crocin and Diabetic-Retinopathy

Diabetic macular edema (DME) is one of the most important sight-threatening complications in patients with diabetes. Owing to neuroprotective properties, crocin, as the main constituent in saffron, is thought to be useful in the treatment and prevention of diabetic maculopathy. The aim of this trial was to evaluate the effects of crocin as a supplement on reducing inflammation in patients with diabetic maculopathy.. Double-masked, placebo controlled, phase 2 randomized clinical trial.. Participants: In this study, 101 eyes of 60 patients with refractory diabetic maculopathy to conventional therapy including macular photocoagulation and intravitreal injection of anti-vascular endothelial growth factor agent (bevacizumab) with or without steroid (triamcinolone) were studied in 3 groups.. Patients in the crocin groups received 5 mg or 15 mg crocin tablets per day for 3 months, whereas patients in the placebo group received 1 placebo tablet per day during the study. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured before, every month during, and 3 months after intervention. Biochemical blood tests were also evaluated before and after trial.. The BCVA and CMT were evaluated as the primary outcomes, whereas HbA1c and fasting blood sugar (FBS) were studied as the secondary outcomes in this trial.. One hundred and one eyes were enrolled in this trial and were divided into 3 groups (crocin 5 mg, n = 34; crocin 15 mg, n = 33; and placebo, n = 34). According to our data, administration of crocin 15 mg tablet per day could significantly decrease HbA1c (P value = .024; 95% confidence interval [CI] 0.3-0.96), and CMT (P value = .005; 95% CI, 32.75-126.99) and improve BCVA (logMAR changes; P value = .012; 95% CI, 0.23-0.69) compared to the placebo group. Although administration of crocin 5 mg tablet per day could clinically improve HbA1c, FBS, CMT, and BCVA, the difference was not significant compared to the placebo group.. This study indicated the effect of crocin as a potent antioxidant and neuroprotective for treatment of refractory DME in the short term; however, the clinical significance is yet to be proved in a study with larger sample size and longer duration of follow-up and also in treatment-naïve patients.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Blood Glucose; Carotenoids; Diabetic Retinopathy; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Liver Function Tests; Macula Lutea; Macular Edema; Male; Middle Aged; Placebos; Tablets; Tomography, Optical Coherence; Visual Acuity

Topics: Carotenoids; Diabetes Mellitus; Diabetic Retinopathy; Humans; Macular Degeneration

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus that is closely associated with the degeneration and loss of retinal ganglion cells (RGCs) caused by diabetic microangiopathy and subsequent oxidative stress and an inflammatory response. Microglial cells are classed as neurogliocytes and play a significant role in neurodegenerative diseases. Over-activated microglial cells may cause neurotoxicity and induce the death and apoptosis of RGCs. Crocin is one of the two most pharmacologically bioactive constituents in saffron. In the present study, we focused on the role of microglial cells in DR, suggesting that DR may cause the over-activation of microglial cells and induce oxidative stress and the release of pro-inflammatory factors. Microglial cells BV-2 and N9 were cultured, and high-glucose (HG) and free fatty acid (FFA) were used to simulate diabetes. The results showed that HG-FFA co-treatment caused the up-regulated expression of CD11b and Iba-1, indicating that BV-2 and N9 cells were over-activated. Moreover, oxidative stress markers and pro-inflammatory factors were significantly enhanced by HG-FFA treatment. We found that crocin prevented the oxidative stress and pro-inflammatory response induced by HG-FFA co-treatment. Moreover, using the PI3K/Akt inhibitor LY294002, we revealed that PI3K/Akt signaling plays a significant role in blocking oxidative stress, suppressing the pro-inflammatory response, and maintaining the neuroprotective effects of crocin. In total, these results provide a new insight into DR and DR-induced oxidative stress and the inflammatory response, which provide a potential therapeutic target for neuronal damage, vision loss, and other DR-induced complications.

Topics: Animals; Antioxidants; Carotenoids; Cell Line; Diabetic Retinopathy; Humans; Inflammation Mediators; Mice; Microglia; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction