• 대한한의학회지
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• 제43권4호
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• pp.20-32
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• 2022

Objectives: Kyungok-go (KOG) is a traditional multi-herbal medicine commonly used for enforcing weakened immunity for long time. Recently, there are several reports that KOG has anti-inflammatory and immuno-stimulatory activities in many experimental models. However, the protective effects of KOG on neuronal inflammation are still undiscovered. Thus, we investigated the neuro-protective activity of KOG on lipopolysaccharide (LPS)-stimulated mouse microglia cells. To find out KOG's anti-neuroinflammatory effects on microglial cells, we examined the production of nitrite using griess assay, and mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α using real time RT-PCR. In addition, to examine the regulating mechanisms of KOG, we investigated the protein expression of mitogen-activated protein kinases (MAPKs) and Iκ-Bα by western blot. KOG inhibited the elevation of nitrite, iNOS and COX-2 on LPS-stimulated BV2 cells. Also, KOG significantly inhibited the pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α on LPS-stimulated BV2 microglial cells. Moreover, KOG inhibited the activation of c-Jun N-terminal kinase (JNK), P38 and degradation of Iκ-Bα but not the activation of extracellular signal regulated kinase (ERK) on LPS-stimulated BV2 microglial cells. These results showed KOG has the anti-inflammatory effects through the inhibition on nitrite, iNOS, COX-2, IL-1β, IL-6, and TNF-α via the deactivation of JNK, p38 and nuclear factor (NF)-κB on LPS-stimulated BV2 microglial cells. Thereby, KOG could offer the new and promising treatment for neurodegenerative disease related to neuroinflammation.

• 대한본초학회지
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• 제21권2호
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• pp.165-173
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• 2006

Objectives : Coptidis Rhizoma has been known traditional medicine with antimicrobial activities. We investigated inhibitory effects of Coptidis Rhizoma extract on lipopolysaccharide(LPS)-induced nitric oxide production from mouse macrophages. Methods : After Coptidis Rhizoma extract was pretreated in BV2, mouse brain macrophages and RAW264.7 mouse macrophages, cells were activated with LPS. To investigate cytotoxicity Coptidis Rhizoma extract, cell viability was measured by MTT assay. The production of nitric oxide(NO) and inducible nitric oxide synthase(iNOS) was determined in each culture supernatant and mRNA by Griess reaction and RT-PCR. The production of $TNF-{\alpha}$ from cells was measured by ELISA. Results : Coptidis Rhizoma extract significantly inhibited LPS-induced NO production in BV2 and RAW264.7 cells. Coptidis Rhizoma extract also greatly suppressed mRNA expression of iNOS in BV2 and RAW264.7 cells activated by LPS. Conclusion : These data suggests that Coptidis Rhizoma extract may have an anti-inflammatory effect through the inhibition of NO production.

• 동의신경정신과학회지
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• 제19권2호
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• pp.65-75
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• 2008

Objective : This experiment was designed to investigate the effect of the KBHT and PMCMT extract on protecting microglia and inhibiting acetylcholinesterase and oxidants. Method : The effects of the KBHT and PMCMT extract on cell death of BV2 microglial cell line treated by ${\gamma}$ ; expression of NO, ROS in BV2 microglial cell line treated by lipopolysaccharide(LPS) ; AChE activity in PC-12 cell treated by NGF were investigated, respectively. Result : The KBHT and PMCMT extract significantly increased cell viability in BV2 microglial cell line treated with ${\gamma}$. The KBHT and PMCMT extract suppressed the NO and ROS production in BV2 microglial cell line treated by LPS. The KBHT and PMCMT extract groups also showed inhibition of AChE activity in PC-12 cell line. Conclusion : According to the above result, it is suggested that the KBHT and PMCMT extract might be usefully applied for prevention and treatment of Alzheimer' s disease.

• 한방재활의학과학회지
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• 제27권1호
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• pp.53-65
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• 2017

Objectives The purpose of this study is to evaluate the safety of Non-toxic bee venom (BV) and observe VAS change before and after Non-toxic BV treatment in pain patients. Methods We surveyed the clinical practitioners who treated with Non-toxic BV in pain patients who visited the Korean medical clinic. The questionnaire survey was conducted for clinical practitioners who agreed to participate after hearing the explanation for the purpose and characteristics of the questionnaire. Patients in the questionnaires were reviewed based on their medical records from July 1, 2016 to October 28, 2016. Results We received 445 cases and selected 403 cases finally. 2 cases, however, were not able to continue treatment for 3 weeks and were eliminated. Depending on when the pain occurred, we divided the 401 cases into three groups (Acute, Subacute, Chronic group). In all groups, VAS scores were significantly decreased after treatment. Adverse reactions following Non-toxic BV treatment had occurred was 16 cases (3.60%). Except for 3 cases with hives, most of adverse reactions were mild or moderate and were not in need of extra treatment. The total safety of treatment for 3 weeks was mostly safe. The number of cases discontinued treatment was 42 cases (9.44%). Most of these cases, treatment was stopped for personal reason unrelated to the Non-toxic BV treatment. Conclusions These results suggest that the Non-toxic BV treatment has no serious adverse reactions and is a relatively safe treatment. Further studies are needed to prove the efficacy and clinical safety of Non-toxic BV treatment.

• 대한약침학회지
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• 제11권1호
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• pp.41-54
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• 2008

Objective : In this study, we investigated the effects of Sweet Bee Venom(SBV) and Bee Venom(BV) at a acupoint, HT7(Shinmun) on the Heart Rate Variability(HRV) in the healthy man. And we tried to observe how Sweet Bee Venom and Bee Venom affects on the balance of the autonomic nervous system. Methods : We investigated on 22 heathy volunteers consisted of 10 subjects in SBV group and 12 subjects in BV group. Study form was a randomized, placebo-controlled, double-blind clinical trial. 22 subjects of each group were injected SBV and BV at HT7(Shinmun). And we measured HRV by QECG-3:LXC3203 (LAXTHA Inc. Korea) on 7 times : before and after injection per 5minutes during 30minutes. Results : 1. After SBV injection, Mean-RR was significantly high from 0 to 10 minutes, Mean-HRV was significantly low from to 10 minutes, SDNN was significantly high after 25minutes, Complexity was significantly high from 5 to 10 minutes and RMSSD was significantly high from 5 to 10minutes. 2. Complexity of SBV Group significantly decreased from 20 to 25minutes, RMSSD of SBV Group significantly increased from 10 to 15minute and from $20{\sim}25$minutes, SDSD of SBV Group significantly increased from 10 to 15 minute and from $20{\sim}25$minutes compared with that of BV group. 3. After SBV injection, Ln(VLF) was significantly from 25 to 30minutes. Conclusions : The results suggest that SBV in heathy adult man tend to activate the autonomic nervous system compared to BV within normal range.

• 대한약침학회지
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• 제3권1호
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• pp.65-87
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• 2000

This study was designed to evaluate the effect of the bee venom(BV) aqua-acupuncture on the neuronal activities of catecholaminergic(tyrosine hydroxylase : TH, dopamine ${\beta}$ hydroxylase : D${\beta}$H) system in the brainstem. After the BV aqua-acupuncture was applied on Chok-Samni(ST36) and the gluteal part(Blank locus) in rats. Also, the number of colocalization between catecholamine containing neurons and Fos immunoreactive neurons were analyzed by using the double immunohistochemical technique. The results of the experiments were summarized as follows : 1. In DR and LC, Chok-Samni group and the Blank locus group showed more significant increase in the number of colocalization between TH containing neurons and Fos immunoreactive neurons than the control group. Furthermore, Chok-Samni group showed more significant increase than the Blank locus group. Also, in Arc, Chok-Samni group showed more significant increase than the Blank locus group and the control group. 2. In LC, Chok-Samni group showed more significant increase in the number of colocalization between D${\beta}$H containing neurons and Fos immunoreactive neurons than the Blank locus group and the control group. Also, in A5, Chok-Samni group and the Blank locus group showed more significant increase than the control group. Chok-Samni group showed more significant increase than the Blank locus group. However, there was no significant change in A7. Consequently, the BV aqua-acupuncture increased more potent the number of Fos immunoreactive neurons and the activity of catecholaminergic neurons. Furthermore, the BV aqua-acupuncture was more effective on Chok-Samni than Blank locus group. These results indicate that the BV aqua-acupuncture is very effective therapy to control pain. The therapeutic effect of BV aqua-acupunture may associated with the endogenous modulatory system such as catecholamine. Those data from the study can be applied to establish the effective treatment of the BV for pain control in the clinical field.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.107-112
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• 2012

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as neuronal protection against excitotoxicity and anti-inflammatory property, the biological activity of 3,4,5-trihydroxycinnamic acid (THC), a derivative of hydroxycinnamic acids, has not been clearly examined. The objective of the present study is to evaluate the anti-inflammatory effects of THC on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. THC significantly suppressed LPS-induced excessive production of nitric oxide (NO) and expression of iNOS, which is responsible for the production of iNOS. THC also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$and TNF-${\alpha}$ in BV2 microgilal cells. Furthermore, THC significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm. Therefore, THC attenuated nuclear translocation of NF-${\kappa}B$, a major pro-inflammatory transcription factor. Taken together, the present study for the first time demonstrates that THC exhibits antiinflammatory activity through the suppression of NF-${\kappa}B$ transcriptional activation in LPS-stimulated BV2 microglial cells.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.210-217
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• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• 대한임상검사과학회지
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• 제54권3호
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• pp.201-208
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• 2022

Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.

• 생명과학회지
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• 제26권6호
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• pp.640-645
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• 2016

본 연구에서는 녹차 유래 polyphenol 중의 하나인 epigallocatechine gallate (EGCG)를 이용한 신경염증 억제 효과를 확인하였다. LPS로 유도된 미세아교세포의 활성화로 분비되는 nitric oxide (NO)와 pro-inflammatory cytokine을 포함하여 iNOS, TNF-a와 IL-1b 유전자의 발현과 LPS 수용체인 TLR-4의 활성에 미치는 EGCG의 억제 효능을 확인하였다. Latex beads를 이용한 phagocytotic activity를 확인한 결과 LPS로 유도된 미세아교세포 활성에 의한 식균활성이 EGCG에 의해 억제되는 것을 볼 수 있었다. 뿐만 아니라, BV-2 미세아교세포 조건배지를 이용하여 도파민성 신경세포 SN4741의 세포 사멸확인에서도 EGCG에 의한 보호 효과를 확인하였다. 본 연구 결과는 녹차 유래 polyphenol인 EGCG의 신경염증 반응억제효능과 신경퇴행성 질환 제어 가능성을 확인하였다. 본 연구의 결과는 녹차 유래 polyphenol인 EGCG의 신경염증 반응과 그로 인한 신경 퇴행성 질환 제어 가능성을 제시하였다.