Danhong Huayu Koufuye Prevents Diabetic Retinopathy in Streptozotocin-Induced Diabetic Rats via Antioxidation and Anti-Inflammation

Chen, Wenpei; Yao, Xiaolan; Zhou, Chixing; Zhang, Ziyang; Gui, Gang; Lin, Baoqin

doi:10.1155/2017/3059763

Cited by 11 publications

(9 citation statements)

References 41 publications

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“…4C, E; all P <0.001, Normal vs DM). These results were consistent with the previous reports [20, 29, 30]. More importantly, α-MSH intravitreal administration significantly increased the thickness of all the retinal layers in diabetic retinas (Fig.…”

Section: Resultssupporting

confidence: 93%

Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R

Cai

Yang

Hou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH’s anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). Methods: Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH’s anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH’s protection. Results: Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested partial rescue of functional defects by α-MSH in diabetic retinas; and H&E staining revealed significantly increased thickness of all layers in α-MSH-treated diabetic retinas. Mechanistically, α-MSH corrected aberrant transcript and protein expression of pro-inflammatory factor and tight junction genes in the diseased retinas; moreover, it prevented abnormal changes in TEER and permeability in HG-stimulated RF6A cells, and this anti-hyperpermeability was abolished by a universal MCR blocker or an antagonist specific to MC4R. Conclusions: This study showed previously undescribed protective effects of α-MSH on inhibiting BRB breakdown and vascular leakage, improving electrophysiological functions and morphology in early diabetic retinas, which may be due to its down-regulating pro-inflammatory factors and augmenting tight junctions. α-MSH acts predominantly on MC4R to antagonize hyperpermeability in retinal microvessel endothelial cells.

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Section: Resultssupporting

confidence: 93%

Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R

Cai

Yang

Hou

et al. 2018

Cell Physiol Biochem

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“…Clinically, DHK is mainly used for treatment of blurred vision and sudden blindness caused by qi stagnation and blood stasis, as well as the absorption period of central retinal vein occlusion. As previous studies reported, DHK has antioxidant and anti‐inflammatory activities, and can effectively prevent deep vein thrombosis (Chen et al, ; Zhang et al, ; Zhang et al, ). However, the bioactive components of DHK are still not well understood, and current quality standards only stipulate the quantitative determination of protocatechualdehyde, which largely restricts the quality control and further development of DHK.…”

Section: Introductionmentioning

confidence: 78%

Quality transitivity of Danhong Huayu Koufuye: A study on chemical profiles of medicinal herbs, compound preparation and dosed rat plasma using ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry

Zhang

Liu

et al. 2020

Biomedical Chromatography

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Danhong Huayu Koufuye (DHK), an effective Chinese medicine preparation, is mainly used for the treatment of blurred vision and sudden blindness caused by qi stagnation and blood stasis, as well as the absorption period of central retinal vein occlusion. However, the current quality standard is relatively low, only stipulating the content of protocatechualdehyde. Chemical transitivity is the basis for discovering quality markers and is used in quality process control of Chinese medicines. Herein, the chemical profiles of seven medicinal herbs, DHK and dosed rat plasma were comprehensively analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. As a result, 134 chemical constituents were identified in seven medicinal herbs, including salvianolic acids, diterpene quinones, phenolic acids, phthalides, cyanogenic glycosides, flavonoids and triterpenoid saponins.Among them, 55 chemical constituents were transferred to DHK along with extraction and preparation, and 26 were further absorbed into blood and metabolized to produce 11 metabolites after oral administration. The transitivity of DHK from medicinal herbs to compound preparation and into blood was analyzed for the first time. This article will be valuable to ascertain the quality markers for quality process control and further pharmacokinetic studies. K E Y W O R D Schemical profiles, Danhong Huayu Koufuye, mass spectrometry, quality transitivity, ultraperformance liquid chromatography

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“…VEGF is a proangiogenic factor regulator that damages the blood-retina barrier (BRB) by several mechanisms, leading to increased vascular permeability and the development of retinal edema. An imbalance between proangiogenic mediators and ischemia result in the growth of abnormal leaky blood vessels, eventually leading to retinal neovascularization [ 3 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

The role of hesperidin in ameliorating retinal changes in rats with experimentally induced type 1 diabetes mellitus and the active role of vascular endothelial growth factor and glial fibrillary acidic protein

et al. 2021

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Patients with type 1 diabetes mellitus (T 1 DM) are vulnerable to developing diabetic retinopathy even under insulin therapy. Thus, this study was designed to evaluate the efficacy of hesperidin and insulin in rats with T 1 DM compared with insulin alone in improving diabetic retinal changes. Eighty rats were divided into four equal groups: group I, control rats without diabetes; group II, untreated rats with diabetes; group III, rats with diabetes treated daily with subcutaneous (SC) doses of long-acting insulin; and group IV, a rat with diabetes in which hesperidin was orally administered with SC insulin. The animals were assessed histologically, morphometrically, and biochemically. In group II, the thickness of all retinal layers decreased histologically. Ultrastructurally, degenerated retinal neurons and congested blood vessels were observed. Immunostaining detected elevated gene expression of advanced glycation end products. Gene expression of vascular endothelial growth factor, and glial fibrillary acidic protein were elevated. In this study, hesperidin supplementation with insulin significantly improved the retinal histological changes, supported by morphometric findings, compared with insulin alone. Moreover, treatment with hesperidin significantly reduced malondialdehyde and elevated serum antioxidant markers, including superoxide dismutase and catalase; furthermore, glutathione peroxidase decreased. Hesperidin might be an effective supplement for improving diabetic retinal complications occurring even with insulin treatment.

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Danhong Huayu Koufuye Prevents Diabetic Retinopathy in Streptozotocin-Induced Diabetic Rats via Antioxidation and Anti-Inflammation

Cited by 11 publications

References 41 publications

Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R

Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R

Quality transitivity of Danhong Huayu Koufuye: A study on chemical profiles of medicinal herbs, compound preparation and dosed rat plasma using ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry

The role of hesperidin in ameliorating retinal changes in rats with experimentally induced type 1 diabetes mellitus and the active role of vascular endothelial growth factor and glial fibrillary acidic protein

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