• Journal of Ginseng Research
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• 제46권5호
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• pp.675-682
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• 2022

Background: Korean Red Ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Methods: Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. Results: KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. Conclusion: The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3569-3573
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• 2013

Aim: Pendulous monkshood root is traditionally used for the treatment of several inflammatory pathologies such as rheumatisms, wounds, pain and tumors in China. In this study, the anti-inflammatory and anticancer activities and the mechanism of crude ethanol extract of pendulous monkshood root (EPMR) were evaluated and investigated in vitro. Materials and Methods: The cytotoxic effects of EPMR on different tumor cell lines were determined by the MTT method. Cell apoptosis and cell nucleus morphology were assessed by Hoechst 33258 staining. Moreover, nitric oxide (NO) levels and intracellular oxidative stress in peritoneal macrophages were determined to further elucidate mechanisms of action. Results: The data showed that EPMR could produce significant dose-dependent toxicity on three kinds of tumor cells. Furthermore, EPMR displayed obvious anti-inflammatory effects on LPS-induced mouse peritoneal macrophages at the dosage of 4 - 200 ${\mu}g/mL$. The results demonstrated the therapeutic potential of Pendulous Monkshood Root on cancer and inflammatory diseases. Conclusion: Our results indicate that EPMR has anti-inflammatory and anticancer properties, suggesting that pendulous monkshood root may be a useful anti-tumor and anti-inflammatory reagent in the clinic.

• Journal of Ginseng Research
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• 제46권3호
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• pp.489-495
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• 2022

Background: Although ginsenosides and saponins in Korea red ginseng (KRG) shows various pharmacological roles, their roles in the inflammatory response are little known. This study investigated the anti-inflammatory role of ginsenosides identified from KRG saponin fraction (RGSF) and the potential mechanism in macrophages. Methods: The ginsenoside composition of RGSF was identified by high-performance liquid chromatography (HPLC) analysis. An anti-inflammatory effect of RGSF and its mechanisms were studied using nitric oxide (NO) and prostaglandin E₂ (PGE₂) production assays, mRNA expression analyses of inflammatory genes and cytokines, luciferase reporter gene assays of transcription factors, and Western blot analyses of inflammatory signaling pathways using the lipopolysaccharide (LPS)-treated RAW264.7 cells. Results: HPLC analysis identified the types and amounts of various panaxadiol ginsenosides in RGSF. RGSF reduced the generation of inflammatory molecules and mRNA levels of inflammatory enzymes and cytokines in LPS-treated RAW264.7 cells. Additionally, RGSF inhibited the signaling pathways of NF-κB and AP-1 by suppressing both transcriptional factors and signaling molecules in LPS-treated RAW264.7 cells. Conclusion: RGSF contains ginsenosides that have anti-inflammatory action via restraining the NF-κB and AP-1 signaling pathways in macrophages during inflammatory responses.

• 대한한방부인과학회지
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• 제21권2호
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• pp.152-165
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• 2008

Purpose: It is the purpose of this study to investigate the anti-inflammatory effects and mechanism of cheukbaekjurpihwan(CBJPH) extract on LPS (lipopolysaccharide)-induced inflammatory mediators in murine peritoneal macrophages. Methods: To evaluate anti-inflammatory effects of CBJPH extract, the production of cytokines(TNF-${\alpha}$(tumor necrosis factor-alpha), IL(interleukin)-6, IL-12) and NO(nitric oxide) was measured in vitro and in vivo. And western blot analysis has been done to look into the mechanism. Results: CBJPH extract reduced LPS-induced NO, TNF-${\alpha}$ and IL-6, IL-12 productions in peritoneal macrophages. CBJPH extract inhibited the activation of JNK(c-Jun N-terminal kinase), but didn't inhibit the activation of MAPKs (mitogen-activated protein kinases) such as p38, ERK1/2(extracelluar signal-regulated kinase1/2) and the degradation of $I_{\kappa}B-{\alpha}$(inhibitory kappa B-alpha) in the LPS-stimulated peritoneal macrophages. CBJPH extract suppressed LPS-induced endotoxin shock and the productions of TNF-${\alpha}$, but not of IL-6, after an oral administration of CBJPH extract Conclusion: CBJPH extract suppressed the productions of LPS-induced NO and cytokines by preventing JNK from phosphorylation, which may provide a clinical basis for anti-inflammatory properties of CBJPH.

• The Korean Journal of Pain
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• 제36권1호
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• pp.72-83
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• 2023

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

• Bulletin of the Korean Chemical Society
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• 제35권11호
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• pp.3169-3174
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• 2014

Numerous studies have examined the role of flavonoids in modulating inflammatory responses in vitro. In this study, we found a novel flavonoid, 3,6,3'-trihydroxyflavone (1), with anti-inflammatory effects. Anti-inflammatory activity and mechanism of action were examined in mouse macrophages stimulated with lipopolysaccharide (LPS). Our results showed that the anti-inflammatory effects of 1 are mediated via p38 mitogen-activated protein kinase (p38 MAPK), Jun-N terminal kinase (JNK), and the extracellular-signal-regulated kinase (ERK) pathway in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Binding studies revealed that 1 had a high binding affinity to JNK1 ($1.568{\times}10^8M^{-1}$) and that the 3- and 6-hydroxyl groups of the C-ring and A-ring of 1 participated in hydrogen bonding interactions with the side chains of Asn114 and Lys55, respectively. The oxygen at the 3' position of the B-ring formed a hydrogen bond with side chain of Met111. Therefore, 1 could be a potential inhibitor of JNKs, with potent anti-inflammatory activity.

• Korean Journal of Acupuncture
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• 제27권2호
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• pp.13-24
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• 2010

Objectives : Ulcerative colitis is a chronic relapsing inflammatory disease in the gastrointestinal tract. We investigated whether Aurantii fructus immaturus (AFI) pharmacopuncture has antioxidative and anti-inflammatory effects. Methods : in vitro experiments, 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging activity, superoxide dismutase (SOD) activity, prevention on $H_2O_2$-induced cell death in RAW264.7 cell line, DNA fragmentation, and cyclooxygenase-2 mRNA expression induced by lipopolysaccharide (LPS), were analyzed to investigate antioxidative and anti-inflammatory effect of AFI pharmacopuncture. in vivo experiment, a murine model of dextran sulfate sodium (DSS)-induced colitis was used to examine the effect of AFI pharmacopuncture on CV12 at different doses of 5 ${\mu}l$, 0.5 ${\mu}l$, 0.05 ${\mu}l$ for 10 days. Body weight, colon length and macroscopic features were investigated. Results : AFI pharmacopuncture showed DPPH free radical scavenging and SOD active effects in a dose-dependent manner. AFI pharmacopuncture showed a protective effect against $H_2O_2$-induced cell injury and also attenuated LPS-induced COX-2 mRNA expression. In a DSS- induced colitis murine model, however, AFI pharmacopuncture at CV12 had no anti-inflammatory effects. Conclusions : The present results suggest that AFI pharmacopuncture extract may have anti- inflammatory and antioxidative effects in vivo test, but further research on the underlying mechanism is required.

• 한방안이비인후피부과학회지
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• 제33권2호
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• pp.100-111
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• 2020

Objectives : The aim of experiment is to examine anti-inflammatory effect and anti-oxidant effect of Naesohwangryun-tang (NSHRT) in LPS-stimulated RAW264.7 macrophage cells. Methods : In the present study, The cell viability was performed by MTT assay. Nitric oxide (NO) production and prostaglandin E₂ (PGE₂) synthesis were performed by NO assay and ELISA KIT. The anti-oxidant effect was performed by DPPH and ABTS radical scavenging activity. The inhibitory effects of pro-inflammatory mediators and cytokines were confirmed by realtime PCR and western blotting. Results : NSHRT was no cytotoxicity at treated group. NO and PGE2 production were inhibited compared to the LPS treated group and also mRNA and protein expressions were significantly decreased compared to the LPS treated group. Conclusions : According to the above experiments, we confirmed that NSHRT has anti-inflammatory and anti-oxidant effects. It is suggested that NSHRT is potential ingredient of skin diseases.

• 대한한의학회지
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• 제37권4호
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• pp.10-21
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• 2016

Objectives: This study was to investigate the anti-oxidative and anti-inflammatory effect of Psoralea corylifolia water extract (PE) on ulcerative colitis which was induced by dextran sulfate sodium (DSS) in mice. Methods: Ulcerative colitis was induced by DSS in male BALB/c mice. The mice were divided into 3 groups. The control group (Ctrl) was not induced ulcerative colitis. The pathological group (CE) was induced the colitis. The experimental group (PT) was administered PE after inducing the colitis. The effects of the PE on ulcerative colitis were evaluated by morphological change in the colon tissue and cells, substance P production, activity of tumor necrosis factor $(TNF)-{\alpha}$ and nuclear factor $(NF)-{\kappa}B$, cyclooxygenase (COX)-2 production, and anti-oxidative activity. Results: In the PT group, PE alleviated hemorrhagic erosion in colon mucosa and infiltration of inflammatory cells in lamina propria mucosae. In the colon of the PT group, COX-2 production was inhibited via regulating the activity of $TNF-{\alpha}$ and $NF-{\kappa}B$ p65. PE also had an anti-oxidative effect via activating nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Conclusions: In this study, we found the utility of treatment with PE and the potential of developing a medicine for ulcerative colitis by applying our results. Further investigations for the anti-inflammatory mechanism of PE may be needed.

• International Journal of Oral Biology
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• 제45권2호
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• pp.33-41
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• 2020

Neuroinflammation is known as the main mechanism implicated in the advancement of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The main feature of neuroinflammation is associated with the activation of microglia. The activated microglia increase proinflammatory cytokine production and induce progressive neuronal cell death. Citrus flavonoids show neuroprotective effects that are associated with the anti-inflammatory action of flavonoids in neurodegenerative diseases. Among these citrus flavonoids, kaempferol, naringin, and nobiletin show inhibitory effects on nuclear factor-κB and mitogen-activated protein kinase signaling pathways that can modulate inflammatory conditions in microglial cells. In the present review, we present the anti-inflammatory activities of citrus flavonoids and therapeutic potential of flavonoids as neuroprotective agents.