Schisandrin ameliorates cognitive deficits, endoplasmic reticulum stress and neuroinflammation in streptozotocin (STZ)-induced Alzheimer’s disease rats

Abstract

Schisandrin, an active component extracted from Schisandra chinensis (Turcz.) Baill has been reported to alleviate the cognitive impairment in neurodegenerative disorder like Alzheimer's disease (AD). However, the mechanism by which schisandrin regulates the cognitive decline is still unclear. In our study, intracerebroventricular injection of streptozotocin (STZ) was employed to establish AD model in male Wistar rats, and indicated dose of schisandrin was further administered. The Morris water maze test was performed to evaluate the ability of learning and memory in rats with schisandrin treatment. The results indicated that schisandrin improved the capacity of cognition in STZ-induced rats. The contents of pro-inflammatory cytokines in brain tissue were determined by ELISA, and the expressions of these cytokines were assessed by western-blot and immunohistochemistry. The results showed that treatment of schisandrin significantly reduced the production of inflammation mediators including tumor necrosis factor-α, interleukin-1β and interleukin-6. Further study suggested a remarkable decrease in the expressions of ER stress maker proteins like C/EBP-homologous protein, glucose-regulated protein 78 and cleaved caspase-12 in the presence of schisandrin, meanwhile the up-regulation of sirtuin 1 (SIRT1) was also observed in the same group. Additionally, the results of western-blot and EMSA demonstrated that schisandrin inhibited NF-κB signaling in the brain of STZ-induced rats. In conclusion, schisandrin ameliorated STZ-induced cognitive dysfunction, ER stress and neuroinflammation which may be associated with up-regulation of sirtuin 1 (SIRT1). Our study provides novel mechanisms for the neuroprotective effect of 3 schisandrin in AD treatment.

Schisandrin Inhibits NLRP1 Inflammasome-Mediated Neuronal Pyroptosis in Mouse Models of Alzheimer’s Disease

“…Moreover, Zhao et al 26 revealed that SCH protects against Aβ 1-42 -induced downregulation of cell viability in SH-SY5Y cells through activation of PI3K/AKT signaling. Song et al 27 indicated that SCH could effectively attenuate the neuroinflammation and cognitive deficits in an streptozotocin-induced AD rat model via inactivation of NF-κB signaling. However, the action mechanism of SCH in AD development remains not fully clear.…”

Therapeutic Effects of Natural Compounds and Small Molecule Inhibitors Targeting Endoplasmic Reticulum Stress in Alzheimer’s Disease

“…It is proved that ER stress and UPR play an essential role in the occurrence and development of AD (Devi and Ohno, 2014;Duran-Aniotz et al, 2017;Uddin et al, 2020). The related findings, both in vivo and in vitro, have shown that many natural compounds and small molecular inhibitors targeting ER stress and ER stress-mediated neuronal apoptosis contribute to the recovery of AD (Xu et al, 2018;Zhu et al, 2019;Song et al, 2020;Oliveira et al, 2021). However, there are still a lot of questions to be considered if we want to convert these agents into a safe and reliable drug for clinical application, such as the safety, efficacy, and applicability.…”

Schizandrin A ameliorates cognitive functions via modulating microglial polarisation in Alzheimer’s disease mice

“…Additionally, Sch A exerts neuroprotective effects in AD progression. Previous study has found that Sch A reduces cognitive disorder of AD mice by inhibiting neuroinflammation, oxidative stress, and endoplasmic reticulum stress (Qi et al 2019;Song et al 2020). Sch A inhibits Ab-mediated neuron damage in AD by activating the PI3K/Akt signalling pathway, and reducing the expression of tau protein (Zhao et al 2019).…”

“… 2019 ; Song et al. 2020 ). Sch A inhibits Aβ-mediated neuron damage in AD by activating the PI3K/Akt signalling pathway, and reducing the expression of tau protein (Zhao et al.…”