scholarly journals Luo Tong Formula Alleviates Diabetic Retinopathy in Rats Through Micro-200b Target

2020 ◽  
Vol 11 ◽  
Author(s):  
Bing Pang ◽  
Qing Ni ◽  
Sha Di ◽  
Li-juan Du ◽  
Ya-li Qin ◽  
...  

Aim: Diabetic retinopathy (DR) is a serious complication of diabetes (DM). Luo Tong formula (LTF) exerts protective effects against DR in rats, but its underlying mechanism remains unknown. Methods: Sprague-Dawley rats injected with streptozotocin (STZ) were used as an experimental diabetes model. LTF or calcium dobesilate (CaD) was administered to diabetic rats via gastric gavage. After the 12 weeks of treatment, blood and tissue samples were collected to determine serum glucose and retinal structure. Blood samples were collected for blood glucose and hemorheology analysis. Gene or protein expression levels were evaluated by immunohistochemistry, western blotting and/or quantitative real-time polymerase chain reaction (PCR). Results: DM rats exhibits significantly increased blood retinal-barrier (BRB) breakdown and VEGF/VEGFR expression in the retina, and decreased miR-200b and tight junction ZO-1/Occludin/ Claudin-5 genes expression, as well as Ang-1/Tie-2 expressions in the retina compared to normal control group. LTF treatment significantly moderated histological abnormalities in diabetic rats, independent of blood glucose level; improved some hemorrheological parameters; decreased the expressions of VEGF/VEGFR and BRB breakdown, significantly increased PEDF and tight junction proteins ZO-1/Occludin, as well as increased retinal miR-200b expression compared to non-treatment diabetic rats. Moreover, LTF prevented the reduction in Ang-1/Tie-2 expression. Conclusions: LTF treatment ameliorated DR through its repair vascular and attenuate vascular leakage. A mechanism involving miR-200b may contribute to benefit effects.

2000 ◽  
Vol 9 (5) ◽  
pp. 243-248 ◽  
Author(s):  
Anália Carmo ◽  
José G. Cunha-Vaz ◽  
Arsélio P. Carvalho ◽  
Maria Celeste Lopes

Background:Our previous results showed that in retinas from streptozotocin (STZ)-induced diabetic rats there is an increased level of interleukin-1β (IL-1β ). This cytokine may be involved in the expression of the inducible isoform of the nitric oxide synthase (iNOS), with consequent synthesis of large amounts of NO and blood–retinal barrier (BRB) breakdown.Aims:The aim of this work was to examine whether the administration of cyclosporin-A (Cs-A) to STZinduced diabetic rats inhibits the synthesis of IL-1β and the expression of the inducible proteins, iNOS and cyclo-oxygenase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown.Methods:The level of IL-1β was evaluated by ELISA and the NO production by L-{3H}-citrulline formation. Expression of iNOS and COX-2 proteins was determined by two methods, western blot and immunohistochemistry. The permeability of the BRB was assessed by quantification of the vitreous protein.Results and discussion:Our results indicated that the levels of IL-1β and NO in retinas from Cs-A-treated diabetic rats are significantly reduced, as compared to that in non-treated diabetic rats. The treatment of diabetic rats with Cs-A also significantly inhibited the expression of the inducible proteins, iNOS and COX2. The evaluation of the vitreous protein content revealed that Cs-A also reduces the BRB permeability. Taken together, these results suggest that the increased production of the inflammatory mediators, IL-1β and NO, in diabetes may affect the BRB permeability and therefore contribute to the development of diabetic retinopathy.


2018 ◽  
Vol 127 (05) ◽  
pp. 320-325 ◽  
Author(s):  
Fatemeh Ramezani-Aliakbari ◽  
Mohammad Badavi ◽  
Mahin Dianat ◽  
Seyed Mard ◽  
Akram Ahangarpour

AbstractTrimetazidine (TMZ), as an anti-ischemic drug, plays a critical role in protecting against cardiovascular complications induced by diabetes. This study was therefore aimed to evaluate the protective effects of TMZ on reperfusion-induced arrhythmias in the diabetic rats. Male Sprague-Dawley rats (250±20 g) were randomly assigned to four (n=8): control rats (C), alloxan induced diabetic rats (D), diabetic rats treated with TMZ (10 mg/kg, D+T10), diabetic rats treated with TMZ (30 mg/kg, D+T30). TMZ was treated orally once daily for 8 weeks. Diabetes was induced by a single intraperitoneal injection of alloxan (120 mg/kg). Ischemia-reperfusion (I/R) was carried out via 30 min of ischemia and following120-min reperfusion. The magnitude and score of arrhythmia, the left ventricular function, infarct size, lactate dehydrogenase (LDH), myocardial creatine kinase (CK-MB) and troponin (cTnI) were measured. The findings were evaluated by two-way repeated measures and one-way ANOVA followed by LSD post hoc test and Fisher's exact test for incidence percentage. The duration, incidence and score of arrhythmia (p<0.001), infarct size (p<0.01) were significantly increased, the cardiac contractility (±dp/dt), LDH, CK-MB (p<0.001) and cTnI (p<0.05) were significantly decreased in the diabetic rats in comparison with the control group. However, treatment with TMZ in the diabetic rats was significantly improved the duration (p<0.001), incidence and score of arrhythmia,±dp/dt LDH, CK-MB, cTnI (p<0.05) and infarct size (p<0.01) in comparison with the untreated diabetic group. The present study indicates anti-arrhythmic effect of TMZ in reducing arrhythmias induced by reperfusion in the diabetic rats.


2020 ◽  
Vol 2 (2) ◽  
pp. 136-140
Author(s):  
Endang Widhiyastuti ◽  
Mastuti Widi Lestari

Diabetes which is well-known in the community as diabetes in Indonesia is a chronic disease, which occurs when the pancreas does not produce enough insulin or when the body cannot utilize the insulin produced by its own products. The Provision of antioxidants in DM mice can reduce blood sugar levels. One of the herbs that can be used for control and management of blood sugar in diabetes is swollen koro. Koro Benguk (Mucuna pruriens L) is a plant that can be used as an alternative treatment because it contains antioxidants that can maintain health without causing toxic effects. The purpose of this study was to determine whether there is an effect of giving koro benguk coffee (Mucuna pruriens L) on blood sugar levels of Streptozotocin-induced Diabetes Mellitus Rats. This study is an experimental study of Sprague Dawley mice. A total of 35 male wistar rats were divided into 5 groups each: normal control (K1); diabetes control (K2); diabetic rats were given a large coffee extract 0.63 mg / g BW rat (P1); diabetic rats were given a large infusion of coffee koro 1.26 mg / g BW rats (P2). Diabetic rats were given an infusion of coffee koro benguk20,52 mg / g BW rats. Fasting blood glucose (GDP) levels were analyzed weekly for 3 weeks using the GOD-PAP method. The results of the study showed a decrease in blood sugar for 4 times the observation time in almost all treatment groups except the positive control group. The conclusions in this study were the provision of related coffee (Mucuna pruriens L) can reduce fasting blood glucose levels in Sprague Dawley rats with diabetes models significantly compared to controls.


2008 ◽  
Vol 29 (3) ◽  
pp. 621-628 ◽  
Author(s):  
Jeong Hun Kim ◽  
Jin Hyoung Kim ◽  
Young Suk Yu ◽  
Chang Sik Cho ◽  
Kyu-Won Kim

Diabetic retinopathy (DR) is the leading cause of vision loss as a major complication of diabetes mellitus. The blood—retinal barrier (BRB) breakdown is a critical early event in the pathogenesis of DR. It has been known that the rennin-angiotensin system (RAS) is important in the progression of the DR via angiotensin II (Ang II), the effector of RAS. In this study, we showed that blockade of Ang II attenuates vascular endothelial growth factor (VEGF)-mediated BRB breakdown in DR. In streptozotocin-induced diabetes, retinal vascular permeability increased with upregulation of VEGF, where Ang II and its receptors were upregulated. Ang II induced VEGF expression in retinal endothelial cells accompanied by loss of tight junction proteins. However, the blockade of Ang II by perindopril, an angiotensin converting enzyme (ACE) inhibitor, inhibited upregulation of VEGF, and prevented the loss of tight junction proteins. Moreover, inhibition of Ang II by perindopril attenuated increased vascular permeability of diabetic retina accompanied by recovery of tight junction proteins in retinal vessels. Therefore, we suggest that the RAS involves in increased vascular permeability during early stage of DR, which is mediated by VEGF. Furthermore, the ACE inhibitor may have a therapeutic potential in the treatment of diabetic BRB breakdown.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Tingting Jiang ◽  
Qing Chang ◽  
Jiyang Cai ◽  
Jiawen Fan ◽  
Xiaozhe Zhang ◽  
...  

Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR). Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Melatonin (10 mg kg−1daily, i.p.) was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL). Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS), was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina.


2014 ◽  
Vol 50 (4) ◽  
pp. 765-771 ◽  
Author(s):  
Ma Song-Tao ◽  
Liu Dong-lian ◽  
Deng Jing-jing ◽  
Peng Yan-juan

Mulberry leaves (Morus alba L.) are a traditional Chinese medicine for blood serum glucose reduction. This study evaluated the protective effects of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats. In this study, 80 Sprague-Dawley rats were divided into five groups: A (control), B (diabetic treated with saline), C-D (diabetic treated with 0.3, 0.1 g/kg mulberry flavonoids once a day for 8 weeks) and E (diabetic treated with 0.3 mg/kg methycobal). The diabetic condition was induced by intraperitoneal injection of 200 mg/kg alloxan dissolved in saline. At the end of the experimental period, blood, and tissue samples were obtained for biochemical and histopathological investigation. Treatment with 0.3 g/kg mulberry flavonoids significantly inhibited the elevated serum glucose (P< 0.01). The increased myelin sheath area (P< 0.01), myelinated fiber cross-sectional area and extramedullary fiber number (P< 0.05) were also reduced in alloxan-induced rats treated with 0.3 g/kg mulberry flavonoids. 0.3 g/kg mulberry flavonoids also markedly decreased onion-bulb type myelin destruction and degenerative changes of mitochondria and Schwann cells. These findings demonstrate that mulberry flavonoids may improve the recovery of a severe peripheral nerve injury in alloxan-induced diabetic rats and is likely to be useful as a potential treatment on peripheral neuropathy (PN) in diabetic rats.


2020 ◽  
Author(s):  
Rui Li ◽  
Huimin Yuan ◽  
Tao Zhao ◽  
Yimin Yan ◽  
Zhaochen Liu ◽  
...  

Abstract Background: miRNAs participate in the development and progression of diabetic retinopathy (DR) and are involved in multiple pathogenesis of DR. High expression of NF-κB signaling pathway boosts the progression of retinopathy in diabetes rats. We found a site where miR-874 bound to the NF-κB p65 by the prediction on a bioinformatics website. Therefore, it was speculated that miR-874 might improve retinopathy in diabetic rats by inhibiting the NF-κB signaling pathway.Methods: Ten healthy Sprague-Dawley rats were taken as the control group. Sixty streptozotocin (60 mg/kg)-induced diabetes model rats were randomly divided into the model group (injection of normal saline), negative control (NC) agomir group (injection of overexpressed NC vector), miR-874 agomir group (injection of miR-874 mimic), miR-874 anti-agomir group (injection of miR-874 inhibitor), EVP4593 group (injection of NF-κB signaling pathway antagonist EVP4593), and miR-874 anti-agomir + EVP4593 group (injection of miR-874 inhibitor and EVP4593). All injection was via caudal vein.Results: miR-874 could target the degradation of p65. Compared with the control group, there were significantly reduced miR-874 expression, increased VEGF and Ang2 protein expressions, lowered end-diastolic velocity and peak systolic velocity of central retinal artery (CRA) and blood velocity of central retinal vein and CRA, heightened plasma viscosity, blood viscosity and erythrocyte sedimentation rate at all shear rates, decreased capillary pericytes, increased vascular endothelial cells, and ascended p65 expression in the retina of rats in the model group (all P < 0.05). It showed that pathological changes appeared in the retina of diabetes rats. These indexes showed the same results after miR-874 was inhibited (all P < 0.05). However, these indexes showed the opposite results in the miR-874 agomir group and EVP4593 group compared with the model group (all P < 0.05). EVP4593 could alleviate the aggravation of retinopathy that was caused by the inhibition of miR-874 in diabetes rats.Conclusions: miR-874 mediates the NF-κB signaling pathway by targeting the degradation of p65 to further improve the retina of diabetes rats, showing the improvement effect of miR-874 on diabetic retinopathy in rats.


2020 ◽  
Vol 11 (4) ◽  
pp. 5067-5070
Author(s):  
Pang Jyh Chayng ◽  
Nurul Ain ◽  
Kaswandi Md Ambia ◽  
Rahim Md Noah

The purpose of this project is to study the anti-diabetic effect of on a diabetic rat model. A total of Twenty male Sprague rats were used and it randomly distributed into four groups which are Group I: , Group II: negative control, Group III: and Group IV: and . In diabetic model were induced with via injection at the dosage of 65mg/kg. and FBG (Fasting Blood Glucose) level of diabetic rats were assessed every three days. Blood was collected via cardiac puncture at day 21 after the induction of treatment. Insulin level of the rats was assessed with the Mercodia Rat Insulin ELISA kit. FBG level of group I (12.16 ±3.96, p&lt;0.05) and group IV (11.34 ±3.67, p&lt;0.05) were significantly decreased. Meanwhile, the for all rats did not show any significant increase. However, the insulin level was escalated in group IV (0.74+0.25, p&lt;0.05) significantly. The present study shows that the and the combination of and lowered blood glucose level and enhanced insulin secretion.


2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.


2015 ◽  
Vol 93 (4) ◽  
pp. 385-395 ◽  
Author(s):  
Chandrabose Sureka ◽  
Thiyagarajan Ramesh ◽  
Vavamohaideen Hazeena Begum

The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190–220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications.


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