• IMMUNE NETWORK
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• v.22 no.1
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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.

• Journal of Life Science
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• v.30 no.4
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• pp.331-342
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• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

• IMMUNE NETWORK
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• v.21 no.3
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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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• v.37 no.1
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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.

• Korean Journal of Pharmacognosy
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• v.45 no.1
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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.

• Journal of Life Science
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• v.31 no.2
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• pp.237-247
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• 2021

Immune responses in the central nervous system (CNS) function as the host's defense system against pathogens and usually help with repair and regeneration. However, chronic and exaggerated neuroinflammation is detrimental and may create neuronal damage in many cases. The NOD-, LRR-, and pyrin domain―containing 3 (NLRP3) inflammasome, a kind of NOD-like receptor, is a cytosolic multiprotein complex that consists of sensors (NLRP3), adaptors (apoptosis-associated speck like protein containing a caspase recruitment domain, ASC) and effectors (caspase 1). It can detect a broad range of microbial pathogens along with foreign and host-derived danger signals, resulting in the assembly and activation of the NLRP3 inflammasome. Upon activation, NLRP3 inflammasome leads to caspase 1-dependent secretion of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. NLRP3 inflammasome is highly expressed in CNS-resident cell types, including microglia and astrocytes, and growing evidence suggests that NLRP3 inflammasome is a crucial player in the pathophysiology of several neuroinflammatory and psychiatric diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and major depressive disorder. Thus, this review describes the molecular mechanisms of NLRP3 inflammasome activation and its crucial roles in the pathogenesis of neurological disorders.

• Fisheries and Aquatic Sciences
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• v.17 no.1
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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.

• Biomedical Science Letters
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• v.24 no.4
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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.

• Journal of Environmental Science International
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• v.32 no.4
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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.

• Journal of Life Science
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• v.30 no.11
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• pp.999-1006
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• 2020

The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH₂) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.