• IMMUNE NETWORK
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• v.12 no.5
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• pp.213-216
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• 2012

Our previous report showed that polyacetylene compound, 1-Heptadecene-11, 13-diyne-8, 9, 10-triol (PA) from the root of Cirsium japonicum var. ussuriense has anti-inflammatory activity. In this study we investigated the role of the PA as inhibitor of caspase-1, which converts prointerleukin-$1{\beta}$ (proIL-$1{\beta}$) to active IL-$1{\beta}$ and is activated by inflammasome involved in the inflammatory process. We tested the effect of PA on the production of pro-inflammatory cytokines, IL-$1{\beta}$ in murine macrophage cell line, RAW264.7. PA inhibited lipopolysaccharide (LPS)-induced IL-$1{\beta}$ production by macrophages at a dose dependent manner. PA also suppressed the activation of caspase-1. The mRNA level of ASC (apoptosis-associated spec-like protein containing a CARD), an important adaptor protein of inflammasome, was decreased in the PA treated group. Therefore our results suggest that the anti-inflammatory effect of PA is due to inhibit the caspase-1 activation.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.172-178
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• 2019

Inflammation is an innate immune response that protects the body from pathogens, toxins, and other dangers and is initiated by recognizing pathogen-associated molecular patterns or danger-associated molecular patterns by pattern-recognition receptors expressing on or in immune cells. Intracellular pattern-recognition receptors, including nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2, and cysteine aspartate-specific protease (caspase)-4/5/11 recognize various pathogen-associated molecular patterns and danger-associated molecular patterns and assemble protein complexes called "inflammasomes." These complexes induce inflammatory responses by activating a downstream effector, caspase-1, leading to gasdermin D-mediated pyroptosis and the secretion of proinflammatory cytokines, such as interleukin $(IL)-1{\beta}$ and IL-18. Ginsenosides are natural steroid glycosides and triterpene saponins found exclusively in the plant genus Panax. Various ginsenosides have been identified, and their abilities to regulate inflammatory responses have been evaluated. These studies have suggested a link between ginsenosides and inflammasome activation in inflammatory responses. Some types of ginsenosides, including Rh1, Rg3, Rb1, compound K, chikusetsu saponin IVa, Rg5, and Rg1, have been clearly demonstrated to inhibit inflammatory responses by suppressing the activation of various inflammasomes, including the NLRP3, NLRP1, and absent in melanoma 2 inflammasomes. Ginsenosides have also been shown to inhibit caspase-1 and to decrease the expression of $IL-1{\beta}$ and IL-18. Given this body of evidence, the functional relationship between ginsenosides and inflammasome activation provides new insight into the understanding of the molecular mechanisms of ginsenoside-mediated antiinflammatory actions. This relationship also has applications regarding the development of antiinflammatory remedies by ginsenoside-mediated targeting of inflammasomes, which could be used to prevent and treat inflammatory diseases.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.709-717
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• 2022

Allergic rhinitis (AR), one of the most common inflammatory diseases, is caused by immunoglobulin E (IgE)-mediated reactions against inhaled allergens. AR involves mucosal inflammation driven by type 2 helper T (Th2) cells. Previously, it was shown that the Streptococcus pneumoniae pep27 mutant (Δpep27) could prevent and treat allergic asthma by reducing Th2 responses. However, the underlying mechanism of Δpep27 immunization in AR remains undetermined. Here, we investigated the role of Δpep27 immunization in the development and progression of AR and elucidated potential mechanisms. In an ovalbumin (OVA)-induced AR mice model, Δpep27 alleviated allergic symptoms (frequency of sneezing and rubbing) and reduced TLR2 and TLR4 expression, Th2 cytokines, and eosinophil infiltration in the nasal mucosa. Mechanistically, Δpep27 reduced the activation of the NLRP3 inflammasome in the nasal mucosa by down-regulating the Toll-like receptor signaling pathway. In conclusion, Δpep27 seems to alleviate TLR signaling and NLRP3 inflammasome activation to subsequently prevent AR.

• Journal of Convergence Korean Medicine
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• v.4 no.1
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• pp.5-11
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• 2022

Objectives: Inflammasomes are molecular platforms that are generated inside cytoplasmic compartments. The objective is to mediate immunological responses of the host to cell damage and infection. Caspase-1 is triggered by inflammasome to generate interleukin-1𝛽 (IL-1𝛽), an inflammatory cytokine, and pyroptosis, an inflammatory form of apoptosis. Methods: In the past two decades, scientists have uncovered several inflammasomes. The most research has been conducted on NLRP3 inflamamsomes, whose activity can be stimulated by a variety of induction factors. However, the unregulated activation of NLRP3 inflammasomes is also a role in the etiology of several human disorders. Previous research has demonstrated that NLRP3 inflammasomes have a significant role in the innate and acquired immune systems, as well as in the prevalence of joint illnesses such rheumatoid arthritis. Conclusion: Within the scope of this review, we will present a brief overview of the biological features of NLRP3 inflamamsomes as well as a description of the underlying mechanisms governing activation and regulation. In particular, we explore the function of inflammasomes in the development of rheumatoid arthritis as well as the promise of recently identified medicines that target inflamasomes.

• Microbiology and Biotechnology Letters
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• v.51 no.4
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• pp.507-516
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• 2023

Eradication of Helicobacter pylori infection is an essential strategy to decrease the risk of developing gastric cancer. However, the standard triple therapy has negative aspects associated with side effects and the emergence of antibiotic resistance. Therefore, alternative therapies are required to enhance the management of H. pylori infection effectively. In this study we examined the effect of emodin on the amelioration of inflammatory response due to H. pylori infection. Our results indicated that emodin treatment effectively decreased the expression of virulence genes, including sabA, vacA, cagL, cagA, sabA, and suppressed the adhesion ability of H. pylori to AGS cells. Emodin has been shown inhibitory effects on the inflammasome pathway through reductions in VacA translocation, lowering ROS stress, cleaved Caspase-1, NLRP3, and cleaved Gasdermin D levels, thereby lowered pyroptosis in infected cells. In summary, our study demonstrated that emodin has the ability to attenuate inflammation caused by H. pylori by modulating virulence gene expression and decreasing VacA translocation. Further study is required to evaluate the therapeutic efficacy of emodin in treating H. pylori infection and better understand the underlying mechanisms.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.1-15
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• 2018

Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin $(IL)-1{\beta}$ and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and $Sj{\ddot{o}}gren^{\prime}s$ syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.

• IMMUNE NETWORK
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• v.13 no.3
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• pp.94-101
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• 2013

Amorphous silica particles, whose applications are increasing in many biomedical fields, are known to be less toxic than crystalline silica. In this study, the inflammatory effects of amorphous silica nanoparticles were investigated using 30-nm amorphous silica nanoparticles and human peripheral blood mononuclear cells (PBMCs) or purified monocytes. As a result, production of IL-$1{\beta}$ and IL-8 were increased. In addition, the mitochondrial reactive oxygen species (ROS) was detected, which may lead to mitochondrial membrane disruption. Most importantly, inflammasome formation was observed. Therefore, these results provide immunological information about amorphous silica nanoparticles and suggest that amorphous silica nanoparticles can evoke innate immune reactions in human monocytes through production of IL-$1{\beta}$ and IL-8.

• BMB Reports
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• v.49 no.5
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• pp.276-281
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• 2016

Corosolic acid (CA), a triterpenoid compound isolated from Lagerstroemia speciosa L. (Banaba) leaves, exerts anti-inflammatory effects by regulating phosphorylation of interleukin receptor- associated kinase (IRAK)-2 via the NF-κB cascade. However, the protective effect of CA against endotoxic shock has not been reported. LPS (200 ng/mL, 30 min) induced phosphorylation of IRAK-1 and treatment with CA (10 μM) significantly attenuated this effect. In addition, CA also reduced protein levels of NLRP3 and ASC which are the main components of the inflammasome in BMDMs. LPS-induced inflammasome assembly through activation of IRAK-1 was down-regulated by CA challenge. Treatment with Bay11-7082, an inhibitor of IκB-α, had no effect on CA-mediated inhibition of IRAK-1 activation, indicating that CA-mediated attenuation of IRAK-1 phosphorylation was independent of NF-κB signaling. These results demonstrate that CA ameliorates acute inflammation in mouse BMDMs and CA may be useful as a pharmacological agent to prevent acute inflammation.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.700-709
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• 2022

Background: Ginsenoside Rd is a natural compound with promising neuroprotective effects. However, the underlying mechanisms are still not well-understood. In this study, we explored whether ginsenoside Rd exerts protective effects on cerebral endothelial cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and its potential docking proteins related to the underlying regulations. Method: Commercially available primary human brain microvessel endothelial cells (HBMECs) were used for in vitro OGD/R studies. Cell viability, pyroptosis-associated protein expression and tight junction protein degradation were evaluated. Molecular docking proteins were predicted. Subsequent surface plasmon resonance (SPR) technology was utilized for validation. Flow cytometry was performed to quantify caspase-1 positive and PI positive (caspase-1+/PI+) pyroptotic cells. Results: Ginsenoside Rd treatment attenuated OGD/R-induced damage of blood-brain barrier (BBB) integrity in vitro. It suppressed NLRP3 inflammasome activation (increased expression of NLRP3, cleaved caspase-1, IL-1β and GSDMD-N terminal (NT)) and subsequent cellular pyroptosis (caspase-1+/PI + cells). Ginsenoside Rd interacted with SLC5A1 with a high affinity and reduced OGD/R-induced sodium influx and potassium efflux in HBMECs. Inhibiting SLC5A1 using phlorizin suppressed OGD/R-activated NLRP3 inflammasome and pyroptosis in HBMECs. Conclusion: Ginsenoside Rd protects HBMECs from OGD/R-induced injury partially via binding to SLC5A1, reducing OGD/R-induced sodium influx and potassium efflux, thereby alleviating NLRP3 inflammasome activation and pyroptosis.