• 약학회지
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• 제48권4호
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• pp.226-230
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• 2004

The pharmacokinetics of orally administered paclitlxel (50 mg/kg) was studied in six rabbits after 1hr pretreatment (2.0 mg/kg and 10 mg/kg) of tetramethoxyflavone or coadministration of (2.0 mg/kg, 10 mg/kg and 20 mg/kg) tetramethoxyflavone. The area under the plasma concentration-tine curve (AUC) and plasma concentration of paclitaxe1 coadministered with tetramethoxyflavone (10 mglkg) were increased significantly (p<0.05) compared with control. However, coadministration of tetramethoxyflavone (2 and 20 mg/kg) showed no significant effect on the pharmacokinetic parameters of paclitaxel. Pretreatment with tetramethoxyflavone significantly (p<0.05) increased the plasma concentration of paclitaxel. The area under the plasma concentration-time curve (AUC) and the peak concentration (C$_{max}$) of paclitaxel pretreated with tetramethoxyflavone were increased significantly (p<0.01, p<0.05) compared with control. The terminal half. life of paclitaxel pretreated with tetramethoxyflavone (2 mg/kg and 10 mg/kg) was significantly (p<0.05) prolonged compared with control. Pretreatment with tetramethoxyflavone (2.0 mg/kg, 10 mg/kg) significantly (p<0.01, p<0.05) increased the absolute bioavailability of paclitaxel compared with the control (154∼179%). On the basis of the results, it might be considered that tetramethoxyflavone may inhibit cytochrome P450 or P-glycoprotein efflux pump which are engaged in paclitaxel metabolism, result in increased AUC and t$_{1}$2/ of paclitaxel. However, further study should be conducted to clarify the roles of cytochrome P450 and P-glycoprotein on paclitaxel bioavailability with/or without tetramethoxyflavone. P-glycoprotein on paclitaxel bioavailability with/or without tetramethoxyflavone.

• 생약학회지
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• 제36권3호통권142호
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• pp.186-190
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• 2005

Searching for inhibitors of lipopolysaccharide (LPS)-induced IL-6 (Interleukin-6) production from medicinal herbs, we isolated two active compounds though bioactivity-guided fractionation from the methanol extract of Chrysanthemum indicum L.. They were determined as kikkanol F monoacetate (1) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (2) by means of spectroscopy techniques such as NMR and MS. The compound 1 and 2 inhibited LPS-induced IL-6 production in the PAW264.7 cells with $IC_{50}$ value of $47\;{\mu}g/ml$ and $27\;{\mu}g/ml$, respectively.

• Natural Product Sciences
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• 제2권2호
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• pp.106-114
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• 1996

Four polymethoxyfavones were isolated from the leaves of Citrus deliciosa, three of which (nobiletin, 5-O-demethylnobiletin, and tangeritin) are bioactive. The fourth (7,4'-dihydroxy-5,6,8,3'-tetramethoxyflavone) is reported for the first time in the genus Citrus and is a potential chemotaxonomic marker. The structures of these flavones were confirmed by analysing their spectral data and comparison with similar compounds. The previously reported $^{13}C$ NMR assignment of 5-O-demethylnobiletin has been revised on the basis of 2D NMR experiments (HETCOR, COSY, and COLOC). The chemotaxonomic value of the present finding is verified.

• Archives of Pharmacal Research
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• 제29권3호
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• pp.199-202
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• 2006

From the leaves of Goniothalamus tenuifolius, a new natural product namely 3'-hydroxy-3,5,7,4'-tetramethoxyflavone (1) was isolated, along with seven other known compounds (2-8). Each of these isolates was evaluated for free radical scavenging activity on the DPPH decoloration test. The data obtained in this study suggested that the ortho 3',4'-diphenolic structure was essential for the activity of these flavonol derivatives.

• Archives of Pharmacal Research
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• 제10권4호
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• pp.260-261
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• 1987

The UV-pattern of several flavones, theier cytotoxicities against L1210 cell and their Inhibiting effects on ATPase from the cell seem to be correlated. 5.2'-Dihydroxy 6, 7, 8, 6'-tetramethoxyflavone ($ED_{50}$ = 2.3 ug/ml) and 5,2',6'-trihydroxy-6, 7, 8 trimethoxy flavone ($ED_{50}$ = 4.5 ug/ml), the most active flavones studied, have shown a narrow range of the absorbance ratio, Log $\varepsilon$ II/Log $\varepsilon$ I = 1.073 -1.109. They have inhibited the ATPase-activity to the greatest extent. These finding ssuggest that a certain angle between the flavone rings B and C plays an important role for the inhibition of the enzyme activity and thus the cytotoxicity.

• Archives of Pharmacal Research
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• 제8권4호
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• pp.253-256
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• 1985

The effect of skullcapflavon II, 5, 2'- dihydroxy-6, 7, 8, 6'-tetramethoxyflavone, on the growth of transplantable L 1210 and sarcoma 180 tumors in mice was studied. Intraperitional treatment of skullcapflavon II cased a significant (T/C = 166%) and a moderate (T/C = 122 %) prolongations of the life spans of ICR and $BDF_{1}$ mice respectively, which had been intraperitioneally inoculated with sarcoma 180 and L 1210 cells. Peritumoral injection of skullacapflavon II on the solid form of sarcoma 180 in mice inhibited the tumor growth strongly (Inhibition rate = 71%).

• 대한화학회지
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• 제65권5호
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• pp.327-332
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• 2021

Shiranuhi is a fruit of Citrus species widely cultivated in Jeju Island, Korea. From an extract of Shiranuhi tree branches were identified five polymethoxyflavones possessing anti-inflammatory effects; nobiletin (1), sinensetin (2), tetramethylscutellarein (3), 6-hydroxy-5,7,3',4'-tetramethoxyflavone (4) and 5-desmethylsinensetin (5). Evaluation of the activities was conducted by monitoring the production of nitric oxide (NO), prostaglandin E₂ and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) as well as the levels of iNOS and COX-2 protein expression in LPS-induced RAW264.7 cells. Among the isolates, the compound 4 exhibited the most significant NO inhibition, and suppressed the levels of iNOS and related cytokines. Therefore, it was suggested that the extract and constituents from Shiranuhi tree branches could be useful as anti-inflammatory ingredient.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9049-9058
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• 2014

Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone) is an active compound isolated from roots, stems, leaves, fruits and seeds of a variety of plants. It is well known for its pharmacological properties and has been utilized as an anti-hyperprolactinemia, anti-tumor, anti-inflammatory, neuroprotetective, analgesic and immunomodulatory agent. Recently, the anticancer activity of casticin has been extensively investigated. The resulkts showed that it exerts protective potential by targeting apoptosis, considered important for cancer therapies. In this article, our aim was to review the pharmacological and therapeutic applications of casticin with specific emphasis on its anticancer functions and related molecular mechanisms. Chemotherapeutic effects are dependent on multiple molecular pathways, which may provide a new perspective of casticin as a candidate anti-neoplastic drug. This review suggests that additional studies and preclinical trials are required to determine specific intracellular sites of action and derivative targets in order to fully understand the mechanisms of its antitumor activity and validate this compound as a medicinal agent for the prevention and treatment of various cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6369-6374
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• 2012

Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an $IC_{50}{\sim}28.8{\mu}M$. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.

• Journal of Nutrition and Health
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• 제42권3호
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• pp.278-290
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• 2009

제주재래종 감귤류 14종의 착즙액에 대해서 수확시기별 flavonoids 13종의 함량변화를 분석하고 항산화성을 검토하고자 하였다. 감귤착즙액의 flavonoids 함량은 수확시기가 늦어질 수록 큰 폭으로 감소하다가 4${\sim}$5차 채취기 이후 서서히 증가하는 경향을 보였다. Quercatagetin, narirutin, hesperidin, neohesperidin은 각각 지각 573.73 mg/100 mL, 사두감 393.99 mg/100 mL, 소유자 29.63 mg/100 mL, 지각 201. 23 mg/100mL으로 미숙과인 8월 하순에 가장 높았다. Polymethoxyflavone류 중 nobiletin, sinensetin, tangeretin은 홍귤에서 8월 하순에 각각 7.39 mg/100 mL, 2.24 mg/100 mL, 0.63 mg/100 mL으로 가장높았고, 다음으로 진귤이 많이 함유되어 있었다. 3,5,6,7,8,3',4'-Heptamethoxyflavone은 편귤에서 0.27 mg/100mL으로 가장 높았고, 3',4',7,8-tetramethoxyflavone, 3',4'-dimethoxyflavone, 4'-methoxyflavone, 5,6,7,3',4',5'-hexamethoxyflavone, scutellarein tetramethylether는 모든 품종에서 ND${\sim}$0.08 mg/100mL로 함량이 낮았다. 총 폴리페놀 함량은 대부분의 시료가 미숙과인 8월 하순에 가장 높았다가 11월까지 감소하다가 12월 하순부터 증가하는 경향을 보였다. 감귤착즙액의 전자공여능은 대체적으로 높은 것으로 나타났으나 flavonoids와 총폴리페놀 함량과의 상관관계는 높지 않은 경향을 보였고 당유자가 가장 높은 항산화활성을 나타내었다. 재래 감귤류 중 지각, 당유지는 quercetagetin이 다른 감귤류에 비해 월등히 높았고, polymethoxyflavone류인 nobiletin과 tangeretin은 미숙과인 홍귤과 진귤에서 함량이 높아 소재 개발로서 경쟁력이 있을 것으로 사료된다.