Obtusin ameliorates diabetic retinopathy by inhibiting oxidative stress and inflammation.

IF 3.5 3区医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-11-03 DOI:10.1007/s00213-024-06689-4

Jingyi Xu, Rongjing Shen, Mengting Qian, Luying Ning, Xinyu Zhang, Bingqing Xie, Yong Jiang, Zhengjun Zhou, Wei Dong

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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.

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奥布曲辛通过抑制氧化应激和炎症改善糖尿病视网膜病变。

理由糖尿病视网膜病变（DR）与精神和神经疾病的风险增加有关，这主要是由于与该疾病相关的慢性炎症、氧化应激和微血管损伤造成的。新的证据表明，决明子提取物具有显著的抗炎和抗氧化特性。然而，决明子中的主要化合物决明素的治疗潜力及其内在机制仍不清楚：本研究旨在评估决明子苷治疗 DR 的疗效：方法：用决明素（5 毫克/千克/天和 10 毫克/千克/天）治疗 Db/db 小鼠 12 周。在整个研究过程中，对体重、血糖水平和血脂状况进行监测。视网膜组织病理学和透射电子显微镜用于评估奥布曲辛在体内的药理作用。此外，还对在高血糖条件下培养的人视网膜微血管内皮细胞进行了体外试验，以探索奥布曲辛在缓解 DR 方面的潜在作用：结果：对糖尿病小鼠进行 Obtusin 治疗后，血糖水平明显降低，血脂异常得到改善，视网膜层增厚，视网膜氧化应激减少，炎症细胞因子上调受到抑制。它还能减轻眼底微血管病变，保护视网膜的正常屏障功能。体外机理分析表明，Obtusin靶向Poldip2-Nox4氧化应激轴和NF-κB-MAPK-VEGFA炎症通路，这两者都与DR有关：我们的研究结果表明，Poldip2-Nox4氧化应激轴和NF-κB-MAPK-VEGFA炎症通路可能是奥布曲星治疗DR及其相关精神和神经疾病的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

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.