybush and their polyphenols.


Subject(s)
Aspalathus/chemistry , Cyclopia Plant/chemistry , Hypoglycemic Agents/pharmacology , Plant Extracts/pharmacology , Teas, Herbal/analysis , Animals , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Humans , Hypoglycemic Agents/chemistry , Plant Extracts/chemistry , Polyphenols/chemistry , Polyphenols/pharmacology , South Africa
2.
BMC Pharmacol Toxicol ; 19(1): 84, 2018 Dec 06.
Article in English | MEDLINE | ID: mdl-30522526

ABSTRACT

BACKGROUND: Diabetes mellitus is a metabolic disease in which the body is unable to produce insulin or respond to insulin production, consequently leading to abnormal metabolism of carbohydrates, lipids and proteins causing elevation of glucose in the blood. Oxidative stress, an imbalance between the production of free radicals and body antioxidant system has been implicated in the pathogenesis of diabetes. Free radicals attack important macromolecules leading to cell damage. Antioxidants are intimately involved in the prevention of damage caused by free radicals. METHODS: The anti-diabetic effects of hybrid compounds (2a-h) of thiosemicarbazone and triazole containing methoxy groups at C (4) positions were tested against genes involved in glucose metabolism (Glut-4, Mef2a and Nrf-1) using quantitative real time PCR (qPCR). Free radical scavenging capacity (FRAP, TEAC, DPPH and ORAC) of the hybrids was also carried out by using established antioxidant capacity assays. RESULTS: From the results, hybrid compounds 2b and 2h showed more pronounced effects in up-regulating diabetes associated genes which are important in the up-regulation of glucose uptake. All the hybrid compounds also showed free radical scavenging abilities. CONCLUSION: In conclusion, hybrid compounds (2b and 2h) can be useful as potential drugs for the management of diabetes mellitus.


Subject(s)
Free Radical Scavengers/pharmacology , Hypoglycemic Agents/pharmacology , Thiosemicarbazones/pharmacology , Triazoles/pharmacology , 3T3-L1 Cells , Animals , Biological Transport , Gene Expression Regulation/drug effects , Glucose/metabolism , Glucose Transporter Type 4/genetics , MEF2 Transcription Factors/genetics , Mice , Nuclear Respiratory Factor 1/genetics
3.
Biochem Biophys Res Commun ; 486(1): 83-87, 2017 04 22.
Article in English | MEDLINE | ID: mdl-28263745

ABSTRACT

Exercise brings changes on the chromatin ensuing the upregulation of many genes that confer protection from type 2 diabetes. In type-2 diabetes, critical genes are down-regulated such as those involved in glucose transport (GLUT4, MEF2A) and also oxidative phosphorylation (NRF-1 and its target genes). Recent reports have shown that NRF-1 not only regulate mitochondrial oxidative genes but also controls MEF2A, the main transcription factor for glucose transporter, GLUT4. Such dual control of the two pathways by NRF-1 place it as critical gene in the design of therapeutic modalities much needed to cure or better manage type 2 diabetes. Although it is known that NRF-1 controls these dual pathways (glucose transport and oxidative phosphorylation), the actual molecular mechanisms involved surrounding this regulation remains elusive. NRF-1 itself is regulated through posttranslational modifications (acetylation, methylation and phosphorylation) resulting in enhanced binding to its target genes. This study is therefore aimed at assessing whether CaMKII, a kinase activated by exercise brings about hyper-acetylation of histones in the vicinity of NRF-1 target gene, Mef2a. Five to six weeks old male Wistar rats were used in this study. Chromatin immunoprecipitation (ChIP) assay was used to investigate the extent through which NRF-1 is bound to the Mef2a gene and if this was associated with hyper-acetylation of histones in the region of NRF-1 binding site of the Mef2a gene. Quantitative real time PCR (qPCR) was used to determine the gene expression of MEF2A and NRF-1. Results from this study indicated that exercise-induced CaMKII activation increased hyper-acetylation of histones in the region of NRF-1 binding site on vicinity of Mef2a gene and this was associated with the increased binding of NRF-1 to Mef2a gene. Exercise also increased the expression of NRF-1 and MEF2A genes. Administration of CaMKII inhibitor (KN93) prior to exercise attenuated the observed exercise-induced increase of NRF-1 and MEF2A expressions. In conclusion, this study demonstrated for the first time in our knowledge one mechanism through which NRF-1 regulates MEF2A, pathway critical in glucose transport.


Subject(s)
Histones/metabolism , NF-E2-Related Factor 1/genetics , Physical Conditioning, Animal , Promoter Regions, Genetic/genetics , Acetylation , Animals , Benzylamines/pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Gene Expression/drug effects , Glucose Transporter Type 4/genetics , Glucose Transporter Type 4/metabolism , MEF2 Transcription Factors/genetics , MEF2 Transcription Factors/metabolism , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , NF-E2-Related Factor 1/metabolism , Protein Binding , Protein Kinase Inhibitors/pharmacology , Rats, Wistar , Response Elements/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sulfonamides/pharmacology
4.
Article in English | MEDLINE | ID: mdl-25395698

ABSTRACT

BACKGROUND: Diabetes mellitus characterized by hyperglycaemia could affect sperm quality as a result of increased oxidative stress. This study was performed to investigate the effects of red palm oil (RPO), aqueous rooibos tea extracts (RTE) as well as their combination (RPO + RTE) on sperm motility parameters in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced by a single administration of streptozotocin (50 mg/kg) and the rats were treated with red palm oil (2 ml/day) and / or aqueous rooibos tea extract (2%) for 7 weeks. Sperm motility parameters were measured using Computer Assisted Sperm Analyzer (CASA). RESULTS: Hyperglycaemia negatively affected the sperm progressive motility significantly at p<0.05. There was a significant decrease (p<0.05) in sperm linearity (LIN) in the diabetic group when compared with the normal control group. RPO supplemented diabetic rats exhibited increased progressive sperm motility, sperm linearity (LIN) and wobble (WOB). Significant decreases (p<0.05) in straight line velocity (VSL) and average path velocity (VAP) of the sperms were observed in all the diabetic groups when compared to the control group. Significant (p<0.05) elevated levels of WOB and LIN were observed following RTE treatment and co-administration with RPO respectively. CONCLUSION: The present study suggests that red palm oil and / or rooibos administration exhibited no adverse effects on sperm motility parameters but rather showed some beneficial effects.


Subject(s)
Arecaceae/chemistry , Aspalathus , Asthenozoospermia/prevention & control , Diabetes Mellitus, Experimental/complications , Plant Oils/therapeutic use , Sperm Motility/drug effects , Spermatozoa/drug effects , Animals , Diabetes Complications/prevention & control , Diabetes Mellitus, Experimental/physiopathology , Hyperglycemia/complications , Male , Oxidative Stress , Palm Oil , Phytotherapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Oils/pharmacology , Rats, Wistar , Spermatozoa/physiology
5.
ScientificWorldJournal ; 2014: 437081, 2014.
Article in English | MEDLINE | ID: mdl-25013856

ABSTRACT

This study was carried out to investigate the in vitro antioxidant potentials of the leaves and fruits of Nauclea latifolia, a straggling shrub or small tree, native to tropical Africa and Asia. Hot water extracts of the leaves and fruits of Nauclea latifolia were assessed for their total polyphenolic, flavanol, and flavonol contents as well as 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability, ferric reducing antioxidant power (FRAP), Trolox equivalence antioxidant capacity (TEAC), and oxygen radical absorbance capacity (ORAC) assays. The aqueous extract of the leaves was found to contain higher level of total polyphenols (11.63 ± 0.023 mg GAE/g), flavanol (1.45 ± 0.10 mg CE/g), and flavonol (2.22 ± 0.37 mg QE/g) than the extract of the fruits with values of 1.75 ± 0.02 mg GAE/g (total polyphenol), 0.15 ± 0.01 mg CE/g (flavanol), and 1.00 ± 0.13 mg QE/g (flavonol). Similarly, the aqueous extract of the leaves also exhibited higher DPPH (IC50 20.64 mg/mL), FRAP (86.10 ± 3.46 µmol AAE/g), TEAC (94.83 ± 3.57 µmol TE/g), and ORAC (196.55 ± 0.073 µmol TE/g) than the extract of the fruits with DPPH (IC50 120.33 mg/mL), FRAP (12.23 ± 0.40 µmol AAE/g), TEAC (12.48 ± 0.21 µmol TE/g), and ORAC (58.88 ± 0.073 µmol TE/g). The present study showed that Nauclea latifolia has strong antioxidant potentials with the leaves demonstrating higher in vitro antioxidant activities than the fruits.


Subject(s)
Antioxidants/chemistry , Plant Extracts/chemistry , Rubiaceae/chemistry , Flavonols/analysis , Fruit/chemistry , Oxidation-Reduction , Plant Leaves/chemistry , Polyphenols/analysis
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