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Bang, Jun Soo,Oh, Da Hee,Choi, Hyun Mi,Sur, Bong-Jun,Lim, Sung-Jig,Kim, Jung Yeon,Yang, Hyung-In,Yoo, Myung Chul,Hahm, Dae-Hyun,Kim, Kyoung Soo BioMed Central 2009 Arthritis research & therapy Vol.11 No.2
<P><B>Introduction</B></P><P>The objective of this study was to determine the anti-inflammatory, nociceptive, and antiarthritic effects of piperine, the active phenolic component in black pepper extract.</P><P><B>Methods</B></P><P>The <I>in vitro </I>anti-inflammatory activity of piperine was tested on interleukin 1β (IL1β)-stimulated fibroblast-like synoviocytes derived form patients with rheumatoid arthritis. The levels of IL6, matrix metalloproteinase (MMPs), cyclo-oxygenase 2 (COX-2), and prostaglandin E2 (PGE<SUB>2</SUB>) were investigated by ELISA and RT-PCR analysis. The analgesic and antiarthritic activities of piperine were investigated on rat models of carrageenan-induced acute paw pain and arthritis. The former were evaluated with a paw pressure test, and the latter by measuring the squeaking score, paw volume, and weight distribution ratio. Piperine was administrated orally to rats at 20 and 100 mg/kg/day for 8 days.</P><P><B>Results</B></P><P>Piperine inhibited the expression of IL6 and MMP13 and reduced the production of PGE<SUB>2 </SUB>in a dose dependant manner at concentrations of 10 to 100 μg/ml. In particular, the production of PGE<SUB>2 </SUB>was significantly inhibited even at 10 μg/ml of piperine. Piperine inhibited the migration of activator protein 1 (AP-1), but not nuclear factor (NF)κB, into the nucleus in IL1β-treated synoviocytes. In rats, piperine significantly reduced nociceptive and arthritic symptoms at days 8 and 4, respectively. Histological staining showed that piperine significantly reduced the inflammatory area in the ankle joints.</P><P><B>Conclusions</B></P><P>These results suggest that piperine has anti-inflammatory, antinociceptive, and antiarthritic effects in an arthritis animal model. Thus, piperine should be further studied with regard to use either as a pharmaceutical or as a dietary supplement for the treatment of arthritis.</P>
Lee, Bombi,Sur, Bong-Jun,Shim, Insop,Hahm, Dae-Hyun,Lee, Hyejung Hindawi Publishing Corporation 2014 Evidence-based Complementary and Alternative Medic Vol.2014 No.-
<P>The purpose of this study was to evaluate whether acupuncture stimulation attenuates withdrawal-induced behaviors in the rats during protracted abstinence following chronic morphine exposure. To do this, male rats were first exposed to morphine gradually from 20 to 100 mg/kg for 5 days, and subsequently naloxone was injected once to extend despair-related withdrawal behaviors for 4 weeks. Acupuncture stimulation was performed once at the SP6 (Sanyinjiao) acupoint on rat's; hind leg for 5 min during protracted abstinence from morphine. The acupuncture stimulation significantly decreased despair-like behavior deficits in the forced swimming test and low sociability in the open-field test as well as increased open-arm exploration in the elevated plus maze test in the last week of 4-week withdrawal period. Also the acupuncture stimulation significantly suppressed the increase in the hypothalamic corticotropin-releasing factor (CRF) expression, the decrease in the tyrosine hydroxylase expression in the locus coeruleus, and the decrease in the hippocampal brain-derived neurotrophic factor mRNA expression, induced by repeated injection of morphine. Taken together, these findings demonstrate that the acupuncture stimulation of SP6 significantly reduces withdrawal-induced behaviors, induced by repeated administration of morphine in rats, possibly through the modulation of hypothalamic CRF and the central noradrenergic system.</P>
Lee, Bombi,Sur, Bong-Jun,Kwon, Sunoh,Jung, Euntaek,Shim, Insop,Lee, Hyejung,Hahm, Dae-Hyun Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-
<P>The purpose of this study was to examine whether acupuncture improves spatial cognitive impairment induced by repeated corticosterone (CORT) administration in rats. The effect of acupuncture on the acetylcholinergic system was also investigated in the hippocampus. Male rats were subcutaneously injected with CORT (5 mg/kg) once daily for 21 days. Acupuncture stimulation was performed at the HT7 (Sinmun) acupoint for 5 min before CORT injection. HT7 acupoint is located at the end of transverse crease of ulnar wrist of forepaw. In CORT-treated rats, reduced spatial cognitive function was associated with significant increases in plasma CORT level (+36%) and hippocampal CORT level (+204%) compared with saline-treated rats. Acupuncture stimulation improved the escape latency for finding the platform in the Morris water maze. Consistently, the acupuncture significantly alleviated memory-associated decreases in cholinergic immunoreactivity and mRNA expression of BDNF and CREB in the hippocampus. These findings demonstrate that stimulation of HT7 acupoint produced significant neuroprotective activity against the neuronal impairment and memory dysfunction.</P>
( Bom Bi Lee ),( Bong Jun Sur ),( Jin Hee Park ),( Sung Hun Kim ),( Sunoh Kwon ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.5
The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and infl ammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinfl ammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic infl ammation and produced defi cits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration signifi cantly decreased expression of pro-infl ammatory mediators such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these fi ndings suggest that GRg3 signifi cantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-infl ammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer`s disease, by improving cognitive and memory functions due to its anti-infl ammatory activity in the brain.
Lee, Bom-Bi,Sur, Bong-Jun,Shim, In-Sop,Lee, Hye-Jung,Hahm, Dae-Hyun The Korean Society of Pharmacology 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-$1{\beta}$, tumor necrosis factor-${\alpha}$ 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.
( Bom Bi Lee ),( Bong Jun Sur ),( Sun Oh Kwon ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.4
Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confi rmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration signifi cantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and signifi cantly blocked increases of TH expression in the locus coeruleus (LC). It also signifi cantly enhanced the total number of line crossing in the open-fi eld test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these fi ndings indicate that the administration of CTN prior to high-dose exogenous CORT signifi cantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders.
Lee, Bom-Bi,Sur, Bong-Jun,Cho, Se-Hyung,Yeom, Mi-Jung,Shim, In-Sop,Lee, Hye-Jung,Hahm, Dae-Hyun The Korean Society for Integrative Biology 2012 Animal cells and systems Vol.16 No.4
The purpose of this study was to examine whether Phellodendri Cortex extract (PCE) could improve learning and memory impairments caused by lipopolysaccharide (LPS)-induced inflammation in the rat brain. The effect of PCE on modulating pro-inflammatory mediators in the hippocampus and its underlying mechanism were investigated. Injection of LPS into the lateral ventricle caused acute regional inflammation and subsequent deficits in spatial learning ability in the rats. Daily administration of PCE (50, 100, and 200 mg/kg, i.p.) for 21 days markedly improved the LPS-induced learning and memory disabilities in the Morris water maze and passive avoidance test. PCE administration significantly decreased the expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and cyclooxygenase-2 mRNA in the hippocampus, as assessed by RT-PCR analysis and immunohistochemistry. Together, these findings suggest that PCE significantly attenuated LPS-induced spatial cognitive impairment through inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggested that PCE may be effective in preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory function because of its anti-inflammation activity in the brain.
( Bom Bi Lee ),( Bong Jun Sur ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.3
Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitaryadrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.