Acteoside isolated from Colebrookea oppositifolia attenuates I/R brain injury in Wistar rats via modulation of HIF-1α, NF-κB, and VEGF pathways,Inflammopharmacology

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Acteoside isolated from Colebrookea oppositifolia attenuates I/R brain injury in Wistar rats via modulation of HIF-1α, NF-κB, and VEGF pathways
Inflammopharmacology ( IF 4.6 ) Pub Date : 2021-08-07 , DOI: 10.1007/s10787-021-00851-6
Gollapalle Lakshminarayanashastry Viswanatha ₁ , Hanumanthappa Shylaja ₂ , Krishnadas Nandakumar ₃ , Subbanna Rajesh ₄ , C H K V L S N Anjana Male ₅

Affiliation

Aims

The objective of this study was to assess the anti-stroke activity of acteoside isolated from methanolic root extract of C. oppositifolia

Methods

Ischemia–reperfusion(I/R) brain injury was induced in Wistar rats to assess the anti-stroke activity of acteoside. Rats were pretreated with acteoside (10, 25 & 50 mg/kg, p.o.) before the induction of I/R injury. Parameters such as neurological, motor-cognitive functions were evaluated along with morphological (brain volume, infarct size), biochemical (SOD, Catalase, GSH, lipid peroxidation, TNF-α, IL-6, IL-10, ICAM-1, HIF-1α, VEGF, and NF-κB), histopathological, and gene expression studies (HIF-1α, VEGF) were performed to study the protective effect of acteoside against I/R induced brain injury.

Results

I/R injury caused significant deterioration of neurological (p < 0.01), motor (p < 0.01) and cognitive (p < 0.01) functions, associated with increase in the brain volume (p < 0.01), and infarct size (p < 0.01); increase in the levels of MDA, TNF-α, IL-6, ICAM-1, HIF-1α, VEGF, and NF-κB along with significant decrease in SOD, catalase, GSH, and IL-10 (p < 0.01 for all parameters) compared to Sham control group. Histology of brain tissue of disease control group exhibited significant vascular changes, neutrophil infiltration, cerebral oedema, and necrosis of the neuronal cells. Further, the gene-expression studies showed significant increase in the HIF-1α (p < 0.01) and VEGF (p < 0.01) mRNA levels in the I/R control compared to Sham control. Interestingly, the acteoside (10, 25 & 50 mg/kg) has prevented the neurological, motor and cognitive dysfunctions, along with inhibiting the morphological, biochemical, histological and gene expression changes induced by I/R-injury (p < 0.05 for 10 mg; p < 0.01 for 25 & 50 mg/kg of acteoside for all the parameters).

Conclusion

These findings suggest that acteoside possess potent anti-stroke activity through modulation of HIF-1α, NF-κB, and VEGF pathway along with its potent antioxidant activity.

Graphic abstract

中文翻译：

从 Colebrookea oppositifolia 中分离的 Acteoside 通过调节 HIF-1α、NF-κB 和 VEGF 通路减轻 Wistar 大鼠的 I/R 脑损伤

目标

本研究的目的是评估从C. oppositifolia甲醇根提取物中分离出的猕猴桃苷的抗中风活性

方法

在 Wistar 大鼠中诱导缺血再灌注 (I/R) 脑损伤，以评估猕猴桃苷的抗中风活性。在诱导 I/R 损伤之前，大鼠用acteoside（10、25 和 50 mg/kg，口服）预处理。神经学、运动认知功能等参数与形态学（脑容量、梗死面积）、生化（SOD、过氧化氢酶、GSH、脂质过氧化、TNF-α、IL-6、IL-10、ICAM-1、HIF -1α、VEGF 和 NF-κB)、组织病理学和基因表达研究 (HIF-1α, VEGF) 以研究鼠尾草苷对 I/R 诱导的脑损伤的保护作用。

结果

I/R 损伤导致神经 ( p < 0.01)、运动 ( p < 0.01) 和认知 ( p < 0.01) 功能显着恶化，与脑容量 ( p < 0.01) 和梗死面积 ( p < 0.01 ) 增加有关); MDA、TNF-α、IL-6、ICAM-1、HIF-1α、VEGF 和 NF-κB 水平升高，SOD、过氧化氢酶、GSH 和 IL-10 显着降低（p < 0.01参数）与假对照组相比。疾病对照组脑组织组织学表现为血管明显改变、中性粒细胞浸润、脑水肿、神经元细胞坏死。此外，基因表达研究显示 HIF-1α 显着增加（p < 0.01) 和 VEGF ( p < 0.01) mRNA 水平在 I/R 控制与 Sham 控制相比。有趣的是，acteoside（10、25 和 50 mg/kg）预防了神经、运动和认知功能障碍，同时抑制了由 I/R 损伤引起的形态学、生化、组织学和基因表达变化（p < 0.05 for 10毫克；对于所有参数，25 和 50 毫克/千克的acteoside p < 0.01）。