• Korean Journal of Pharmacognosy
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• v.40 no.1
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• pp.70-76
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• 2009

Thirty six essential oils from herb drugs entered in Korean official formulary, which are frequently used in oriental region, were tested for antibiotic resistance inhibition. When the oils were combined with ampicillin (Am) or amoxicillin (Amx) they showed significant inhibitory effects on the growth of multi-drug resistant Staphylococcus aureus SA2 in considerably low concentration. The most effective combinations were oils from Acanthopanacis Cortex ($0.49{\mu}g/mL$) with Am and Cnidii Rhizoma and Lonicerae Flos (2.77 and $2.79{\mu}g/mL$, respectively) with Amx as shown in minimum resistance inhibitory concentrations.

• YAKHAK HOEJI
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• v.48 no.1
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• pp.27-29
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• 2004

The essential oil fractions from six plant parts including leaf of Zanthoxylum piperitum and flower of Lindera obtusiloba have revealed to possess resistance inhibitory activity on antibiotic resistant Staphylococcus aureus SA2 when combined with ohloramphenicol (Cm). The combination of Cm and essential oil mixtures showed potent resistance inhibition in the level of 10∼20 $\mu\textrm{g}$/ml.

• Archives of Pharmacal Research
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• v.21 no.1
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• pp.62-66
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• 1998

The resistance inhibitory activities of 54 odorant mixtures (essential oil) from 41 Korean aromatic herbs were tested against multi-drug resistant Staphylococcus aureus SA2, which has resistances to 10 usual antibiotics including chloramphenicol. As results, combinations of 28 kinds of samples from 21 herbs and chloramphenicol have resistance inhibitory activities in dose dependent manner.

• Journal of Korean Neurosurgical Society
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• v.48 no.4
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• pp.319-324
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• 2010

Objective : The aim of this study was to analyze the correlation between thromboembolic complications and anti platelet drugs before and after neurointervention. Methods : Blood samples and radiographic data of patients who received a neurointervention (coil embolization, stent placement or both) were collected prospectively. Rapid platelet function assay-aspirin (RPFA-ASA) was used to calculate aspirin resistance in aspirin reaction units (ARU). For clopidogrel resistance, a P2Y12 assay was used to analyze the percentage of platelet inhibition. ARU > 550 and platelet inhibition < 40% were defined as aspirin and clopidogrel resistance, respectively. Results : Both aspirin and clopidogrel oral pills were administered in fifty-three patients before and after neurointerventional procedures. The mean resistance values of all patients were 484 ARU and < 39%. Ten (17.0%) of 53 patients showed resistance to aspirin with an average of 597 ARU, and 33 (62.3%) of 53 patients showed resistance to clopidogrel with an average of < 26%. Ten patients demonstrated resistance to both drugs, 5 of which suffered a thromboembolic complication after neurointervention (mean values : 640 ARU and platelet inhibition < 23%). Diabetic patients and patients with hypercholesterolemia displayed mean aspirin resistances of 513.7 and 501.8 ARU, and mean clopidogrel resistances of < 33.8% and < 40.7%, respectively. Conclusion : Identifying individuals with poor platelet inhibition using standard regimens is of great clinical importance and may help prevent cerebral ischemic events in the future. Neurointerventional research should focus on ideal doses, timing, choices, safety, and reliable measurements of anti platelet drug therapy, as well as confirming the clinical relevance of aggregometry in cerebrovascular patients.

• Natural Product Sciences
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• v.6 no.1
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• pp.36-39
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• 2000

Acorenone, a diterpene isolated from Acorus gramineus, showed strong resistance inhibitory activity against multi-drug resistant microorganisms such as Staphylococcus aureus SA2, which has resistance to 10 usual antibiotics including chloramphenicol (Cm). At the level of $5\;{\mu}g/ml$ when combined with $50\;{\mu}g/ml$ of Cm. Bacterial resistance to Cm is due to the presence in resistant bacteria of an enzyme, chloramphenicol acetyltransferase (CAT), which catalyses the acetyl-CoA dependent acetylation of the antibiotic at C-3 hydroxyl group. To elucidate the mechanism of resistant inhibitory effect, the acorenone which had the strongest resistant inhibitory activity, was investigated on the CAT assay. As the result, the combination of Cm and acorenone showed the strongest inhibitory activity on CAT as noncompetitive and dose dependent manner.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.320-326
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• 2015

The clinical benefits of oncogenic BRAF inhibitor therapies are limited by the emergence of drug resistance. In this study, we investigated the role of a negative regulator of the MAPK pathway, Spry2, in acquired resistance using BRAF inhibitor-resistant derivatives of the BRAF-V600E melanoma (A375P/Mdr). Real-time RT-PCR analysis indicated that the expression of Spry2 was higher in A375P cells harboring the BRAF V600E mutation compared with wild-type BRAF-bearing cells (SK-MEL-2) that are resistant to BRAF inhibitors. This result suggests the ability of BRAF V600E to evade feedback suppression in cell lines with BRAF V600E mutations despite high Spry2 expression. Most interestingly, Spry2 exhibited strongly reduced expression in A375P/Mdr cells with acquired resistance to BRAF inhibitors. Furthermore, the overexpression of Spry2 partially restored sensitivity to the BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P cells, indicating that negative feedback including Spry2 may be bypassed in BRAF mutant melanoma cells. In addition, the siRNA-mediated knockdown of Raf-1 attenuated the rebound activation of ERK stimulated by PLX4720 in A375P cells, strongly suggesting the positive role of Raf-1 kinase in ERK activation in response to BRAF inhibition. Taken together, these data suggest that RAF signaling may be released from negative feedback inhibition through interacting with Spry2, leading to ERK rebound and, consequently, the induction of acquired resistance to BRAF inhibitors.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.114-120
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• 2013

Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 ($IC_{50}$ < $0.5{\mu}M$), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 ($IC_{50}$ < $20{\mu}M$). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at $G_0/G_1$ with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.734-737
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• 1998

The hexane fractions from methanolic extracts of Anetheum graveolens L. (Umbelliferae) and Acorus gramineus Soland. (Araceae) revealed potent inhibitory activities against the resistance of multi-drug resistant Staphylococcus aureus SA2 when combined with ampicillin (Am) or chloramphenicol (Cm). As active principles, carvone and the liquid mixture containing carvone from Anetheum graveolens L. and a liquid mixture mainly consisting of benzoic acid phenyl-methyl ester (benzyl benzoate) from Acorus gramineus Soland. were identified. They showed resistance inhibition at the level of 20-50${\mu}g$/ml when combined with 100 or ${\mu}g$/ml of Am or Cm, respectively.

• Natural Product Sciences
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• v.1 no.1
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• pp.50-54
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• 1995

Staphylococcus aureus SA2, which was isolated from patient, is resistant to 10 usual antibiotics. The methanolic extracts of 21 well-known herb materials were combined with 10 antibiotics and applied to cheek inhibitory effects on the resistance of S. aureus SA2. The hexane fractions from methanolic extracts of Acori graminei Rhizoma and Anethi Fructus had most potent activity to inhibit the resistance of the bacteria when combined with ampicilin or chloramphenicol.

• Journal of Microbiology and Biotechnology
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• v.13 no.1
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• pp.90-98
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• 2003

In vivo $^31p$ Nuclear Magnetic Resonance ($^31p$NMR) and metabolic studies were carried out on an acetic acid tolerant mutant, Zymomonas mobilis $ZM4/Ac^R$, and compared to those of the parent strain, Z. mobilis ZM4, to evaluate possible mechanisms of acetic acid resistance. This investigation was initiated to determine whether or not the mutant strain might be used as a suitable recombinant host far ethanol production from lignocellulose hydrolysates containing various inhibitory compounds. $ZM4/Ac^R$ showed multiple resistance to other lignocellulosic toxic compounds such as syringaldehyde, furfural, hydroxymethyl furfural, vanillin, and vanillic acid. The mutant strain was resistant to higher concentrations of ethanol or lower pH in the presence of sodium acetate, compared to ZM4 which showed more additive inhibition. in vivo $^31p$ NMR studies revealed that intracellular acidification and de-energization were two mechanisms by which acetic acid exerted its inhibitory effect. For $ZM4/Ac^R$, the internal pH and the energy status were less affected by sodium acetate compared to the parent strain. This resistance to pH change and de-energization caused by acetic acid is a possible explanation for the development of resistance by this strain.