Abstract
Lignans from Schisandra chinensis (Turcz.) Baill can ameliorate cognitive impairment in animals with Alzheimer’s disease (AD). However, the metabolism of absorbed ingredients and the potential targets of the lignans from S. chinensis in animals with AD have not been systematically investigated. Therefore, for the first time, we performed an in-vivo ingredient analysis and implemented a target-network pharmacology strategy to assess the effects of lignans from S. chinensis in rats with AD. Ten absorbed prototype constituents and 39 metabolites were identified or tentatively characterized in the plasma of dosed rats with AD using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Based on the results of analysis of the effective constituents in vivo, the potential therapeutic mechanism of the effective constituents in the rats with AD was investigated using a target-network pharmacology approach and independent experimental validation. The results showed that the treatment effects of lignans from S. chinensis on cognitive impairment might involve the regulation of amyloid precursor protein metabolism, neurofibrillary tangles, neurotransmitter metabolism, inflammatory response, and antioxidant system. Overall, we identified the effective components of lignans in S. chinensis that can improve the cognitive impairment induced by AD and proposed potential therapeutic metabolic pathways. The results might serve as the basis for a fundamental strategy to explore effective therapeutic drugs to treat AD.
Highlights
Alzheimer’s disease (AD) has become one of the leading diseases affecting the health of the elderly population, with a prevalence of 5% after 65 years of age, which increases to approximately30% in people aged 85 years or older [1]
According to the above potential target analysis, we found that the lignans from S. chinensis were associated with amyloid precursor protein (APP) metabolism, tau phosphorylation, neurotransmitter metabolism, nitric oxide (NO) anabolism, inflammatory response, retinol metabolism, lipid metabolism, glutathione (GSH) metabolism, oxidative stress, cell-cycle progression, and apoptosis
The absorbed constituents and metabolites of lignans isolated from S. chinensis in the plasma of rats with AD were separated and identified by UHPLC–Q-TOF-MS
Summary
Alzheimer’s disease (AD) has become one of the leading diseases affecting the health of the elderly population, with a prevalence of 5% after 65 years of age, which increases to approximately. 30% in people aged 85 years or older [1]. It is characterized by progressive cognitive impairment, including impaired judgment, decision-making, and orientation; the disease is often accompanied by psycho–behavioral disturbances and language impairment in the later stages [2]. The pathogenesis of AD is still unclear. A widely accepted hypothesis is the amyloid cascade hypothesis, which suggests that amyloid beta (Aβ) deposition might trigger neuronal dysfunction and death in the brain, resulting in AD [3]. Alzheimer’s disease has imposed a heavy burden on the healthcare and socio-economic development of elderly population. Acetylcholinesterase inhibitors (AChEIs) and non-competitive N-methyl-D-aspartate antagonists are the first line drugs for treating AD
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