title: Crocin Inhibits Oxidative Stress and Pro-inflammatory Response of Microglial Cells Associated with Diabetic Retinopathy Through the Activation of PI3K/Akt Signaling Pathway.
abstract: 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.
authors.affiliation: Shaanxi Ophthalmic Medical Center, Xi'an No. 4 Hospital, Guangren Hospital Affiliated to School of Medicine of Xi'an Jiaotong University, No. 21 Jiefang Road, Xi'an, Shaanxi, 710004, People's Republic of China.
authors.forename: Xinguang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Huo
authors.affiliation: Shaanxi Ophthalmic Medical Center, Xi'an No. 4 Hospital, Guangren Hospital Affiliated to School of Medicine of Xi'an Jiaotong University, No. 21 Jiefang Road, Xi'an, Shaanxi, 710004, People's Republic of China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Shaanxi Ophthalmic Medical Center, Xi'an No. 4 Hospital, Guangren Hospital Affiliated to School of Medicine of Xi'an Jiaotong University, No. 21 Jiefang Road, Xi'an, Shaanxi, 710004, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Anatomy, Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan, Ningxia, 750004, People's Republic of China.
authors.forename: Junping
authors.initials: J
authors.lastname: Li
authors.affiliation: Shaanxi Ophthalmic Medical Center, Xi'an No. 4 Hospital, Guangren Hospital Affiliated to School of Medicine of Xi'an Jiaotong University, No. 21 Jiefang Road, Xi'an, Shaanxi, 710004, People's Republic of China. drzhuzhongqiao@163.com.
authors.forename: Zhongqiao
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Shaanxi Ophthalmic Medical Center, Xi'an No. 4 Hospital, Guangren Hospital Affiliated to School of Medicine of Xi'an Jiaotong University, No. 21 Jiefang Road, Xi'an, Shaanxi, 710004, People's Republic of China. lyubochang@163.com.
authors.forename: Bochang
authors.initials: B
authors.lastname: Lv
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D002460:Cell Line; D003930:Diabetic Retinopathy / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D002338:Carotenoids; C029036:crocin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Crocin; Diabetic retinopathy; Microglial cells; PI3K/Akt