Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration

Bae, Gi-Sang,Kim, Dong-Goo,Jo, Il-Joo,Choi, Sun-Bok,Kim, Myoung-Jin,Shin, Joon Yeon,Kim, Dong-Uk,Song, Ho-Joon,Joo, Myungsoo,Park, Sung-Joo ELSEVIER 2019 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.69 No.-

<P><B>Abstract</B></P> <P>Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 μg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Desoxo-narchinol-A (DN) is a natural compound of HO-1 inducer in pancreas. </LI> <LI> Mechanism of DN-induced HO-1 is mediated by MAPK/Activator Protein-1/HO-1 signaling. </LI> <LI> DN-induced HO-1 blocks neutrophil infiltration into pancreas via inhibition of CXCL2. </LI> <LI> DN inhibits cerulein-induced acute pancreatitis (AP) and AP-associated lung injury. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

Lee, Eun-Mi,Lee, Young-Eun,Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Moon, Sung-Dae,Song, Ki-Ho,Ahn, Yu-Bae Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.</P><P><B>Results</B></P><P>CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.</P><P><B>Conclusion</B></P><P>Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.</P>

Korean Red ginseng prevents endothelial senescence by downregulating the HO-1/NF-κB/miRNA-155-5p/eNOS pathway

Tae-Hoon Kim,Ji-Yoon Kim,Jieun Bae,Young-Mi Kim,Moo-Ho Won,Kwon-Soo Ha,Young-Guen Kwon,Young-Myeong Kim 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.2

Background: Korean Red ginseng extract (KRGE) has beneficial effects on the cardiovascular system by improving endothelial cell function. However, its pharmacological effect on endothelial cell senescence has not been clearly elucidated. Therefore, we examined the effect and molecular mechanism of KRGE on the senescence of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were grown in normal or KRGE-supplemented medium. Furthermore, they were transfected with heme oxygenase-1 (HO-1) gene or treated with its inhibitor, a NF-κB inhibitor, and a miR-155-5p mimic or inhibitor. Senescence-associated characteristics of endothelial cells were determined by biochemical and immunohistochemical analyses. Results: Treatment of HUVECs with KRGE resulted in delayed onset and progression of senescence-associated characteristics, such as increased lysosomal acidic β-galactosidase and decreased telomerase activity, angiogenic dysfunction, and abnormal cell morphology. KRGE preserved the levels of anti-senescent factors, such as eNOS-derived NO, MnSOD, and cyclins D and A: however, it decreased the levels of senescence-promoting factors, such as ROS, activated NF-κB, endothelial cell inflammation, and p21 expression. The beneficial effects of KRGE were due to the induction of HO-1 and the inhibition of NF-κB-dependent biogenesis of miR-155-5p that led to the downregulation of eNOS. Moreover, treatment with inhibitors of HO-1, NF-κB, and miR-155-5p abolished the anti-senescence effects of KRGE. Conclusion: KRGE delayed or prevented HUVEC senescence through a signaling cascade involving the induction of HO-1, the inhibition of NF-κB-dependent miR-155-5p biogenesis, and the maintenance of the eNOS/NO axis activity, suggesting that it may protect against vascular diseases associated with endothelial senescence.

Competition Responses of Populus alba Clone ‘Bolleana’ to red:far-red light

Bae,Han-hong,Kang,Ho-duck,Richard B,Hall 한국자원식물학회 2004 Plant Resources Vol.7 No.1

The reduced ratio of red:far-red (R:FR) light acts as a measure of the proximity of competitors and plants can detect the potentially competing neighbor plants by perceiving reflected R:FR signals and initiate the response of “shade avoidance” before actual shading occurs. The phytochrome system is responsible for monitoring the changes in the R:FR and initiating the shade avoidance response. The response to low R:FR ratio was studied in a white aspen Populus alba clone ‘Bolleana’ using two filter systems: a clear plastic filter system that allows a R:FR ratio less than 1.0 to pass from adjacent border plant reflection; and a special commercial plastic that blocks FR light and creates a R:FR ratio above 3.0. The reduced R:FR signals enhanced the stem elongation in response to competition at the expense of relative stem diameter growth. Trees grown inside clear chambers were 27 % taller than trees grown inside the FR-blocking filter chambers. Stem taper of clear chamber trees was 16% less than the FR-blocking filter trees. Low R:FR also induced 22% more stem dry weight and 13% greater petiole length per leaf compared to the FR-blocking filter trees. There were no statistically significant differences in leaf area, leaf number increment, and total dry weight between the two light filter treatments.

난치성 만성정신분열증 환자의 생활의 질에 미치는 정신사회치료 프로그램의 효과에 대한 예비연구

송동호,배민진,이종호,이홍식,김선경,서호석,김찬형,전지용 大韓神經精神醫學會 1995 신경정신의학 Vol.34 No.4

Objects : Recent studies of psychosocial adjustment after hospitalization have found that the combination of maintenance antipsychotic drug treatment and psychosocial treatment including psychoeducational program are highly predictive of social rehabilitation and reduction of subsequent relapse. Two groups of patients with refractory chronic schizophrenia were preliminarily compared to determine the effect of a psychosocial treatment program on the quality of life in refractory chronic schizophrenics in an open comparative trial. Methods : One group(N=11) was assigned to approximately six months of the psychosocial treatment program(including psychoeducation program and activity program such as interpersonal relationship program, social skill training, self management program, outings, etc), in a group format, twice a week and a fixed maintenance dosage of clozapine ; while scale(QLS) was used to provide an objective measure of changes in patient's psychosocial functioning and a general assessment of psychopathology was made using the Brief Psychiatric Rating Scale(BPRS). Results : Both BPRS total positive score and the QLS total score, especially in the intrapsychic foundation factor of the scale showed a statistically significant improvement in the psychosocial treatment group. But there was no significant change in both BPRS and QLS scores over a 6-month period in the non-psychosocial treatment group. A significant negative correlation was found between the negative symptom and changes of QLS total, instrumental role and common object and activities scores respectively after receiving a 6-month of the psychosocial treatment program. Conclusion : These results suggest that a psychosocial treatment program including the integration of psychoeducation and a skill training oriented activity program serve as an outpatient treatment modality to improve the quality of the life in refractory chronic schizophrenia. To further clarify the effect of psychosocial treatment in chronic schizophrenia, a randomized trial should be done.

카드뮴 축적 변이주인 Pseudomonas maltophilia H - 8M의 특성

류병호(Beung-Ho Ryu),노명훈(Myung-Hoon Rho),정수자(Su-Ja Jung),배기철(Ki-ChuI Bae) 한국식품영양과학회 1992 한국식품영양과학회지 Vol.21 No.1

본 연구는 cadmium의 축적균주인 Pseudomonas maltophilia H-8을 MNNG로 처리하여 cadmium축적능이 가장 우수한 변이균주인 Pseudomonas maltophilia H-8M을 얻었고 그 특성을 조사하였다. 변이주 Pseudomonas maltophilia H-8M은 카드뮴농도 1,000ppm에서 36시간 배양했을 시 대조구에 비해 약 80%정도의 성장율을 나타내었다. 카드뮴 이외의 중금속의 첨가에 따른 생육상은 Pb^(2+), Zn^(2+), Hg^(2+), Cu^(2+), Cr^(2+), Co^(2+)등에는 별다른 성장 억제는 없었으나 Sn^(2+)에서는 생육억제가나타났다. 또한 50ppm의 카드뮴을 배지에 첨가 하였을 때 균체내 카드뮴 축적율은 52.92%로 가장 높게 나타났으며 축적부위는 세포벽에 80.3%의 축적율을 나타내었다. This study was carried out to investigate the characteristics of a mutant, Pseudomonas maltophilia Ho8M selected with the treatment of Pseudomonas maltophilia H-8 by N-methyl-N-nitro-N-nitrosoguanidine (MNNG). This mutant showed highest ability of cadmium accumulation. The growth rate of Pseudomonas maltophilia H-8M showed about 80% in 1000ppm Cd containing medium when compare with control for 36h at 30℃. Pseudomonas maltophilia H-8M not inhibited on the growth in addition of various heavy metal such as Hg^(2+), Zn^(2+), Pb^(2+), Cu^(2+), Cr^(2+) and Co^(2+), but inhibited in Sn^(2+) containing medium, respectively. Pseudomonas maltophilia H-8M was accumulated the highest cadmium level of 62.3% on whole cell in the medium containing 50 ppm and 80% of accumulated cadmium was distributed in the cell wall.

한국산 배의 Polyphenol 화합물군이 쥐의 면역기능에 미치는 영향

최희진,한호석,박정혜,배종호,우희섭,안봉전,배만종,김현구,최청 한국식생활문화학회 2003 韓國食生活文化學會誌 Vol.18 No.4

This study was conducted to investigate immunofunctional activity of the polyphenol fractions isolated from Korean pear. In the experimental of Rosette forming cell, the results showed that all the polyphenol fractions enhance the cell count compared with the control group. Especially polyphenol fraction II and III showed highly significant effect on Rosette forming cell, and allergy inhibition. After antigen challenge, histamine content of blood of the polyphenol groups was lowered to near the normal group.

신규 방사성 항암제 DW-166HC 의 소핵시험

문은이(Eun Yi Moon),이진(Jin Lee),이원용(Won Yong Lee),최청하(Chung Ha Choi),이덕근(Dug Keun Lee),유제만(Jei Man Ryu),정용호(Yong Ho Chung),윤성준(Sung June Yoon),박경배(Kyung Bae Park) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3

DW-166HC (^(166)Holmium (^(166)Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumorigenic spectrum, especially against human hepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous arid intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I (^(165)Ho-Chitosan complex : cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC (^(166)Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr arid 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative controi group but there was significant difference of this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.

Antioxidant activity in vitro and mucosal protective effect of Rhei Rhizoma on reflux esophagitis induced in rats

Ah Reum Lee,Yu Ock Shin,Joo Young Lee,Min Yeong Kim,Sung Ho Shin,Bu-Il Seo,Young-Bae Seo,Man Hee Rhee,TakakoYokozawa,Chan Hum Park,Seong-SooRoh 한국약용작물학회 2015 한국약용작물학술대회 발표집 Vol.2015 No.05

Purpose Rhei Rhizoma (RR) is one of the herbal medicines traditionally used to treat diverse inflammatory diseases. The present study was undertaken to elucidate the antioxidant and anti-inflammatory activities of Rhei Rhizoma on experimental reflux esophagitis (RE) in rats. Methods The antioxidant activity of RR in vitro was measured in terms of radical scavenging capacity such as DPPH and ABTS. RE was produced by ligating both the pylorus and the transitional junction between the forestomach and the corpus. Rhei Rhizoma (125 and 250 mg/kg) were administered every day for 7 days, and its effect was estimated on comparison with RE control and normal rats. Results RR scavenged DPPH and ABTS effectively and IC50ofDPPH and ABTS radical scavenging activity of RR were 4.8 μg/ml and 15.75 μg/ml. The administration of RR decreased the elevated serum ROS in RE control rats. The RE control rats exhibited the down-regulation of antioxidant-related proteins such as Nrf2 and HO-1expression levels in the esophagitis; however, the level in the RR-treated RE rats was significantly higher than that in the RE control rats. Moreover, RE control rats exhibited the up-regulation of the protein expression related to oxidative stress at the esophagitis, but RR administration significantly reduced the expression of inflammatory proteins through the MAPK-independent signaling pathways. The expression of inflammatory mediators and cytokines by NF-κB activation was modulated through blocking the degradation of IκBα. In addition, the oral administration of RR regulated the gastric mucosal damage in RE rats. Conclusion The administration of Rhei Rhizoma effectively ameliorates the inflammatory damage of esophageal mucosa through radical scavenging activity and the activation of the Nrf2/HO-1 pathway.