2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside attenuates MPP plus /MPTP-induced neurotoxicity in vitro and in vivo by restoring the BDNF-TrkB and FGF2-Akt signaling axis and inhibition of apoptosis
2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside attenuates MPP plus /MPTP-induced neurotoxicity in vitro and in vivo by restoring the BDNF-TrkB and FGF2-Akt signaling axis and inhibition of apoptosis
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DOI：
10.1039/c9fo01309a
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发表时间：
2019-09-01
期刊：
影响因子：
6.1
通讯作者：
Qin, Xiao-Yan
中科院分区：
文献类型：
--
作者：
Yu, Yun;Lang, Xiu-Yuan;Qin, Xiao-Yan
何首乌的主要生物活性成分THSG具有抗氧化、抗衰老和抗炎特性。越来越多的证据支持 THSG 能够改善小鼠模型中神经营养素的生化及其下游信号轴，从而减轻阿尔茨海默病和帕金森病等神经退行性疾病。在本研究中，THSG 的神经保护作用在体外和体内进行了研究。在培养的中脑多巴胺神经元和SH-SY5Y细胞系中，发现THSG通过恢复FGF2和BDNF的表达及其下游信号通路来抑制细胞凋亡并促进细胞存活，从而保护细胞体的完整性和神经突分支免受MPP+诱导的毒性。 LY294002 对 Akt 信号传导的抑制或 K252a 对 TrkB 活性的抑制消除了 THSG 的神经保护作用。在 MPTP 诱导的帕金森病小鼠模型中，THSG 改善了动物针对 MPTP 诱导的神经毒性的行为，这一点通过杆试验和悬尾试验得到了证明。生化和免疫组织化学分析验证了 THSG 介导的黑质和纹状体中 FGF2-Akt 和 BDNF-TrkB 信号轴的恢复以及多巴胺能神经元的恢复。这些结果确立了THSG在体外和体内的神经保护作用，揭示了抗毒素引起的神经萎缩的潜在机制，为食药抗神经退行性疾病的使用和药理学研究提供了新的途径。
The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.