Qin Meilin, Guo Xinxin, Xu Nuo, Su Yan, Pan Mengfen, Zhang Zhengbao, Zeng Huaicai
Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, School of Public Health, Guilin Medical University, Guilin 541199, China.
Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, School of Public Health, Guilin Medical University, Guilin 541199, China.
Toxics. 2025 Feb 25;13(3):162. doi: 10.3390/toxics13030162.
Bisphenol S (BPS) is a widespread environmental endocrine disrupter that can cause hepatotoxicity, neurotoxicity and negative effects on reproduction. Puerarin (PUE) has been found to have anti-inflammatory, antioxidant, and neuroprotective properties, however, its potential protective effects against BPS-induced neurotoxicity and the underlying mechanisms are still not fully understood. In this study, HT22 cells were exposed to different concentrations of BPS with or without PUE. Cell viability, apoptosis, oxidative damage, and the expression level of axon-injury-related genes and the BDNF/TrkB/CREB pathway were analyzed. The results showed that 40 μM to 180 μM BPS and 100 μM to 180 μM PUE significantly decreased the cell viability of HT22 cells, but in the 80 μM PUE group, the cell viability was higher than control group, and the ratio of 1.1. Meanwhile, BPS increased the production of ROS and MDA but decreased the GSH and SOD. However, supplementation with PUE was alleviated the oxidative damage. PUE also alleviated the apoptosis rate that induced by BPS. Additionally, BPS decreased the expression levels of mRNA and proteins of synaptic-related genes, but inhibited the expression levels of mRNA and proteins of the BDNF/TrkB/CREB signaling pathway. Interestingly, PUE was found to significantly recover the expression of synaptic related genes, but also upregulated the expression of the BDNF/TrkB/CREB pathway. In conclusion, our study proved that PUE can attenuate the neurotoxicity effect of bisphenol S, which related to oxidative damage in HT22 cells by regulating the BDNF/TrkB/CREB signaling pathway. This study is not only the first to demonstrate that PUE can mitigate BPS-induced neurotoxicity through oxidative stress modulation, but also provides a novel therapeutic approach involving the BDNF/TrkB/CREB pathway. These findings offer promising insights into natural-based strategies for protecting against environmental neurotoxins and provide a foundation for future therapeutic developments targeting BPS-induced neurotoxicity.
双酚S（BPS）是一种广泛存在的环境内分泌干扰物，可导致肝毒性、神经毒性及对生殖产生负面影响。葛根素（PUE）已被发现具有抗炎、抗氧化和神经保护特性，然而，其对BPS诱导的神经毒性的潜在保护作用及潜在机制仍未完全明确。在本研究中，HT22细胞暴露于不同浓度的BPS，同时或不添加PUE。分析细胞活力、凋亡、氧化损伤以及轴突损伤相关基因的表达水平和BDNF/TrkB/CREB信号通路。结果显示，40μM至180μM的BPS和100μM至180μM的PUE显著降低了HT22细胞的活力，但在100μM PUE组中，细胞活力高于对照组，比值为1.1。同时，BPS增加了活性氧（ROS）和丙二醛（MDA）的产生，但降低了谷胱甘肽（GSH）和超氧化物歧化酶（SOD）。然而，补充PUE减轻了氧化损伤。PUE还减轻了BPS诱导的凋亡率。此外，BPS降低了突触相关基因的mRNA和蛋白质表达水平，但抑制了BDNF/TrkB/CREB信号通路的mRNA和蛋白质表达水平。有趣的是，发现PUE能显著恢复突触相关基因的表达，还上调了BDNF/TrkB/CREB信号通路的表达。总之，我们的研究证明PUE可减轻双酚S的神经毒性作用，这与通过调节BDNF/TrkB/CREB信号通路减轻HT22细胞中的氧化损伤有关。本研究不仅首次证明PUE可通过氧化应激调节减轻BPS诱导的神经毒性，还提供了一种涉及BDNF/TrkB/CREB信号通路的新治疗方法。这些发现为基于天然物质的预防环境神经毒素策略提供了有前景的见解，并为未来针对BPS诱导的神经毒性的治疗发展奠定了基础。
