Dipiperamides A, B, and C: bisalkaloids from the white pepper Piper nigrum inhibiting CYP3A4 activity

Tsukamoto, Sachiko; Cheon, Bae; Ohta, Tomihisa

doi:10.1016/s0040-4020(02)00048-0

Cited by 44 publications

(33 citation statements)

References 23 publications

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“…To date, highly potent CYP3A4 inhibitors in food have been reported, e.g. paradisins A and B (IC 50 , 0.07 and 0.07 µM) from grapefruit juice (15), dipiperamide A (IC 50 , 0.18 µM) from white pepper (17) and gomisin C (IC 50 , 0.254 µM) from Schisandra fruit (29). Although the IC 50 value of each isolate was moderate, the high content of a series of cognates in the supplement could result in the exhibition of significant CYP inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, the inhibition by grapefruit juice has been well studied and it is reported that concomitant intake of the juice alters the pharmacokinetics of various drugs, including cyclosporin (9,10), midazolam (11), dihydropyridine-type calcium channel blockers (12) and triazolam (13). In the course of our study on CYP inhibitors from foods, we have reported the isolation and structural elucidation of CYP inhibitors from grapefruit ( Citrus paradisii ) juice (14–16), white pepper, Piper nigrum (17,18) and the strawberry fruit, Fragaria ananassa (19). Recently, we found that the commercially available black cohosh, C. racemosa Nutt, showed CYP3A4 inhibition.…”

Section: Introductionmentioning

confidence: 99%

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Isolation of CYP3A4 Inhibitors from the Black Cohosh (Cimicifuga racemosa)

Tsukamoto

Aburatani

Ohta

2005

Evidence-Based Complementary and Alternative Medicine

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Recent investigation on drug interaction has shown that some foods and herbal medicines increase the oral availability of a variety of CYP3A4 substrates, which is caused by the reduction of CYP3A4 in intestinal epithelium. During the course of our investigation on CYP3A4 interaction, we found that the commercially available dietary supplement made from black cohosh (Cimicifuga racemosa) showed CYP3A4 inhibition. Black cohosh has been used for the treatment of menopausal and post-menopausal symptoms as a dietary supplement. Bioassay-guided isolation from the supplement afforded six active principles, which were identified as cycloartanoid triterpene glycosides.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Isolation of CYP3A4 Inhibitors from the Black Cohosh (Cimicifuga racemosa)

Tsukamoto

Aburatani

Ohta

2005

Evidence-Based Complementary and Alternative Medicine

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“…Moreover, pipernonaline, guineensine, isobutylamide of 11-(3,4-methylenedioxy-phenyl)undeca-2,4,10-trienoic acid, piperchabamides A, piperchabamides B, piperchabamides C, piperlonguminine, retrofractamide B, N-isobutyl-(2E,4E,14Z)-eicosatrienamide and methylpiperate were isolated from Piper chaba by Dagli (2004). Several compounds, including pipercyclobutanamides A, B (Fujiwara et al, 2001), dipiperamides A, B, C (Tsukamoto et al, 2002), germacrene D, limonene,ˇ-caryophyllene, -phellandrene,ˇ-pinene,˛-pinene, cis-ˇ-ocimene (Jirovetz et al, 2002), piperylin, alkamide, retrofractamide A, pipercide, pellitorin, and dehydroretrofractamide C were discovered in Piper nigrum (Rho et al, 2007).…”

Section: Plants With Anthelmintic Activitymentioning

confidence: 99%

In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand

Atjanasuppat

Wongkham

Meepowpan

et al. 2009

Journal of Ethnopharmacology

111

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“…In cDNA-expressed human microsomes, piperine inhibited CYP3A4 activity (Tsukamoto et al, 2002). Singh and coworkers (2000) reported the structure -activity relationships of piperine and its analogues for CYP inhibitory activity and found that saturation of the side chain resulted in enhancement of CYP inhibition.…”

Section: Piperinementioning

confidence: 99%

Interactions of Herbs with Cytochrome P450

Zhou

Gao²,

Jiang

et al. 2003

Drug Metabolism Reviews

358

207

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A resurgence in the use of medical herbs in the Western world, and the co-use of modern and traditional therapies is becoming more common. Thus there is the potential for both pharmacokinetic and pharmacodynamic herb-drug interactions. For example, systems such as the cytochrome P450 (CYP) may be particularly vulnerable to modulation by the multiple active constituents of herbs, as it is well known that the CYPs are subject to induction and inhibition by exposure to a wide variety of xenobiotics. Using in vitro, in silico, and in vivo approaches, many herbs and natural compounds isolated from herbs have been identified as substrates, inhibitors, and/or inducers of various CYP enzymes. For example, St. John's wort is a potent inducer of CYP3A4, which is mediated by activating the orphan pregnane X receptor. It also contains ingredients that inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Many other common medicinal herbs also exhibited inducing or inhibiting effects on the CYP system, with the latter being competitive, noncompetitive, or mechanism-based. It appears that the regulation of CYPs by herbal products is complex, depending on the herb type, their administration dose and route, the target organ and species. Due to the difficulties in identifying the active constituents responsible for the modulation of CYP enzymes, prediction of herb -drug metabolic interactions is difficult. However, herb-CYP interactions may have important clinical and toxicological consequences. For example, induction of CYP3A4 by St. John's wort may partly provide an explanation for the enhanced plasma clearance of a number of drugs, such as cyclosporine and innadivir, which are known substrates of CYP3A4, although other mechanisms including modulation of gastric absorption and drug transporters cannot be ruled out. In contrast, many organosulfur compounds, such as diallyl sulfide from garlic, are potent inhibitors of CYP2E1; this may provide an explanation for garlic's chemoproventive effects, as many mutagens require activation by CYP2E1. Therefore, known or potential herb -CYP interactions exist, and further studies on their clinical and toxicological roles are warranted. Given that increasing numbers of people are exposed to a number of herbal preparations that contain many constituents with potential of CYP modulation, high-throughput screening assays should be developed to explore herb-CYP interactions.Key Words: Herb; Cytochrome P450; Drug interactions.Abbreviations: Ah, aryl hydrocarbon; AUC, the area of the plasma concentrationtime curve; B[a]P, benzo[a]pyrene; C max , the maximum plasma concentration; CL int , intrinsic clearance; CYP, cytochrome P450; DAD, diallyl disulfide; DAS, diallyl sulfide; DASO, diallyl sulfoxide; DASO 2 , diallyl sulfone; DPS, dipropyl sulfide; DPDS, dipropyl disulfide; K i , inhibition constant; K m , Michaelis -Menten constant; NADPH, nicotinamide adenine dinucleotide phosphate; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; N-PiP, N-nitrosopiperidine; PgP, P-glycoprotein; PhIP...

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Dipiperamides A, B, and C: bisalkaloids from the white pepper Piper nigrum inhibiting CYP3A4 activity

Cited by 44 publications

References 23 publications

Isolation of CYP3A4 Inhibitors from the Black Cohosh (Cimicifuga racemosa)

Isolation of CYP3A4 Inhibitors from the Black Cohosh (Cimicifuga racemosa)

In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand

Interactions of Herbs with Cytochrome P450

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