Antidepressant-Like and Neuroprotective Effects of Ethanol Extract from the Root Bark of Hibiscus syriacus L.

Abstract

Hibiscus syriacus L. (Malvaceae) is an important ornamental shrub in horticulture and has been widely used as a medical material in Asia. The aim of this study was to assess the antidepressant and neuroprotective effects of a root bark extract of H. syriacus (HSR) and to investigate the underlying molecular mechanisms. Using an animal model of restraint stress, we investigated the effects of HSR on depressive-like behaviors and on the expression levels of serotonin, corticosterone, and neurotrophic factors in the brain. The mice were exposed to restraint stress for 2 h per day over a period of 3 weeks and orally treated with HSR (100, 200, or 400 mg/kg/day). We also examined the neuroprotective effect of HSR using corticosterone-treated human neuroblastoma SK-N-SH cells. The cells were incubated with the extract for 24 h, followed by corticosterone stimulation for 1 h, and then cell viability assay, cellular ATP assay, mitochondrial membrane potential (MMP) assay, cellular reactive oxygen species (ROS) assay, and western blotting were used to investigate the neuroprotective effects of HSR. Administration of HSR not only reduced the immobility times of the restraint-stressed mice in the forced swimming and tail suspension tests, but also significantly increased sucrose preference in the sucrose preference test. In addition, HSR significantly reduced the plasma levels of corticosterone and increased the brain levels of serotonin. The extract also increased the phosphorylation level of cyclic AMP response element-binding (CREB) protein and the expression level of brain-derived neurotrophic factor (BDNF). The in vitro assays showed that HSR pretreatment increased cell viability and ATP levels, recovered MMP, decreased ROS levels, and increased the expression of CREB and BDNF in corticosterone-induced neurotoxicity. Taken together, our data suggest that HSR may have the potential to control neuronal cell damage and depressive behaviors caused by chronic stress.

Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats

“…The results that serum corticosterone in the rats of the CUMS group increased significantly were in accordance with previous studies [ 2 , 47 ]. As a typical antidepressant agent, fluoxetine could effectively prevent the elevation of serum corticosterone level in CUMS-treated rats [ 1 , 48 ]. Disrupting the HPA axis and elevating the levels of serum corticosterone by CUMS were increasingly recognized [ 49 , 50 ].…”

“…As one of the most common neuropsychiatric illness, depression has affected 300 million people of all ages in the modern world [ 1 ]. According to the WHO's prediction, depression is expected to become the world's second leading cause of disability by 2020 [ 2 ], leading to a huge social and economic burden on the modern society [ 3 ].…”

Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities

“…Depression is among the most common neuropsychiatric illnesses, affecting approximately 300 million people of all ages worldwide 1 and representing a vast economic and social burden. 2 Although the causative factors underlying depression are not clearly understood, sufficient evidence has suggested that neural oxidative insults, inflammation, and apoptosis, associated with neurodegeneration and reduced neurogenesis and neural plasticity, underlies the onset of major depressive disorder.…”

Anthocyanins from Hibiscus syriacus L. Inhibit Melanogenesis by Activating the ERK Signaling Pathway

“…Next, cAMP-responsive element binding protein (CREB) leads to the phosphorylation and upregulation of MITF expression [11]. In contrast, previous studies revealed that extracellular signal-regulated kinase (ERK) phosphorylation inhibits melanogenesis by accelerating proteasomal degradation of MITF, which is accompanied by mitochondrial fission [12,13]. Recent studies have also found melanogenesis inhibitors that negatively regulate the cAMP-dependent pathway and positively stimulate the ERK pathway [5,6].…”

“…Recent studies also revealed that extracts of the bark and rhizosphere of H. syriacus L. exert significant wound healing activity and protective activity against UV-mediated photoaging in fibroblasts and keratinocytes by stimulating collagen and fibronectin synthesis [16,17]. Moreover, new medicinal effects of H. syriacus L. have been elucidated, namely anti-depressant and neuroprotective [12], anti-cancer [18,19] and anti-oxidant [20] activities. Nevertheless, the flower petals of H. syriacus L. have not been investigated for medicinal and functional effects.…”