• BMB Reports
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• 제46권7호
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• pp.352-357
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• 2013

Atherosclerosis, which manifests as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic inflammatory disease of the arterial wall. Prunella vulgaris, a perennial herb with a worldwide distribution, has been used as a traditional medicine in inflammatory disease. Here, we investigated the effects of P. vulgaris ethanol extract on TNF-${\alpha}$-induced inflammatory responses in human aortic smooth muscle cells (HASMCs). We found that P. vulgaris ethanol extract inhibited adhesion of monocyte/macrophage-like THP-1 cells to activated HASMCs. It also decreased expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and ROS, No production in TNF-${\alpha}$-induced HASMCs and reduced NF-${\kappa}B$ activation. Furthermore, P. vulgaris extract suppressed TNF-${\alpha}$-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). These results demonstrate that P. vulgaris possesses anti-inflammatory properties and can regulate TNF-${\alpha}$-induced expression of adhesion molecules by inhibiting the p38 MAPK/ERK signaling pathway.

• Nutritional Sciences
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• 제8권3호
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• pp.153-158
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• 2005

Numerous natural herbal compounds have been reported to inhibit adhesion and migration of leukocytes to the site of inflammation Licorice extracts, which have been widely used in traditional Chinese medicinal preparation, possess various pharmacological effects. Isoliquiritigenin, a biogenetic precursor of flavonoids with various pharmacological effects, is a natural pigment present in licorice. We attempted to explore whether licorice extracts and isoliquiritigenin mitigate monocyte adhesion to tumor necrosis factor-$\alpha$ (TNF-$\alpha$)-activated human umbilical vein endothelial cells (HUVEC). In addition, it was tested whether the inhibition of monocyte adhesion to the activated HUVEC accompanied a reduction in vascular cell adhesion molecule-l expression(VCAM-l). Dry-roasted licorice extracts in methylene chloride but not in ethanol markedly interfered with THP-l monocyte adhesion to INF-$\alpha$-activated endothelial cells. licochalcone A compound isolated from licorice extract in methylene chloride appeared to modestly inhibit the interaction of THP-l monocytes and activated endothelium. In addition, isoliquiritigenin abolished the monocyte adhesion with attenuating VCAM-l protein expression on HUVEC induced by INF-$\alpha$. These results demonstrated that non-polar components from dry-roasted licorice extracts containing licochalcone A as well as isoliquiritigenin were active in blocking monocyte adhesion to cytokine-activated endothelimn, which appeared to be mediated most likely through the inhibition of VCAM-l expression on HUVEC. Therefore, licorice may hamper initial inflammatory events on the vascular endothelium involving induction of endothelial cell adhesion molecules.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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• pp.133-137
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• 2013

Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-${\kappa}B$) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaB${\alpha}$ ($I{\kappa}B{\alpha}$) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of $I{\kappa}B{\alpha}$ expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.231-236
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• 2008

Heparin is a well-known anticoagulant widely used in various clinical settings. Interestingly, recent studies have indicated that heparin also has anti-inflammatory effects on neuroinflammation-related diseases, such as Alzheimer's disease and meningitis. However, the underlying mechanism of its actions remains unclear. In the present study, we examined the anti-inflammatory mechanism of heparin in cultured cerebral endothelial cells (CECs), and found that heparin inhibited the tumor necrosis factor $\alpha$ ($TNF{\alpha}$)-induced and nuclear factor kappa B (NF-${\kappa}B$)-dependent expression of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), which are crucial for inflammatory responses. Heparin selectively interfered with NF-${\kappa}B$ DNA-binding activity in the nucleus, which is stimulated by $TNF{\alpha}$. In addition, non-anticoagulant 2,3-O desulfated heparin (ODS) prevented NF-${\kappa}B$ activation by $TNF{\alpha}$, suggesting that the anti-inflammatory mechanism of heparin action in CECs lies in heparin's ability to inhibit the expression of cell adhesion molecules, as opposed to its anticoagulant actions.

• Tuberculosis and Respiratory Diseases
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• 제40권2호
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• pp.185-191
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• 1993

연구배경 : ICAM-1은 90 kD의 당단백으로서 ${\beta}_2$ integrin과 관계를 가지며, 특발성 폐섬유증의 병인론에 있어서 ICAM-1의 발현과 밀접한 관계가 있다고 보고되고 있다. 특발성 폐섬유종에 있어서 ICAM-1의 발현 정도는 상향조절된다. 특발성 폐섬유증에 있어서 ICAM-1의 발현 양상에 대한 보고는 드물다. 방법 : 본 연구는 특발성 폐섬유증에 있어서 ICAM-1의 발현 양상을 연구하고자 개흉폐생검으로 채취된 특발성 간질성 폐섬유증 3예의 6절편과 폐절제시 채취한 3예의 정상조직을 연구재료로 하여 ICAM-1의 단세포군항체를 이용하여 연역조직화학적 검색을 실시하였다. 결과 : ICAM-1은 3예의 정상조직의 기관지 상피세포나 폐포 세포에서는 발현되지 않았다. 3예의 특발성 폐섬유증 6절편 중 5절편에서 폐포벽의 간질성 섬유아 세포들에서 발현되었고, 1절편에서는 증식된 폐포내 폐포세포에서 발현되었다. 그 정도는 비균질적인 양상을 보였다. 3예의 6절편 중 5절편에서 강한 발현을 1절편에서는 약한 발현정도를 나타냈다. 결론 : 위의 연구 결과를 종합하여 보면, ICAM-1의 발현 증가는 특발성 폐섬유증의 병인과 상당한 관련이 있음을 암시해 주는 것으로 추정된다.

• Biomolecules & Therapeutics
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• 제12권3호
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• pp.133-137
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• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum (Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CCl4), D-galactosamine (DGal) and Bacillus Calmette-Guerin (BCG) plus lipopolysaccharides (LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts (AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-l) induced by ox-LDL and AGE.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2004년도 Annual Meeting of KSAP : New Drug Development from Natural Products
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• pp.61-77
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• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum(Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CC14), D-galactosamine (DGal) and Bacillus Calmette-Guerin(BCG) plus lipopolysaccharides(LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts(AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-l (ICAM-1) and vascular cell adhesion molecule-l (VCAM-1) induced by ox-LDL and AGE.

• Journal of Ginseng Research
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• 제33권4호
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• pp.330-336
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• 2009

G-Rb1에 의한 단핵구 세포주인 U937 세포와 대식세포주인 RAW264.7 세포의 유착조절 능, 세포표면 단백질 발현율 및 세포모양 변화능 조절효과를 조사하여 다음과 같은 결론을 얻었다. 1. G-Rb1은 CD29항체 (MEM101A) 및 CD43 항체(161-46) 처리에 의해 유도된 세포-세포간 유착현상을 20%에서 35%까지 유의적으로 상승하였다. 2. G-Rb1은 fibronectin처리에 의해 유도된 U937 세포-fibronectin간 유착현상을 상승시켰다. 3. G-Rb1은 CD29 및 CD43의 세포표면 발현 수준을 유의적으로 증가시켰으나 CD82의 발현은 억제시켰다. 4. G-Rb1은 PMA에 의해 유도된 형태변화는 촉진경향을 반면에 LPS에 의한 변화는 억제경향을 나타내었다. 인삼의 주요사포닌 성분인 G-Rb1의 약리작용이 활발히 연구되고 있다. 특별히, 본 화합물이 갖는 면역증강 및 항암 효능은 인삼이 갖는 이들 효과를 대신하는 것으로 보고 되어져 있다. 그러나, 세포유착과정이 다양한 염증과정, 알러지 반응 및 암세포의 이동과 전이성 등에 관련이 있다는 관점에서 볼 때 본 연구결과는 이들 약물이 갖는 치료기전을 설명하기에는 충분하지 않는 것으로 판단된다. 오히려, 본 결과는 G-Rb1이 특정 농도 ($25-50\;{\mu}M$ 수준)에서 세포의 활성을 촉진할 수 있다는 가능성을 시사한다고 하겠다. 특별히, G-Rb1의 세포유착 촉진 기능에 관한 기전 이해를 위해, 이후, 세포유착 유도 신호전달 단백질의 활성을 포함한 다양한 분자적 수준에서의 추가적인 실험들을 진행하고 한다.

• Molecules and Cells
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• 제38권7호
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• pp.643-650
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• 2015

The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.

• The Korean Journal of Physiology and Pharmacology
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• 제10권4호
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• pp.217-222
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• 2006

Atherosclerosis is considered as a chronic inflammatory process. However, the nature of the oxidant signaling that regulates monocyte adhesion and its underlying mechanism is poorly understood. We investigated the role of reactive oxygen species on the vascular cell adhesion molecule-1 (VCAM-1) and monocyte adhesion in the cultured endothelial cells. $TNF-{\alpha}$ at a range of $1{\sim}30\;ng/ml$ induced VCAM-1 expression dose-dependently. BCECF-AM-labeled U937 cells firmly adhered on the surface of endothelial cells when the endothelial cells were incubated with $TNF-{\alpha}$ (15 ng/ml). Ten $\;{\mu}mol/L$ of SB203580, an inhibitor of p38 MAPK, significantly reduced $TNF-{\alpha}-induced$ VCAM-1 expression, compared to the JNK inhibitor ($40\;{\mu}mol/L$ of SP60015) or ERK inhibitor ($40\;{\mu}mol/L$ of U0126). Also, SB203580 significantly inhibited $TNF-{\alpha}-induced$ monocyte adhesion in HUVEC. Superoxide production was minimal in the basal condition, however, treatment of $TNF-{\alpha}$ induced superoxide production in the dihydroethidineloaded endothelial cells. Diphenyleneiodonium (DPI, $10\;{\mu}mol/L$), an inhibitor of NADPH oxidase, and rotenone $(1\;{\mu}mol/L)$, an inhibitor of mitochondrial complex I inhibited $TNF-{\alpha}-induced$ superoxide production, VCAM-1 expression and monocyte adhesion in the endothelial cells. Taken together, our data suggest that NADPH oxidase and mitochondrial ROS were involved in $TNF-{\alpha}-induced$ VCAM-1 and monocyte adhesion in the endothelial cells.