Retinoprotective Effects Of Crocin And Crocetin via Anti-Angiogenic Mechanism in High Glucose-Induced Human Retinal Pigment Epithelium Cells.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common side effects of diabetes. We aimed to investigate the effects of crocin and crocetin (as a deglycosylated form of crocin in blood stream) in gene expression or protein levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor-receptor1 (VEGFR-1), matrix metalloproteinases2 (MMP-2), matrix metalloproteinases9 (MMP-9) and thrombospondin-2 (TSP-2) in high glucose cell culture media. METHODS: The retinal pigment epithelium (RPE) cells were exposed to high glucose (HG, 30 mM glucose concentration) and normal glucose (NG, 24.5 mM mannitol + 5.5 mM glucose) for six days. RPE cells were treated in four treatment groups (crocin, crocetin, Bevacizumab, and crocin + Bevacizumab). Gene expressions were measured using quantitative real-time PCR, and protein levels were evaluated by western blot. RESULTS: Findings showed that VEGF gene expression and protein level significantly decreased in all treatment groups. In addition, reduction in VEGFR1 gene expression was significantly higher in Bevacizumab and crocin + Bevacizumab groups than other groups. Only crocin and crocetin could reduce the gene levels of MMP-2 and MMP-9. In addition, TSP-2 protein levels increased when HG cells were exposed to crocin or crocin + Bevacizumab groups. CONCLUSION: Our data showed that crocin and crocetin have anti-VEGF function similar to Bevacizumab, act as an anti-angiogenic agent. Also, crocin and crocetin could decrease MMP-2 and MMP-9 gene levels being inflammatory and angiogenesis factors. As a result, crocin and crocetin have protective effects against angiogenesis and inflammation in DR.

Pharmacological Effects of Saffron and its Constituents in Ocular Disorders from in vitro Studies to Clinical Trials: A Systematic Review.

INTRODUCTION: Some medicinal plants have shown promising therapeutic potential for the management of the diseases. We aimed to systematically review the literature wherein the therapeutic effects of saffron have been studied on eye disorders. METHODS: A systematic literature search was performed in PubMed, Scopus, Web of Science, Google scholar and other databases using eye disorders and saffron as key terms. No strict inclusion criteria were defined, and almost all clinical studies, as well as in vivo and in vitro studies were included. The reported data in each study were extracted and then qualitatively described. RESULTS: Finally, 78 articles were found but only 29 relevant articles were included. Nine articles were clinical trials and 20 articles were studies conducted on cellular and molecular aspects of saffron on eye disorders. According to the included studies, crocin prevented the pro-inflammatory response in retinal cells and decreased glucose levels in diabetic mice. Also, crocetin prevented retinal degeneration and saffron protected photoreceptors from light-induced damage in retinal cells. Saffron also improved visual function in age-related macular edema and decreased intraocular pressure in patients with glaucoma. In addition, it was shown that crocin can improve best corrected visual acuity and decrease central macular thickness in patients with diabetic maculopathy. CONCLUSION: The results of this review indicated that saffron and its main ingredients such as crocin could be a potential candidate for the treatment of ocular disease especially eye inflammation; however, further clinical studies are needed to confirm such efficiency.

ROS-scavenging and Anti-tyrosinase Properties of Crocetin on B16F10 Murine Melanoma Cells.

BACKGROUND: Crocus sativus (Iridaceae) has been traditionally used in the Iranian folk medicine and as a culinary additive. Major components of the plant that are responsible for biological properties are saffranal, crocin, picrocrocin and crocetin. Although the level of crocetin is not high, some of the important activities of saffron such as antioxidant activity have been attributed to crocetin. OBJECTIVE: In the present study, we investigated the effects of crocetin on melanogenesis in B16 melanoma cells. METHODS: The effect of crocetin on intracellular and mushroom tyrosinase activity and the content of melanin was evaluated spectrophotometrically. Tyrosinase and Microphthalmia-Associated Transcription Factor (MITF) protein levels were compared between Crocetin-treated and control cells after western blot analysis. The antioxidative activity of crocetin was also investigated. RESULTS: Crocetin could inhibit mushroom tyrosinase activity and lower the amount of melanin in B16 melanoma cells. Protein levels of tyrosinase and MITF were also decreased by crocetin. Crocetin also showed antioxidant activity and depleted cellular Reactive Oxygen Species (ROS) content but had no cytotoxicity in alamarBlue® assay. CONCLUSION: Taken together, decreased tyrosinase activity, melanin content, tyrosinase and MITF proteins levels, and ROS production showed the inhibition of melanogenesis in B16F10 cells by crocetin. Hence, crocetin could be suggested as a potential dermatological whitening agent in skin care products.

Myocardial perfusion and left ventricular function indices assessed by gated myocardial perfusion SPECT in methamphetamine abusers.

OBJECTIVES: Methamphetamine (MA) is associated with alterations of cardiac structure and function, although it is less known. In this study, we assessed possible abnormality in myocardial perfusion and left ventricular function using gated myocardial perfusion SPECT. METHODS: Fifteen patients with MA abuse, on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) MA dependency determined by Structured Clinical Interview for DSM-IV, underwent 2-day dipyridamole stress/rest Tc-sestamibi gated myocardial perfusion SPECT. RESULTS: An average daily dose of MA use was 0.91±1.1 (0.2-4) g. The duration of MA use was 3.4±2.1 (1-7) years. In visual and semiquantitative analyses, all patients had normal gated myocardial perfusion SPECT, with no perfusion defects. In all gated SPECT images, there was no abnormality in left ventricular wall motion and thickening. All summed stress scores and summed rest scores were below 3. Calculated left ventricular functional indices including the end-diastolic volume, end-systolic volume, and left ventricular ejection fraction were normal. CONCLUSION: Many cardiac findings because of MA mentioned in previous reports are less likely because of significant epicardial coronary artery stenosis.