Flavonoids in the black rhizomes of Boesenbergia panduta

Jaipetch, Tharworn; Reutrakul, Vichai; Tuntiwachwuttikul, Pittaya; Santisuk, Thawatchai

doi:10.1016/0031-9422(83)83075-1

Cited by 91 publications

(42 citation statements)

References 11 publications

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“…7-MF is found in the extract from Meliaceae and Rutaceae plants (Ambrozin et al, 2004), and 7,4Ј-DMF has been identified in fruits and leaves from neotropical nutmeg species (Cavalcante et al, 1985;Santos et al, 1996), as well as from propolis (Popravko et al, 1969). 5,7-DMF, as mentioned in a previous study, was found in the leaves of a Malaysian Piper species (Ahmad et al, 1997), and 5,7,4Ј-TMF is a citrus flavonoid, present also in other plants used in folk medicine (Jaipetch et al, 1983;Yenjai et al, 2004). Several of these compounds have already been described as having potent cancer chemopreventive properties at the cancer initiation stage Walle, 2005, 2006a;Tsuji and Walle, 2006).…”

Section: Discussionmentioning

confidence: 97%

Methylated Flavonoids Have Greatly Improved Intestinal Absorption and Metabolic Stability

2006

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ABSTRACT:To better understand the relationship between the chemical structure and biological fate of dietary polyphenols, the hepatic metabolic stability and intestinal absorption of methylated polyphenols, in comparison with unmethylated polyphenols, were investigated in pooled human liver S9 fraction and human colon adenocarcinoma (Caco-2) cells. Consistent with previous in vivo studies, the two well known unmethylated polyphenols resveratrol (3,5,4-trihydroxystilbene) and quercetin (3,5,7,3,4-pentahydroxyflavone) were rapidly eliminated by the S9 fraction in the presence of the appropriate cofactors for conjugation and oxidation. In contrast, the methylated flavones, i.e., 7-methoxyflavone, 7,4-dimethoxyflavone, 5,7-dimethoxyflavone, and 5,7,4-trimethoxyflavone, were relatively stable, indicating high resistance to hepatic metabolism. The corresponding unmethylated flavones, i.e., 7-hydroxyflavone, 7,4-dihydroxyflavone, chrysin (5,7-dihydroxyflavone), and apigenin (5,7,4-trihydroxyflavone), were rapidly eliminated because of extensive glucuronidation and/or sulfation just as resveratrol and quercetin were. The rate of intestinal absorption was evaluated using Caco-2 cells grown in porous inserts. The methylated flavones showed approximately 5-to 8-fold higher apparent permeability (P app , 22.6-27.6 ؋ 10 ؊6 cm s ؊1 ) of apical to basolateral flux than the unmethylated flavones (P app , 3.0-7.8 ؋ 10 ؊6 cm s ؊1 ). The lower P app values for the unmethylated flavones correlated with their extensive metabolism in the Caco-2 cells. Thus, combined use of the hepatic S9 fraction and Caco-2 cells will be useful for predicting the oral bioavailability of dietary polyphenols. The higher hepatic metabolic stability and intestinal absorption of the methylated polyphenols make them more favorable than the unmethylated polyphenols to be developed as potential cancer chemopreventive agents.

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Section: Discussionmentioning

confidence: 97%

Methylated Flavonoids Have Greatly Improved Intestinal Absorption and Metabolic Stability

2006

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“…For example, 5,7,4'-TMF is a citrus flavonoid [39], also present in other plants used in folk medicine [40,41]. 7,4'-DMF has been identified in fruits and leaves from neotropical nutmeg species [42,43] as well as from propolis [44].…”

Section: Discussionmentioning

confidence: 99%

Cancer chemopreventive properties of orally bioavailable flavonoids—Methylated versus unmethylated flavones

Walle

Kawamori

et al. 2007

Biochemical Pharmacology

197

175

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Poor oral bioavailability has been a major limitation for the successful use of dietary flavonoids as cancer chemopreventive agents. In this study, we examined fully methylated flavones as promising improved agents. In the humanoral SCC-9 cancer cells, 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone were both ten times more potent inhibitors of cell proliferation (IC 50 values 5-8 μM) than the corresponding unmethylated analogs chrysin and apigenin. Flow cytometry indicated that both methylated flavones arrested the SCC-9 cells in the G1 phase with a concomitant decrease in the S phase, dramatically different from the unmethylated analogs, which promoted G2/M phase arrest. Both methylated compounds inhibited the proliferation of two other cancer cell lines with very little effect on two immortalized normal cell lines. Examination of additional flavone structures indicated that methylated flavones in general have antiproliferative properties. Finally, we demonstrated that 5,7-dimethoxyflavone, in contrast to its unmethylated analog chrysin, was well absorbed and had high oral bioavailability as well as tissue accumulation in vivo in the rat. Thus, fully methylated flavones appear to have great potential as cancer chemopreventive/ chemotherapeutic agents, in particular in oral cancer.

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“…5,7-DMF is abundant in the leaves of a Malaysian Piper species (Ahmad et al, 1997) and has been found in several herbs, and 5,7,4Ј-TMF, like sinensetin and tangeretin, is a citrus flavonoid, present also in other plants used in folk medicine (Jaipetch et al, 1983;Yenjai et al, 2004). 5,7-DMF and 3Ј,4Ј-DMF have already been described as having potent cancer chemopreventive properties at the cancer initiation stage .…”

Section: Discussionmentioning

confidence: 99%

Bioavailable Flavonoids: Cytochrome P450-Mediated Metabolism of Methoxyflavones

Walle

Walle²

2007

Drug Metab Dispos

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ABSTRACT:Methoxylated flavones were recently shown to be promising cancer chemopreventive agents. Their high metabolic stability compared with the hydroxylated analogs was shown in our laboratory using the human hepatic S9 fraction with cofactors for glucuronidation, sulfation, and oxidation. In the present study, the resistance of methoxylated flavones toward oxidative metabolism was investigated with human liver microsomes and recombinant cytochrome P450 (P450) isoforms. Among 15 methoxylated flavones investigated, the two partially methylated compounds, tectochrysin and kaempferide, were among the most susceptible to microsomal oxidation (Cl int 283 and 82 ml/min/kg). Of the fully methylated compounds, 5,7-dimethoxyflavone and 5-methoxyflavone were the most stable (Cl int 13 and 18 ml/min/kg, respectively), whereas 4-methoxyflavone, 3-methoxyflavone, 5,4-dimethoxyflavone, and 7,3-dimethoxyflavone were the least stable (Cl int 161, 140, 119, and 92 ml/min/kg, respectively), emphasizing the importance of the positions of the methoxy substituents in the flavone ring system. Among the five P450 isoforms tested, CYP1A1 showed the highest rate of metabolism of fully methylated compounds, followed by CYP1A2 and CYP3A4. CYP2C9 and CYP2D6 gave minimal disappearance of the parent compound. Finally, in incubations with hepatic S9 fraction with cofactors for oxidation and both conjugation reactions, partially methylated flavones, as expected, were much less metabolically stable than fully methylated flavones, confirming that oxidative demethylation is the ratelimiting metabolic reaction for fully methylated flavones only. In summary, the rate of oxidative metabolism of methoxylated flavones, mainly involving CYP1A1 and CYP1A2, varied widely, even between compounds with very similar structures.

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Flavonoids in the black rhizomes of Boesenbergia panduta

Cited by 91 publications

References 11 publications

Methylated Flavonoids Have Greatly Improved Intestinal Absorption and Metabolic Stability

Methylated Flavonoids Have Greatly Improved Intestinal Absorption and Metabolic Stability

Cancer chemopreventive properties of orally bioavailable flavonoids—Methylated versus unmethylated flavones

Bioavailable Flavonoids: Cytochrome P450-Mediated Metabolism of Methoxyflavones

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