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BACKGROUND

The escalating global burden of diabetes and its associated cognitive impairment underscores the urgency for effective interventions. Bergenin shows promise in regulating glucose metabolism, mitigating inflammation, and improving cognitive function. Zebrafish models offer a unique platform for assessing drug efficacy and exploring pharmacological mechanisms, complemented by subsequent investigations in cell and rat models.

METHODS

The experimental subjects included zebrafish larvae (CZ98: ), adult zebrafish (immersed in 2% glucose), BV2 cell line (50 mM glucose + 10 μm Aβ), and a streptozotocin (STZ) bilateral intracerebroventricular injection rat model. Bergenin's effects on the toxicity, behavior, and cognitive function of zebrafish larvae and adults were evaluated. The Morris water maze assessed cognitive function in rats. Neuronal histopathological changes were evaluated using HE and Nissl staining. qPCR and Western blot detected the expression of glycolysis enzymes, inflammatory factors, and Bergenin's regulation of PPAR/NF-κB pathway in these three models.

RESULTS

In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased expression and increased expression of , , and , suggesting a reduction in insulin resistance. It also altered the expression of and . 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1β, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus.

CONCLUSION

Bergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.

BACKGROUND

METHODS

RESULTS

In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased expression and increased expression of , , and , suggesting a reduction in insulin resistance. It also altered the expression of and . 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1β, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus.

CONCLUSION

Bergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.

背景

全球糖尿病负担及其相关认知障碍不断升级，凸显了有效干预措施的紧迫性。岩白菜素在调节葡萄糖代谢、减轻炎症和改善认知功能方面显示出前景。斑马鱼模型为评估药物疗效和探索药理机制提供了一个独特的平台，并辅以随后在细胞和大鼠模型中的研究。

方法

实验对象包括斑马鱼幼虫（CZ98：）、成年斑马鱼（浸泡在2%葡萄糖中）、BV2细胞系（50 mM葡萄糖 + 10 μm Aβ）以及链脲佐菌素（STZ）双侧脑室内注射大鼠模型。评估了岩白菜素对斑马鱼幼虫和成年鱼的毒性、行为和认知功能的影响。Morris水迷宫评估大鼠的认知功能。使用HE和尼氏染色评估神经元组织病理学变化。qPCR和蛋白质印迹法检测这三种模型中糖酵解酶、炎症因子的表达以及岩白菜素对PPAR/NF-κB通路的调节作用。

结果

1）在斑马鱼幼虫中，岩白菜素干预显著降低了葡萄糖水平，提高了存活率，同时降低了致畸率。脑中的小胶质细胞荧光显著降低，改变的游泳行为趋于正常化。2）在成年斑马鱼中，给予岩白菜素可降低体重指数和血糖水平，将游泳行为改变为较慢速度和更规则的轨迹，增强识别能力，降低脑葡萄糖和乳酸水平，减弱糖酵解酶活性，改善端脑和鳃的病理变化，降低促炎细胞因子的表达，降低和的表达并增加和的表达，表明胰岛素抵抗降低。它还改变了和的表达。3）在BV2细胞系中，岩白菜素显著降低了糖酵解酶（GLUT1、HK2、PKFKB3和PKM2）的蛋白质表达，降低了IL-1β、IL-6和TNF-α mRNA表达，提高了PPAR-γ蛋白质表达，并降低了P-NF-κB-p65蛋白质表达。4）在大鼠模型中，岩白菜素改善了STZ诱导大鼠的学习和记忆能力，减轻了海马区的神经元损伤，并降低了炎症因子IL-1β、IL-6和TNF-α的表达。岩白菜素降低了脑葡萄糖和乳酸水平以及糖酵解酶活性。此外，岩白菜素增加了海马体中PPARγ的表达，并降低了p-NF-κB p65/NF-κB p65的表达。