Syzygium aromaticum Reduces Diabetes-induced Glucotoxicity via the NRF2/Glo1 Pathway

Planta Medica ◽  
2020 ◽  
Vol 86 (12) ◽  
pp. 876-883
Author(s):  
Moon Ho Do ◽  
Jiwon Choi ◽  
Yoonsook Kim ◽  
Sang Keun Ha ◽  
Guijae Yoo ◽  
...  

AbstractAdvanced glycation end products and methylglyoxal are known to show increased levels in diabetic conditions and induce diverse metabolic disorders. However, the antiglycation ability of the bark of Syzygium aromaticum is not yet studied. In this study, we determined the inhibitory effects of S. aromaticum on AGE formation. Moreover, S. aromaticum showed breakage and inhibitory ability against the formation of AGE-collagen crosslinks. In SV40 MES13 cells, treatment with the S. aromaticum extract significantly ameliorated MG-induced oxidative stress as well as cytotoxicity. Furthermore, in the S. aromaticum extract-treated group, there was a reduction in levels of several diabetic markers, such as blood glucose, kidney weight, and urinary albumin to creatinine ratio in streptozotocin-induced diabetic rats. Treatment with the S. aromaticum extract significantly increased the expression of nuclear factor erythroid 2-related factor 2, a transcription factor involved in the expression of antioxidant enzymes. Moreover, the treatment significantly upregulated the expression of glyoxalase 1 and downregulated the expression of receptor for AGEs. These results suggest that the S. aromaticum extract might ameliorate diabetes-induced renal damage by inhibiting the AGE-induced glucotoxicity and oxidative stress through the Nrf2/Glo1 pathway.

Author(s):  
Sangita Devrao Jogdand ◽  
Raju Shinde ◽  
Vivek Sinha ◽  
Naman Chandrakar

Background: Commonly used aminoglycosides have frequent side effect of nephrotoxicity, still are preferred by clinicians because of efficacy against gram negative bacteria, resistant bacteria, nosocomial infections and cost effectiveness. Gentamicin produces oxidative stress; substances ameliorating stress are used to reduce toxicity. Turmeric has multiple medicinal properties including potent antioxidant activity, hence study was undertaken.Methods: Eight groups containing six animals in each group, treated for 15 days. First group treated with normal saline. Second, fourth and sixth group treated with only gentamicin- sacrificed at 16, 22, 29th day. Third, fifth and seventh group treated with gentamicin and turmeric simultaneously and sacrificed on 16, 22, 29th day. Eighth group was pre-treated with turmeric for thirty days and concurrently treated with gentamicin and turmeric for 15 days and sacrificed on 16th day. Levels of blood urea, serum creatinine, superoxide dismutase and histopathological grades were assessed each time.Results: Severe renal dysfunction (146 ± 9.2, 2.03 ± 0.26), highest renal injury grading (3.66 ± 0.24) was observed in only gentamicin treated groups followed by spontaneous recovery after withdrawal of drug but with higher levels of oxidative stress (0.04 ± 0.01). Gentamicin and Turmeric treated groups maintained renal function and had lower level of renal damage grades and oxidative stress. Turmeric pre-treated group was having lowest oxidative stress (0.12 ± 0.03), histopathology grade (0.60 ± 0.06) with normal renal functions.Conclusions: Turmeric has potent antioxidant property which effectively protects kidney from damage induced because of gentamicin.


Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 160 ◽  
Author(s):  
Weronika Wojnar ◽  
Maria Zych ◽  
Sławomir Borymski ◽  
Ilona Kaczmarczyk-Sedlak

Prolonged hyperglycemia is one of the main causes of reactive oxygen species and free radicals generation in diabetes which may affect various organs, including the eye. Oxidative damage to proteins and lipids in the eye lens could lead to cataract formation. To cope with oxidative stress, the endogenous antioxidative system may be supported by the supplementation of exogenous antioxidants. The aim of this study was to evaluate the effect of chrysin, a natural flavonoid, on oxidative stress and polyol pathway-related markers in the lenses of streptozotocin-induced type 1 male diabetic rats. Chrysin at doses of 50 and 100 mg/kg was administered by gavage for 28 days. This treatment resulted in a decrease in antioxidative enzymes activity and oxidative stress index. Moreover, chrysin administration elevated the reduced glutathione level in the lenses. A decrease in the markers linked to oxidative damage to proteins and lipids in the lenses was noted, especially after treatment with 50 mg/kg of chrysin. Neither of the chrysin doses affected glycemia-related markers in the serum or altered parameters related to the polyol pathway and advanced glycation end-products level in the lenses of diabetic rats. Upon obtaining results, it can be concluded that chrysin reveals antioxidative activity in the lenses but shows no antihyperglycemic or antiglycation properties.


Author(s):  
Yogesh A. Kulkarni ◽  
Sachin V. Suryavanshi

Background: Diabetes is a metabolic disorder affecting large percentage of population worldwide. Chronic hyperglycemic condition leads to generation of advanced glycation end products, reactive oxygen species and inflammatory cytokines, which worsen functioning of kidney. Clinical management of diabetic nephropathy is difficult as it requires multifocused approach. Hence, Combination of lisinopril a drug used in clinical practice for nephropathy and naringenin, a flavonoid reported to have significant effect in nephropathy may show additive of synergistic effect with less side effects. Objective: The objective of present study was to evaluate the effect of combination of lisinopril with naringenin in diabetic nephropathy. Methods: Diabetes was induced in male Sprague Dawley rats by streptozotocin (55 mg/kg, i.p.). After four weeks of diabetes induction animals were treated with naringenin alone and combination of Lisinopril and naringenin for next four weeks. At the end of study, various urine and biochemical parameters were evaluated. Oxidative stress parameters like malondialdehyde, reduced glutathione; catalase and superoxide dismutase for kidney tissues were estimated and histopathology studies of kidney were carried out. Results: Combination of lisinopril (10 mg/kg) and naringenin (25 and 50 mg/kg) treatment showed significant improvement in the biochemical and urine parameters. Combination treatment also attenuated renal oxidative stress and renal damage as observed in histopathological studies. Conclusion: Treatment with combination of lisinopril and naringenin showed promising effect in diabetic nephropathy in rats.


2020 ◽  
Vol 26 (4) ◽  
pp. 432-447
Author(s):  
Tala Pourlak ◽  
◽  
Monireh Halimi ◽  
Tannaz Pourlak ◽  
Parham Maroufi ◽  
...  

Aims: In this study, we investigated the effect of clove extract (Syzygium aromaticum) on liver cell damage and oxidative stress caused by diabetes in adult rats. Methods & Materials: For this study, 28 female rats were collected and divided into four groups: A: Control group; B: Diabetic Control group (DC) which received 20% glycerol dissolved in normal saline as carriers; C: Diabetic rats (DSA) treated with cloves hydroalcoholic extract (4 mg/kg); d) diabetic rats (DG) treated with glibenclamide (5 mg/kg) as a standard drug. Findings: The fasting blood sugar and serum triglyceride levels in the DC group increased significantly compared to the control group (P<0.05). In DC, DG, and DSA groups, high-density lipoprotein, and serum insulin levels decreased significantly compared to the control group (P<0.05). Also, in DG and DSA groups, high-density lipoprotein and serum insulin levels increased significantly compared to the DC group. Conclusion: Cloves can affect fasting blood sugar, serum insulin levels, serum fat profile levels, and prevent liver tissue damage in diabetic rats caused by streptozotocin.


2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.


2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.


Author(s):  
Basiru Olaitan Ajiboye ◽  
Babatunji Emmanuel Oyinloye ◽  
Jennifer Chidera Awurum ◽  
Sunday Amos Onikanni ◽  
Adedotun Adefolalu ◽  
...  

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.


2016 ◽  
Vol 32 (3) ◽  
pp. 329-336 ◽  
Author(s):  
Abolfazl Nasiri ◽  
Nasrin Ziamajidi ◽  
Roghayeh Abbasalipourkabir ◽  
Mohammad Taghi Goodarzi ◽  
Massoud Saidijam ◽  
...  

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