Targeting autophagy and neuroinflammation pathways with plant‐derived natural compounds as potential antidepressant agents

Abstract

Major depressive disorder (MDD) is a life‐threatening disease that presents several characteristics. The pathogenesis of depression still remains poorly understood. Moreover, the mechanistic interactions of natural components in treating depression to target autophagy and neuroinflammation are yet to be evaluated. This study overviewed the effects of plant‐derived natural components in regulating critical pathways, particularly neuroinflammation and autophagy, associated with depression. A list of natural components, including luteolin, apigenin, hyperforin, resveratrol, salvianolic acid b, isoliquiritin, nobiletin, andrographolide, and oridonin, have been investigated. All peer‐reviewed journal articles were searched by Scopus, MEDLINE, PubMed, Web of Science, and Google Scholar using the appropriated keywords, including depression, neuroinflammation, autophagy, plant, natural components, etc. The neuroinflammation and autophagy dysfunction are critically associated with the pathophysiology of depression. Natural components with higher efficiency and lower complications can be used for targeting neuroinflammation and autophagy. These components with different doses showed the beneficial antidepressant properties in rodents. These can modulate autophagy markers, mainly AMPK, LC3II/LC3I ratio, Beclin‐1. Moreover, they can regulate the NLRP3 inflammasome, resulting in the suppression of proinflammatory cytokines (e.g., IL‐1β and IL‐18). Future in vitro and in vivo studies are required to develop novel therapeutic approaches based on plant‐derived active components to treat MDD.

Resveratrol attenuates chronic social isolation stress‐induced affective disorders: Involvement of NF‐κB/NLRP3 axis

“…In a systematic review by Moore et al, [78] RV was dose-dependently effective for the treatment of depression in animal models at doses between 10 and 80 mg/kg daily Our results indicated that RV, like FL, exhibited anxiolytic and antidepressant effects through control of the NF-B/NLRP3 axis similarly inhibition of NLRP3 by anti-inflammatory agents has been shown to alleviate mood disorders in animals. [79,80] Molecular studies showed that the RV administration attenuated the NF-κB/NLRP3 pathway through the regulation of NF-κB and NLRP3 inflammasome components (NLRP3, ASC, and proCaspase-1) in the HC. In line with our findings, RV treatment (40 or 80 mg/kg/day) could reverse behavioral changes animals induced by CUMS through regulating proinflammatory mediators (IL-6, IL-1β, & TNF-α) in the PFC and HC.…”

Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies

“…Certain constituents among these compounds demonstrate the ability to prevent the activation of NLRP3 inflammasomes. Compounds such as dihydroquercetin [ 76 ], resveratrol [ 77 ], quercetin [ 78 ], isoliquiritigenin [ 79 ], icariin [ 80 ], and oridonin [ 81 ] exhibit properties that suggest their suitability as promising candidates for regulating the activation of SARS-CoV-2-induced NLRP3 inflammasomes.…”

Role of NLRP3 Inflammasome in Post-Spinal-Cord-Injury Anxiety and Depression: Molecular Mechanisms and Therapeutic Implications

“…The activation of inflammasomes involves two distinct signaling pathways: Signal 1, known as the priming signal, and Signal 2, which corresponds to the activation signal, often referred to as the assembly step of the protein complex . The priming process is initiated by the activation of PRRs, such as NOD2 and Toll-like receptors (TLRs), by diverse stimuli.…”