Role of High Mobility Group Box 1 in Inflammatory Disease: Focus on Sepsis

배종섭 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.9

High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein present in the nuclei and cytoplasm of nearly all cell types. In response to infection or injury, HMGB1 is actively secreted by innate immune cells and/or released passively by injured or damaged cells. Thus, serum and tissue levels of HMGB1 are elevated during infection, and especially during sepsis. Sepsis is a systemic inflammatory response to disease and the most severe complication of infections, and HMGB1 acts as a potent proinflammatory cytokine and is involved in delayed endotoxin lethality and sepsis. Furthermore, the targeting of HMGB1 with antibodies or specific antagonists has been found to have protective effects in established preclinical inflammatory disease models, including models of lethal endotoxemia and sepsis. In the present study, emerging evidence supporting the notion that extracellular HMGB1 acts as a proinflammatory danger signal is reviewed, and the potential therapeutic effects of a wide array of HMGB1 inhibitors agents in sepsis and ischemic injury are discussed.

The Therapeutic Potential of (+)-Afzelechin for Alleviating Sepsis-Associated Pulmonary Injury

배종섭,Sanghee Cho,Yun Jin Park,Eunjeong Kim 한국식품영양과학회 2024 Journal of medicinal food Vol.27 No.1

Sepsis-induced acute lung injury (ALI) poses a common and formidable challenge in clinical practice, currentlylacking efficacious therapeutic approaches. This study delves into the evaluation of (+)-afzelechin (AZC), a naturalcompound derived from Bergenia ligulata with a diverse array of properties, encompassing antioxidant, anticancer, antimicrobial,and cardiovascular effects to ascertain its effectiveness and underlying mechanisms in mitigating sepsis-inducedALI through animal experimentation. An ALI mouse model induced by sepsis was established through lipopolysaccharide(LPS) administration, and various analytical techniques, including quantitative real-time polymerase chain reaction, Westernblotting, and enzyme-linked immunosorbent assay were employed to gauge inflammatory cytokine levels, lung injury, andassociated signaling pathways. The animal experiments revealed that AZC offered safeguards against lung injury induced byLPS while reducing inflammatory cytokine levels in both blood serum and lung tissue. Western blotting experiments revealedAZC’s downregulation of the toll-like receptor (TLR)4/NF-jB pathway and the upregulation of PI3K/Akt, coupled withinhibition of the Hippo and Rho signaling pathways. These findings underscore AZC’s efficacy in ameliorating sepsis-inducedALI by modulating cytokine storms and curtailing inflammation via the regulation of TLR4/NF-jB, PI3K/Akt, Hippo, andRho signaling pathways. This work serves as a foundation for additional exploration into AZC’s mechanisms and its potentialas a therapy for sepsis-induced ALI. Animals in accordance with Kyungpook National University (IRB No. KNU 2022-174).

과립제와 환제 및 현탁액으로 만들어진 생약제제의 중금속 농도

배종섭(Jong-Sup Bae),박종필(Jong-Pil Park),김용웅(Yong-Ung Kim),박문기(Moon-Ki Park) 한국생물공학회 2010 KSBB Journal Vol.25 No.1

This study is an endeavor to evaluate the safety of medicines from heavy metals, prescribed on the basis of herbal medicinal system and oriental medical prescription which are circulated much recently. For that, six globular types, six granular types and seven liquid types of herbal medicines were bought to compare and analyze the content of heavy metals, such as As, Pb, Cd and Hg, which are harmful to human body. The concentration of As was 0.219 mg/kg to 1.243 mg/kg, Cd was 0.0282 mg/kg to 0.8481 mg/kg, Pb was 0.9582 mg/kg to 5.233 mg/kg and Hg was 0.001 mg/kg to 0.01 mg/kg in globular and granular types. Otherwise, in the liquid types, As was 0.0123 mg/kg to 0.5024 mg/kg, Cd was 0.0128 mg/kg to 0.0568 mg/kg, Pb was 0.1755 mg/kg to 0.712 mg/kg, and Hg was 0.001 mg/kg to 0.002 mg/kg. It was found that the concentration of heavy metals in liquid types herbal medicines was relatively lower than globular and granular types. It is required to treat, manufacture and manage herbal medicines for safety.

수용성 EPCR에 의한 활성화된 단백질 C의 항염증 작용에 관한 연구

배종섭 ( Jong Sup Bae ),박문기 ( Moon Ki Park ),박상욱 ( Sang Wook Park ) 한국화학공학회 2009 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.47 No.4

쑥부쟁이 추출물의 아세틸콜린에스테라제 저해 및 항산화 활성

배종섭 ( Jong Sup Bae ),김태훈 ( Tae Hoon Kim ) 대한본초학회 2009 大韓本草學會誌 Vol.24 No.4

Objectives: To evaluate the radical scavenging and acetylcholinesterase (AChE) inhibitory activities of the ethylacetate (EtOAc)-soluble portion of a methanolic extract of Aster yomena, three different assay systems were performed. Methods: The antioxidant activity of A. yomena extract was tested as its capacity to scavenging free radicals of DPPH and ABTS+, which has been widely used to evaluate the antioxidant activity of natural products from plant sources. AChE inhibitory activity was tested against mouse brain AChE by spectrophotometric method of Ellman using ELISA microplate reader. Results: The methanolic extract of A. yomena was fractionated and the EtOAc-soluble portion showed significant AChE inhibitory and free radical scavenging effects. Also the EtOAc-soluble portion revealed the highest phenolic contents as compared to the other extracts. Conclusions: These results indicate that phenolic compounds may be important constituents that give rise to the anti-AChE and antioxidative activities of A. yomena extract. Further phytochemical studies on this plant, for nutraceutical or pharmaceutical application, are warranted.

오배자 추출물의 Acetylcholinesterase 저해 및 항산화 활성 평가

배종섭 ( Jong Sup Bae ),이현식 ( Hyun Shik Lee ),이하영 ( Ha Yeong Lee ),유병혁 ( Byung Hyuk Yoo ),김태완 ( Tae Wan Kim ),김용한 ( Yong Han Kim ),김태훈 ( Tae Hoon Kim ) 한국식품저장유통학회(구 한국농산물저장유통학회) 2012 한국식품저장유통학회지 Vol.19 No.5

Antioxidant capacity and acetylcholinesterase (AChE) inhibitory activity of the aqueous methanolic extract of Rhus javanica were investigated in vitro. The antioxidant properties was measured by radical scavenging assays using DPPH and ABTS+ radicals. The AChE inhibitory efficacy of R. javanica was tested by Ellman`s assay and the total phenolic content was determined using a spectrophotometric method. All tested samples showed a dose-dependent AChE inhibitory and radical scavenging activities. In particularly, ethyl acetate (EtOAc)-soluble portion from the methanolic extract of R. javanica showed significantly higher inhibitory activity than other organic solvent soluble-portions in an AChE and radical scavenging assay systems. These results suggest that R. javanica may be possess potential benefits which might be useful in development of antioxidant and anti-alzheimer`s disease ingredient.

엑스과립과 환으로 만들어진 한방생약제제의 aflatoxin B1 연구

배종섭 ( Jong Sup Bae ),김용웅 ( Yong Ung Kim ),박문기 ( Moon Ki Park ) 한국환경과학회 2010 한국환경과학회지 Vol.19 No.2

생강 추출물의 pancreatic Lipase 저해 및 항산화 활성

배종섭 ( Jong Sup Bae ),김태훈 ( Tae Hoon Kim ) 한국식품저장유통학회(구 한국농산물저장유통학회) 2011 한국식품저장유통학회지 Vol.18 No.3

Ginger (Zingiber officinale) is a well-known herb that is widely consumed as spice for the flavoring of foods. As part of our continuing search for bioactive materials, the in vitro pancreatic lipase inhibition and antioxidant properties of an aqueous ethanolic extract of Z. officinale were investigated. The total phenolic content was determined using a spectrophotometric method. The antioxidant efficacies of the extract was studied with radical scavenging assays using DPPH and ABTS+ radicals. Further more, the antiobesity effect of the extract was evaluated by porcine pancreatic lipase assay. In particularly, the pancreatic lipase inhibitory activity of the ethyl acetate (EtOAc)-soluble portion from Z. officinale was significantly higher than that of the other solvent-soluble portions. The results suggest that Z. officinale may have therapeutic potential that may be useful in development of an anti-obesity agent or its precursors.

혈관내피세포에서 트롬빈이 TNF-α에 의해 유도되는 IL-6에 미치는 영향

배종섭(Jong-Sup Bae),박문기(Moon-Ki Park) 한국생물공학회 2010 KSBB Journal Vol.25 No.1

본 논문에서는 혈관내피세포에서 저농도의 트롬빈이 TNF-α가 NF-kB의 활성화를 통해 생성되는 IL-6의 생성량에 미치는 영향을 관찰하였다. TNF-α는 혈관내피세포에서 NF-kB의 활성화를 통해 염증을 유발시킨다는 것은 잘 알려진 사실이다. 이 논문에서는 TNF-α가 매개하는 염증작용에서 저농도의 트롬빈은 TNF-α가 생성시키는 IL-6의 생성량을 감소시켰고, 여기에는 트롬빈의 수용체인 PAR-1이 작용 하다는 것을 확인하였다. 뿐만 아니라, 세포내의 PI3-Kinase 역시 저농도 트롬빈이 관여한다는 것을 확인하였다. 이것은 저농도의 트롬빈이 수용체인 PAR-1을 활성화시키고, 활성화된 PAR-1은 PI3-Kinase의 활성화을 통해 항염증작용을 보여준다는 것을 의미한다. 이 결과는 향후 중증 패혈증 및 각종 염증질환을 치료할 수 있는 신약개발에 있어 중요한 단서를 제공하고 혈관내피세포에서 아직 명확하게 밝혀지지 않은 트롬빈의 염증작용 및 항염증작용의 기전을 밝히는 데 좋은 정보를 제공할 것이다. Here, we evaluated the effect of thrombin on the interleukin-6 production induced by tumor-necrosis-factor-α in endothelial cells. It is well known that tumor-necrosis-factor-α mediates inflammatory responses by activation of nuclear factor-kappa-B in endothelial cells. Here, we showed that lower concentration of thrombin decreased the production of interleukin-6 induced by tumor-necrosis-factor-α and this inhibitory effect of thrombin on interleukin-6 production was mediated by interacting with protease-activated-receptor-1. In addition, phosphoinositide-3-kinase was also involved the anti-inflammatory responses by lower concentration of thrombin in endothelial cells. These results suggested that lower concentration of thrombin mediated anti-inflammatory responses by interacting with protease-activated-receptor-1 on the cell membrane and phosphoinositide-3-kinase in the cell. These findings will provide the important evidence in the development of new medicine for the treatment of severe sepsis and inflammatory diseases and good clue for understanding unknown mechanisms by which thrombin showed the pro-inflammatory or anti-inflammatory activities in endothelial cells.

Hepatic Protective Effects of Jujuboside B through the Modulation of Inflammatory Pathways

이인철,배종섭 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.3

Jujubisode B (JB) is a product extracted from the seeds of Zizyphi Spinosi Semen with the pharmacological activities such as antianxiety, anti-inflammation, and antiplatelet aggregation. In this study, we evaluated the effect of JB on liver failure induced by lipopolysaccharide (LPS) and the underlying mechanisms. We established a hepatic injury model by LPS administration. Methyl Thiazolyl Tetrazolium (MTT) assay was used to detect the cellular viability effect of JB on cell proliferation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, and histological analysis were used to evaluate the hepatic protective effect of JB. Western blot or enzymelinked immunosorbent assay (ELISA) was used to detect protein expression. JB suppressed LPS-induced mice lethality and serum levels of liver damage markers without affecting the survival rate. Additionally, JB reduced inflammatory cytokines and toll-like receptor 4 (TLR4) protein expression, which were increased by LPS. LPS induced hepatic injury was also suppressed by JB treatment. The mechanism of this hepatoprotective effect of JB is mediated by the inhibiting the increased MyD88-dependent signaling, mitogen-activated protein kinase activation, and expression of inflammatory genes hepatic failure by LPS. These results suggest that JB is a potential therapeutic agent for liver disease through the inhibition of the TLR4 signaling pathway.