• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.115-121
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• 2011

에토포시드와 아피제닌의 약동학적 상호작용 연구를 위하여 아피제닌 (0.4, 2.0 또는 8 mg/kg)과 에토포시드의 경구(6 mg/kg) 및 정맥 (2 mg/kg) 투여 하여 본 연구를 실시하였다. 아피제닌이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다. 아피제닌의 CYP3A4의 50% 효소활성억제는 $1.8{\mu}M$ 이었다. 아피제닌은 MCF-7/ADR 세포의 로다마인-123 세포 축적을 증가 시키므로 P-gp를 억제시켰다. 아피제닌은 에토포시드의 혈장곡선하면적과 최고혈장농도 (AUC and $C_{max}$)를 유의성 있게 증가시켰으나, 에토포시드의 최고혈장농도 도달시간 ($T_{max}$)과 생물학적 반감기 ($t_{1/2}$)에는 영향을 미치지 않았다. 따라서, 아피제닌 존재하에 에토포시드의 절대적생체이용률 (AB)은 대조군과 비교하여 유의성있게 증가되었다. 경구투여시와는 대조적으로, 아피제닌은 정맥 내로 투여된 에토포시드에서는 약동학적 파라미터에 어떤 영향도 미치지 않았다. 따라서 아피제닌이 에토포시드의 생체이용률을 증가시킨 것은 아피제닌이 소장과 간장에서 CYP3A4을 억제 및 소장에서 P-gp를 억제 시켰기 때문으로 사료된다.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.485-491
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• 2011

Previously, we have reported that apigenin, a natural flavonoid found in a variety of vegetables and fruits, stimulated melanogenesis through the activation of $K^+-Cl^-$-cotransport (KCC) in B16 melanoma cells. In this study we investigated the possible involvement of reactive oxygen species (ROS) in the mechanism of apigenin-induced melanogenesis in B16 cells. Apigenin elevated intracellular ROS level in a dose-dependent manner. Treatment with various inhibitors of NADPH oxidase, diphenylene iodonium (DPI), apocynin (Apo) and neopterine (NP) significantly inhibited both the generation of ROS and melanogenesis induced by apigenin. In addition these inhibitors profoundly inhibited apigenin-induced $Cl^-$-dependent $K^+$ efflux, a hallmark of KCC activity. However, the apigenin-induced ROS generation was not significantly affected by treatment with a specific KCC inhibitor R-(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]acetic acid (DIOA). These results indicate that the ROS production may be a upstream regulator of the apigenin-induced KCC stimulation, and in turn, melanogenesis in the B16 cells. Taken together, these results suggest that the NADPH oxidase-mediated ROS production may play an important role in the apigenin-induced melanogenesis in B16 cells. These results further suggest that NADPH oxidase may be a good target for the management of hyperpigmentation disorders.

• YAKHAK HOEJI
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• v.52 no.6
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• pp.500-506
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• 2008

Apigenin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. In this study we found that apigenin stimulated melanin synthesis in a dose-dependent manner in B16 murine melanoma cells. Since in our previous study $K^+$-$Cl^-$-cotransport (KCC) has been shown to mediate the mechanism of action of apigenin in neuronal cells, we further investigated the role of KCC in the melanogenesis-stimulating effect of apigenin in B16 cells. At nontoxic concentrations apigenin induced $Cl^-$-dependent $K^+$ efflux, a hallmark of KCC activity, which was markedly prevented by a specific KCC inhibitor R-(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]acetic acid (DIOA). These results indicate that KCC is functionally present, and activated by apigenin in the B16 cells. In addition, the apigenin-induced stimulation of melanogenesis was also significantly inhibited by DIOA. NEthylmaleimide (NEM), a known KCC activator, induced $Cl^-$ efflux and stimulated melanogenesis in a concentration-dependent fashion. Both effects of NEM were significantly inhibited by DIOA. Taken together, these results suggest that apigenin can modulate melanogenesis through the activation of a membrane ion transporter, KCC in B16 cells. These results further suggest that apigenin may be a good candidate in the therapeutic strategy for hypopigmentation disorders, such as vitiligo.

• YAKHAK HOEJI
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• v.54 no.5
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• pp.370-376
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• 2010

The aim of this study is to investigate the effect of apigenin on the pharmacokinetics of tamoxifen in rats. Tamoxifen was administered orally (10 mg/kg) or intravenously (2 mg/kg) without or with oral administration of apigenin (0.4, 2.0 or 8.0 mg/kg) to rats. The effect of apigenin on the P-glycoprotein (P-gp) and CYP3A4 activity was also evaluated. Apigenin inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly enhanced the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. The plasma concentrations of tamoxifen were increased significantly by apigenin compared to control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations ($IC_{max}$) of tamoxifen with apigenin were significantly higher than those of the control group. Consequently, the relative bioavailability (RB%) of tamoxifen with apigenin was 2-3-fold higher than the control, and absolute bioavailability (AB%) of tamoxifen were significantly higher (p<0.05 with co-administration, p<0.01 with pretreatment) than those of the control. The increased bioavailability of tamoxifen in rats with apigenin might be associated with the inhibition of an efflux pump P-glycoprotein and CYP3A4 by apigenin. From these results, dosage regimen of tamoxifen may be need to adjust when concomitantly administered with apigenin.

• Journal of the Korean Applied Science and Technology
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• v.40 no.5
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• pp.1010-1021
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• 2023

In this study, we would like to confirm the collagen recovery effect through cell experiments of the flavonoid apigenin and baicalein and propose results that can support the collagen recovery effect through comparative transcriptome analysis. As a result of the study, it was confirmed that apigenin and baicalein were effective in recovering type I collagen damaged by UV in the HS68 cell line, and that both substances resulted in changes in the expression of ECM-related genes. Not only did it show a common mechanism for regulating the ECM, but it also showed the results of changing different categories of genes, making it possible to predict that it would have various effects on cells.

• Journal of Applied Biological Chemistry
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• v.63 no.3
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• pp.249-257
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• 2020

This study investigated whether the extracts from cosmos flowers exhibit antibacterial activities and identified which components were ascribed to the antibacterial effects. The antibacterial effects of extracts from white, pink, and violet cosmos flowers were observed for 24 h after inoculation with four kinds of bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli. Among the three fractions of cosmos flower extracts, the best antibacterial activity against the four bacteria was observed in the extracts isolated from the EtOAc layer. However, the extracts from the CHCl₃ layer were also effective against S. aureus. Moreover, the first of white, second of pink, and first of violet silica gel fractions (Fr.) isolated from the EtOAc layer exhibited minimal inhibition at a concentration of 0.1 mg/mL. Comparison of NMR and High-Pressure Liquid Chromatography results between silica gel Fr. and apigenin suggested that the effective fractions can contain a component including apigenin moiety.

• The Korean Journal of Food And Nutrition
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• v.34 no.2
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• pp.233-241
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• 2021

The purpose of this study was to investigate the contents of apigenin and luteolin in vegetables mainly distributed and consumed in Korea. In this study, the contents of apigenin, apigenin-7-O-glucoside, luteolin, and luteolin-7-O-glucoside in vegetables were surveyed by using liquid chromatography coupled to mass spectrometry (LC-MS/MS). According to the analysis of 27 items (91 samples) in vegetables, the content of total apigenin (the sum of apigenin and apigenin-7-O-glucoside) was quantified in 8 out of the 27 items in vegetables, followed by pepper leaves, parsley, celery, chamnamul, foremost mugwort, and perilla leaves. The content of total luteolin (the sum of luteolin and luteolin-7-O-glucoside) was found in 11 of the 27 items in vegetables, followed by pepper leaves, dandelion, celery, red lettuce, foremost mugwort, and perilla leaves. Celery was divided into stalks and leaves for comparing the contents of apigenin and luteolin. Celery showed higher contents of apigenin and luteolin in leaves than in stalks.