• Biomolecules & Therapeutics
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• 제22권2호
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• pp.155-160
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• 2014

Thelephoric acid is an antioxidant produced by the hydrolysis of polyozellin, which is isolated from Polyozellus multiplex. In the present study, the inhibitory effects of polyozellin and thelephoric acid on 9 cytochrome P450 (CYP) family members (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) were examined in pooled human liver microsomes (HLMs) using a cocktail probe assay. Polyozellin exhibited weak inhibitory effects on the activities of all 9 CYPs examined, whereas thelephoric acid exhibited dose- and time-dependent inhibition of all 9 CYP isoforms ($IC_{50}$ values, $3.2-33.7{\mu}M$). Dixon plots of CYP inhibition indicated that thelephoric acid was a competitive inhibitor of CYP1A2 and CYP3A4. In contrast, thelephoric acid was a noncompetitive inhibitor of CYP2D6. Our findings indicate that thelephoric acid may be a novel, non-specific CYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of CYP enzymes on the metabolism of given compounds.

• Applied Biological Chemistry
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• 제47권2호
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• pp.283-286
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• 2004

In the course of screening for reactive oxygen species scavengers from natural products, two antioxidants were isolated from the edible mushroom Polyozellus multiflex and identified as polyozellin and thelephoric acid. Thelephoric acid inhibited 45.7% of the super oxide anion radical, 74.6% of the hydroxyl radical, and 44.0% of the DPPH radical at 0.1 mM, while the positive control ${\alpha}-tocopherol$ did 22.1%, 75.6%, and 26.5% of each radical, respectively. Polyozellin, the reductive acetylated form of thelephoric acid, showed almost same scavenging activity against above mentioned radicals. The isolated compounds showed scavenging activity on the superoxide anion radical in the ESR method ($IC_{50}$ of polyozellin and thelephoric acid were $218.0\;{\mu}M$ and $21.1\;{\mu}M$, respenctively). However, they showed no significant activity on the hydrogen peroxide radical.

• 생명과학회지
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• 제23권9호
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• pp.1126-1132
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• 2013

CYP2J2 효소는 간외의 조직에 존재 하는 효소로써, 주로 심혈관계에 발현되어 있다. CYP2J2는 내인성 대사체 및 여러 치료 약물들의 대사에 중요한 작용을 하고 있다. 또한 CYP2J2는 인체의 종양조직이나 종양 세포주에서 과발현되어 있어, 종양 치료를 위한 새로운 표적이 되고 있다. 본 연구에서는 천연물 10종을 대상으로 시토크롬 2J2 동효소에 저해능을 가지는 화합물을 발굴하고자 하였다. 10종의 천연물 중 thelephoric acid는 CYP2J2에 의해 매개되는 에바스틴($IC_{50}=5.32{\mu}M$), 아스테미졸($IC_{50}3.23{\mu}M$) 및 터페나딘($IC_{50}=3.27{\mu}M$) 대사를 강력하게 저해하였다. 향후, 이 약물을 대상으로 한 항암 활성 평가가 필요할 것으로 판단된다.

• Journal of Microbiology and Biotechnology
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• 제9권6호
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• pp.798-803
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• 1999

Prolyl endopeptidase [PEP; EC 3.4.21.26], a serine protease which is known to cleave peptide bonds on the carboxy side of a proline residue, plays an important role in the degradation of proline-containing neuropeptides that have been suggested to participate in learning and memory processes. An abnormal increase in the level of PEP, which can lead to generation of $A{\beta}$, is also suggested to be involved in Alzheimer's type senile dementia. In the course of screening PEP inhibitors from Basidiomycetes, the mushroom Polyozellus multiplex exhibited a high inhibitory activity against PEP. Two active compounds were isolated from the ethyl acetate soluble fraction by consecutive purification, using silica gel, Sephadex LH-20, and Lobar RP-18 chromatography. The chemical structures of these compounds were identified as thelephoric acid and 12-acety1-2,3,7,8-tetrahydroxy-[12H]-12-hydroxymethylbenzobis[I.2b,3.4b'] benzofuran-11-one (kynapcin-9) by spectral data including UV, IR, MS, HR-MS, $^1H-,{\;}^{13}C-$, and 2D-NMR. The $IC_{50}$ values of the thelephoric acid and kynapcin-9 were 0.157 ppm (446nM) and 0.087 ppm (212nM) and their inhibitor constants ($K_i$) were 0.73ppm ($2.09{\;}\mu\textrm{m}$) and 0.060 ppm (146 nM), respectively. Furthermore, they were non-competitive with a substrate in Dixon plots.

• 한국미생물·생명공학회지
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• 제24권5호
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• pp.591-596
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• 1996

In the course of screening lipid peroxidation inhibitor from basidiomycetes, a mushroom, which was collected at O-Dae mountain in Kangweon- Do, was found to have active compound. The mushroom was identified as Polyzellus multiplex, which belongs to Aphylloporalles Thelephoraceae, on the basis of macroscopic and microscopic characteristics of the fruiting body. The methanol extract of fruiting body was extracted with benzene and ethylacetate, sequentially. By using various kinds of chromatographies, PM1, and PM2 and PM3, were purified from the ethylacetate extract and the benzene extract, respectively. Color reaction and analyses of IR, UV, and NMR spectra indicated that PM1 was a derivative of thelephoric acid, and PM2 and PM3 were linoleic acid and oleic acid, respectively. IC$_{50}$ of PM1 for inhibition of lipid peroxidation was 1.96 ppm and LD$_{50}$ was 500 mg/kg.