Phellodendron amurense and Its Major Alkaloid Compound, Berberine Ameliorates Scopolamine-Induced Neuronal Impairment and Memory Dysfunction in Rats

Bombi Lee,Bongjun Sur,Insop Shim,Hyejung Lee,Dae-Hyun Hahm 대한생리학회-대한약리학회 2012 The Korean Journal of Physiology & Pharmacology Vol.16 No.2

We examine whether Phellodendron amurense (PA) and its major alkaloid compound, berberine (BER), improved memory defects caused by administering scopolamine in rats. Effects of PA and BER on the acetylcholinergic system and pro-inflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of PA (100 and 200 mg/kg, i.p.) and BER (20 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of PA and BER improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Administration of PA and BER significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored brain-derived neurotrophic factor and cAMP-response element-binding protein mRNA expression in the hippocampus. PA and BER also decreased significantly the expression of proinflammatory cytokines such as interleukin-1Ղ, tumor necrosis factor-Ձ and cyclooxygenase-2 mRNA in the hippocampus. These results demonstrated that PA and BER had significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that PA and BER may be useful as therapeutic agents for improving cognitive functioning by stimulating cholinergic enzyme activity and alleviating inflammatory responses.

Korean Red Ginseng prevents posttraumatic stress disorder – triggered depression-like behaviors in rats via activation of the serotonergic system

Bombi Lee,서봉준,HYE-JUNGLEE,오세관 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.4

Background: Posttraumatic stress disorder (PTSD), a mental disorder induced by traumatic stress andoften accompanied by depression and/or anxiety, may involve an imbalance in the neurotransmittersassociated with the fear response. Korean Red Ginseng (KRG) has long been used as a traditionalmedicine and is known to be involved in a variety of pharmacological activities. We used the open fieldtest and forced swimming test to examine the effects of KRG on the depression-like response of rats afterexposure to single prolonged stress (SPS), leading to activation of the serotonergic system. Methods: Male rats received KRG (30, 50, and 100 mg/kg, intraperitoneal injection) once daily for 14 daysafter exposure to SPS. Results: Daily KRG administration significantly improved depression-like behaviors in the forcedswimming test, increased the number of lines crossed and time spent in the central zone in the openfield test, and decreased freezing behavior in contextual and cued fear conditioning. KRG treatmentattenuated SPS-induced decreases in serotonin (5-HT) tissue concentrations in the hippocampus andmedial prefrontal cortex. The increased 5-HT concentration during KRG treatment may be partiallyattributable to the 5-hydroxyindoleacetic acid/5-HT ratio in the hippocampus of rats with PTSD. Theseeffects may be caused by the activation of hippocampal genes encoding tryptophan hydroxylase-1 and 2mRNA levels.

Berberine alleviates symptoms of anxiety by enhancing dopamine expression in rats with post-traumatic stress disorder

Bombi Lee,Insop Shim,Hyejung Lee,Dae-Hyun Hahm 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.2

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

Neuroprotective effect of Korean Red Ginseng against single prolonged stress-induced memory impairments and inflammation in the rat brain associated with BDNF expression

Bombi Lee,Bongjun Sur,오세관 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.3

Post-traumatic stress disorder (PTSD) is a psychiatric disease that develops followingexposure to a traumatic event and is a stress-associated mental disorder characterized by an imbalanceof neuroinflammation. Korean Red Ginseng (KRG) is the herbal supplement that is known to be involvedin a variety of pharmacological activities. We aimed to investigate the effects of KRG on neuroinflammation as a potential mechanism involved in single prolonged stress (SPS) that negatively influences memory formation and consolidation and leads to cognitive and spatial impairment byregulating BDNF signaling, synaptic proteins, and the activation of NF-kB. Methods: We analyzed the cognitive and spatial memory, and inflammatory cytokine levels during theSPS procedure. SPS model rats were injected intraperitoneally with 20, 50, or 100 mg/kg/day KRG for 14days. Results: KRG administration significantly attenuated the cognitive and spatial memory deficits, as well asthe inflammatory reaction in the hippocampus associated with activation of NF-kB in the hippocampusinduced by SPS. Moreover, the effects of KRG were equivalent to those exerted by paroxetine. In addition,KRG improved the expression of BDNF mRNA and the synaptic protein PSD-95 in the hippocampus. Taken together, these findings demonstrate that KRG exerts memory-improving actions by regulatinganti-inflammatory activities and the NF-kB and neurotrophic pathway. Conclusion: Our findings suggest that KRG is a potential functional ingredient for protecting againstmemory deficits in mental diseases, such as PTSD.

Chronic Administration of Baicalein Decreases Depression-Like Behavior Induced by Repeated Restraint Stress in Rats

Bombi Lee,Bongjun Sur,Jinhee Park,Sung-Hun Kim,Sunoh Kwon,Mijung Yeom,Insop Shim,Hyejung Lee,Dae-hyun Hahm 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.5

Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.

Diagnostic Performance of US,MRI and CT for Detecting Axillary Response after Neoadjuvant Chemotherapy in Axillary Node Positive Breast Cancer Patients

Bombi Park 대한외과학회 2022 대한외과학회 학술대회 초록집 Vol.2022 No.5

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats

Bombi Lee,Mijung Yeom,Insop Shim,Hyejung Lee,and Dae-hyun Hahm 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.1

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

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

( Bombi Lee ),( Bongjun Sur ),( Seong-guk Cho ),( Mijung Yeom ),( Insop Shim ),( Hyejung Lee ),( And Dae-hyun Hahm ) 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.

Tetramethylpyrazine reverses anxiety-like behaviors in a rat model of post-traumatic stress disorder

Bombi Lee,Insop Shim,Hyejung Lee,Dae-Hyun Hahm 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.5

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p. ) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

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

( Bombi Lee ),( Bongjun Sur ),( Seong Guk Cho ),( Mijung Yeom ),( Insop Shim ),( Hyejung Lee ),( Dae Hyun Hahm ) 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.