• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6939-6944
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• 2014

Sulfasalazine (SSZ) is an anti-inflammatory drug that has been used to treat inflammatory bowel disease and rheumatoid arthritis for decades. Recently, some reports have suggested that SSZ also has anti-cancer properties against human tumors. However, little is known about the effects of SSZ on oral cancer. The aim of this study was to investigate the anti-cancer effects of SSZ in oral squamous cell carcinoma (OSCC) cells and to elucidate the mechanisms involved. The authors investigated the anti-proliferative effect of SSZ using the MTT method in HSC-4 cells (an OSCC cell line). Cell cycle analysis, acidic vesicular organelle (AVO) staining, monodansylcadaverine (MDC) staining and Western blotting were also conducted to investigate the cytotoxic mechanism of SSZ. SSZ significantly inhibited the proliferation of HSC-4 cells in a dose-dependent manner. In addition, SSZ induced autophagic cell death, increased microtubule-associated protein 1 light chain (MAP1-LC; also known as LC) 3-II levels, as well as induced punctate AVO and MDC staining, resulted in autophagic cell death. Furthermore, these observations were accompanied by the inhibition of the Akt pathway and the activation of ERK pathway. These results suggest that SSZ promotes autophagic cell death via Akt and ERK pathways and has chemotherapeutic potential for the treatment of oral cancer.

• Korean Journal of Medicinal Crop Science
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• v.20 no.5
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• pp.381-386
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• 2012

Eucommia ulmoides OLIVER (EU) is a traditional Korean herbal used for the treatment of rheumatoid arthritis (RA). In the present study, the molecular pharmacology basis of its anti-inflammatory effect is revealed in this work, EU was studied in lipopolysaccharide (LPS)-activated macrophage cells (RAW 264.7) as an established inflammation model. After activation, nitric oxide (NO) production and iNOS mRNA were measured by using a colorimetric assay (Griess reagent), and reverse transcription polymerase chain reaction (RT-PCR), respectively. The change in the content of $PGE_2$, $TNF{\alpha}$, and IL-6 was concurrently monitored by ELISA. In results, we found that in the concentration range without showing cytotoxicity, EU produced a remarkable anti-inflammatory effect and showed a dose-dependent inhibition of LPSinduced NO production. Compared with indomethacin, EU has more potency and a specific action of NO inhibition, $PGE_2$, IL-6, and TNF-${\alpha}$ inhibition. These results suggest that EU may be a suitable herbal medicine to yield the greatest anti-inflammatory activity for food additives and medicine.

• Korean Journal of Pharmacognosy
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• v.36 no.4 s.143
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• pp.311-317
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• 2005

GCSB-5 is a purified extract from a mixture of 6 Oriental herbs (Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen, and Eucommiae Cortex) that have been widely used for the treatment of inflammatory diseases in the East Asia. The aim of this study was to investigate the anti-inflammatory potential of GCSB-5. The animals used in this study were administered either vehicle or GCSB-5 (30, 100, 300, and 600 mg/kg) orally. The GCSB-5 significantly inhibited the increased of acetic acid-induced vascular permeability (30.9%-34.2% inhibition at 30-300 mg/kg). The swelling of the rat's hind paw induced by carrageenan was significantly inhibited by GCSB-5 in doses of 100, 300, and 600 mg/kg. Maximal inhibition (50.9%) was obtained with GCSB-5 at dose of 300 mg/kg. However, it did not have any anti-inflammatory action in the rheumatoid arthritis induced by Freund's complete adjuvant or in the granuloma induced by carrageenan. Our finding suggest that GCSB-5 has a anti-inflammatory activity.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.324-329
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• 2009

Cell-cell adhesion managed by various adhesion molecules is known to be one of pathophysiological phenomena found in numerous immunological diseases such as rheumatoid arthritis and allergic diseases. In this study, we examined the regulatory role of ginsenosides (G)- Rh1, reported to display anti-inflammatory and anti-allergic effects, on CD29-mediated cell adhesion. G-Rh1 significantly suppressed U937 cell-cell adhesion mediated by CD29 but not CD43. It also blocked U937 cell-fibronectin adhesion, mediated by activated CD29, up to 30%. In agreement, this compound also significantly decreased the surface level of CD29 but not CD43 as well as other costimulatory molecules such as CD69, CD80, and CD86. Therefore, these results suggest that G-Rh1 may have inhibitory function on CD29-mediated cell adhesion events, probably contributing to its anti-inflammatory and anti-allergic activities.

• Journal of Acupuncture Research
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• v.18 no.2
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• pp.200-213
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• 2001

Objectives : This study was purposed to investigate the Anti-inflammatory and Analgesic Effects of Gold injection Aqua-acupuncture on the experimental model of rheumatoid arthritis. Methods : The experimental groups were divided into 4 groups : Control group (group injected with normal saline), J-NS (group injected with normal saline into bilateral Choksamni(ST36)), J-GS (group injected with Gold Injection into bilateral Choksamni(ST36)), and N-GS (injected with Gold Injection into the blank locus of the root of mouse tail). In addition, Diclofenac-Na as a comparative medicine is injected into bilateral Choksamni(ST36) and the blank locus of the root of mouse tail. So we measured the mice paw edema induced by Carrageenin and Dextran, the chronic rat paw edema induced by adjuvant, vascular permeability induced by Acetic acid in mice, the writhing syndrome induced by Acetic acid in mice, the heat-induced pain threshold in mice. Results : The following result have been obtained. 1. The mice paw edema induced by Carrageenin was significantly decreased in J-GS as compared with the control group. 2. The mice paw edema induced by Dextran was significantly decreased in J-GS and N-GS as compared with the control group. 3. The chronic rat paw edema induced by Adjuvant was significantly decreased in J-GS and N-GS as compared with the control group. Serum Iron content was significantly decreased in J-GS and N-GS as compared with the control group. But the effect on the Serum Copper contents has no significance statistically. 4. Vascular permeability induced by Acetic acid in mice was significantly decreased in J-GS and N-GS as compared with the control group. 5. The level of Acetic acid-induced Writhing syndrome and Heat-induced Pain Threshold in mice were all significantly decreased in J-GS and N-GS as compared with the control group. Conclusion : According to the result, gold injection aqua-acupuncture has significant anti-inflammatory and analgesic effects on the experimental model of rheumatiod arthiritis.

• Journal of the Korean Society of Food Culture
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• v.36 no.2
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• pp.235-245
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• 2021

Lindera glauca Blume has been used in Korean traditional medicine to treat the symptoms of paralysis, abdominal pain, speech disorders, extravasations, contusions, and pain caused by rheumatoid arthritis. We investigated the effect of L. glauca Blume extracts on the proliferation of colorectal cancer cells in vitro using HCT116 human colorectal cancer cell lines. We also investigated its mechanism of action. For this purpose, we used the MTT assay, western blotting, DNA fragmentation analysis, and flow cytometry. HCT116 cells were cultured in several concentrations of ethanol extracts of L. glauca Blume root (0, 50, 100 ㎍/mL). In this study, colon cancer cell growth was inhibited by L. glauca Blume root extract in a dose-dependent manner. It was associated with induction of apoptosis as assessed by nuclear fragmentation and cell cycle analysis. Apoptosis was assessed using western blotting for TNF-α, IL-6, NF-κB, Caspase-3, PARP, Bax, Bcl-2, and SIRT1. The extract also dose-dependently upregulated the expression Bax, the pro-apoptotic gene and downregulated the expression of the anti-apoptotic gene Bcl-2. Furthermore, the extract enhanced Caspase-3 activity in a dose-dependent manner. Our findings provide evidence that L. glauca Blume extract may mediate its anti-proliferative effect via the modulation of apoptosis.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.57-62
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• 2013

Objectives : Lonicerae Japonicae Flos (LJF) has been shown anti-oxidant, anti-inflammatory, anti-viral, anti-rheumatoid properties. However, it is still largely unknown whether LJF inhibits skin injury against oxidative stress in human keratinocyte, HaCaT cells. The purpose of this study was to evaluate the protective effects of LJF against hydrogen peroxide($H_2O_2$)-induced oxidative stress in human keratinocytes, HaCaT cells. Methods : To evaluate out the protective effects of LJF on oxidative injury in HaCaT cells, an oxidative stress model of HaCaT cells was established under a suitable concentration (500 ${\mu}M$) hydrogen peroxide. HaCaT keratinocyte cells were pre-treated with LJF (0.1, 0.25 or 0.5 mg/ml), and then stimulated with $H_2O_2$. Then, the cells were harvested to measure the cell viability, DNA damage, and release of reactive oxygen species (ROS). Results : LJF (0.1, 0.25 or 0.5 mg/ml) itself did not show any significant toxicity in HaCaT cells. The treatment of $H_2O_2$ caused the oxidative stress, leading to the cell death, and DNA injury. However, pretreatment with LJF reduced cell death, and DNA injury. The stimulation of $H_2O_2$ on HaCaT cells resulted in excessive release of ROS, which is the main factor of oxidative stress. The excessive release of ROS was inhibited by LJF treatment significantly. Conclusions : These results could suggest that LJF exhibited the protective effects of HaCaT cells against $H_2O_2$-induced oxidative stress by inhibiting ROS release. It could be explained that LJF inhibit skin damages against oxidative stress. Thus, LJF would be useful for the development of drug or cosmetics treating skin troubles.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.2
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• pp.119-128
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• 2023

Purpose : The fruit of Actinidia polygama has been used in oriental medicine for the treatment of gout, rheumatoid arthritis, and inflammation. Though A. polygama exhibited anti-inflammatory activity in RAW 264.7 cells and carrageenan-induced rat paw edema, the exact mechanism for anti-inflammation was not evaluated yet. In this study, the anti-inflammatory mechanisms of A. polygama ethanol extract (APEE) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Methods : WST-1 assay was applied to analyze the cytotoxic effect of APEE in RAW 264.7 cells. The productions of nitric oxide (NO) and prostaglandin (PG) E₂ were analyzed by the Griess reaction and enzyme immunoassay (EIA) assay, respectively. In addition, protein expressions for inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured by Western blot analysis. The activated status of an inflammatory transcription factor, NF-κ B, and its upstream signaling molecules, mitogen-activated protein kinases (MAPKs), was also evaluated by Western blot analysis. Results : As a result, APEE treatment did not exhibit any cytotoxicity until the concentration of 200 ㎍/㎖. APEE treatment significantly inhibited NO and PGE₂ productions as well as their enzymes, iNOS and COX-2 in a dose-dependent manner. The inflammatory transcription factor, NF-κ B, was also attenuated by APEE treatment. In addition, the phosphorylated status of MAPKs such as extracellular regulated kinase (ERK), c-jun NH2 kinase (JNK), and p38, were significantly diminished by APEE treatment in LPS stimulated RAW 264.7 cells. Conclusion : Consequently, APEE treatment significantly attenuated the production of inflammatory mediators and their enzyme expressions in LPS-stimulated RAW 264.7 cells. The inflammatory transcription factor, NF-κ B, and upstream signaling molecules, MAPKs, were also significantly attenuated by APEE treatment in LPS-activated RAW 264.7 cells. These results indicate that APEE might be a candidate to be utilized as a promising candidate for the treatment of inflammatory disorders.

• The Journal of Korean Medicine
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• v.30 no.1
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

• 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.