{"title":"Obtusin ameliorates diabetic retinopathy by inhibiting oxidative stress and inflammation.","authors":"Jingyi Xu, Rongjing Shen, Mengting Qian, Luying Ning, Xinyu Zhang, Bingqing Xie, Yong Jiang, Zhengjun Zhou, Wei Dong","doi":"10.1007/s00213-024-06689-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Diabetic retinopathy (DR) is linked to an increased risk of psychiatric and neurological conditions, largely due to chronic inflammation, oxidative stress, and microvascular damage associated with the disease. Emerging evidence suggests that Cassia seed extract has significant anti-inflammatory and antioxidant properties. However, the therapeutic potential of obtusin, a major compound in Cassia seed, and its underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>This study aimed to evaluate the therapeutic efficacy of obtusin in the treatment of DR.</p><p><strong>Methods: </strong>Db/db mice were treated with obtusin (5 and 10 mg/kg/day) for 12 weeks. Throughout the study, body weight, blood glucose levels, and lipid profiles were monitored. Retinal histopathology and transmission electron microscopy were used to assess the pharmacological effects of obtusin in vivo. Additionally, in vitro assays were conducted on human retinal microvascular endothelial cells cultured under high glucose conditions to explore obtusin's potential role in mitigating DR.</p><p><strong>Results: </strong>Obtusin treatment in diabetic mice significantly reduced blood glucose levels, improved dyslipidemia, thickened retinal layers, reduced retinal oxidative stress, and inhibited the upregulation of inflammatory cytokines. It also lessened fundus microangiopathy and preserved the retina's normal barrier function. Mechanistic in vitro analysis suggested that obtusin targets the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway, both of which are implicated in DR.</p><p><strong>Conclusions: </strong>Our findings suggest that the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway could be therapeutic targets for obtusin in the treatment of DR and its associated psychiatric and neurological conditions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2471-2484"},"PeriodicalIF":3.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1007/s00213-024-06689-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale: Diabetic retinopathy (DR) is linked to an increased risk of psychiatric and neurological conditions, largely due to chronic inflammation, oxidative stress, and microvascular damage associated with the disease. Emerging evidence suggests that Cassia seed extract has significant anti-inflammatory and antioxidant properties. However, the therapeutic potential of obtusin, a major compound in Cassia seed, and its underlying mechanisms remain unclear.
Objective: This study aimed to evaluate the therapeutic efficacy of obtusin in the treatment of DR.
Methods: Db/db mice were treated with obtusin (5 and 10 mg/kg/day) for 12 weeks. Throughout the study, body weight, blood glucose levels, and lipid profiles were monitored. Retinal histopathology and transmission electron microscopy were used to assess the pharmacological effects of obtusin in vivo. Additionally, in vitro assays were conducted on human retinal microvascular endothelial cells cultured under high glucose conditions to explore obtusin's potential role in mitigating DR.
Results: Obtusin treatment in diabetic mice significantly reduced blood glucose levels, improved dyslipidemia, thickened retinal layers, reduced retinal oxidative stress, and inhibited the upregulation of inflammatory cytokines. It also lessened fundus microangiopathy and preserved the retina's normal barrier function. Mechanistic in vitro analysis suggested that obtusin targets the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway, both of which are implicated in DR.
Conclusions: Our findings suggest that the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway could be therapeutic targets for obtusin in the treatment of DR and its associated psychiatric and neurological conditions.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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