• 대한화학회지
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• 제26권3호
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• pp.172-178
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• 1982

4',5'-디히드로소랄렌(DHP)을 합성하여 상온 및 77K에서 이 화합물의 형광 양자수율은 0.08, 인광양자수율은 0.013, 형광수명은 0.95ns, 인광수명은 0.039s 임을 알았다. 이 결과로부터 형광수명은 5,7-디메톡시쿠마린보다 작은반면 소랄렌보다 크고 반면 인광수명은 DMC 보다 크고 소랄렌보다 작음을 알았다. 소랄렌 유도체들의 광독성을 분자적 차원에서 규명하고 DNA에의 광부가 반응을 알아내기 위하여 DHP와 TME의 광부가 반응을 연구하였다. 주 생성물은 TLC로 분석하고 Preparative TLC와 용매추출로 분리해냈다. 분리된 생성물의 구조는 질량분석기, UV, IR, NMR 그리고 원소분석결과에 의해 DHP와 TME외 광고리화첨가반응에 의한 생성물 임을 알았다. DHP는 형광의 자체소광 효과를 볼 수 없으며 TME, 에틸푸마레이트, 푸마로니트릴에 의해 형광이 효과적으로 소광된다. 광부가 반응의 양자수율과 소광실험에서 DHP의 광첨가반응은 단일상태와 삼중상태에서 다 일어나는 것으로 추측된다.

• Archives of Pharmacal Research
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• 제29권8호
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• pp.617-623
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• 2006

In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2\;(PGD_2)$ and leukotriene $C_4\;(LTC_4)$ in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with ${\beta}-sitosterol$ (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was isolated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)- marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids.

• The Korean Journal of Physiology and Pharmacology
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• 제6권5호
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• pp.275-279
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• 2002

Nerve growth factor (NGF) is an important autocrine growth factor and also a survival factor for keratinocytes. NGF may act in the hyperproliferative condition, psoriasis. Clinically, the combination of psoralen and UVA (PUVA) has been used in the treatment of a wide variety of cutaneous disorders, such as psoriasis and vitiligo. However, the precise therapeutic mechanism of PUVA on the dermatologic diseases remains unclear. The purpose of this study was to examine whether the expression of NGF in cultured keratinocytes is influenced by PUVA. Thus, normal human keratinocytes were isolated from neonatal foreskin, and the third to fifth-passaged cells were used in this study. The cells were exposed to various doses of UVA (30, 60, 120 $mJ/cm^2)$ after adding 8-methoxypsoralen (8-MOP) to examine the expression of NGF mRNA. The RNA and protein of the cells were extracted at various time points (1, 8, 24 hours) after UVA irradiation to examine the expression of NGF mRNA and production of NGF protein. In keratinocytes, there were no differences in the expression of NGF mRNA between the different doses of UVA irradiation, however, the expression of NGF mRNA in UVA and PUVA groups tended to increase as the time increased. The expression of NGF mRNA was the highest in PUVA group, followed by UVA group and the lowest in 8-MOP group. The expressions of NGF protein at 1 and 8 hours after UVA irradiation were lower in the PUVA group than in the other groups. This study showed that the expression level of NGF protein in keratinocytes was relatively lower in the PUVA groups than in the other groups, suggesting that the therapeutic mechanism of PUVA in psoriasis is related to the decrease of NGF protein.

• Mass Spectrometry Letters
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• 제8권2호
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• pp.23-28
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• 2017

Arctigenin is the main active ingredient of Fructus Arctii, which has been reported with a variety of therapeutic activities including anti-cancer, anti-inflammation, anti-virus, and anti-obesity effects. In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arctigenin in rat plasma. The assay utilized a simple protein precipitation with methanol and the mobile phase consisted of 100% methanol and water containing 0.1% formic acid (65:35 v/v). Arctigenin and the internal standard (psoralen) were monitored using a positive electrospray turbo ionspray mode with multiple reaction monitoring transitions of m/z $373.2{\rightarrow}136.9$ and m/z $187.2{\rightarrow}130.9$, respectively, and total chromatographic run time was within 5 min. The lower limit of quantification (LLOQ) of arctigenin was 5 ng/mL in the rat plasma. The intra- and inter-day accuracy of arctigenin at LLOQ and matrix-matched quality control samples ranged 97.4 - 104.8% and 97.2 - 102.0%, respectively. The intra-day precision was within 4.80% and the inter-day precision was within 5.92%. Application of the present method was demonstrated through a pharmacokinetic study after intravenous and oral administration of arctigenin in male Sprague Dawley rats.

• Journal of Oral Medicine and Pain
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• 제25권2호
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• pp.159-165
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• 2000

Subsequent to an allogenic stem cell transplantation(ASCT) on patients with hematologic malignancy(AML, ALL, CML, multiple myeloma, lymphoma etc.), chronic GVHD(graft versus host disease), which is an immunological reaction, occurs. With treatment results from patients who were diagnosed with ALL(acute lymphocytic leukemia), undergone BMT(bone marrow transplantation) and showed oral and skin lesions due to GVHD, treatment of oral manifestations of leukemia and its general management were studied. 90% of patients with chronic GVHD show change in the oral mucosa causing oral manifestations such as leukoplakia, lichenoid change of the oral mucosa, mucosal atrophy, erythema, ulceration and xerostomia. In treating GVHD, extensive systemic immunosuppression cause bacterial, viral, fungal infection that are fatal, and even if the treatment is successful, the patient is already in a severe immunosuppressed state. Therefore, localized target therapy is preferred. In another words, topical application(rinse, cream, ointment etc.) of cyclosporin and steroid in treating oral chronic GVHD is highly recommended, and the use of PUVA(Psoralen Ultraviolet A) and thalidomide is reported to be effective. In treating such diseases, dental treatment to control pain and prevent secondary infection of oral manifestations is very important. To those patients with systemic diseases who show limited effect by general dental treatment, non-invasive treatment such as the dental laser, in addition to the use of drugs, may be necessary to actively treat pain and help the healing process. For greater results, new effective methods are to be developed for treatment.

• Biomolecules & Therapeutics
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• 제31권2호
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• pp.219-226
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• 2023

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOP-induced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

• 생명과학회지
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• 제15권4호
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• pp.542-547
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• 2005

시스플래틴이나 마이토마이신 C (MMC)와 같은 DNA 사슬간 교차결합 (interstrand cross-link ; ICL) 물질에 대해 Brca1 결손세포들이 보이는 높은 감수성은 Brca1 단백질이 세포의 ICL복구반응에 중요한 역할을 담당하고 있음을 암시하고 있다. Brca1 단백질은 재조합 의존성 또는 재조합 비의존성 경로를 통한 DNA 이중사슬 절단(double-strand break ; DSB) 복구에 필수적인 역할을 담당한다. 최근 본인이 속한 연구그룹에서 재조합 의존성 경로를 통한 세포의 ICL복구반응에 Brca1이 관여한다는 것을 밝혀 보고한바 있다. 본 연구에서는 Brca1 단백질의 재조합 비의존성 복구반응에 대한 관여여부를 $p53^{-/-}$와 $p53^{-/-}\;Brcal^{-/-}$ 세포주를 사용하여 연구하였다. 교차결합 복구 실험에서 Brca1 결손 세포주는 Brca1 정상 세포주보다 현저히 낮은 활성을 보였다. 또한, Brca1 결손세포 주의 MMC 에 대한 감수성과 ICL복구능이 Brca1 단백질 발현을 통해 회복되는 것을 확인하였다. 흥미롭게도, Brca1의 11번 엑손 결손세포주 $(Brca1^{\Delta11})$는 높은 MMC저항성과 ICL 복구능을 보였다. 이러한 결과들을 종합하여 볼 때, Brca1 단백질은 ICL복구에 재조합 의존성 경로뿐만 아니라 재조합 비의존성 경로를 통해서도 관여하며, 이러한 활성에는 엑손 11 부분이 아닌 N 말단의 RING 핑거 도메인이나 C 말단의 BRCT도메인이 중요하다는 것을 알 수 있다.