Therapeutic effects of Morinda citrifolia L. leaves extract on Streptozotocin induced diabetic retinopathy in rats

Diabetic retinopathy is the diabetic complication that affects eyes. It is caused by damage to the blood vessels at the retina tissue. Morinda citrifolia, folklore medicine has been known for its biological activities for treating various diseases. Previous studies showed that the plant possesses the significant anti-cataract capability to maintain lens opacity in glucose-induced bovine lens model and retain the physiological function of chick lens epithelial cells during oxidative stress. The objective of the study was to determine a possible prophylactic characteristic of Morinda citrifolia leaves extract (MLE) on diabetic retinopathy by employing rats as a model. The first part of the study was conducted to investigate the antioxidant property and the bioactive compounds available in the MLE. The antioxidant and free radical- scavenging activity were measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2- azinobis-(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) methods. The extracts obtained at a higher temperature exhibited a significant free radical-scavenging activity compared with extraction at a lower temperatures (p<0.05). Subsequently, the phenolic compounds in MLE extracted at the optimum temperature of 60˚C were identified in this study through LC-ESI-MS/MS. The findings revealed that phenolic compounds presented in the MLE was mainly flavonol glycoside. To determine the effect of MLE on diabetic retinopathy and cataract, second part of the study was to examine biochemical parameters changes after MLE treatment. In this case, the diabetic rats’ model was used by streptozotocin induction. Development of retinopathy and cataract were observed with slit lamp and ophthalmoscope. The supplementation of MLE (200 and 400 mg/kg b.w) for 8 weeks significantly reduced (p<0.05) the plasma glucose level compared to diabetic control (DC) rats with reduction of 24.09% and 12.02% respectively. MLE200 had lowest opacity index compared with MLE400 and gliclazide (GLI). The results of biochemical parameters showed that MLE administration could increase glutathione peroxidase (GPx) activity, decreased malondialdehyde (MDA) level and reactive oxidative stress in the diabetic rats. Accumulation of sorbitol in serum of MLE 200 and MLE 400 was significantly inhibited by 33.23 % and 43.92 % respectively. Decreasing level of sorbitol was accompanied with lower level of aldose reductase in the treated groups. Additionally, MLE has produced 50% inhibition of advanced glycation end products (AGEs) formation. Thus, MLE may have beneficial role in attenuation of diabetic complications with the demonstrated inhibitory potential of MLE against formation of AGEs, accumulation of sorbitol and activation of aldose reductase enzyme. The third part of the study was to determine the influence of MLE on the gene expression profile and biochemical pathways underlying the mitigating effect of MLE. Microarray analysis resulted in a total of 496 genes were up-regulated and 251 were down-regulated in MLE 200 group. Whereas in MLE400, 273 genes were up-regulated and 155 were down-regulated. From protein-protein interaction constructed with STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), MLE200 network consists of 111 nodes while MLE400 network has 26 nodes. Twenty-five hub genes were identified from MLE200 network with connection degree equal and more than 5. The identified hub genes were primarily involved in extracellular matrix organization and cellular migration. Our results provide insight into region-specific gene expression of differentially expressed genes in the treated diabetic rats. These observations provide foundation toward understanding of the molecular and cellular mechanisms of MLE regulating diabetic retinopathy. Collectively, the findings here suggesting that MLE has potential in development and application as therapeutic alternative for diabetic retinopathy prevention.

Text FPSK (p) 2021 45 - Declaration Form.pdf Restricted to Repository staff only Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (371kB) Text FPSK (p) 2021 45 - Full Text.pdf Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (8MB) Text FPSK (p) 2021 45.pdf Restricted to Repository staff only Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (8MB)

Actions (login required)

View Item