Simvastatin mitigates depressive-like behavior in ovariectomized rats: Possible role of NLRP3 inflammasome and estrogen receptors’ modulation

Menze, Esther T.; Ezzat, Hager; Shawky, Salma; Sami, Marwa; Selim, Eman H.; Ahmed, Samar; Maged, Nouran; Nadeem, Nancy; Eldash, Shorouk; Michel, Haidy E.

doi:10.1016/j.intimp.2021.107582

Cited by 24 publications

(16 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The microglia membrane is rich in P2X7, activating the NLRP3 inflammasome in the microglia under chronic stress, thus mediating depression-like behavior [127][128][129]. Therapy such as electroacupuncture, curcumin, and simvastatin exhibit the antidepressant effect and alleviate neuroinflammation by inhibiting the NLRP3 inflammasome and inflammatory mediators [130][131][132][133][134][135]. Selective serotonin reuptake inhibitors (SSRI) are the firstline treatment for depression.…”

Section: Microsphere Embolism Modelmentioning

confidence: 99%

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

Xia

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Poststroke depression (PSD) does not exist before and occurs after the stroke. PSD can appear shortly after the onset of stroke or be observed in the weeks and months after the acute or subacute phase of stroke. The pathogenesis of PSD is unclear, resulting in poor treatment effects. With research advancement, immunoactive cells in the central nervous system, particularly microglia, play a role in the occurrence and development of PSD. Microglia affects the homeostasis of the central nervous system through various factors, leading to the occurrence of depression. The research progress of microglia in PSD has been summarized to review the evidence regarding the pathogenesis and treatment target of PSD in the future.

show abstract

Section: Microsphere Embolism Modelmentioning

confidence: 99%

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

Xia

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…This antidepressant effect was also observed in high-fat diet mice along with an attenuation of neuroinflammatory factors in the hippocampus [266]. In ovariectomized rats, simvastatin decreased depressive-like behaviors, downregulated the expression of toll-like receptors 2 and 4, reduced IL-1β and IL-18 expression, and limited microglia activation in the hippocampus [267]. When co-administered with an opioid receptor antagonist (naloxone), the antidepressant effect of simvastatin was reduced, suggesting that opioid receptors could be involved in statin's mechanism of action [268].…”

Section: Cholesterol Biosynthesis Pathwaymentioning

confidence: 57%

Novel Pharmacological Approaches to the Treatment of Depression

Elias

Zhang

Manners

2022

Life

View full text Add to dashboard Cite

Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies.

show abstract

“…Studies have shown that E2 is a strong endogenous antioxidant that inhibits oxidative stress-induced lipid peroxidation and ROS production in rat liver mitochondria ( Yagi, 1997 ; Omoya et al, 2001 ). Simvastatin could activate the expression of ERα and ERβ, thereby inhibiting the activation of the NLRP3 inflammasome and decreasing the levels of pro-inflammatory mediators ( Menze et al, 2021 ). 17β-estradiol can reduce NLRP3 inflammasome activation to abrogate airway inflammation ( Cheng et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Saikosaponin d Alleviates Liver Fibrosis by Negatively Regulating the ROS/NLRP3 Inflammasome Through Activating the ERβ Pathway

Zhang

Lei²,

Zhu³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Background and aims: Saikosaponin d (SSd) has a steroidal structure and significant anti-inflammatory effects. The purpose of this study was to explore the mechanism underlying SSd’s inhibitory effects on liver fibrosis.Methods: Wild-type and estrogen receptor knockout (ERKO) mice were treated with CCl4 to establish liver fibrosis mouse models. The effects of SSd on hepatic fibrogenesis were studied in these mouse models. Hepatic stellate cells (HSCs) were activated by H2O2 to investigate the potential molecular mechanisms. The establishment of the models and the degrees of inflammation and liver tissue fibrosis were evaluated by detecting changes in serum liver enzymes and liver histopathology. The expression of α-SMA and TGF-β1 was determined by immunohistochemistry. The expression and significance of NLRP3 inflammasome proteins were explored by RT-PCR and Western blotting analyses. The mitochondrial ROS-related indexes were evaluated by MitoSOX Red.Results: In wild-type and ERKO mice treated with CCl4, the fluorescence expression of mitochondrial ROS was up-regulated, while the mitochondrial membrane potential and ATP content were decreased, suggesting that the mitochondria were damaged. In addition, the expression of NLRP3 inflammatory bodies and fibrosis markers (α-SMA, TGF-β, TIMP-1, MMP-2, and Vimentin) in liver tissue increased. Furthermore, the above indexes showed the same expression trend in activated HSCs. In addition, the peripheral serum ALT and AST levels increased in CCl4-induced liver injury model mice. And HE staining showed a large number of inflammatory cell infiltration in the liver of model mice. Picric acid-Sirius staining and Masson staining showed that there was significant collagen fibrous tissue deposition in mice liver sections. IHC and WB detection confirmed that the expression of α-SMA and TGF-β1 increased. Liver fibrosis scores were also elevated. Then, after SSd intervention, the expression of ROS in wild-type mice and αERKO mice decreased, mitochondrial membrane potential recovered, ATP level increased, NLRP3 inflammasome and fibrosis indexes decreased, liver enzyme levels decreased, and liver pathology showed liver inflammation. The damage and collagen deposition were significantly relieved, the expression of α-SMA and TGF-β1 was decreased, and the fibrosis score was also decreased. More importantly, the effect of SSd in alleviating liver injury and liver fibrosis had no effect on βERKO mice.Conclusion: SSd alleviated liver fibrosis by negatively regulating the ROS/NLRP3 inflammasome through activating the ERβ pathway. By establishing liver fibrosis models using wild-type and ERKO mice, we demonstrated that SSd could alleviate liver fibrosis by inhibiting the ROS/NLRP3 inflammasome axis through activating the ERβ pathway.

show abstract

Simvastatin mitigates depressive-like behavior in ovariectomized rats: Possible role of NLRP3 inflammasome and estrogen receptors’ modulation

Cited by 24 publications

References 92 publications

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

Novel Pharmacological Approaches to the Treatment of Depression

Saikosaponin d Alleviates Liver Fibrosis by Negatively Regulating the ROS/NLRP3 Inflammasome Through Activating the ERβ Pathway

Contact Info

Product

Resources

About