• Biomolecules & Therapeutics
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• 제21권1호
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• pp.66-71
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• 2013

Broussonetia papyrifera and Lonicera japonica have long been used in the treatment of inflammatory disorders in Chinese medicine, especially respiratory inflammation. Previously, a new phytoformula (BL) containing B. papyrifera and L. japonica was found to exert strong anti-inflammatory activity against several animal models of inflammation, especially against an animal model of acute bronchitis. In the present investigation, the effects of BL on animal models of septic inflammation and chronic bronchitis are examined. Against lipopolysaccharide (LPS)-induced septic inflammation in mice, BL (200-400 mg/kg) reduced the induction of some important proinflammatory cytokines. At 1 h after LPS treatment, BL was found to considerably inhibit TNF-${\alpha}$ production when measured by cytokine array. At 3 h after LPS treatment, BL inhibited the induction of several proinflammatory cytokines, including IFN-${\gamma}$ and IL-$1{\beta}$, although dexamethasone, which was used as a reference, showed a higher inhibitory action on these biomarkers. Against chronic bronchitis induced by LPS/elastase instillation in rats for 4 weeks, BL (200-400 mg/kg/day) significantly inhibited cell recruitment in bronchoalveolar lavage fluid. Furthermore, BL considerably reduced lung injury, as revealed by histological observation. Taken together, these results indicate that BL may have a potential to treat systemic septic inflammation as well as chronic bronchitis.

• 약학회지
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• 제51권6호
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• pp.476-481
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• 2007

A polymorphic fungus, Candida albicans, causes various forms of infections such as disseminated candidiasis and vaginitis. Recent reports indicate that the fungus is a main etiological agent for the arthritis. In search of new sources for treatment of the fungal arthritis, we examined $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) against C. albicans-caused septic arthritis. The compound is isolated from Glycyrrhizae Radix that is known to have various immunomodulating activities and is one of the most popular herbal medicines. For induction of animal model of a septic arthritis, mice were given an emulsion form of C. albicans cell wall mixed with Complete Freund's Adjuvant (CFA) via footpad-injection. To determine prophylactic and therapeutic effects, the component was given to the animals before or after the induction of the arthritis, respectively. Data showed that intraperitoneal administration of $18{\beta}$-GA resulted in reduction of the inflammation, indicating the component had both prophylactic and therapeutic activities. For investigation of mechanism of the $18{\beta}$-GA, inhibitory effects on NO (nitiric oxide) and on T-lymphocyte proliferation were determined. Results demonstrated that $18{\beta}$-GA suppressed NO production from LPS (lipopolysaccharide)-treated macrophages and also inhibited proliferation of Con A (concanavalin A)activated T-cells. Taken together, $18{\beta}$-GA, a pentacyclic triterpene, has anti-arthritic activity against C. albicans-caused septic arthritis, possibly by blocking NO production and T-cell suppression.

• The Korean Journal of Physiology and Pharmacology
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• 제26권6호
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• pp.511-518
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• 2022

Sepsis-associated myocardial injury, an invertible myocardial depression, is a common complication of sepsis. Neogambogic acid is an active compound in garcinia and exerts anthelmintic, anti-inflammatory, and detoxification properties. The role of neogambogic acid in sepsis-associated myocardial injury was assessed. Firstly, mice were pretreated with neogambogic acid and then subjected to lipopolysaccharide treatment to induce sepsis. Results showed that lipopolysaccharide treatment induced up-regulation of biomarkers involved in cardiac injury, including lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and troponin I (cTnI). However, pretreatment with neogambogic acid reduced levels of LDH, CK-MB, and cTnI, and ameliorated histopathological changes in the heart tissues of septic mice. Secondly, neogambogic acid also improved cardiac function in septic mice through reduction in left ventricular end-diastolic pressure, and enhancement of ejection fraction, fractional shortening, and left ventricular systolic mean pressure. Moreover, neogambogic acid suppressed cardiac apoptosis and inflammation in septic mice and reduced cardiac fibrosis. Lastly, protein expression of p-p38, p-JNK, and p-NF-κB in septic mice was decreased by neogambogic acid. In conclusion, neogambogic acid exerted anti-apoptotic, anti-fibrotic, and anti-inflammatory effects in septic mice through the inactivation of MAPK/NF-κB pathway.

• 약학회지
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• 제45권1호
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• pp.16-22
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• 2001

Novel yakuchinone derivatives have been designed, synthesized and evaluated their inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages. From this study, some enone compounds have been found to be highly active in the assay. In view of the importance of NO in septic shock and inflammation, these compounds may be useful candidates for the development of new drug to treat endotoxemia and inflammation accompanying overproduction of NO.

• BMB Reports
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• 제48권6호
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• pp.336-341
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• 2015

Sepsis is a life-threatening, infectious, systemic inflammatory disease. In this study, we investigated the therapeutic effect of α-cubebenoate, a novel compound isolated from Schisandra chinensis against polymicrobial sepsis in a cecal ligation and puncture (CLP) experimental model. Administration of α-cubebenoate strongly enhanced survival in the CLP model. α-cubebenoate administration also markedly blocked CLP-induced lung inflammation and increased bactericidal activity by enhancing phagocytic activity and hydrogen peroxide generation in mouse bone marrow-derived macrophages and neutrophils. Expression of two important inflammatory cytokines, IL-1 and IL-6, was strongly increased in the CLP model, and this was dramatically blocked by α-cubebenoate. Lymphocyte apoptosis and caspase-3 activation, which are associated with immune paralysis during sepsis, were markedly attenuated by α-cubebenoate. Taken together, our findings indicate that α-cubebenoate, a natural compound isolated from Schisandra chinensis, is a powerful potential anti-septic agent. [BMB Reports 2015; 48(6): 336-341]

• 약학회지
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• 제56권1호
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• pp.20-25
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• 2012

In Northeast Asia, Paeoniae Radix has been used in treatments of inflammation-causing diseases such as arthritis for many centuries. Paeoniflorin, one of the principle bioactive monoterpene glucosides from the paeony root, is reported to be mostly responsible for the effectiveness of the treatments. However, the anti-inflammatory effect of a monoterpene, paeoniflorigenone (PFG) which partially has the moiety of paeoniflorin minus a glucose structure is unknown. Thus, the aim of this work was to investigate anti-inflammatory activity of PFG. For the investigation, PFG activity on the NO (nitric oxide) production from LPS-stimulated macrophages, and the anti-inflammatory effect was tested in the animal model of septic arthritis caused by Candida albicans, a major etiological agent for septic arthritis. For induction of the arthritis, mice were administered with an emulsion of C. albicans cell wall (CACW) mixed with Complete Freund's Adjuvant (CFA) via footpad-injection (Day 0); PFG at a dose of 0.5 or 1 mg/mouse (25 or 50 mg/kg of body-weight) was given to the animals on Day 3, 6, and 9; footpads were scored for arthritis. Moreover, the PFG effect on proliferation of T-lymphocyte that causes aggravation of arthritis was additionally tested. Data resulting from those tests showed that PFG inhibited the NO production from the stimulated macrophage in a dose dependent manner (P<0.05), indicating that PFG is an anti-inflammatory. To confirm the in-vitro results, anti-inflammatory activity of PFG was determined against C. albicans-caused septic arthritis. Data showed that PFG-treatment reduced footpad-swelling which indicates that PFG has anti-arthritic effect (P<0.05), which is therapeutic. The anti-arthritic effect appeared to be mediated by PFG suppression of T-cell proliferation. Ultimately, PFG, a monoterpene component, has anti-inflammatory activity analogous to paeoniflorin. The anti-inflammatory activity treats the septic arthritis due to a pathogenic fungus C. albicans.

• Tuberculosis and Respiratory Diseases
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• 제47권4호
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• pp.451-459
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• 1999

배 경 : 패혈증에서 과도한 활성산소종의 생성은 급성 폐손상의 병리 기전에 중요한 역할을 한다. Catalase 및 MnSOD 등의 항산화 단백은 패혈증 환자의 혈청내 증가하며 급성호흡곤란증후군의 발생 예측 인자 및 패혈증의 예후 인자로 알려져 있다. Peroxiredoxin(Prx) 는 최근 독특하고 중요한 세포내 항산화 단백으로 알려져 있다. 본 연구는 대식세포인 mouse monocyte-macrophages(RAW 264.7) 세포에 산화 스트레스 및 내독소 처리후 Prx I 및 Prx II의 발현 평가하고 패혈증 동물 모델에서 복강세척액 및 기관지폐포세척액내 Prx I, Prx II 및 Trx의 양을 측정하였다. 방 법 : Prx I, Prx II 및 Trx에 대한 특이 항체를 이용하여 immunoblot 분석으로 호중구, 대식세포 및 적혈구에 이들의 분포를 평가하였다. Mouse monocyte-macrophages 세포에 $5\;{\mu}M$ menadione 및 1 mg/ml lipopolysaccharide(LPS) 을 처치하여 Prx I 및 Prx II의 발현을 평가하였으며 6 mg/Kg LPS를 복강내 투여하여 유발한 복강내 패혈증 동물의 복강세척액내 Prx I, Prx II 및 Trx의 양을 측정하였으며 복강내 패혈증 동물 및 5 mg/Kg LPS를 정맥내 투여하여 유발한 정맥내 패혈증 동물에서 기관지폐포세척액내 Prx I, Prx II 및 Trx을 측정하였으며 폐장의 염증 정도와 비교하였다. 결 과 : Prx I 및 Prx II의 분포는 호중구, 폐포대식세포 및 적혈구에서 서로 다른 양상을 보였다. Mouse monocyte-macrophages 세포에 $5\;{\mu}M$ menadione 및 $1\;{\mu}g/ml$ lipopolysaccharide을 처치하였을 때 Prx I 발현은 증가하였으나 Prx II 발현은 변화하지 않았다. 복강내 패혈증 동물에서 복강세척액내 Prx I, Prx II 및 Trx의 양은 증가하였으나 복강내 패혈증 및 정맥내 패혈증 동물에서 기관지폐포세척액내 폐장 염증 정도와 관계없이 Prx I, Prx II 및 Trx의 양은 증가하지 않았다. 결 론 : 세포내 항산화 단백으로서 mouse monocyte-macrophages 세포에서 Prx I의 발현은 산화 스트레스 및 내독소 처치후 증가한다. Prx I, Prx II 및 Trx양은 패혈증 동물 모델에서 국소 염증 부위에서 증가하나 손상된 폐장에서는 증가하지 않는다.

• Clinical and Experimental Pediatrics
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• 제46권8호
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• pp.777-783
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• 2003

목 적 : E. coli 패혈성 폐가 유도된 신생자돈에서 Nitric oxide(NO) 가스 흡입요법이 혈역학, 가스교환 및 폐 염증 소견에 미치는 영향을 알아보고자 본 연구를 실시하였다. 방 법 : 23마리의 신생자돈에서 도관 삽입과 기도 삽관을 시행하여 기계적 가스 인공환기를 시키면서 CON군(n=6)은 생리적 식염수 5 mL, PCON(n=9) 및 PNO(n=8) 군은 Escherichia coli strain $69{\times}10^9cfu$(10 mL)를 투여한 후 time-cycled pressure-limited 인공환기기로 PIP 30 $cmH_2O$, 호흡수 분당 30회, $FiO_2$ 1.0, PEEP 4 $cmH_2O$의 설정에서 6시간 동안 유지하였다. PNO군에서는 NO 10 ppm을 E. coli 투여 후부터 실험 종료 시까지 기도 내로 투여하였다. 모든 신생자돈에서 가스교환, 혈역학, 폐기능 지수들을 1시간 간격으로 측정하였고 실험 종료후 폐 조직을 얻어 염증반응 정도 지표인 myeloperoxidase 활성을 측정하였다. 결 과 : E. coli가 기도 내로 투여된 PCON 및 PNO군 모두에서 실험 종료시 E. coli 패혈증이 발생하였다. PCON군에서는 시간에 따라 진행되는 폐동맥 고혈압, 저산소혈증, 고탄산혈증, 및 폐 내 단락과 폐 내 사강의 비율의 증가를 보였고 대조군에서는 실험 종료시까지 의미 있는 변화를 보이지 않았다. NO가 투여된 PNO군에서 폐동맥 고혈압이 감소되지 않았으나 폐 내 단락의 의미 있는 개선과 폐 내 사강 비율 증가의 일부 감소에 기인한 저산소혈증 진행의 완화가 관찰되었다. 폐 염증정도의 지표인 폐조직의 myeloperoxidase 활성도는 PCON군에서 CON군에 비해 의미 있게 증가되었으며 이는 PNO군에서 의미 있게 완화되었다. 결 론 : E. coli 패혈성 폐가 유도된 신생자돈에서 NO 가스 흡입요법은 폐 내 단락 개선을 통해 산소화를 향상시켰으며 또한 폐 염증 소견을 완화시켰다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.203.2-204
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• 2003

Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidate for the treatment of inflammatory diseases accompanied by the overproduction of NO. We prepared alcoholic extracts of woody plants and screened the inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages after the treatment of these extracts. (omitted)

• 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.