Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity

Abstract

Amyloid beta is a major constituent of the plaques found in the brains of patients suffering from Alzheimer's disease (AD). A growing body of research work suggests that neuroinflammation plays important roles in the development of AD. Thus, considerable efforts are directed towards identification of compounds that can reduce or inhibit neuroinflammation. Here, we show that sinomenine, a compound present in a Chinese medicinal plant, Sinomenium acutum, inhibits oligomeric amyloid beta-induced production of reactive oxygen species (ROS), nitric oxide (NO) and inflammation-related molecules from astrocytic cells. The conditioned medium from oligomeric amyloid beta-treated astrocytic cells induces cell death in the hippocampal neuronal cells. Importantly, sinomenine inhibits this cell death. In addition, this compound has inhibitory effects on the production of ROS, NO and inflammationrelated factors from oligomeric amyloid-beta treated human astrocytes. Finally, the conditioned medium from oligomeric amyloid beta-treated human astrocytes induces cell death in the primary culture of human neurons, which is inhibited by sinomenine. Thus, sinomenine inhibits amyloid beta-induced production of toxic factors from astrocytes, and confers protection to hippocampal neuronal cells as well as human neurons against indirect toxicity. The results suggest that this compound could provide beneficial effects in AD and other neurodegenerative conditions by reducing inflammation and neuronal cell death.

Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain

“…Astrocytes are key elements in maintaining homeostasis and regulators of multiple physiological functions in brain [71]. However, they are responsive to various stimuli, and astrocyte dysfunction may impair neuronal function and thus lead to neurodegeneration [72]. Many studies showed that activated astrocytes are a common neuropathological feature of brain disorders that respond to Aβ metabolically, morphologically, and/or functionally [73].…”

Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease

“…In China, Sinomenine is a recommended medicine for the patient against rheumatoid arthritis. It has shown neuroprotection against Aβ-induced glial-mediated toxicity to neurons [ 150 , 151 ]. The mechanism of Sinomenine is not clearly understood.…”

Astrocytic MicroRNA in Ageing, Inflammation, and Neurodegenerative Disease

“…Astrocytes have been shown to surround these plaques ( Olabarria et al, 2010 ; Perez-Nievas and Serrano-Pozo, 2018 ) and ingest Aβ molecules ( Jones et al, 2013 ; Söllvander et al, 2016 ). Exposure to aggregated Aβ induces reactive astrogliosis and increases astrocytic production of inflammatory mediators ( Singh et al, 2020 ), while ingestion of aggregated Aβ can impair lysosome function, hinder astrocytic degradation of Aβ protofibrils and alter the cargo of ADEVs ( Söllvander et al, 2016 ).…”