• YAKHAK HOEJI
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• v.56 no.5
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• pp.326-332
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• 2012

Mast cells play pivotal pathologic roles in allergic disease involving T helper 2 (Th2) cytokine such as interleukin (IL)-4 and IL-13. Fisetin has been known as an anti-allergic agent having inhibitory effects on the IL-4 and IL-13 gene expressions in inflammatory immune cells. However, its molecular mechanisms for suppressive effects of fisetin on IL-4 and IL-13 in activated mast cells have been incompletely elucidated. In this study we found that fisetin significantly inhibited the phorbol 12-myristate 13-acetate (PMA) and ionomycin (PI)-induced production of IL-4 and IL-13 in mast cells. The levels of mRNA were dramatically decreased by fisetin, indicating the suppression might be regulated at the transcriptional levels. Western blot analysis of the nuclear expression of various transcription factors involved in the promoter activation indicated that suppression of c-Fos was prominent together with significant down-regulation of nuclear factor of activated T-cell (NF-AT) and NF-${\kappa}B$, but not c-Jun. Furthermore, the nuclear expression of GATA binding protein 2 (GATA-2) transcription factor was significantly down-regulated by fisetin. Taken together, our study indicated fisetin has suppressive effects on IL-4 and IL-13 gene expression through the regulation of selective transcription factors.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.475-482
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• 2009

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-$\alpha$ Since NF-${\kappa}B$ is a major transcription factor that regulates genes for TLR2 and TNF-$\alpha$, we examined the effect of rifampicin on the LPS-induced NF-${\kappa}B$ activation. Rifampicin inhibited NF-${\kappa}B$ DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK$\alpha/\beta$ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-${\kappa}B$ p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-${\kappa}B$ p65, suggesting pregnane X receptor interferes with NF-${\kappa}B$ binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-${\kappa}B$ DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-${\kappa}B$ DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

• Journal of Acupuncture Research
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• v.21 no.4
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• pp.177-196
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• 2004

Objective : Rheumatoid arthritis is an autoimmune disease that pathogenesis is not fully understood and one of the most intractable musculoskeletal diseases. The concern in the immunopathogenesis of rheumatoid arthritis has been increased since 1980's and many immunotherapeutic agents including disease-modifying antirheumatic drugs (DMARDs) were developed and became the mainstay of treatment of rheumatoid arthritis. However, the cure of the disease has hardly been achieved. In oriental medicine, rheumatoid arthritis is related to Bi-Zheng(痺證), that presents pain, swelling, andlor loss of joint function as major clinical manifestations, and also known to be deeply involved in suppression of immune function related to weakness of Jung-Ki(正氣). The herbal medicine, empirically used, could be a potential resource of development of new immunotherapeutic agents for rheumatoid arthritis. Methods : We developed a search strategy using terms to include "rheumatoid arthritis and herbal medicine" combined with "Chinese medicine" and/or "Oriental medicine". The search was focused on experimental studies of herbal medicine (January 1999 to May 2004), which is known to have effects on immune function of patients with rheumatoid arthritis. Computerized search used Internet databases including KISS and RISS4U (Korea), CNKI (China), MOMJ (Main Oriental Medicine Journal, Japan), and PubMed. The articles were selected from journals of universities or major research institutes. Results : The literature search for experimental studies on effects of herbal medicine on immunity of rheumatoid arthritis retrieved a total of 21 articles (Korea; 8, China ; 12, Japan ; 1). Of 21 articles, 10 were related to single-drug formula, 2 to drug interaction, and 9 to multi-drug formula. Single-drug formula was mainly used for aqua-acupuncture and researches on active components. Studies of drug interaction emphasized harmony of Ki-Hyul(氣血) and balance of Han-Yeul(寒熱). Multi-drug regimen was mainly found among formulas for Bo-Ki-Hyul(補氣血) and Bo-Sin(補腎). Conclusion : Studies on rheumatoid arthritis were performed both in vitro and in vivo in vitro study, LPS-stimulated splenocytes and synoviocytes were treated with herbal medicine, resulting in proliferation and activation of immune cells and suppression of cytokine activities in vivo study CIA animal model demonstrated that herbal medicine decreased antibody production and improved function of immune cells. In cellular and molecular study herbal medicine showed profound effects on the level of mRNA expression of certain cytokines related to immune function. This study revealed that herbal medicine has significant immune modulatory action and could be used for recovery of immune dysfunction of rheumatoid arthritis patients.

• Environmental Analysis Health and Toxicology
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• v.20 no.2 s.49
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• pp.143-151
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• 2005

Exposure of skin to UV-B radiation can cause inflammatory response and immunosuppression. It has been reported that Korean Red Ginseng (KRG) has several pharmacological and physiological effects such as antioxidant, anticancer and improving immune function. In this study, we investigated that topical KRG and KRG + EGb 761 (Ginkgo biloba extract) combination prevented UV-B induced inflammation and inhibition of contact hypersensitivity response. Topical application of KRG, f days prior to or 5 days after exposure to 1MED and 2MED of UV-B, reduced skin thickness compared to non -treated group and resulted in protection against immunosuppression. However, KRG+EGb 761 combination has a little protection against the only 1MED UV-B. In conclusion. Topical application of KRG was more effective than combination in protection against UV-B induced inflammation and immune suppression. Also, we suggest that KRG can provide protection from inflammation and immunosuppression by UV-B radiation.

• Advances in Traditional Medicine
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• v.10 no.3
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• pp.150-154
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• 2010

The immunosuppressive activity of the Methanol extract of bark of Madhuca longifolia (Koenig) consisting of a mixture of saponins, flavonoids, tannins, steroids, phenol and glycosides was studied on the immune responses in mice. Methanol extract of Madhuca longifolia (MLL) was administered orally at doses of 50, 100 and 150 mg/kg/day to healthy mice divided into four groups consisting of six animals each. The assessment of immunomodulatory activity was carried out by testing the humoral (antibody titre) and cellular (foot pad swelling) immune responses to the antigenic challenge by sheep RBCs. Furthermore, the effect on hematological parameters as well as relative organ weight was determined. On oral administration MML showed a significant decrease delayed type hypersensitivity (DTH) response whereas the humoral response to sheep RBCs was unaffected. Thus MLL significantly suppressed the cellular immunity by decreasing the footpad thickness response to sheep RBCs in sensitized mice. With a dose of 100 and 150 mg/kg/day the DTH response was $7.66{\pm}2.75$ and $6.41{\pm}1.21$ respectively in comparison to corresponding value of $14.50{\pm}2.38$ for untreated control group. These differences in DTH response were statistically significant (P < 0.05). The study demonstrates that MLL shows preferential suppression of the components of cell-mediated immunity and shows no effect on the humoral immunity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1450-1455
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• 2007

Evodiae Fructus(EF) has been used as Traditional medicine for the treatment of headache, abdominal pain, hemorrhage, and menorrhae in many Asian countries. The present study was conducted to investigate the immunomodulatory effect on cyclophosphamide(CY)-induced immunesuppression of water extracted EF(EFE). In the mouse spleen cell proliferation assay, EFE enhanced mitogenic activity and restored the CY-induced cell suppression. In the nitric oxide(NO) assay, EFE inhibited NO production and iNOS protein levels in LPS-stimulated RAW 264.7 cells. In the GC-MS analysis, many ingredients of EFE were detected by solvents. These results indicated that EFE can modulate immune response through immune cell proliferation, the regulation of NO production and the inhibition of CY-induced immunotoxicity.

• Molecules and Cells
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• v.46 no.3
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• pp.142-152
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• 2023

Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4781-4786
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• 2015

Siberian ginseng (Eleutherococcus senticosus) is used primarily as an adaptogen herb and also for its immune stimulant properties in Western herbal medicine. Another closely related species used in East Asian medicine systems i.e. Kampo, TCM (Manchuria, Korea, Japan and Ainu of Hokkaido) and also called Siberian ginseng (Acanthopanax senticosus) also displays immune-stimulant and anti-cancer properties. These may affect tumour growth and also provide an anti-fatigue effect for cancer patients, in particular for those suffering from lung cancer. There is some evidence that a carbohydrate in Siberian ginseng may possess not only immune stimulatory but also anti-tumour effects and also display other various anti-cancer properties. Our study aimed to determine the inhibitory and also proliferative effects of a methanol plant extract of Siberan ginseng (E. senticosus) on various cancer and normal cell lines including: A-549 (small cell lung cancer), XWLC-05 (Yunnan lung cancer cell line), CNE (human nasopharyngeal carcinoma cell line), HCT-116 (human colon cancer) and Beas-2b (human lung epithelial). These cell lines were treated with an extract from E. senticosus that was evaporated and reconstituted in DMSO. Treatment of A-549 (small cell lung cancer) cells with E. senticosus methanolic extract showed a concentration-dependent inhibitory trend from $12.5-50{\mu}g/mL$, and then a plateau, whereas at 12.5 and $25{\mu}g/mL$, there is a slight growth suppression in QBC-939 cells, but then a steady suppression from 50, 100 and $200{\mu}g/mL$. Further, in XWLC-05 (Yunnan lung cancer cell line), E. senticosus methanolic extract displayed an inhibitory effect which plateaued with increasing dosage. Next, in CNE (human nasopharyngeal carcinoma cell line) there was a dose dependent proliferative response, whereas in Beas-2 (human lung epithelial cell line), an inhibitory effect. Finally in colon cancer cell line (HCT-116) we observed an initially weak inhibitory effect and then plateau.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.914-920
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• 2002

This experiment is carried out for test whether the addition temperament drugs of Danchisoyo-san have an anti-inflammatory effect and have suppression effect on immunocyte in the state of inflammation which induced by carageenan and zymosan. The freezing lyophilization powder which were extracted from Danchisoyo-san divided low dose group(200mg/kg-DSL) and high dose group(500mg/kg-DSH) and after melting in water, it was orally administered to the mouse. Compared with inflammation induced group which were induced by triggering-inflammation reagent carageenan and zymosan and normal contrast group, we measured the edema decrement effect, macrophage and spleen cell activation. 1. Danchisoyo-san has suppress inflammatory reaction induced by carrageenan. 2. Danchisoyo-san has suppress increasing activation of abdominal cavity macrophage cell in the carrageenan induced inflammation. 3. Danchisoyo-san has suppress increasing activation of spleen cell in the carrageenan induced inflammation. 4. Danchisoyo-san has suppress increasing activation of abdominal cavity macrophage in the zymosan induced inflammation. 5. Danchisoyo-san has suppress increasing activation of spleen cell in the zymosan induced inflammation. Based on the above result, Danchisoyo-san was improved its suppression effect to the inflammatory reaction through the suppression of spleen cell and macrophage activation. So we concluded that Danchisoyo-san is prospected as a anti-inflammatory agent to cure inflammation.

• Journal of Environmental Health Sciences
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• v.31 no.1
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• pp.7-14
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• 2005

Exposure of skin to UVB radiation can cause the induction of inflammation and impairment of contact hypersensitivity(CHS) response. Several studies have shown that polyphenolic compounds isolated from EGb 761 afford protection against UVB. In this study, we demonstrated that topical application of EGb 761, before 1MED(1.4 KJ/$m^2$), 1.5MED (2.1 KJ/$m^2$), 2MED (2.8 KJ/$m^2$) of UVB exposure to ICR mice prevented UVB-induced inflammation and inhibition of the contact hypersensitivity response. The skin-fold swelling from 1MED, 1.5MED, 2MED of UVB exposure highly significantly increased after twice irradiation. Topical application of EGb 761(0.1%, 1%, 4%), 5 days prior to UVB exposure reduced skin thickness compared to non-treated mice. Exposure of shaved abdominal skin of mice to 1MED, 1.5MED and 2MED of UVB radiation resulted in suppression of contact sensitization through the skin to 56.23%, 65.12%, 74.02%, compared to normal unirradiated skin. Topical application of EGb 761(0.1%, 1%, 4%), 5 days prior to or 5 days after exposure to 1MED and 2MED of UVB resulted in protection against suppression of contact hypersensitivity in mouse dorsal skin. These protective effects were dependent on the dose of EGb 761 employed. The present study show that EGb 761 protect UVB-induced inflammation and immune suppression. Also, we suggest that EGb 761 can provide protection from photoimmunosuppression.