• IMMUNE NETWORK
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• 제22권1호
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• pp.9.1-9.23
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• 2022

In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.

• 생명과학회지
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• 제30권4호
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• pp.331-342
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• 2020

미세교세포(Microglial cells)에서 신경염증반응(neuroinflammatory responses)의 억제는 알츠하이머질환, 파킨슨질환, 헌팅턴질환과 같은 신경퇴행성질환(neurodegenerative diseases)을 치료하기 위한 주요 표적으로 고려되고 있다. 천문동(Asparagus cochinchinesis)은 열, 기침, 신장 질환, 유방암, 염증성질환 및 뇌질환을 치료하는 데 오랫동안 사용 되어온 전통 치료제(Traditional medicine)이다. 본 연구에서는 lipopolysaccharide (LPS)로 활성화된 BV-2 미세교세포에서 항염증효과가 있는 천문동 뿌리 열수추출물(Aqueous extract from A. cochinchinesis root, AEAC)의 신경보호 메커니즘을 연구하였다. 먼저, 어떤 유의적인 세포독성은 플라보노이드(flavonoid), 페놀(phenol), 사포닌(saponin)을 함유하는 AEAC를 4가지 농도로 처리된 BV-2세포에서 검출되지 않았다. 또한, nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA 및 inducible nitric oxide synthase (iNOS) mRNA 수준은 AEAC+LPS 처리군에서 비하여 21%정도 감소하였다. 전염증성 사이토카인(TNF-α과 IL-1β) 및 항염증성 사이토카인(IL-6와 IL-10)농도에 대한 유사한 감소는 비록 감소비율은 다르지만, Vehicle+LPS 처리군에 비해 AEAC+LPS 처리군에서 검출되었다. 더불어, LPS 처리 후 mitogen-activated protein (MAP) kinase의 인산화수준의 증가는 AEAC 전처리군에서 유의하게 회복되었고, 세포주기에서 G2/M의 억제(arrest)는 AEAC+LPS 처리군에서 개선되었다. 또한, LPS 처리로 유도된 ROS의 증가도 AEAC 전처리군에서 감소되었다. 따라서, 이러한 결과는 AEAC가 MAPK 신호전달 경로, 세포주기 및 ROS (reactive oxygen species) 생성의 조절을 통해 LPS 자극에 대한 항신경염증 활성을 유도함을 제시하고 있다.

• IMMUNE NETWORK
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• 제21권3호
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• pp.21.1-21.22
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• 2021

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes. Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.

• Journal of Ginseng Research
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• 제37권1호
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• pp.8-29
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• 2013

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

• 생약학회지
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• 제45권1호
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• pp.17-22
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• 2014

Grapes has long been used for food, and reported as containing polyphenol which has antioxidant and anti-cancer effects. Neuroinflammation is chronic inflammation at the brain, lead to neurodegenerative diseases. In this study, quercetin-3-O-glucuronide (QG) isolated from the leaf of Vitis labruscana has anti-neuroinflammatory effects. QG were investigated using MTT assay, western blot, nitric oxide (NO) assay, prostaglandin $E_2$ ($PGE_2$) assay, cytokine assay in lipopolysaccharide (LPS)-induced inflammation in BV2 cells. QG dose-dependently attenuated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), accordingly inhibited the production of NO and $PGE_2$. QG decreases the levels of proinflammatory cytokine such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interlukin-$1{\beta}$ (IL-$1{\beta}$). Thereby, QG may offer therapeutic potential for treatment of neurodegenerative disease related to neuroinflammation.

• 생명과학회지
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• 제31권2호
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• pp.237-247
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• 2021

신경염증(neuroinflammation)은 여러 신경 질환의 원인 인자로 확인되고있다. 중추 신경계에 발현되는 단백질 복합체인 NLRP3 인플라마좀은 미생물, 응집되고 잘못 접힌 단백질, ATP와 같은 광범위한 외인성 및 내인성 자극에 의해 감지되고 캐스페이즈-1(capase-1)을 활성화할 수 있다. 활성을 띠는 캐스페이즈-1은 IL-1b와 IL-18과 같은 염증성 사이토카인(pro-inflammatory cytokine)을 활성화시키고 급속한 세포사멸(파이롭토시스, pyroptosis)를 야기한다. IL-1b와 IL-18, 그리고 파이롭토시스를 통해 분비된 DAMPs은 다양한 신호 전달 경로를 통해 신경염증 반응을 유도하여 신경 손상을 유발한다. 따라서 NLRP3 인플라마좀은 신경염증으로 인한 여러 가지 신경질환 발병에 중요한 역할을 할 것으로 여겨진다. 본 리뷰 에서는 NLRP3 인플라마좀의 구조와 활성화에 대해 간략히 알아 보고 다양한 형태의 신경 질환에서 NLRP3 인플라마좀의 역할에 대해 논의하고자 한다.

• Fisheries and Aquatic Sciences
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• 제17권1호
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• pp.27-35
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• 2014

Marine brown algae have been identified as a rich source of structurally diverse bioactive compounds. Whether Myagropsis yendoi ethanolic extracts (MYE) inhibit inflammatory responses was investigated using lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. MYE inhibited LPS-induced nitric oxide (NO) production in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase in BV-2 cells. MYE also reduced the production of pro-inflammatory cytokines in LPS-stimulated BV-2 cells. LPS-induced nuclear factor-${\kappa}B$ (NF-${\kappa}B$) transcriptional activity and NF-${\kappa}B$ translocation into the nucleus were significantly inhibited by MYE treatment through preventing degradation of the inhibitor ${\kappa}B-{\alpha}$. Moreover, MYE inhibited the phosphorylation of AKT, ERK, JNK, and p38 mitogen-activated protein kinase in LPS-stimulated BV-2 cells. These results indicate that MYE is a potential source of therapeutic or functional agents for neuroinflammatory diseases.

• 대한의생명과학회지
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• 제24권4호
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• pp.398-404
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• 2018

To evaluate the antioxidant and anti-neuroinflammatory effects of defatted Perilla frutescens extract (DPE) in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Cell viabilities were estimated by MTT assay. LPS-stimulated BV-2 microglia were used to study the expression and production of inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), Cyclooxygenase-2 (COX-2), and prostaglandin $E_2$ ($PGE_2$). Pretreatment with DPE prior to LPS treatment significantly inhibited excessive production of NO (10, 25, 50, 75, and $100{\mu}g/mL$) in a dose-dependent manner, and was associated with down regulation of expression of iNOS and COX-2. DPE also suppressed the LPS-induced increase in $PGE_2$ level (10, 25, 50, 75, and $100{\mu}g/mL$) in BV-2 cells. Therefore, DPE can be considered as a useful therapeutic and preventive approach for the treatment of several neurodegenerative diseases.

• 한국환경과학회지
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• 제32권4호
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• pp.259-266
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• 2023

Today, environmental pollution has been found to be one of the causes of various diseases, including brain and nervous system diseases. In particular, neurodegenerative diseases have been found to be caused by hyperactivation of immune system cells such as microglia. Preventive and therapeutic measures are needed to suppress them. Hirudo is known as a traditional herbal medicine, based on its multiple biological activities such as anti-eczema and anti-coagulation. In the present study, the anti-neuroinflammatory potential of hirudo extract was investigated in lipopolysccharide (LPS)-stimulated BV2 microglial cells and in mice. Hirudo extract significantly inhibited LPS-stimulated nitric oxide (NO) production and cytokine (IL-1Ra, KC, MCP-5, and RANTES) expression in a dose-dependent manner without causing cytotoxicity. Pretreatment with hirudo extract suppressed LPS-induced NF-κB p65 nuclear translocation. Moreover, hirudo extract reduced LPS-stimulated microglial acitivation and improved memory impairments. The results demonstrated that hirudo extract exerts anti-neuroinflammation activities, partly through inhibition of the NF-κB signaling pathway. These findings suggest that hirudo extract might have therapeutic potential with respect to neuroinflammation and neurodegenerative diseases.

• 생명과학회지
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• 제30권11호
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• pp.999-1006
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• 2020

최근 중추신경계에서 면역기능을 담당하는 미세아교세포(microglia)의 염증반응을 효율적으로 조절하는 것은 알츠하이머 병, 파킨슨 병 및 헌팅턴 병과 같은 퇴행성 뇌질환의 치료를 위한 중요한 타겟으로 인식되고 있다. 왕귀뚜라미(Teleogryllus emma)는 다양한 치료효능으로 인해 세계적으로 널리 이용되고 있으며, 본 연구팀에서는 최근 왕귀뚜라미의 전사체 분석을 통하여 항균활성을 가지는 다양한 종류의 새로운 항균 펩타이드(antimicrobial peptide; AMP) 후보들을 선별한 바 있다. 항균 펩타이드는 미생물에서부터 포유류까지 매우 다양한 종으로부터 발견되었으며, 현재는 항균활성뿐만 아니라 염증반응과 같은 다양한 질병의 치료제 개발을 위한 후보 물질로 관심을 받고 있다. 본 연구에서는 선행연구를 통하여 선별된 왕귀뚜라미 유래 항균 펩타이드들 중에서 Teleogryllusine(VKWKR-LNNNKVLQKIYFVKI-NH₂)으로 명명된 항균 펩타이드의 신경염증 억제 효능을 관찰하였다. Teleogryllusine의 신경염증 억제 효능을 관찰 하기 위하여 immortalized mouse microglia 세포주인 BV-2 세포에 Teleogryllusine을 1시간 전처리 한 후 LPS를 이용하여 BV-2 세포의 염증 반응을 유도하였다. 그 결과 Teleogryllusin은 최대 처리 농도인 80 ㎍/ml까지 세포독성 없이 nitric oxide (NO) 생성을 현저히 감소시킴을 확인할 수 있었다. 또한 염증반응 매개인자인 iNOS와 COX-2 및 cytokine (Il-6, TNF-α)의 발현을 유전자 수준과 단백질 수준에서 확인한 결과 Teleogryllusine 처리농도에 의존적으로 감소됨을 확인할 수 있었다. 또한 Teleogryllusine의 신경염증 억제작용 기작을 확인한 결과 mitogen activated protein kinases (MAPKs)와 IκB의 인산화 및 proteosome에 의한 IκB의 분해를 억제함으로서 BV-2 세포의 신경염증반응이 조절됨을 확인할 수 있었다. 이러한 결과로 보아 왕귀뚜라미 유래 Teleogryllusine 펩타이드는 신경염증반응에 의해 유도되는 퇴행성 뇌질환 치료 및 예방을 위한 의료용 소재로 사용될 수 있을 것으로 기대된다.