Sinomenine Attenuates Trimethyltin-Induced Cognitive Decline via Targeting Hippocampal Oxidative Stress and Neuroinflammation

Potential therapeutic effects and pharmacological evidence of sinomenine in central nervous system disorders

“…These results support the conclusions from the in vitro studies and suggest that suppression of neuroinflammation and oxidative stress is critical for the effect of sinomenine against AD. Curiously, sinomenine did not affect the levels of glutathione (GSH), catalase, glutathione reductase, and glutathione peroxidase in the hippocampus of trimethyltin-treated rats (Rostami et al, 2022) (Table 2), suggesting that the effect of sinomenine against oxidative stress in this trimethyltin model may not be comparable to the effect observed in other models of CNS disorders. Together with the previously reported effect of sinomenine on IL-10 in Aβ-stimulated astrocytes (Singh et al, 2020) and the fact that IL-10 is a classical antineuroinflammatory factor, researchers should investigate why sinomenine selectively affects the processes involving proneuroinflammatory responses and pro-oxidative stress.…”

“…Inhibition of AchE expression or activity is a potential strategy for the treatment of AD. Administration of sinomenine was shown to suppress the trimethyltin-induced increase in AChE activity in rat hippocampal tissue (Figure 3; Table 2) (Rostami et al, 2022), suggesting that inhibition of AchE is a potential mechanism for the anti-AD effect of sinomenine. In addition to AchE, βsecretase 1 (BACE1) is another molecule that may mediate the pathogenesis of AD.…”

“…Administration of sinomenine (p.o. ; 1 h after the stimuli, once daily, 3 weeks, 100 mg/kg) reverses the trimethyltininduced 1) increase in discrimination index in novel object detection, 2) impairment of alternation in the short-term Y maze, 3) decrease in step-through latency in the passive avoidance paradigm, and 4) increase in probe trial error and latency in the Barnes maze task in rats (Rostami et al, 2022) (Table 2). Further analysis revealed that sinomenine administration could suppress the trimethyltin-induced increase in MDA, ROS, NO, TNF-α, and IL-6 and the trimethyltin-induced decrease in SOD in rat hippocampal tissue (Figure 3; Table 2) (Rostami et al, 2022).…”

“…It is responsible for the proteolytic processing of the amyloid precursor molecule and the formation of Aβ fragments (Taylor et al, 2022). Administration of sinomenine can suppress the increase in BACE1 activity induced by trimethyltin in rat hippocampal tissue (Figure 3; Table 2), suggesting that inhibition of BACE1 may be also a possible mechanism for the anti-AD effect of sinomenine (Rostami et al, 2022). Because Aβ Frontiers in Pharmacology frontiersin.org accumulation may be an important pathogenesis for AD, clarifying whether sinomenine administration could reduce Aβ accumulation in the brain could help confirm the anti-AD effect of sinomenine.…”

The Mechanism of TNF-α-Mediated Accumulation of Phosphorylated Tau Protein and Its Modulation by Propofol in Primary Mouse Hippocampal Neurons: Role of Mitophagy, NLRP3, and p62/Keap1/Nrf2 Pathway

“…SOD is a group of metal-containing enzymes that catalyze the dismutation of superoxide radicals to molecular oxygen and hydrogen peroxide, providing cellular defense against reactive oxygen species. It was reported that sinomenine may improve hippocampal and cognitive dysfunction through modulating SOD activity and ROS, while it was also suggested that catalase, glutathione reductase, glutathione peroxidase, and myeloperoxidase were not involved [55]. HO-1 is a cytoprotective enzyme that catalyzes the degradation of heme to carbon monoxide, iron, and biliverdin, and its induction has been regarded as an adaptive cellular response against inflammatory response and oxidative injury.…”