• Journal of Microbiology and Biotechnology
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• 제29권11호
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• pp.1707-1716
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• 2019

The development of new antimicrobial agents is essential for the effective treatment of diseases such as sepsis. We previously developed a new short peptide, Pap12-6, using the 12 N-terminal residues of papiliocin, which showed potent and effective antimicrobial activity against multidrug-resistant Gram-negative bacteria. Here, we investigated the antimicrobial mechanism of Pap12-6 and a newly designed peptide, Pap12-7, in which the 12^th Trp residue of Pap12-6 was replaced with Val to develop a potent peptide with high bacterial selectivity and a different antibacterial mechanism. Both peptides showed high antimicrobial activity against Gram-negative bacteria, including multidrug-resistant Gram-negative bacteria. In addition, the two peptides showed similar anti-inflammatory activity against lipopolysaccharide-stimulated RAW 264.7 cells, but Pap12-7 showed very low toxicities against sheep red blood cells and mammalian cells compared to that showed by Pap12-6. A calcein dye leakage assay, membrane depolarization, and confocal microscopy observations revealed that the two peptides with one single amino acid change have different mechanisms of antibacterial action: Pap12-6 directly targets the bacterial cell membrane, whereas Pap12-7 appears to penetrate the bacterial cell membrane and exert its activities in the cell. The therapeutic efficacy of Pap12-7 was further examined in a mouse model of sepsis, which increased the survival rate of septic mice. For the first time, we showed that both peptides showed anti-septic activity by reducing the infiltration of neutrophils and the production of inflammatory factors. Overall, these results indicate Pap12-7 as a novel non-toxic peptide with potent antibacterial and anti-septic activities via penetrating the cell membrane.

• 한국약용작물학회지
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• 제20권5호
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• pp.381-386
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• 2012

Eucommia ulmoides OLIVER (EU) is a traditional Korean herbal used for the treatment of rheumatoid arthritis (RA). In the present study, the molecular pharmacology basis of its anti-inflammatory effect is revealed in this work, EU was studied in lipopolysaccharide (LPS)-activated macrophage cells (RAW 264.7) as an established inflammation model. After activation, nitric oxide (NO) production and iNOS mRNA were measured by using a colorimetric assay (Griess reagent), and reverse transcription polymerase chain reaction (RT-PCR), respectively. The change in the content of $PGE_2$, $TNF{\alpha}$, and IL-6 was concurrently monitored by ELISA. In results, we found that in the concentration range without showing cytotoxicity, EU produced a remarkable anti-inflammatory effect and showed a dose-dependent inhibition of LPSinduced NO production. Compared with indomethacin, EU has more potency and a specific action of NO inhibition, $PGE_2$, IL-6, and TNF-${\alpha}$ inhibition. These results suggest that EU may be a suitable herbal medicine to yield the greatest anti-inflammatory activity for food additives and medicine.

• 생약학회지
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• 제36권4호통권143호
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• pp.311-317
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• 2005

GCSB-5 is a purified extract from a mixture of 6 Oriental herbs (Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen, and Eucommiae Cortex) that have been widely used for the treatment of inflammatory diseases in the East Asia. The aim of this study was to investigate the anti-inflammatory potential of GCSB-5. The animals used in this study were administered either vehicle or GCSB-5 (30, 100, 300, and 600 mg/kg) orally. The GCSB-5 significantly inhibited the increased of acetic acid-induced vascular permeability (30.9%-34.2% inhibition at 30-300 mg/kg). The swelling of the rat's hind paw induced by carrageenan was significantly inhibited by GCSB-5 in doses of 100, 300, and 600 mg/kg. Maximal inhibition (50.9%) was obtained with GCSB-5 at dose of 300 mg/kg. However, it did not have any anti-inflammatory action in the rheumatoid arthritis induced by Freund's complete adjuvant or in the granuloma induced by carrageenan. Our finding suggest that GCSB-5 has a anti-inflammatory activity.

• 한국약용작물학회지
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• 제12권1호
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• pp.47-52
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• 2004

패장 (Patrinia villosa Jussieu, Valerianaceae)의 뿌리는 한국에서 오래전부터 감염성 질환의 치료에 사용되어왔다. 본 논문에서는 패장근의 물 추출물 엑스 (PVWX)가 proteinase 활성수용체-2 (PAR2)에 의하여 유발된 흰쥐 발바닥 부종에 대한 항염증효과를 연구하였다. 발바닥 부종은 trypsin이나 $trans-cinnamoyl-LIGRLO-NH_2\;(tc-NH_2)$를 쥐의 발바닥에 주사하여 유발시켰다. PVWX (10, 50, 100 and 200 mg/kg)는 부종유발 1시간 전에 경구로 투여하였다 50, 100 및 200 mg/kg의 PVWX 투여시 부종의 부피와 혈관투과성의 변화에 유의성 있는 억제를 나타냈다. PVWX (100 mg/kg)은 발바닥 조직에서 PAR2 작동약으로 유발된 myeloperoxidase (MPO)활성을 유의성 있게 억제하였다. 이러한 결과들은 PVWX가 PAR2로 유발된 쥐의 발바닥 부종에서 항염증효과가 있음을 보여준다.

• 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.

• Archives of Pharmacal Research
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• 제28권12호
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• pp.1350-1357
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• 2005

Nuclear factor kappa B (NF-$\kappa$B) regulates the expression of multiple cytokines, chemokines, and cell adhesion molecules that are involved in the pathogenesis of asthma. We investigated the anti-asthmatic effects and the mechanism of action of DA-9201, an extract of the black rice, in a mouse model of asthma. Mice immunized with ovalbumin (OVA) were administered with DA-9201 (30, 100 or 300 mg/kg) or dexamethasone (DEXA, 3 mg/kg) for 2 weeks and challenged with aerosolized OVA during the last 3 days. Anti-asthmatic effects were assessed by means of enhanced pauses, level of total lgE and Th2 cytokines in plasma or bronchoalveolar lavage fluid (BALF), the percentage of eosinophils in BALF, and histopathological examination. The expression of NF-$\kappa$B in nuclear and cytoplasmic fraction and its DNA-binding activity in lung tissues were analyzed by means of Western blotting and electrophoretic gel mobility shift assay (EMSA), respectively. DA-9201 significantly reduced airway hyperrespon-siveness (AHR), total lgE level in plasma and BALF, IL-4, IL-5, and IL-13 levels in BALF, and the percentage of eosinophils in BALF. Tissue inflammation was significantly improved by DA­9201 treatment. In addition, DA-9201 dramatically suppressed the expression of NF-$\kappa$B and its DNA-binding activity. These results suggest that DA-9201 may be useful for the treatment of asthma and its efficacy is related to suppression of NF-$\kappa$B pathway.

• 대한약침학회지
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• 제22권1호
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• pp.16-27
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• 2019

Generative and vegetative parts of the cactuses have had a long-lasting position in folk medicine and their effects could partly be confirmed in scientific experiments. Nowadays, the cactus, fruits, and cladodes are the focus of many studies because of their desirable properties. Therefore, the summarized reports of valuable properties of medicinal plants may be a good way to familiarize researches with a new source of drugs with lower side effects and higher efficacy. Opuntia dillenii, a well-known member of the Cactaceae family, is used as a medicinal plant in various countries and grows in the desert, semi-desert, tropical and sub-tropical areas. It shows diverse pharmacological activities such as: antioxidant, anti-inflammatory, anti-tumor, neuroprotective, hepatoprotective, hypotensive etc. OD fruit also possesses valuable constitutes for instance: betalains, ascorbic acid, total phenol, protein as well as essential elements which suggest the significant potential of this plant as a complementary therapy against several pathological conditions. This review describes experimental evidence about pharmacological and therapeutic potential of OD in order to give the basis of its application in the prevention and treatment of some chronic diseases. More studies on OD can help better understanding of its pharmacological mechanism of action to explain its traditional uses and to identify its potential new therapeutic applications.

• 대한본초학회지
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• 제28권5호
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• pp.21-28
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• 2013

Objectives : The aim of this study was to investigate the neuroprotective effects and mechanisms of Cyperi Rhizoma extracts (CRE) using in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the neuroprotective effect of CRE against 1-methyl-4-phenylpyridinium (MPP+) toxicity using tyrosine hydroxylase immunohistochemistry (IHC) in primary rat mesencephalic dopaminergic neurons. In addition, the effect of CRE was evaluated in mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For evaluations, C57bl/6 mice were orally treated with CRE 50 mg/kg for 5 days and were injected intraperitoneally with MPTP (20 mg/kg) at 2 h intervals on the last day. To identify the CRE affects on MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum of mice, the behavioral tests and IHC analysis were carried out. Also, we conducted nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) assay in dopaminergic neurons and IHC using glial markers in SNpc of mice to assess the anti-inflammation effects. Results : In primary mesencephalic culture system, CRE protected dopaminergic cells against $10{\mu}M$ MPP+-induced toxicity at 0.2 and $1.0{\mu}g/mL$. In the behavior tests, CRE treated group showed improved motor deteriorations than those in the MPTP only treated group. CRE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, CRE inhibited productions of NO and TNF-${\alpha}$ in dopaminergic culture system and activation of astrocyte and microglia in SNpc of the mice. Conclusion : We concluded that CRE shows anti-parkinsonian effect by protecting dopaminergic neurons against MPP+/MPTP toxicities through anti-inflammatory actions.

• The Korean Journal of Pain
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• 제37권2호
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• pp.151-163
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• 2024

Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalin-induced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX-2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenan-triggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF-κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

• 한방안이비인후피부과학회지
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• 제22권2호
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• pp.92-103
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• 2009

Objectives : The present study was examined to evaluate the anti-inflammatory effects of the Humulus japonicus MeOH extracts (HJE) in vivo. Methods : The effects of HJE on anti-inflammation were measured by production of NO, iNOS (inducible Nitric Oxide Synthase), COX-2, I$\kappa$B$\alpha$ (Inhibitor kappa B alpha), NF$\kappa$B (Nuclear Factor kappa B), TNF-$\alpha$ (Tumor Necrosis Factor-alpha) and IL-1$\beta$ (Interleukin-1$\beta$), IL-6 in Raw 264.7 macrophage cells stimulated with LPS. Results : 1. All concentrations of HJE(0.03 and 0.10 mg/ml) had no significant cytotoxicity in Raw 264.7 cell during the entire experimental period. 2. The level of NO and iNOS in culture medium was dramatically increased by LPS application. However, these increases were dose-dependently(0.03 and 0.10 mg/ml) attenuated by treatment with HJE. 3. HJE extract reduced PGE2 levels in a dose-dependent manner as a consequence of inhibition of COX-2 protein expression in Raw 264.7 macrophage cells stimulated with LPS. 4. 0.10 mg/ml HJE significantly inhibited the phosphorylation of I$\kappa$B$\alpha$ indicating the suppression of NF-$\kappa$B pathway in Raw 264.7 macrophage cells stimulated with LPS. 5. 0.10 mg/ml HJE significantly inhibited the production of TNF-$\alpha$ in Raw 264.7 macrophage cells stimulated with LPS. 6. All concentrations of HJE significantly inhibited the production of IL-1$\beta$, IL-6 in Raw 264.7 macrophage cells stimulated with LPS. Conclusions : These results provide evidences that therapeutic effect of HJE on heat syndrome, especially due to the acute inflammation, are partly due to the reduction of some of inflammatory factors by inhibiting iNOS and COX-2 through the suppression of p-I$\kappa$B$\alpha$. Moreover, it suggests that the mechanism of action of HJE comes from the suppression of inflammatory mediators, such as NO, PGE$_2$ and pro-inflammatory cytokines.