Antidepressant-Like Activity of Myelophil via Attenuation of Microglial-Mediated Neuroinflammation in Mice Undergoing Unpredictable Chronic Mild Stress

Abstract

Myelophil, a 30% ethanol extract that has an equal rate in both Astragali Radix and Salviae Radix , is a remedy for the treatment of fatigue-linked disorders in traditional Oriental medicine. The majority of patients with chronic fatigue have a risk of comorbidity with depression symptoms. To evaluate the anti-depressant activity of Myelophil, mice were subjected to unpredictable chronic mild stress (UCMS, eight different stresses) for 3 weeks with daily administration of distilled water, Myelophil (25, 50, or 100 mg/kg), or n -acetyl- l -cysteine (NAC) (100 mg/kg). After the final stress exposure, three behavioral tests, including the open field test (OFT), forced swimming test (FST), and tail suspension test (TST), and stress-derived alterations of the serotonergic signal and inflammatory response in the hippocampus were measured. UCMS notably induced depressive behaviors, whereas these behavioral alterations were significantly reversed by the administration of Myelophil in regard to the OFT, FST, and TST results. Myelophil also significantly attenuated the over-activation of microglial cells and the inflammatory response in the hippocampal region (TNF-α, tumor necrosis factor-alpha; IL-1β, interleukin-1beta; and caspase-1). Furthermore, Myelophil significantly restored the distortions of serotonergic function in the dorsal raphe nuclei and neurogenesis in the subgranular zone of the hippocampus. These results support the clinical relevance of the anti-depressant activity of Myelophil, specifically by modulating serotonergic function and the neuroinflammatory response.

Neuroinflammatory alterations in trait anxiety: modulatory effects of minocycline

“…Furthermore, modulating microglia activity locally in the DG, via long-term minocycline microinjection, was also sufficient to attenuate hyperanxiety in HAB. Together, the current findings suggest that central inflammatory disturbances are evident in individuals with high trait anxiety, even in the absence of known triggers of inflammation such as chronic stress 56,57 . Furthermore, inflammation-targeting approaches, such as inhibitors of microglia 'activation', could serve as alternative or complementary treatment approaches in patient sub-groups presenting with genetically determined hyperanxiety.…”

High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling

“…Mice were individually placed in a glass cylinder (24 cm height, 15 cm diameter) filled with water (25°C) for 10 min (pretest) and 24 h later were re-exposed for 6 minutes. The room illumination was set to 30 lux ( Lee et al, 2019 ). The duration of immobility was measured for the last 5 minutes of the exposure period.…”

“…Mice were individually placed in a glass cylinder (24 cm height, 15 cm diameter) filled with water (25 • C) for 10 min (pretest) and 24 h later were re-exposed for 6 minutes. The room illumination was set to 30 lux (Lee et al, 2019).The duration of immobility was measured for the last 5 minutes of the exposure period. The mice were tracked using a horizontally mounted camera adjacent to the cylinder and EthoVision XT15 software (Noldus Information Technology) was used for analysis (Fitzgerald et al, 2019).…”

Isoliquiritin ameliorates depression by suppressing NLRP3-mediated pyroptosis via miRNA-27a/SYK/NF-κB axis

“…Depression is a pervasive and debilitating psychiatric disorder that is characterized by low mood, loss of pleasure, social avoidance, etc. It affects approximately 322 million people worldwide, leading to a major social and economic burden [ 1 ]. Although multiple antidepressants are available for depression treatment, first-line drugs, including selective serotonin reuptake inhibitors (SSRIs), exhibit low curative ratio, extensive side effects, and poor treatment compliance.…”