Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer’s disease

Duan, Songwei; Guan, Xiaoying; Lin, Runxuan; Liu, Xincheng; Yan, Ying; Lin, Ruibang; Zhang, Tianqi; Chen, Xueman; Huang, Jiaqi; Sun, Xicui; Li, Qingqing; Fang, Shaoliang; Xu, Jun; Ye, Zhibin; Gu, Huaiyu

doi:10.1016/j.neurobiolaging.2015.02.002

Cited by 104 publications

(60 citation statements)

References 60 publications

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“…Hesperidin at the dose of 100 mg/kg and silibinin (100 and 200 mg/kg) significantly prevented the AChE elevation in the hippocampus. Our results are in accordance with the earlier studies with regards to the AChE inhibitor activity of hesperidin and silibinin [32,56,61,62]. Inhibition of AlCl 3 -evoked hippocampal AChE level by hesperidin and silibinin might be attributed to the improvement in the memory function.…”

Section: Discussionsupporting

confidence: 93%

“…Our study is corroborated by a recent study which showed that AlCl 3 impaired the long-term memory through modulation of cAMP-PKA-CREB signaling and BDNF level in the hippocampus [54]. Previous experimental reports suggested that hesperidin and silibinin exerted neuroprotection through elevation of the BDNF level [55,56]. Our present study showed a prominent increase in hippocampal BDNF level in the groups treated with hesperidin and silibinin.…”

Section: Discussionsupporting

confidence: 91%

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Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus

Jangra

Kasbe

Pandey

et al. 2015

Biol Trace Elem Res

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Mounting evidence suggests that long-term aluminum exposure results in severe toxic effects, including neurobehavioral and neurochemical anomalies. The present study was performed to examine the neuroprotective potential of hesperidin and silibinin against aluminum chloride (AlCl3)-induced neurotoxicity in mice. AlCl3 (100 mg/kg/day) was injected daily through oral gavage for 42 days. Concomitantly, hesperidin (50 and 100 mg/kg/day, p.o.) and silibinin (100 and 200 mg/kg/day, p.o.) was administered for 42 days in different groups. The extent of cognitive impairment was assessed by Morris water maze and novel object recognition test on the 43rd day. Neurotoxicity was assessed by measuring oxido-nitrosative stress and proinflammatory cytokines in the hippocampus of mice. Six weeks treatment with AlCl3 caused cognitive impairment as indicated by an increase in the retention latency time and reduction in the percentage of recognition index. AlCl3-treated group showed oxido-nitrosative stress as indicated by increase in the level of lipid peroxidation, nitrite and depleted reduced glutathione, catalase activity in the hippocampus. Moreover, the chronic AlCl3 administration raised the proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) level and increased acetylcholinesterase activity and reduced the BDNF content in the hippocampus of AlCl3-treated animals. However, chronic treatment with hesperidin and silibinin at higher doses significantly ameliorated the AlCl3-induced cognitive impairment and hippocampal biochemical anomalies. The present study clearly indicated that hesperidin and silibinin exert neuroprotective effects against AlCl3-induced cognitive impairment and neurochemical changes. Amelioration of cognitive impairment may be attributed to the impediment of oxido-nitrosative stress and inflammation in the hippocampus.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus

Jangra

Kasbe

Pandey

et al. 2015

Biol Trace Elem Res

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“…Silybin, the major active molecule of silymarin, is a very potent antioxidant compound capable of scavenging free radicals and ROS, and has been shown to exert neuroprotective (28–30), hepatoprotective (31,32) and anti-carcinogenic effects (33–35). It is now being used as a traditional medicine for the treatment of various liver disorders in China.…”

Section: Discussionmentioning

confidence: 99%

Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation

Zhang

Wang

Cao

et al. 2017

International Journal of Molecular Medicine

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Silybin is one of the main flavonoids produced by milk thistle, which has been used in the treatment of liver diseases. In this study, we examined the protective effects and possible mechanisms of action of silybin in lipopolysaccharide (LPS)-induced lung injury and inflammation. Pre-treatment of mice with silybin significantly inhibited LPS-induced airway inflammatory cell recruitment, including macrophages, T cells and neutrophils. The production of cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in bronchoalveolar fluid and serum was also decreased following treatment with silybin. Elevated cytokine mRNA levels induced by LPS in lung tissue were all suppressed by silybin and lung histological alterations were also improved. In addition, experiments using cells indicated that silybin significantly decreased the mRNA levels and secretion of IL-1β and TNF-α in THP-1 cells. Moreover, the mechanisms responsible for these effects were attributed to the inhibitory effect of silybin on nuclear factor-κB (NF-κB) signaling and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. The data form our study thus support the utility of silybin as a potential medicine for the treatment of acute lung injury-associated inflammation and pathological changes. Silybin exerts protective effects against lung injury by regulating NF-κB signaling and the NLRP3 inflammasome activation.

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“…So MWM has been applied in the novel drug candidate discoveries widely. For example, MWM was used to evaluate the effect of silibinin on AD, and the result showed that silibinin could improve the performance of APP/PS1 transgenic mice after dosing with silibinin [68]. And the mechanism revealed that silibinin might act as a dual-target drug for the treatment of AD by inhibiting amyloid β peptide aggregation and the acetylcholinesterase activity [68].…”

Section: Mwm In Novel Drug Candidate Discoveriesmentioning

confidence: 99%

“…For example, MWM was used to evaluate the effect of silibinin on AD, and the result showed that silibinin could improve the performance of APP/PS1 transgenic mice after dosing with silibinin [68]. And the mechanism revealed that silibinin might act as a dual-target drug for the treatment of AD by inhibiting amyloid β peptide aggregation and the acetylcholinesterase activity [68]. For another example, lycopene was found to abrogate neuroinflammatory cascade in intra cerebroventricular injection of β-amyloid1-42-induced learning and memory impairment mice using MWM [69].…”

Section: Mwm In Novel Drug Candidate Discoveriesmentioning

confidence: 99%

Animal models for Alzheimer’s disease: a focused review of transgenic rodent models and behavioral assessment methods

Wu¹,

Li²,

Zhou³

et al. 2015

ADMET DMPK

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Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer’s disease

Cited by 104 publications

References 60 publications

Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus

Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus

Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation

Animal models for Alzheimer’s disease: a focused review of transgenic rodent models and behavioral assessment methods

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