α-Cyperone Confers Antidepressant-Like Effects in Mice via Neuroplasticity Enhancement by SIRT3/ROS Mediated NLRP3 Inflammasome Deactivation

Abstract

α-Cyperone (Cy) is a major active compound of Cyperus rotundus that has various pharmacological activities. But whether Cy possesses antidepressant effect is unknown. In this study, we exposed mice to chronic unpredictable mild stress (CUMS) with or without intervention with Cy. Our results showed that Cy significantly improved the depressive phenotypes in sucrose preference test, tail suspension test and forced swimming test. Meanwhile, increased SIRT3 expression, reduced ROS production and activated NF-κB signal were detected in the hippocampus of mice. NLRP3 inflammasome related proteins including NLRP3, ASC, Caspase-1, IL-1β, IL-18 and GSDMD-N were downregulated after Cy administration. Synaptic proteins including Synapsin-1 and PSD-95 and dendritic spine density were improved after Cy treatment. Moreover, the protective effects of Cy in CUMS mice were compromised when co-administrated with SIRT3 inhibitor 3-TYP. Taken together, these findings suggested that Cy has therapeutic potential for treating depression and that this antidepressant effect may be attributed to SIRT3 stimulated neuroplasticity enhancement by suppressing NLRP3 inflammasome.

Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy

“…Collectively, these studies have demonstrated a positive feedback interaction between SIRT3 and PGC-1α, providing SIRT3/PGC-1α activation as a viable strategy for the intervention of DCM. Moreover, SIRT3 has been reported to be a crucial negative regulator of NLRP3 [40][41][42][43]. Mechanistically, SIRT3 deacetylates SOD2, leading to SOD2 activation, which impairs NLRP3 inflammasome assembly and activation [41].…”

The Anti-Endometriotic Effect of Cyperi Rhizoma Extract, Inhibiting Cell Adhesion and the Expression of Pain-Related Factors through Akt and NF-kB Pathways

“…In fact, most of the biological activities of the rhizomes of C. rotundus have been attributed to the sesquiterpenes [ 36 ]. It is reported that isocyperol and α-cyperone, known as major sesquiterpene components of the rhizomes of C. rotundus , have various pharmacological activities, such as anti-inflammation, antivirulence, antigenotoxic, antibacterial and anti-depressant effects [ 37 , 38 , 39 , 40 , 41 , 42 ]. For example, isocyperol and α-cyperone have an inhibitory effect on inflammation through suppression of the NF-κB pathway [ 37 , 38 ].…”

To Explore the Network Pharmacology and Molecular Docking Mechanism of Chaihu Shugan Powder with the “Same Treatment for Different Diseases” for Insomnia and Depression Based on the COVID-19 Pandemic

“…Saikosaponin, the main chemical component of Chaihu, has sedative, antipyretic, immune enhancement, anti-in ammatory, antiviral, liver, and antitumor effects. The α-germanone of Xiangfu has an antidepressant-like effect [31], and Jiawei Xiangfu Decoction combined with acupuncture can signi cantly improve the sleep state of menopausal insomnia patients with liver stagnation and qi stagnation [32]. The main active ingredients of Chuanxiong have both a sedative effect [26] and the potential to improve depression.…”