• 한국미생물·생명공학회지
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• 제44권2호
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• pp.218-226
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• 2016

헬리코박터 파이로리균은 인간의 위에 감염하여 위염, 위궤양, 심지어 위암을 포함한 다양한 위장 질환의 발생시키는 원인으로 알려져 있다. 이러한 헬리코박터균의 제균을 위해 항생제 치료법이 이용되고 있지만 이러한 항생제들에 대한 헬리코박터균의 내성 증가가 전세계적인 문제로 대두되고 있다. 보고들에 따르면, 천연물질인 plumbagin은 항균 및 항암 효과를 가지고 있는 것으로 알려져있다. 따라서 본 연구에서는 헬리코박터 표준균주(ATCC 49503)에 plumbagin을 처리한 후 항균효과를 확인하였으며, 세균의 성장 및 병원성과 관련된 다양한 물질들의 발현에 미치는 영향을 immunoblotting 및 RT-PCR 방법을 이용하여 조사하였다. plumbagin의 헬리코박터균 억제효과를 확인하기 위해 한천희석법과 액체배지희석법을 이용해 최소억제농도를 도출하였다. 위와 같은 Plumbagin에 의한 헬리코박터균의 억제기전을 이해하기 위하여 헬리코박터균에 plumbagin을 처리한 후 세균 의 증식과 관련된 물질들을 대상으로 RT-PCR을 수행한 결과 RNA polymerase subunit α (rpoA)의 mRNA 발현이 감소한 것을 확인하였다. 또한, 헬리코박터균에 plumbagin을 처리한 후 주요 병원성인자들의 발현을 조사한 결과 CagA와 VacA 독소들의 mRNA 및 단백질양이 감소한 것을 확인하였으며, 유레아제(ureA)와 부착단백(alpA)의 발현도 plumbagin 처리에 의해 감소한 것을확인하였다. 위와 같은 결과들을 토대로, plumbagin은 본 연구에서 밝힌 기전들을 통해 헬리코박터균의 성장, 감염 및 발병을 억제하는 것으로 사료된다.

• Journal of Plant Biotechnology
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• 제5권3호
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• pp.181-185
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• 2003

Callus and suspension cultures derived from leaf explants of Plumbago rosea were established on Murashige and Skoog's medium containing 1 mg/L IAA, 0.5 mg/L NAA and 0.3 mg/L BAP. Callus cultures were tested for their growth and accumulation of plumbagin, a naphthoquinone and was identified by $^1H$ NMR and electron ionization mass spectroscopy. While auxins (not 2,4-D) influenced growth and plumbagin accumulation, cytokinins did not influence them much. Increasing concentrations of IAA in presence of NAA and BAP increased plumbagin in suspensions only up to 1 mg/L. Growth of callus was optimum (8.3 g DCW/I) at a hormonal combination of 1.5 mg/L IAA, 0.5 mg/L NAA and 0.3 mg/L BAP, but high plumbagin accumulation (4.9 mg/g DCW) was recorded at 1.0 mg/L IAA plus 0.3 mg/L BAP. Since instability in growth and secondary metabolite accumulation was noticed, several cell lines/clumps of callus were screened for plumbagin accumulation by visual and analytical methods. Biomass and accumulation of plumbagin showed a negative correlation in several cell lines. But one cell line showed stability both in terms of biomass and plumbagin accumulation over a period of 6 months.

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.687-694
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• 2017

Plumbagin, a hydroxy 1,4-naphthoquinone compound from plant metabolites, exhibits anticancer, antibacterial, and antifungal activities via modulating various signaling molecules. However, its effects on vascular functions are rarely studied except in pulmonary and coronary arteries where NADPH oxidase (NOX) inhibition was suggested as a mechanism. Here we investigate the effects of plumbagin on the contractility of skeletal artery (deep femoral artery, DFA), mesenteric artery (MA) and renal artery (RA) in rats. Although plumbagin alone had no effect on the isometric tone of DFA, $1{\mu}M$ phenylephrine (PhE)-induced partial contraction was largely augmented by plumbagin (${\Delta}T_{Plum}$, 125% of 80 mM KCl-induced contraction at $1{\mu}M$). With relatively higher concentrations (>$5{\mu}M$), plumbagin induced a transient contraction followed by tonic relaxation of DFA. Similar biphasic augmentation of the PhE-induced contraction was observed in MA and RA. VAS2870 and GKT137831, specific NOX4 inhibitors, neither mimicked nor inhibited ${\Delta}T_{Plum}$ in DFA. Also, pretreatment with tiron or catalase did not affect ${\Delta}T_{Plum}$ of DFA. Under the inhibition of PhE-contraction with L-type $Ca^{2+}$ channel blocker (nifedipine, $1{\mu}M$), plumbagin still induced tonic contraction, suggesting $Ca^{2+}$-sensitization mechanism of smooth muscle. Although ${\Delta}T_{Plum}$ was consistently observed under pretreatment with Rho A-kinase inhibitor (Y27632, $1{\mu}M$), a PKC inhibitor (GF 109203X, $10{\mu}M$) largely suppressed ${\Delta}T_{Plum}$. Taken together, it is suggested that plumbagin facilitates the PKC activation in the presence of vasoactive agonists in skeletal arteries. The biphasic contractile effects on the systemic arteries should be considered in the pharmacological studies of plumbagin and 1,4-naphthoquinones.

• Natural Product Sciences
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• 제12권1호
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• pp.50-54
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• 2006

The wound healing activity of plumbagin and the chloroform extract of Plumbago rosea Linn. (Yoot), incorporated into ointments with yellow soft paraffin, have been investigated on rats. Wound healing activity was studied using excision and incision wound models in rats following topical application. Both plumbagin and the Plumbago rosea root extract produced a significant response in both of the wound models studied. The wound contracted in 14 days in the case of plumbagin (0.1%) and 16 days in case of Plumbago rosea root extract (0.5%), as against in 22 days in the case of control animals. The results were also comparable to those of a standard drug, framycetin sulphate cream (1% w/w) in terms of wound contracting ability, wound closure time, tensile strength of wound and regeneration of tissues at the wound site. Histological studies revealed evidences for the healing process by formation of fibrovascular tissue, epithelization and increased collagenization when compared to control.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2325-2331
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• 2013

Objective: To detect effects of plumbagin on proliferation and apoptosis in non-small cell lung cancer cell lines, and investigate the underlying mechanisms. Materials and Methods: Human non-small cell lung cancer cell lines A549, H292 and H460 were treated with various concentrations of plumbagin. Cell proliferation rates was determined using both cell counting kit-8 (CCK-8) and clonogenic assays. Apoptosis was detected by annexin V/propidium iodide double-labeled flow cytometry and TUNEL assay. The levels of reactive oxygen species (ROS) were detected by flow cytometry. Activity of NF-${\kappa}B$ was examined by electrophoretic mobility shift assay (EMSA) and luciferase reporter assay. Western blotting was used to assess the expression of both NF-${\kappa}B$ regulated apoptotic-related gene and activation of p65 and $I{\kappa}B{\kappa}$. Results: Plumbagin dose-dependently inhibited proliferation of the lung cancer cells. The IC50 values of plumbagin in A549, H292, and H460 cells were 10.3 ${\mu}mol/L$, 7.3 ${\mu}mol/L$, and 6.1 ${\mu}mol/L$ for 12 hours, respectively. The compound concentration-dependently induced apoptosis of the three cell lines. Treatment with plumbagin increased the intracellular level of ROS, and inhibited the activation of NK-${\kappa}B$. In addition to inhibition of NF-${\kappa}B$/p65 nuclear translocation, the compound also suppressed the degradation of $I{\kappa}B{\kappa}$. ROS scavenger NAC highly reversed the effect of plumbagin on apoptosis and inactivation of NK-${\kappa}B$ in H460 cell line. Treatment with plumbagin also increased the activity of caspase-9 and caspase-3, downregulated the expression of Bcl-2, upregulated the expression of Bax, Bak, and CytC. Conclusions: Plumbagin inhibits cell growth and induces apoptosis in human lung cancer cells through an NF-${\kappa}B$-regulated mitochondrial-mediated pathway, involving activation of ROS.

• Journal of Microbiology and Biotechnology
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• 제18권2호
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• pp.314-321
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• 2008

Acaricidal effects of materials derived from Diospyros kaki roots against Dermatophagoides farinae and D. pteronyssinus were assessed using impregnated fabric disk bioassay and compared with that of the commercial benzyl benzoate. The observed responses varied according to dosage and mite species. The $LD_{50}$ values of the chloroform extract of Diospyros kaki roots were 1.66 and $0.96{\mu}g/cm^2$ against D. farinae and D. pteronyssinus. The chloroform extract of Diospyros kaki roots was approximately 15.2 more toxic than benzyl benzoate against D. farinae, and 7.6 times more toxic against D. pteronyssinus. Purification of the biologically active constituent from D. kaki roots was done by using silica gel chromatography and high-performance liquid chromatography. The structure of the acaricidal component was analyzed by GC-MS, $^1H-NMR,\;^{13}C-NMR,\;^1H-^{13}C$ COSY-NMR, and DEPT-NMR spectra, and identified as plumbagin. The acaricidal activity of plumbagin and its derivatives (naphthazarin, dichlon, 2,3-dibromo-1,4-naphthoquinone, and 2-bromo-1,4-naphthoquinone) was examined. On the basis of $LD_{50}$ values, the most toxic compound against D. farinae was naphthazarin $(0.011{\mu}g/cm^2)$ followed by plumbagin $(0.019{\mu}g/cm^2),$ 2-bromo-1,4-naphthoquinone $(0.079{\mu}g/cm^2)$, dichlon $(0.422{\mu}g/cm^2)$, and benzyl benzoate $(9.14{\mu}g/cm^2)$. Additionally, the skin color of the dust mites was changed from colorless-transparent to dark brown-black by the treatment of plumbagin. Similar results have been exhibited in its derivatives (naphthazarin, dichlon, and 2-bromo-1,4-naphthoquinone). In contrast, little or no discoloration was observed for benzyl benzoate. From this point of view, plumbagin and its derivatives can be very useful for the potential control agents, lead compounds, and indicator of house dust mites.

• 생명과학회지
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• 제27권3호
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• pp.325-333
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• 2017

심혈관계 질환은 질환별 사망률 순위에 있어서 세계에서는 1위이며, 우리나라에서는 2위인 질병이다. 심혈관계 질환 발생의 주 위험 요인인 콜레스테롤은 HMG-CoA reductase에 의해 간에서 신생합성이 조절된다. 현재 고콜레스테롤혈증 치료에 statin이 널리 사용되고 있지만 광범위한 부작용이 보고되고 있어서 이를 대체하거나 보조할 수 있는 천연물 유래의 기능성 물질 개발이 필요한 실정이다. 따라서 본 연구에서는 혈장 콜레스테롤 감소 활성을 가지는 물질을 발굴하고자 71종의 페놀 및 그와 관련된 화합물들을 대상으로 10ug/ml 농도에서 HMG-CoA reductase 저해 활성을 탐색하였다. 그 결과, 1,4-naphthoquinone의 HMG-CoA reductase 저해율이 99.4%로 가장 높았고, 다음으로 plumbagin 91.4%, pentagalloyl ${\beta}-D-glucose$ 46.6%, 2,4-dihydroxybenzoic acid 40.9%, shikonin 37.7%, 1,2-naphthoquinone 36.6%, trans-cinnamic acid 32.0%, acetonylgeraniin 30.2%, benzoic acid 28.5%, geraniin 28.3%, gentisic acid 22.3%의 순이었다. $IC_{50}$값을 계산한 결과, 1,4-naphthoquinone가 $2.1{\mu}g/ml$로 가장 낮았으며, plumbagin과 pentagalloyl ${\beta}-D-glucose$은 각각 $5.8{\mu}g/ml$과 $13.1{\mu}g/ml$으로 나타났다. 1,4-naphthoquinone과 plumbagin의 경우, $5{\mu}g/ml$에서도 각각 90.3%와 43.3%의 저해율을 나타내었다.

• The Plant Pathology Journal
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• 제23권2호
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• pp.113-115
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• 2007

A kind of naphthoquinone, plumbagin was purified and identified from the leaves of Nepenthes $ventricosa\;{\times}\;maxima$ through solvent extraction, silica gel column chromatography, and recrystallization. The yield (0.51%) was higher than that of the root of Plumbago scandens (0.26%), P. capensis (0.15%), and N. thorelii (0.092%). It exhibited antifungal activity against all plant pathogenic fungi tested, Alternaria alternata, Aspergillus niger, Bipolaris oryzae, Fusarium oxysporum, Phytophthora capsici, Rhizoctonia solani, Rhizopus stolonifer var. stolonifer and Sclerotinia sclerotiorum. The minimum inhibitory concentration values ranged from about 4.8 to $56.6\;{\mu}g/ml$ against the above eight fungi and R. solani was the most sensitive.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2011년도 춘계학술발표회
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• pp.106-107
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• 2011

• 한국미생물·생명공학회지
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• 제28권1호
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• pp.1-7
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• 2000

The bacterial strain JW-2 which conferred resistance against paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride) was isolated from soil. The strain was identified as an Ochrobactrum anthropi based on its morphological, physiological, biological and fatty acid composition, and was designated as Ochrobactrum anthropi JW-2. We compard paraquat resistance of O. anthropi JW-2 with Escherichia coli J105. In the presence of 100mM paraquat, E. coli JM105 was not grown whereas the growth rate of O. anthropi was about 70% of control. We compared the sensitivity of O. anthropi JW-2 and E. coli J105 to redox-cycling compounds such as paraquat, plumbagin or menadione, which are known to exacebate wuperoxide generation. O. anthropi JW-2 did not show cross-resistance to plumbagin or menadione. superoxide dismutase activity was increased in paraqunt-treated E. coli JM105 while it was not increased in O.anthropi JW-2. These results suggest that the mechanism of paraquat resistance in O.anthropi JW-2 is probably due to selectively decreased permeability toward paraquat by membrane protein.