Silibinin ameliorates depression/anxiety-like behaviors of Parkinson's disease mouse model and is associated with attenuated STING-IRF3-IFN-β pathway activation and neuroinflammation

Liu, Xiumin; Chen, Wenhui; Wang, Chenkang; Liu, Weiwei; Hayashi, Toshihiko; Mizuno, Kazunori; Fujisaki, Hitomi; Ikejima, Takashi

doi:10.1016/j.physbeh.2021.113593

Cited by 23 publications

(8 citation statements)

References 56 publications

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“…Liu, Chen, et al. ( 2021 ) observed a decrease in the number of entries and time spent in the center area in MPTP‐treated mice in the OFT, and with silibinin administration, they observed a significant increase in these parameters compared to the MPTP group.…”

Section: Discussionmentioning

confidence: 96%

“…Although our study did not conduct a brain tissue analysis, the results of our study align with existing behavioral literature data stating protective effects on memory tests such as the Morris maze or preventing apoptosis (Liu et al., 2020 ). It is stated in the literature that silibinin exhibits a protective effect in neuronal diseases such as Parkinson's and Alzheimer's (Lee et al., 2020 ; Liu, Chen, et al., 2021 ). Silibinin is shown to exert protective effects not only on rodent models but also on human trials (Hussain et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

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Silibinin as a promising treatment for diabetes: Insights into behavioral and metabolic changes in an animal model

Dagli Gul,

Boyuk Ozcan,

Arihan

2024

Food Science & Nutrition

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Diabetes mellitus is causing serious health problems in the chronic period. Silibinin is a flavonoid obtained from the milk thistle (Silybum marianum), which is among the herbal ethnopharmacological administrations. In studies with silibinin, it has been reported that it increases the activity of pancreatic beta cells and insulin sensitivity and has a hyperglycemia‐reducing effect. However, behavioral parameters have not been evaluated together with insulin levels and liver function tests. Our aim in this study was to examine the effects of silibinin on insulin secretion, anxiety‐like behaviors, and learning in a streptozotocin (STZ)‐induced rat diabetes model. Wistar albino rats weighing 200–250 g were divided into 4 groups. Control: Saline solution, Diabetes: STZ 45 mg/kg, S 100: STZ 45 mg/kg + Silibinin 100 mg/kg, S 200: STZ 45 mg/kg + Silibinin 200 mg/kg. Administrations were continued for 21 days. On the 21st day, open field and elevated plus maze as unconditional anxiety tests; Barnes maze for learning and memory; and rotarod test for locomotor activity were conducted. Following behavioral tests, blood samples were taken under anesthesia. Blood glucose levels and ALT values were measured. Insulin levels were measured with an ELISA plate reader. Silibinin shortened the time to find the correct hole. Silibinin prevented the decrease in insulin due to STZ, exhibited a hyperglycemia‐reducing effect and decreased the elevation of ALT.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Silibinin as a promising treatment for diabetes: Insights into behavioral and metabolic changes in an animal model

Dagli Gul,

Boyuk Ozcan,

Arihan

2024

Food Science & Nutrition

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“…In PD model mice, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) has been shown to induce depression‐like behavior, and this is accompanied by an increase in the expression levels of STING and IRF3 in the hippocampus. However, silibinin significantly attenuates MPTP‐induced depression/anxiety and downregulates the levels of IL‐1β, TNF‐α and IFN‐β, as well as the levels of STING and IRF3 266 . These findings suggest that the cGAS–STING signaling pathway is associated with the development of depression and autism.…”

Section: Activation and Inhibition Of Cgas–sting Under The Pathologic...mentioning

confidence: 89%

“…However, silibinin significantly attenuates MPTP‐induced depression/anxiety and downregulates the levels of IL‐1β, TNF‐α and IFN‐β, as well as the levels of STING and IRF3. 266 These findings suggest that the cGAS–STING signaling pathway is associated with the development of depression and autism.…”

Section: Activation and Inhibition Of Cgas–sting Under The Pathologic...mentioning

confidence: 96%

cGAS–STING, an important signaling pathway in diseases and their therapy

Li,

Wu,

et al. 2024

MedComm

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Since cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism of cGAS–STING signaling pathway in the past decade. Meanwhile, the triggering and transduction mechanisms have been continuously illuminated. cGAS–STING plays a key role in human diseases, particularly DNA‐triggered inflammatory diseases, making it a potentially effective therapeutic target for inflammation‐related diseases. Here, we aim to summarize the ancient origin of the cGAS–STING defense mechanism, as well as the triggers, transduction, and regulating mechanisms of the cGAS–STING. We will also focus on the important roles of cGAS–STING signal under pathological conditions, such as infections, cancers, autoimmune diseases, neurological diseases, and visceral inflammations, and review the progress in drug development targeting cGAS–STING signaling pathway. The main directions and potential obstacles in the regulating mechanism research and therapeutic drug development of the cGAS–STING signaling pathway for inflammatory diseases and cancers will be discussed. These research advancements expand our understanding of cGAS–STING, provide a theoretical basis for further exploration of the roles of cGAS–STING in diseases, and open up new strategies for targeting cGAS–STING as a promising therapeutic intervention in multiple diseases.

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“…Silibinin ( 31 , Figure 6) is an antioxidant extracted from Milk Thistle. All the results of the open field test, elevated maze test, tail suspension test, and forced swimming test show that Silibinin administration can significantly reduce the anxiety‐like behavior of Parkinson's mouse model caused by 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, significantly restore the level of 5‐HT and NA in the hippocampus, and attenuate STING‐IRF3‐IFN‐ β activation of pathways and neuroinflammation (X. Liu et al, 2021).…”

Section: Anxiolytic Effects Of Natural Flavonoidsmentioning

confidence: 99%

The research progress on the anxiolytic effect of plant‐derived flavonoids by regulating neurotransmitters

Wang

Yang

Deng

et al. 2023

Drug Development Research

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Phytopharmaceuticals have attracted a lot of attention due to their multicomponent and multiple targets. The natural phenolic chemicals known as flavonoids are found in a wide variety of plants, fruits, vegetables, and herbs. Recently, they have been found to have modulatory effects on anxiety disorders, with current research focusing on the modulation of neurotransmitters. There has not yet been a review of the various natural flavonoid monomer compounds and total plant flavonoids that have been found to have anxiolytic effects. The study on the anti‐anxiety effects of plant‐derived flavonoids on neurotransmitters was reviewed in this paper. We, therefore, anticipate that further study on the conformational interaction underlying flavonoids’ anti‐anxiety effects will offer a theoretical framework for the creation of pertinent treatments.

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Silibinin ameliorates depression/anxiety-like behaviors of Parkinson's disease mouse model and is associated with attenuated STING-IRF3-IFN-β pathway activation and neuroinflammation

Cited by 23 publications

References 56 publications

Silibinin as a promising treatment for diabetes: Insights into behavioral and metabolic changes in an animal model

Silibinin as a promising treatment for diabetes: Insights into behavioral and metabolic changes in an animal model

cGAS–STING, an important signaling pathway in diseases and their therapy

The research progress on the anxiolytic effect of plant‐derived flavonoids by regulating neurotransmitters

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