• 한국약용작물학회지
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• 제16권2호
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• pp.100-105
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• 2008

We previously examined extracts, isolated from Scutellaria baicalensis (SB), chemical mediators, and IgE by mesenteric lymph node (MLN) lymphocytes in rats. The present study was to evaluate the effects of extracts of SB on the MLN lymphocytes function of mice given orally by 20 mg/kg for 2 weeks with dextran sulfate sodium (DS)-induced colitis. Results show that IgE levels in MLN lymphocytes was low, while IgA was high, in mice given SB compared to that fed water. Concentrations of $Inteferon-{\gamma}$ and interleukin (IL)-2 of T cells by concanavalin A treatment was significantly higher in the SB fed group than the normal group. Activation-induced IL-4 and IL-10 secretion was lower in SB fed mice compared control mice after DS-induced colitis. These results suggested that SB suppresses the inflammation in DS-induced colitis through the modulation of Th1/Th2 balance to down-regulate $Th_2$ response in MLN lymphocytes.

• Journal of Microbiology and Biotechnology
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• 제34권7호
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• pp.1501-1510
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• 2024

Inflammatory bowel disease (IBD), characterized by chronic inflammation of the gut, is caused by several factors. Among these factors, microbial factors are correlated with the gut microbiota, which produces short-chain fatty acids (SCFAs) via anaerobic fermentation. Fermented foods are known to regulate the gut microbiota composition. Ganjang (GJ), a traditional fermented Korean soy sauce consumed worldwide, has been shown to exhibit antioxidant, anticancer, anti-colitis, and antihypertensive activities. However, its effects on the gut microbiota remain unknown. In the present study, we aimed to compare the anti-inflammatory effects of GJ manufactured using different methods and investigate its effect on SCFA production in the gut. To evaluate the anti-inflammatory effects of GJ in the gut, we performed animal experiments using a mouse model of dextran sulfate sodium (DSS)-induced colitis. All GJ samples attenuated DSS-induced colitis symptoms, including reduced colonic length, by suppressing the expression of inflammatory cytokines. In addition, GJ administration modulated SCFA production in the DSS-induced colitis model. Overall, GJ exerted anti-inflammatory effects by reducing DSS-induced symptoms via regulation of inflammation and modulation of SCFA levels in a DSS-induced colitis model. Thus, GJ is a promising fermented food with the potential to prevent IBD.

• 대한약침학회지
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• 제27권2호
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• pp.59-69
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• 2024

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

• 한국환경성돌연변이발암원학회지
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• 제23권3호
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• pp.99-102
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• 2003

IARC classified areca quid as a human carcinogen. Areca quid chewed in Taiwan includes Piper betle inflorescence, which contains high concentrations of safrole (15 mg/fresh weight). Safrole is a documented rodent hepatocarcinogen, and chewing areca quid may contribute to human exposure (420 $\mu$m in saliva). The carcinogenicity of safrole is mediated through 1'-hydroxysafrole formation, followed by sulfonation to an unstable sulfate that reacts to form DNA adducts. Using human liver microsomes and Escherichia coli membranes expressing bicistronic human P450s, CYP2E1 and CYP2C9 were identified as the main P450s involved in the activation of safrole. We have demonstrated the presence of stable safrole-dGMP adducts in human oral tissues following areca quid chewing using $^{32}$ P-postlabeling and HPLC mass spectrometry methods. By studying 88 subjects with a known AQ chewing history and 161 matched controls, we have demonstrated that the presence of safrole-DNA adducts in peripheral blood cells was correlated to AQ chewing, and CYP2E1 seemed to play an important role in the modulation of safrole-DNA adduct formation. We have also shown that safrole can form stable safrole-DNA adducts as well as oxidative damages in rodent liver. However, the stable safrole-DNA adducts may represent a more significant initial lesion as compared to the rapidly repaired safrole-induced 8-hydroxy-2'-deoxyguanosine. This oxidative DNA damage is mediated through the formation of hydoryxchavicol, the major safrole metabolite in human urine. Hydroxychavicol may have gone through two-electron oxidation to the o-quinone; then via one-electron reduction to semiquinone radicals to generate oxidative DNA damage. However, these reactive metabolites can be efficiently conjugated by GSH. These data suggest that safrole may contribute to the initiation of oral carcinogenesis through safrole-DNA adduct and not oxidative DNA damage. In addition, CYP2E1 may modulate this adduct formation.

• Journal of Microbiology and Biotechnology
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• 제29권9호
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• pp.1478-1487
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• 2019

Ulcerative colitis (UC), a chronic inflammatory bowel disease, substantially impacts patients' health-related quality of life. In this study, an effective strategy for discovering high-efficiency probiotics has been developed. First, in order to survive in the conditions of the stomach and intestine, high bile salt-resistant and strong acid-resistant strains were screened out from the fecal flora of healthy adults. Next, the probiotic candidates were rescreened by examining the induction ability of IL-10 (anti-inflammatory factor) production in dextran sodium sulfate (DSS)-induced colitis mice, and Lactobacillus sakei 07 (L07) was identified and selected as probiotic P. In the end, fourteen bifidobacterium strains isolated from stools of healthy males were examined for their antimicrobial activity. Bifidobacterium bifidum B10 (73.75% inhibition rate) was selected as probiotic B. Moreover, the colonic IL-6 and $TNF-{\alpha}$ expression of the DSS-induced colitis mice treated with L. sakei 07 (L07) - B. bifidum B10 combination (PB) significantly decreased and the IL-10 expression was up-regulated by PB compared to the DSS group. Furthermore, Bacteroidetes and Actinobacteria decreased and Firmicutes increased in the DSS group mice, significantly. More interestingly, the intestinal flora biodiversity of DSS colitis mice was increased by PB. Of those, the level of B. bifidum increased significantly. The Bacteriodetes/Firmicutes (B/F) ratio increased, and the concentration of homocysteine and LPS in plasma was down-regulated by PB in the DSS-induced colitis mice. Upon administration of PB, the intestinal permeability of the the DSS-induced colitis mice was decreased by approximately 2.01-fold. This method is expected to be used in high-throughput screening of the probiotics against colitis. In addition, the L. sakei 07 - B. bifidum B10 combination holds potential in UC remission by immunomodulatory and gut microbiota modulation.

• Nutrition Research and Practice
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• 제14권2호
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• pp.117-126
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• 2020

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months. SUBJECTS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6-12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections). RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D. CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

• 생명과학회지
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• 제28권10호
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• pp.1212-1219
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• 2018

열 충격 단백질인 heat shock protein 90 (Hsp90)은 종양 형성 과정에서 중요한 역할을 하고 있으며, 이에 따라 1세대 및 2세대 Hsp90저해제들이 개발되어, 다양한 암에서의 항암 효과가 보고되어 있다. 2세대 Hsp90저해제로 개발된 BIIB021는 1세대 Hsp90저해제인 17-allylamino-17-demethoxygeldanamycin (17-AAG)에 내성을 나타내는 항암제 다제내성(MDR) 암세포에 감수성을 가진다고 알려져 있지만, 본 연구에서 BIIB021에 내성인 MDR세포로서, MCF7-MDR 및 HeyA8-MDR세포가 해당됨을 밝혔다. BIIB021 감수성을 증강시키는 물질로 비스테로이드성 항염증약물(NSAID)인 dimethyl-celecoxib (DMC)의 BIIB021의 효과 증강 활성을 BIIB021-내성 및 -감수성 MDR 세포에서 확인하였다. MDR세포에 NSAID와 BIIB021의 병합 처리한 경우, NSAID의 자가분해(autophagy) 유도 활성에 의해 MDR세포에서 과잉 발현하는 변이형 mutant p53 (mutp53)을 분해할 뿐만 아니라 BIIB021 처리로 유도되는 Hsp70 발현을 억제하므로써, 암세포의 BIIB021 내성을 극복할 수 있는 활성을 나타내었다. 또한 NSAID 물질인 sulindac sulfate 및 FDA 승인 약물인 niclosamide 도 자가분해 유도 활성으로 Hsp90의 타켓 단백질 인 mutp53 및 c-Myc의 분해를 유도하므로서, 17-AAG 효과를 증강시켰다. 그러므로 본 연구에서는 새로운 BIIB021에 대한 효과 증강 및 내성 극복 물질로서, NSAIDs 및 niclosamide를 발굴하였으며, 이들 물질의 자가분해 경로 활성화에 의하여, BIIB021 효과를 극대화 시킴을 밝혔다.