Biomedical subjects

Y Tezuka

Publications and source records attributed to Y Tezuka.

At least 55 records · Page 3Linked to original sources

PubMed2000

Hepatoprotective effect of Apocynum venetum and its active constituents.

The leaves of Apocynum venetum L. are used as a tea material in north China and Japan. A water extract (500 mg/kg/day, one week administration) of the leaves of A. venetum showed protective effects against carbon tetrachloride (CCl4, 30 microliters/mouse) or D-galactosamine (D-GalN, 700 mg/kg)/lipopolysaccharide (LPS, 20 micrograms/kg)-induced liver injury in mice. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is the most crucial mediator in the D-GalN/LPS-induced liver injury model. The extract had no significant inhibition on the increase of serum TNF-alpha (1169 +/- 132 pg/ml vs. 1595 +/- 314 pg/ml of control), but exhibited a complete inhibition at the concentration of 100 micrograms/ml on TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized mouse hepatocytes. Further activity-guided fractionation resulted in the isolation of fifteen flavonoids viz. (-)-epicatechin (1), (-)-epigallocatechin (2), isoquercetin (3), hyperin (4), (+)-catechin (5), (+)-gallocatechin (6), kaempferol-6'-O-acetate (7), isoquercetin-6'-O-acetate (8), catechin-[8,7-e]-4 alpha-(3,4-dihydroxpyhenyl)-dihydro-2(3H)-pyranone (9), apocynin B (10), apocynin A (11), cinchonain Ia (12), apocynin C (13), apocynin D (14) and quercetin (15). All the compounds showed inhibitory effects on TNF-alpha-induced cell death with different intensities. The flavonol glycosides 3, 4, 7 and 8 and the phenylpropanoid-substituted flavan-3-ols 11 and 12 showed potent inhibitory effects on TNF-alpha-induced cell death with IC50 values of 37.5, 14.5, 31.2, 55.1, 71.9 and 41.2 microM, respectively. In contrast, the clinically used 5 and its analogues 1, 2 and 6 showed apparent activity only at 80 microM. These flavonoids appeared to be the hepatoprotective principles of the leaves of A. venetum. The hepatoprotective effects exhibited by the extract and its constituents suggest a validation of the leaves as a tea material.

Animals↗

PubMed2000

Blood-pressure lowering, positive chronotropy and inotropy by the Veratrum alkaloids germidine and germerine but negative chronotropy by veratridine in mice.

Germidine and germerine, the Veratrum alkaloids lowered blood pressure accompanied with positive chronotropy and inotropy in mice. Germerine was more potent than germidine in both blood-pressure lowering and positive inotropy, whereas veratridine produced negative chronotropy and positive inotropy. An acyl group (an acetyl or a 2-methylbutyroyl group) at 3-O-R1 position and a 2-methylbutyroyl group at 15-O-R2 position in germine were important to produce the positive inotropy and chronotropy. The presence of a veratroyl group at 3-O-R1 position and a free hydroxyl group at 15-O-R2 position may be essential to produce the negative chronotropy by veratridine. The positive inotropy by germidine and veratridine may be due to TTX-resistant Na+ channel activation.

Animals↗

PubMed2000

Highly selective antibacterial activity of novel alkyl quinolone alkaloids from a Chinese herbal medicine, Gosyuyu (Wu-Chu-Yu), against Helicobacter pylori in vitro.

To elucidate the antibacterial activity of Gosyuyu, the crude extract from the fruit of Evodia rutaecarpa, a Chinese herbal medicine, has been fractionated chromatographically, and each fraction was assayed for antibacterial activity against Helicobacterpylori (H. pylori) in vitro. As the result, a single spot having marked antibacterial activity against H. pylori was obtained and the chemical structure was analyzed. The isolated compound was revealed to be a novel alkyl quinolone alkaloid based on the solubility, IR spectra, NMR analysis and mass spectrometric data after purification by TLC of silica. We compared the antimicrobial activity of this compound with that of other antimicrobial agents and examined susceptibility of various intestinal pathogens. As the result, the new quinolone compounds obtained from Gosyuyu extracts were found to be a mixture of two quinolone alkaloids, 1-methyl-2-[(Z)-8-tridecenyl]-4-(1H)-quinolone and 1-methyl-2-[(Z)-7-tridecenyl]-4-(1H)-quinolone (MW: 339), reported previously. The minimum inhibitory concentration (MIC) of these compounds against reference strains and clinically isolated H. pylori strains were less than 0.05 microg/ml, which was similar to the MIC of amoxicillin and clarithromycin that are used worldwide for the eradication of H. pylori, clinically. Furthermore, it was noted that the antimicrobial activity of these compounds was highly selective against H. pylori and almost non-active against other intestinal pathogens. The above results showed that these alkyl methyl quinolone (AM quinolones) alkaloids were useful for the eradication of H. pylori without affecting other intestinal flora.

Alkaloids↗

PubMed2000

Hepatoprotective constituents of the seeds of Combretum quadrangulare.

Hepatoprotective effect of MeOH, MeOH-H2O (1:1) and H2O extracts of Combretum quadrangulare seeds were examined on D-galactosamine (D-GalN)/tumor necrosis factor-alpha(TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. The MeOH extract showed the strongest inhibitory effect on D-GalN/TNF-alpha-induced cell death (IC50, 56.4 microg/ml). Moreover, the MeOH extract also significantly lowered the serum glutamic pyruvic transaminase (sGPT) level on D-GalN/lipopolysaccharide (LPS)-induced liver injury in mice. Bioguided separation of the MeOH extract led to the isolation of 38 compounds of various classes including triterpene glucosides, lignans and catechin derivatives. Among the isolated triterpene glucosides, lupane-type (1-3; IC50, 63.1, 59.8 and 76.2 microM, respectively) and ursane-type (11, mixture of 12 and 14; IC50, 30.2 and 34.6 microM, respectively) compounds exhibited strong hepatoprotective activity. 1-O-Galloyl-6-O-(4-hydroxy-3,5-dimethoxy)benzoyl-beta-D-glucose (26; IC50, 7.2 microM), methyl gallate (28; IC50, 19.9 microM), and (-)-epicatechin (31; IC50, 71.2 microM) also had a potent hepatoprotective effect on D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes.

Animals↗

PubMed2000

Pharmacokinetics of ginsenoside deglycosylated by intestinal bacteria and its transformation to biologically active fatty acid esters.

Ginsenosides are deglycosylated by intestinal bacteria to active forms after oral administration. The present study demonstrated the pharmacodynamics of 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (M1), an intestinal bacterial metabolite of ginsenosides, and the in vitro and in vivo antitumor activities of M1-metabolites in comparison with M1 using C57BL/6 mice and Wistar rats. M1 was selectively accumulated into the liver soon after its intravenous administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EM1) in the liver. EM1 was isolated from rats in a recovery dose of approximately 24 mol%. Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as M1 was, it was accumulated in the liver longer than M1. Although the cytotoxicity of M1 against B16-F10 melanoma cells was attenuated by fatty acid esterification, EM1 inhibited tumor growth more than M1 in vivo. These results suggest that the fatty acid M1 esters may be the real active principles of ginsenosides in the body.

Animals↗

PubMed2000

Hepatoprotective effect of Combretum quadrangulare and its constituents.

The MeOH extract of leaves of Combretum quadrangulare showed significant hepatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced experimental liver injury in mice and on D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Phytochemical investigation led to the isolation of thirty cycloartane-type triterpenes together with betulinic acid, beta-sitosterol, beta-sitosterol glucoside, 4 flavones (34-37), and 3 flavone C-glucosides (38-40). These compounds showed various potencies of hepatoprotective effect on D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. Quadrangularol B (29), methyl quadrangularate I (33), kamatakenin (34), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (35), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (36) and isokaempferide (37) showed strong inhibitory effect on TNF-alpha-induced cell death with IC50 values of 34.3, 33.7, 13.3, 22.4, 13.4 and 22.8 microM, respectively, whereas clinically-used silibinin had an IC50 value of 39.6 microM and glycyrrhizin showed very weak inhibitory effect. Methyl quadrangularates A (30) and N (32), norquadrangularic acid B (31) and vitexin (40) also showed potent inhibition on TNF-alpha-induced cell death with IC50 values of 45.7, 89.3, 67.6 and 40.1 microM, respectively. The flavonoids and some of the cycloartane-type triterpenes appeared to be the hepatoprotective principles of the leaves of C. quadrangulare.

Animals↗

PubMed2000

Prolyl endopeptidase inhibitory activity of fourteen Kampo formulas and inhibitory constituents of Tokaku-joki-to.

Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme playing a role in the metabolism of proline-containing neuropeptides which have been suggested to be involved in learning and memory processes. In screening for PEP inhibitors from fourteen traditional Kampo formulas, we found that Tokaku-joki-to shows a significant inhibitory activity. Examination of the constituents of the Kampo formula resulted in the isolation of two new compounds, cis-3,5,4'-trihydroxystilbene 4'-O-beta-D-(6-O-galloyl)glucopyranoside (10) and 4-(4-hydroxyphenyl)-2-butanone 4'-O-beta-D-(6-O-galloyl-2-O-cinnamoyl)glucopyranoside (16), along with twenty-five known compounds, cinnamic acid (1), protocatechuic acid (2), gallic acid (3), torachrysone 8-O-beta-D-glucoside (4), emodin (5), emodin 8-O-beta-D-glucoside (6), 3,5,4'-trihydroxystilbene 4'-O-beta-D-glucopyranoside (7), 3,5,4'-trihydroxystilbene 4'-O-beta-D-(2-O-galloyl)glucopyranoside (8), 3,5,4'-trihydroxystilbene 4'-O-beta-D-(6-O-galloyl)glucopyranoside (9), 4-(4-hydroxyphenyl)-2-butanone 4'-O-beta-D-glucopyranoside (11), isolindleyin (12), lindleyin (13), 4(4-hydroxyphenyl)-2-butanone 4'-O-beta-D-(2,6-di-O-galloyl)glucopyranoside (14), 4-(4-hydroxyphenyl)-2-butanone 4'-O-beta-D-(2-O-galloyl-6-O-cinnamoyl)glucopyranoside (15), 1-O-galloylglucose (17), 1,2,6-tri-O-galloylglucose (18), gallic acid 4-O-beta-D-(6-O-galloyl)glucopyranoside (19), liquiritigenin (20), liquiritigenin 4'-O-beta-D-glucoside (21), liquiritigenin 7,4'-diglucoside (22), liquiritigenin 4'-O-beta-D-apiofuranosyl-(1-->2)-beta-D-glucopyranoside (23), licuroside (24), (-)-epicatechin (25), (-)-epicatechin 3-O-gallate (26) and (+)-catechin (27). Among these compounds, twelve (7-10, 14-16, 18, 19, 24-26) showed noncompetitive inhibition with an IC50 of 22.9, 3.0, 14.9, 2.8, 10.5, 0.69, 8.2, 0.44, 9.39, 26.5, 28.1 and 0.052 microM, respectively.

Drugs, Chinese Herbal↗

PubMed2000

Quadranosides VI-XI, six new triterpene glucosides from the seeds of Combretum quadrangulare.

Six new triterpene glucosides, quadranosides VI-XI (1-6), belonging to three different [ursane- (1-4), oleanane- (5) and lupane-type (6)] triterpene classes, have been isolated from a MeOH extract of the seeds of Combretum quadrangulare KURZ (Combretaceae), together with nine known compounds, rosamutin (7), 28-O-beta-D-glucopyranosyl-6beta,23-dihydroxytormentic acid (8), arjunetin (9), arjunglucoside II (10), combreglucoside (11), chebuloside II (12), vitexin (13), (+)-catechin (14) and (-)-epigallocatechin (15). The structures of these compounds were elucidated by spectroscopic analysis.

Glucosides↗

PubMed2000

Constituents of the Vietnamese medicinal plant Orthosiphon stamineus.

From the MeOH extract of the aerial part of Vietnamese Orthosiphon stamineus, five new isopimarane-type diterpenes [orthosiphols F-J (1-5)] and two new diterpenes [staminols A (6) and B (7)] with a novel carbon-framework, to which we proposed the name "staminane", and three new highly-oxygenated staminane-type diterpenes [staminolactones A (8) and B (9) and norstaminol A (10)1 were isolated. Moreover, staminolactone A (8) is 8,14-secostaminane-type and staminolactone B (9) is 13,14-secostaminane-type, while norstaminol A (10) is 14-norstaminen-type. Together with these new diterpenes, sixteen known compounds were also isolated and identified to be: 7,3',4'-tri-O-methylluteolin (11), eupatorin (12), sinensetin (13), 5-hydroxy-6,7,3',4'-tetramethoxyflavone (14), salvigenin (15), ladanein (16), tetramethylscutellarein (17), 6-hydroxy-5,7,4'-trimethoxyflavone (18), vomifoliol (19), aurantiamide acetate (20), rosmarinic acid (21), caffeic acid (22), oleanolic acid (23), ursolic acid (24), betulinic acid (25), and beta-sitosterol (26). All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the new diterpenes, except for 4, and flavonoids (11, 12, 16, 18) showed cytotoxicity with an ED50 value between 10 and 90 microg/ml.

Animals↗

PubMed2000

Methyl quadrangularates A-D and related triterpenes from Combretum quadrangulare.

From the MeOH extract of leaves of Combretum quadrangulare, fifteen new cycloartane-type triterpenes, methyl quadrangularates A-D (1-4) and N-P (8, 6, 12), methyl 24-epiquadrangularate C (5), quadrangularic acid E (9), 23-deoxojessic acid (10), 1-O-acetyl-23-deoxojessic acid (11), quadragularols A (7) and B (13) and norquadrangularic acids B (14) and C (15) were isolated together with two known cycloartane-type triterpenes, methyl 23-deoxojessate (16) and 4beta,14alpha-dimethyl-5alpha-ergosta-9beta++ +,19-cyclo-24(31)-en-3beta-hydroxy-4alpha-carboxylic acid (17). Betulinic acid (18), beta-sitosterol (19), kamatakenin (20), isokaempferide (21), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (22) and 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (23) were also obtained from the same extract. The structures of the new compounds were elucidated on the basis of spectral analysis and chemical conversions. All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the cycloartane-type triterpenes showed various degrees of cytotoxicity, whereas all the flavonoids possessed strong cytotoxicity with ED50 values equal to or less than 6 microM.

Magnetic Resonance Spectroscopy↗

PubMed1999

Epicalyxin F and calyxin I: two novel antiproliferative diarylheptanoids from the seeds of Alpinia blepharocalyx.

[formula: see text] Epicalyxin F (1) and calyxin I (2), two novel diarylheptanoids, were isolated from a residual fraction of an EtOH extract of Alpinia blepharocalyx. Calyxin I (2) represented a new carbon skeleton, and epicalyxin F (1) possessed potent antiproliferative activity toward HT-1080 fibrosarcoma and colon 26-L5 carcinoma with ED50 values of 1.71 and 0.89 microM, respectively.

Antineoplastic Agents, Phytogenic↗

PubMed1999

Staminolactones A and B and norstaminol A: three highly oxygenated staminane-type diterpenes from Orthosiphon stamineus.

[formula: see text] Staminolactones A (1) and B (2) and norstaminol A (3), three highly oxygenated staminane-type diterpenes having mild cytotoxic activities against highly liver-metastatic colon 26-L5 carcinoma cells, were isolated from the aerial part of the Vietnamese medicinal plant Orthosiphon stamineus (Lamiaceae). Their structures were elucidated on the basis of the extensive spectral analyses.

Antineoplastic Agents↗

PubMed1999

Evidence of simple intramolecular rearrangement at polymer end groups in secondary ion mass spectrometry.

Polystyrenes with various end groups were analyzed by time-of-flight secondary ion mass spectrometry (TOF-SIMS). These end groups were obtained by termination of the active anionic group by sulfonate or chlorosilane derivatives. Characteristic end group fragments for each sulfonate derivative were observed. On the one hand, for PS capped by methyl sulfonate, or -(CH(2))(4)-O-SO(2)-CH(3), almost complete end group fragment is observed at m/z 95 and a [O-SO(2)-CH(3)](-) molecular structure. On the other hand, when PS is terminated by silyl methyl sulfonate, or -Si(CH(3))(2)-(CH(2))(3)-O-SO(2)-CH(3), the most characteristic fragment in the fingerprint secondary ion mass spectrum is located at m/z 153 with [Si(CH(3))(2)-O-SO(2)-CH(3)](+) and the complete end group peak, [Si(CH(3))(2)-(CH(2))(3)-O-SO(2)-CH(3)](+), at m/z 201, is absent. According to the molecular structure, characteristic end group secondary ions can be emitted as complete or rearranged fragments. Various silylalkyl alcohol or sulfonate functionalities are analyzed and fragmentation pathways are discussed. To our knowledge, this is the first time that such rearrangement at silyl functions has been observed and demonstrated in fingerprint secondary ion mass spectra. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

PubMed1999

Expression of mucin 1 (MUC1) in esophageal squamous-cell carcinoma: its relationship with prognosis.

Using 2 anti-mucin 1 (MUC1) monoclonal antibodies (MAbs), DF3 and BCP8, we examined MUC1 expression immunohistochemically in 192 esophageal squamous-cell carcinomas (SCCs). In normal squamous epithelium of the esophagus, DF3 was not expressed, but BCP8 was expressed on the cell membrane, mainly in the surface layer. In esophageal SCCs, DF3 and BCP8 were expressed mainly on the cell membrane of SCC cells, but also in the cytoplasm in several cases. To analyze the correlation of MUC1 expression and the prognosis of the patients, the 192 cases were divided into 2 groups: high-expression group (HEG, > 50% of the neoplastic cells stained) and low-expression group (LEG, < 50% of neoplastic cells stained). DF3-HEG (24 patients) showed a significantly poorer survival rate than DF3-LEG (168 patients), whereas there was no significant difference in survival between BCP8-HEG (43 patients) and BCP8-LEG (149 patients). Also, in the analysis of 162 patients with advanced stage (submucosal or deeper invasion) to exclude the influence of low expression of DF3 and BCP8 in 30 patients with early stage (up to the level of muscularis mucosae), DF3-HEG (24 patients) showed significantly poorer survival than DF3-LEG (138 patients), whereas there was no significant difference in survival between BCP8-HEG (42 patients) and BCP8-LEG (120 patients). The results of our study on esophageal SCC suggest that the expression of sialyl oligosaccharides detected by DF3 is related to poor prognosis.

Carcinoma, Squamous Cell↗

PubMed1999

Synthesis and evaluation of glucocerebrosidase inhibitory activity of anhydro deoxyinositols from (+)-epi- and (-)-vibo-quercitols.

Twelve 1,2- and 2,3-anhydro-1,2,3,4,5-cyclohexanepentols were synthesized from (+)-epi- and (-)-vibo-quercitols, readily available by bioconversion of myo-inositol, and assayed for inhibitory activity against glucocerebrosidase (mouse liver). Among them 1L-1,2-anhydro-1,2,4/3,5-cyclohexanepentol, the 3-deoxy derivative of the irreversible inhibitor conduritol B epoxide (CBE), has been demonstrated to be a highly potent and specific inhibitor, almost comparable to the parent compound.

Animals↗

PubMed1999

Acteoside inhibits apoptosis in D-galactosamine and lipopolysaccharide-induced liver injury.

We assessed the effect of acteoside, a naturally occurring antioxidative phenylethanoid, on hepatic apoptosis and the subsequent liver failure induced by D-Galactosamine (D-GalN) and lipopolysaccharide (LPS). A co-administration of D-GalN (700 mg/kg) and LPS (35 microg/kg) to mice evoked typical hepatic apoptosis characterized by DNA fragmentation and apoptotic body formation, resulting in fulminant hepatitis and lethality of mice. Pre-administration of acteoside at 10 or 50 mg/kg subcutaneously at 12 and 1 h prior to D-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is an important mediator of apoptosis in this model. Acteoside showed no apparent effect on the marked elevation of serum TNF-alpha, but it partially prevented in vitro TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 microM. These results indicated that D-GalN/LPS-induced hepatic apoptosis can be blocked by an exogenous antioxidant, suggesting the involvement of reactive oxygen intermediates (ROIs) in TNF-alpha-dependent hepatic apoptosis.

Alanine Transaminase↗

PubMed1999

Active-oxygen scavenging activity of traditional nourishing-tonic herbal medicines and active constituents of Rhodiola sacra.

The active-oxygen scavenging activity of 70 traditional herbal medicines used in China and Japan as nourishing tonics were evaluated by electron spin resonance (ESR) technique, in order to evaluate their effectiveness for anti-aging and to search for new active-oxygen scavengers from natural resources. Most of the 70 herbal medicines showed scavenging activity with various intensities. Areca catechu (methanol extract), Dendrobium plicatile (methanol extract), Juglans regia (water extract), Paeonia lactiflora (methanol extract), Psychotria serpens (water and methanol extracts), Rhodiola sacra (water and methanol extracts) and Uncaria rhynchophylla (water extract) especially showed strong scavenging activity against superoxide anion radical (*O2-), while J. regia (water and methanol extracts), Morus alba (water extract) and Schisandra chinensis (water extract) revealed strong scavenging activity against hydroxyl radical (HO*). In addition, the active-oxygen scavenging activities of 19 compounds isolated from R. sacra were also examined, and hydroquinone (1), caffeic acid (3), protocatechuic acid (6), gallic acid (7), (-)-epigallocatechin 3-O-gallate (8), 3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate (10), heterodendrin (17) and gallic acid 4-O-beta-D-glucopyranoside (19) were found to show mild or strong inhibitory activity against superoxide anion radical (*O2-), while 4-hydroxybenzoic acid (2), 3, 4-hydroxycinnamic acid (4), 6-8 and 19 inhibited hydroxyl radical (OH*). These active-oxygen scavengers may contribute, to different extents, to their anti-aging action.

Antioxidants↗

PubMed1999

Screening of crude drug extracts for prolyl endopeptidase inhibitory activity.

Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme to play a role in metabolism of proline-containing neuropeptides, such as vasopressin, substance P and thyrotropin-releasing hormone (TRH), which were suggested to be involved with learning and memory processes. Then, specific inhibitor of PEP is expected to have antiamnesic effects, and thus we screened forty-six water- and methanol-extracts from crude drugs selected on the basis of traditional Chinese medicine theory, for Flavobacterium prolyl endopeptidase inhibition. Among them, the water-extracts of Rhodiola sacra (IC50, 0.77 microgram/ml) and the methanol-extracts of Lycopodium clavatum (IC50, 1.3 micrograms/ml), Paeonia lactiflora var. trichocarpa (IC50, 5.7 micrograms/ml), Paeonia veitchii (IC50, 2.4 micrograms/ml) and Rhodiola sacra (IC50, 0.67 microgram/ml) showed strong inhibitory activity. In addition, we also examined the PEP inhibitory activity of eleven compounds from Salvia deserta, and found that in addition to a catechol group alpha-hydroxy-para-quinone group may be related to the PEP inhibition.

China↗