Luteolin reduces fear, anxiety, and depression in rats with post-traumatic stress disorder

서봉준,이봄비 한국통합생물학회 2022 Animal cells and systems Vol.26 No.4

Exposure to severe stress can lead to the development of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). The cause of PTSD is dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and an imbalance of monoamines. Fruits and vegetables contain large amounts of luteolin (LU; 3′,4′,5,7-tetrahydroxylflavone), which has various pharmacological activities such as anti-inflammatory, antioxidant, and anti-allergic effects. We investigated the effects of LU on fear, depression, and anxiety following monoamine imbalance and hyperactivation of the HPA axis in rats exposed to single prolonged stress (SPS). Male rats were dosed with LU (10 and 20 mg/kg) once daily for 14 days after exposure to SPS. Administration of LU reduced fear freezing responses to extinction recall and depression- and anxiety-like behaviors, and suppressed increases in plasma corticosterone and adrenocorticotropic hormone levels. Also, administration of LU restored the increased norepinephrine and decreased serotonin levels in the structures within the fear circuit, medial prefrontal cortex, and hippocampus. Our results showed that administration of LU improved freezing behavior according in a situation-dependent manner, and showed anti-depressant and anxiolytic effects. Thus, LU may be a useful therapeutic agent to prevent traumatic stress such as PTSD.

Myricetin prevents sleep deprivation-induced cognitive impairment and neuroinflammation in rat brain via regulation of brain-derived neurotropic factor

서봉준,이봄비 대한약리학회 2022 The Korean Journal of Physiology & Pharmacology Vol.26 No.6

Memory formation in the hippocampus is formed and maintained by circadian clock genes during sleep. Sleep deprivation (SD) can lead to memory impairment and neuroinflammation, and there remains no effective pharmacological treatment for these effects. Myricetin (MYR) is a common natural flavonoid that has various pharmacological activities. In this study, we investigated the effects of MYR on memory impairment, neuroinflammation, and neurotrophic factors in sleepdeprived rats. We analyzed SD-induced cognitive and spatial memory, as well as pro-inflammatory cytokine levels during SD. SD model rats were intraperitoneally injected with 10 and 20 mg/kg/day MYR for 14 days. MYR administration significantly ameliorated SD-induced cognitive and spatial memory deficits; it also attenuated the SD-induced inflammatory response associated with nuclear factor kappa B activation in the hippocampus. In addition, MYR enhanced the mRNA expression of brainderived neurotropic factor (BDNF) in the hippocampus. Our results showed that MYR improved memory impairment by means of anti-inflammatory activity and appropriate regulation of BDNF expression. Our findings suggest that MYR is a potential functional ingredient that protects cognitive function from SD.

Inhibitory Effect of Phosphatidylserine on Atopy-like Dermatitis in NC/Nga Mice

서봉준,Bombi Lee,염미정,Jeong-Jun Han,Hee-Don Choi,이혜정,김석중,Suk Hoo Yoon,함대현 한국식품과학회 2010 Food Science and Biotechnology Vol.19 No.6

In the present study, the anti-atopic effect of phosphatidylserine (PS) extracted from soybean was investigated in NC/Nga mice. The atopic symptoms were evaluated by scoring spontaneous scratching behavior and skin lesions, by measuring serum levels of immunoglobulin E (IgE) and interleukin-4 (IL-4), and by observing skin histology. After observing the maximum severity of atopic symptoms, PS was initiated. The PS treatment significantly alleviated apparent symptoms of atopic dermatitis and scratching behavior. The suppression of atopic dermatitis by PS was verified by decreases in the serum levels of IgE (p<0.05 after 8 weeks; p<0.001 after 9 weeks) and IL-4(p<0.01 after 7 weeks; p<0.001 after 9 weeks). Histological observations also indicated that the thickening process of skin and the infiltration of inflammatory cells were significantly inhibited. Taken together, PS from soybean might be useful for alleviating atopic dermatitis symptoms and thus for developing a new medicine for treating human atopic disease.

캐리지난에 의해 유도된 쥐의 급성관절염에서 약물의 억제효과

서봉준 慶熙大學校 大學院 2010 高凰論集 Vol.46 No.-

The purpose of this study is to determine the anti arthritic activities of several bioactive substances such as piperine, phosphatidylserine and dandelion extracts. The anti arthritic activities of these substances were investigated in the rat models with carrageenan induced ankle monoarthritis. The arthritic symptoms of the model rats were evaluated by measuring paw volume, weight distribution ratio, and squeaking score. The bioactive substances were administrated orally to the rats for 7 days. In all treated rats, arthritic symptoms were significantly decreased during day 4 to 7. These results suggest that this animal model is highly effective for screening anti arthritic substances isolated from the natural resources and the bioactive substances, chosen in the present study, have significant anti arthritic activities. It indicates that these substances can be used as primary materials to develop either pharmaceuticals or dietary supplements for treating human arthritic disease or pain.

The Anxiolytic-Like Effects of Protocatechuic Acid in an Animal Model of Post-Traumatic Stress Disorder

서봉준,Sunoh Kwon,DAE HYUN HAHM,Bombi Lee 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.5

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder characterized by impaired fear extinction, depression, and anxiety caused by dysregulation of the hypothalamic–pituitary–adrenal axis and an imbalance of monoamines. Protocatechuic acid (PCA; 3,4-dihydroxybenzoic acid), a major polyphenol metabolite, has various pharmacological effects, such as anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. In this study, the efficacy of PCA for fear extinction, antidepressant, and anxiolytic effects in PTSD-mediated psychiatric disorders, were evaluated by exposing rats to single prolonged stress (SPS). Male rats were administered PCA (100 or 200 mg/kg) once daily for 14 days after exposure to SPS. PCA significantly decreased situational fear, depressive and anxiety-like behaviors, and corticosterone levels. In addition, PCA regulated the imbalance of serotonin and norepinephrine in the fear circuit region (i.e., the medial prefrontal cortex and hippocampus [Hipp]), and suppressed the decrease in brain-derived neurotrophic factor mRNA expression in the Hipp. The results showed that PCA administration improves freezing behavior and has antidepressant and anti-anxiety effects through modulation of the serotonergic nervous system and monoamines in rats. These results indicated that PCA may be useful as a food ingredient to prevent PTSD.

Recent research news : APOBEC3 inhibits mouse mammary tumour virus replication in vivo

서봉준,함대현 한국생화학분자생물학회 (구 한국생화학회) 2007 생화학분자생물학회 소식 Vol.27 No.2

Effects of systemic administration of ibuprofen on stress response in a rat model of post-traumatic stress disorder

이봄비,서봉준,염미정,심인섭,이혜정,함대현 대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.4

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open field after SPS. IBU administration significantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These findings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

Effect of Beta-Asarone on Impairment of Spatial Working Memory and Apoptosis in the Hippocampus of Rats Exposed to Chronic Corticosterone Administration

이봄비,서봉준,조성국,염미정,심인섭,이혜정,함대현 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6

β-asarone (BAS) is an active component of Acori graminei rhizoma, a traditional medicine used clinically in treating dementia and chronic stress in Korea. However, the cognitive effects of BAS and its mechanism of action have remained elusive. The purpose of this study was to examine whether BAS improved spatial cognitive impairment induced in rats following chronic corticosterone (CORT) administration. CORT administration (40 mg/kg, i.p., 21 days) resulted in cognitive impairment in the avoidance conditioning test (AAT) and the Morris water maze (MWM) test that was reversed by BAS (200 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and RT-PCR analysis, the administration of BAS significantly alleviated memory-associated decreases in the expression levels of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) proteins and mRNAs in the hippocampus. Also, BAS administration significantly restored the expression of Bax and Bcl-2 mRNAs in the hippocampus. Thus, BAS may be an effective therapeutic for learning and memory disturbances, and its neuroprotective effect was mediated, in part, by normalizing the CORT response, resulting in regulation of BDNF and CREB functions and anti-apoptosis in rats. Key Words: β-asaron

Wogonin Attenuates Hippocampal Neuronal Loss and Cognitive Dysfunction in Trimethyltin-Intoxicated Rats

이봄비,서봉준,조성국,염미정,심인섭,이혜정,함대현 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3

We examined whether wogonin (WO) improved hippocampal neuronal activity, behavioral alterations and cognitive impairment, in rats induced by administration of trimethyltin (TMT), an organotin compound that is neurotoxic to these animals. The ability of WO to improve cognitive efficacy in the TMT-induced neurodegenerative rats was investigated using a passive avoidance test, and the Morris water maze test, and using immunohistochemistry to detect components of the acetylcholinergic system, brain-derived neurotrophic factor (BDNF), and cAMP-response element-binding protein (CREB) expression. Rats injected with TMT showed impairments in learning and memory and daily administration of WO improved memory function, and reduced aggressive behavior. Administration of WO significantly alleviated the TMT-induced loss of cholinergic immunoreactivity and restored the hippocampal expression levels of BDNF and CREB proteins and their encoding mRNAs to normal levels. These findings suggest that WO might be useful as a new therapy for treatment of various neurodegenerative diseases.

Fucoidan Ameliorates Scopolamine-induced Neuronal Impairment and Memory Dysfunction in Rats via Activation of Cholinergic System and Regulation of cAMP-response Element-binding Protein and Brain-derived Neurotrophic Factor Expressions

이봄비,서봉준,Jin-Hee Park,Heungsop Shin,권선오,염미정,김석중,김경수,In-SopShim,인창식,이혜정,함대현 한국응용생명화학회 2012 Applied Biological Chemistry (Appl Biol Chem) Vol.55 No.6

Effect of fucoidan (FCN) treatment on improving memory defects caused by administration of scopolamine (SCO)to the rats was examined. The effects of FCN on the acetylcholinergic system as well as the expression of cAMP-response elementbinding protein (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of FCN (10,20, and 50 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of FCN improved memory impairment as measured by the passive avoidance test (PAT) and reduced the escape latency for finding the platform in the Morris water maze (MWM) test. Administration of FCN significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored the expression level of BDNF and CREB mRNAs in the hippocampus. Additionally, FCN significantly decreased the expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)mRNAs in the hippocampus. These results demonstrated that FCN has significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. Thus, these findings suggest that FCN is useful as a therapeutic agent for improving cognitive functioning via stimulation of cholinergic enzyme activities and regulation of CREB and BDNF expressions in the brain.