• Journal of Applied Biological Chemistry
• /
• 제66권
• /
• pp.213-220
• /
• 2023

본 연구는 비자나무(Torreya nucifera (L.) Siebold & Zucc, TN)와 생물전환 된 비자나무 추출물(TNB)의 항염증 효과를 평가하기 위해 수행되었으며 이를 위해 C. acnes에 의해 유도된 RAW264.7 염증 모델에서 염증인자의 발현을 조사하였다. 실험 결과, TNB는 50, 100, 200 ㎍/mL 농도에서 TN의 높은 세포독성을 개선하였으며 nitric oxide (NO)와 NO 합성 효소인 inducible NO synthase (iNOS) 및 prostaglandin의 합성 효소인 cyclooxygenase-2 (COX-2)의 발현을 유의하게 억제하였다. 또한 TNB는 염증성 사이토카인인 tumor necrosis factor-α (TNF-α) 및 interleukin (IL)-1β, IL-6, IL-8의 발현을 유의하게 억제하였으며 특히 IL-6, IL-8의 경우 가장 고 농도인 200 ㎍/mL에서 정상세포 수준으로 감소하였다. 이후 진행된 western blot에서 인산화 된 IκB-α 및 NF-κB의 발현이 농도의존적으로 억제됨을 확인하였으며 인산화가 억제되면서 degradation이 감소하여 TNB처리 농도가 높아짐에 따라 IκB-α의 농도가 증가하는 경향을 보였다. 결론적으로, TNB는 NF-κB신호 전달 경로를 차단함으로써 다양한 염증 매개 인자의 발현을 효과적으로 하향 조절할 수 있으며 이를 통해 항 염증 활성을 유도하는 것으로 확인된다. 이러한 결과를 근거로 TNB가 C. acnes에 의해 유발된 염증성질환의 치료에 효과적인 천연물 소재로 적용될 수 있음을 제안한다.

• 대한본초학회지
• /
• 제22권3호
• /
• pp.27-37
• /
• 2007

Objectives: Hepatocellular carcinoma is the most common primary malignant tumor of the liver worldwide. In-Jin-Ho-Tang(IJHT) has been used as a traditional Chinese herbal medicine since ancient time. and today it is widely applied as a medication for jaundice which is associated with inflammation in liver. In this study, I investigated whether methanol extract of IJHT induced HepG2 cancer cell death. Methods: Cytotoxic activity of IJHT on HepG2 cells was using XTT assay. Apoptosis induction by Ros A in HCT116 cells was verified by the induction of cleavage of poly ADP-ribose polymerase (PARP). and activation of caspase-3, -8 and -9. The release of cytochrome c from mitochondria to cytosol. the level of Bcl-2 and Bax and the expression of p53 and p21 were examined by western blotting analysis. Furthermore, MAPKs activation was analyzed by western blotting analysis. Results: IJHT induced apoptosis in HepG2 cells. And treatment of IJHT resulted in the release of cytochrome c into cytosol, decreased anti-apoptotic Bcl-2, and increased pri-apoptotic Bax expression. IJHT markedly inactivated extracellular signal-regulated kinase (ERK1/2), and activated p38 mitogen-activated protein (MAP) kinase. Sodium orthovanadate (SOV), a phosphatase inhibitor, to reverse IJHT-induced ERK1/2 inactivation and SB203580, a specific p38 MAP Kinase inhibitor efficiently blocked apoptosis of HepG2. Thus, IJHT induces apoptosis in HepG2 cells via MAP kinase modulation. Conclusion: These results indicated that IJHT has some potential for use as an anti-cancer agent.

• 생명과학회지
• /
• 제18권10호
• /
• pp.1342-1347
• /
• 2008

알코올 급여 흰쥐에서 알코올성 간독성에 대한 누에배설물(silkworm excrement powder)의 영향을 검토하기 위하여 반합성 식이에 누에배설물을 3% (w/w) 수준으로 첨가하여 30일간 급여한 후 혈중 알코올 및 지질 농도, 간 기능 지표 효소 활성 및 간 조직 검사를 실시하였다. 임상생화학적으로 중요한 간 기능 지표 효소인 alanine aminotransferase (ALT), aspartate aminotransferase (AST), $\gamma$-glutamyl transpeptidase ($\gamma$-GTP) 및 lactate dehydrogenase (LDH) 활성이 알코올 대조군에서 증가하였다. 또한 혈중 알코올 농도도 알코올 섭취에 의해 증가하였다. 그러나 누에배설물 투여에 의해 혈중 ALT 및 LDH 활성은 현저하게 감소하였다. 혈중 중성지질, 콜레스테롤 농도는 알코올 대조군에 비해 누에배설물 투여에 의해 현저히 감소하였다. 또한 간 조직 검사에서 알코올 대조군에서 많은 지방적이 나타나 지방간이 확인되었으나 누에배설물 투여에 의해서는 지방적의 크기와 수가 많이 줄어드는 결과를 얻었다. 이상의 결과에서 누에배설물에 의한 알코올-유발 간독성의 개선효과는 간 조직의 임상생화학적 지표 효소의 활성 감소에 기인하는 것으로 나타났다.

• Toxicological Research
• /
• 제23권1호
• /
• pp.87-96
• /
• 2007

Single and repeated-dose toxicity of anti-diabetic herb extract microcapsule (ADHEM) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity test, kneading ADHEM with sterilized water were administered orally once at dose levels of 0 and 2,000 mg/kg and examined for 14 days. No dead animals, clinical signs and abnormal necropsy findings were observed and also no significant difference in body weights was found. Therefore, the $LD_{50}$ of ADHEM was considered to be higher than 2,000 mg/kg in both male and female rats. For repeated-dose toxicity test, ADHEM were mixed with powder fodder and administerd orally for 28 days at dose levels of 0, 500, 1000 and 2000 mg/kg/day. No dead animals, clinical signs and significant difference in body weights were found. In hematology and serum biochemistry, all values were included within the normal ranges. In relative organ weights, kidney or liver were significantly increased in the 500, 1000 or 2000 mg/kg/day male groups, uterus was significantly increased in the 500 mg/kg/day female group and left adrenal glands were significantly decreased in the 2000 mg/kg/day female group. In histopathological examinations, vacuolation and microgranuloma in the liver, chronic progressive nephropathy and inflammation in the kidney were observed in the 500, 1000 or 2000 mg/kg/day both male and female groups. Therefore, the no observed adverse effect level (NOAEL) of ADHEM was considered to be lower than 500 mg/kg/day in both male and female rats.

• Biomolecules & Therapeutics
• /
• 제25권5호
• /
• pp.545-552
• /
• 2017

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

• Journal of Microbiology and Biotechnology
• /
• 제27권8호
• /
• pp.1529-1538
• /
• 2017

Klebsiella pneumoniae is an opportunistic and clinically significant emerging pathogen. We investigated the relative roles of Toll-like receptor (TLR) 2 and TLR4 in initiating host defenses against K. pneumoniae. TLR2 knockout (KO), TLR4 KO, TLR2/4 double KO (DKO), and wild-type (WT) mice were inoculated with K. pneumoniae. Mice in each group were sacrificed after either 12 or 24h, and the lungs, liver, and blood were harvested to enumerate bacterial colony-forming units (CFU). Cytokine and chemokine levels were analyzed using enzyme-linked immunosorbent assay and real-time PCR, and pneumonia severity was determined by histopathological analysis. Survival was significantly shortened in TLR4 KO and TLR2/4 DKO mice compared with that of WT mice after infection with $5{\times}10^3CFU$. TLR2 KO mice were more susceptible to infection than WT mice after exposure to a higher infectious dose. Bacterial burdens in the lungs and liver were significantly higher in TLR2/4 DKO mice than in WT mice. Serum $TNF-{\alpha}$, MCP-1, MIP-2, and nitric oxide levels were significantly decreased in TLR2/4 DKO mice relative to those in WT mice, and TLR2/4 DKO mice showed significantly decreased levels of $TNF-{\alpha}$, IL-6, MCP-1, and inducible nitric oxide synthase mRNA in the lung compared with those in WT mice. Collectively, these data indicate that TLR2/4 DKO mice were more susceptible to K. pneumoniae infection than single TLR2 KO and TLR4 KO mice. These results suggest that TLR2 and TLR4 play cooperative roles in lung innate immune responses and bacterial dissemination, resulting in systemic inflammation during K. pneumoniae infection.

• 한방재활의학과학회지
• /
• 제24권2호
• /
• pp.65-81
• /
• 2014

Objectives This study was carried out to find out the anti-osteoarthritic effects of Mahwangbujaseshin- tang (Mahuangfuzixixintang ) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injecting MIA ($50{\mu}l$) into the knee joint of rats. Rats were divided into a 3 groups (n=7). The injection did not fit the normal group. A week later, after the injection of MIA, while control group took normal saline 2 ml, the extract of Mahwangbujaseshin-tang (Mahuangfuzixixintang ) (MBST) (200 mg/kg) was injected to treated group. After that, we examined hind paw weight bearing ability, functions of liver and kidney, serum TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, TIMP-1, MMP-9 and hematology. Volume of cartilage was measured by micro CT arthrography. Injury of synovial tissue was measured by H & E, Safranin-O immunofluorescence. Results 1) DPPH and ABTS free radical scavenging activity of MBST was increased according to concentration of MBST and total phenolic contents were in high level. 2) In RAW 264.7 cells, ROS production was significantly decreased in MBST (at 10, $100{\mu}g/ml$) and NO was also decreased but meaningless in MBST (at $100{\mu}g/ml$). 3) In RAW 264.7 cells, IL-6 production was significantly decreased in MBST (at $100{\mu}g/ml$) and TNF-$\alpha$ and IL-$1{\beta}$ production were also decreased but meaningless in MBST (at $100{\mu}g/ml$). 4) In hind legs weight-bearing measurement, level of weight-bearing was increased. 5) Functions of liver and kidney were not affected. 6) TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, MMP-9 and TIMP-1 production were significantly decreased. 7) In hematology, the levels of neutrophils, monocytes were significantly decreased and the levels of white blood cells, lymphocytes were also decreased but meaningless. 8) In micro CT-arthrography, cartilage volume was significantly increased. 9) Histopathologically, injury on cartilage and synovial membrane of MBST group was decreased. Conclusions Based on all results mentioned above, Mahwangbujaseshin-tang (Mahuangfuzixixintang) is believed to be meaningful for suppressing the progress of osteoarthritis. And it is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• 대한방사선기술학회지:방사선기술과학
• /
• 제39권4호
• /
• pp.623-630
• /
• 2016

방사선 피폭에 의한 간조직의 장해는 경화성 위축으로 복수가 발생하고 황달과 피로감이 수반된다. 이러한 장해에는 간세포의 형태학적 변화가 동반되고 소기관들의 손상이 연관되어 있다. 본 연구는 이러한 소기관들의 형태적 손상을 알아보고자 하였다. 특히 에너지 대사와 관련된 미토콘드리아와 세포질그물 핵막을 중심으로 관찰하였으며, 방사선 방어제 연구와 병행하였다. 방어제는 혈류 증가 작용이 있는 알리인을 투여하였다. 세포 관찰은 투과전자현미경을 활용하였다. 실험결과, 7 Gy 전신 조사에서 간세포의 핵막이 비후되고, 소기관들 주변에 염증성 변화가 관찰되었다. 20일 경과된 세포에서는 과산화소체와 미토콘드리아 막이 손상되었고 세포질에서 공포가 확인되었다. 30일 경과된 세포에서는 거대한 지방세포들이 관찰되었고. 조면소포체에는 리보솜이 분리된 것을 확인하였다. 알리인 투여 후 간세포에서는 핵막 주변에 많은 수의 조면소포체들이 선명하게 관찰되었고 핵막도 비후되지 않았다. 세포질에는 공포화되거나 염증성 증후들이 관찰되지 않았다. 미토콘드리아의 막손상도 없었으며 글리코겐도 정상적으로 확인되었다. 따라서 일부 방어효과가 있는 것으로 확인되었다.

• 대한임상검사과학회지
• /
• 제48권2호
• /
• pp.68-73
• /
• 2016

암모니아는 매우 독성이 있으며, 흥분 독성, 산화 스트레스, 염증을 통해 신경 세포의 손상을 유발한다. 간이 암모니아 대사를 위한 일차 기관이라는 사실에 근거하여 선천성 대사 오류의 원인이 된다. 혈중 암모니아 판정은 측정값의 일부 범위에서 결정하게 되는데 최근 진단분야에서 혈중 암모니아를 가능한 동시다발적으로 측정하게 되었다. 그러나 혈액검체의 수집, 처리, 저장 및 분석은 오류의 모든 잠재적인 요인이다. 신속하고 신뢰할 수 있는 혈중 암모니아 측정의 평가를 위해 DRI-CHEM 100 (Fuji Film Co., Japan) 및 COBAS 8000 (Roche Diagnostic Ltd., Switzerland) 분석기를 이용해 비교평가 분석하였고 높은 상관성을 얻었으며 one-step 방법은 암모니아 분석에 적합하였다. 암모니아의 채혈 후 시간대별 측정에서는 30, 90, 180분에 각각 46.5, 57.4, 79.0 (${\mu}g/dL$)로 상승하는 경향을 보였다. 또한 암모니아의 용량별 측정에서는 7, 10, 13 (${\mu}L$)에 각각 39, 46, 43 (${\mu}g/dL$)으로 나타났으며 $10{\mu}L$에서 유의성을 보였다(p<0.001). 결론적으로 위 평가 분석은 임상적용에서 유용한 정보를 제공 할 수 있을 것이다.

• Pediatric Infection and Vaccine
• /
• 제24권3호
• /
• pp.141-145
• /
• 2017

목적: 농뇨가 동반된 가와사키병(Kawasaki disease [KD]) 환아와 농뇨 동반이 없는 KD 환아의 임상 및 검사실 지표들을 비교하여 농뇨 동반 KD의 임상적 특징을 파악하고자 하였다. 방법: 2015년 1월부터 2016년 12월까지 KD로 입원한 140명(남아 86명, 여아 54명) 환아의 의무기록을 후향적으로 조사하였다. 결과: 48명의 KD 환아(34.3%)에서 농뇨가 관찰되었다. 농뇨 KD군은 비농뇨 KD군보다 높은 C-반응단백(C-reactive protein [CRP]) 값을 보였고 간 효소치가 증가한 환아의 비율이 높았다. 두 군 간의면역글로불린(intravenous immunoglobulin) 치료 저항성과 관상동맥병변(coronary artery lesion) 발생률에 대한 차이점은 없었다. 농뇨 KD군 중 6명(12.5%)은 요로감염(urinary tract infection)을 감별하기 위해 신장 영상검사를 받았고, 농뇨 KD군의 2/3(66.7%)는 KD 표준치료에 추가로 항생제 치료를 받았다. 결론: 농뇨가 동반된 KD 환아들은 농뇨 동반이 없는 KD 환아들보다 더 높은 CRP 값과 더 많은 경우의 간 효소치 증가를 보였다. 이는 농뇨가 동반된 KD 환아가 농뇨 동반이 없는 KD 환아보다 더 심한 전신염증반응을 보인다는 점을 시사한다.