&lt;i&gt;In Vitro&lt;/i&gt; Inhibitory Effects of Sesamin on CYP4F2 Activity

Watanabe, Hiroaki; Yamaori, Satoshi; Kamijo, Shinobu; Aikawa, Kaori; Ohmori, Shigeru

doi:10.1248/bpb.b19-00953

Cited by 8 publications

(6 citation statements)

References 22 publications

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“…While the specific activity of CYP4F2 for linezolid 2-hydroxylation was 6-fold lower than CYP2J2, the expression level in liver for CYP4F2 is greater, ranging up to 30 pmol/mg protein (Michaels and Wang, 2014). Sesamin, a known inhibitor of CYP4F2 (Watanabe, et al, 2020) was shown to cause nearly complete inhibition of linezolid 2-hydroxylation in both recombinant CYP4F2 and human liver microsomes (Figure 5). At first glance, this could be viewed as contrasting the result obtained for LKY-047 in liver microsomes showing the aforementioned ~50-60% contribution by CYP2J2.…”

Section: Discussionmentioning

confidence: 99%

Linezolid Metabolism Is Catalyzed by Cytochrome P450 2J2, 4F2, and 1B1

Obach

2022

Drug Metab Dispos

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The oxazolidinone antibacterial linezolid has been in clinical use for over twenty years, yet knowledge of the contributions of specific cytochrome P450 enzymes to the metabolic clearance of this drug were mostly unknown. In this investigation it was revealed that three P450 enzymes that had not been previously explored in linezolid metabolism, CYP2J2, CYP4F1, and CYP1B1, catalyzed the 2-hydroxylation and deethyleneation of the morpholine moiety of linezolid. The intrinsic clearance for linezolid metabolism in pooled human liver microsomes was low at 0.51 µL/min/mg protein, consistent with its in vivo clearance in humans, and the K M was high (>200 µM). In recombinant human P450 enzymes, a rank order of intrinsic clearance values for linezolid 2-hydroxylation were CYP2J2>>CYP4F2>CYP2C8>CYP1B1≈CYP2D6≈CYP3A4>CYP1A1>CYP3A5, with nine other P450 enzymesshowing no linezolid metabolism The effect of selective inhibitors for these eight P450 enzymes on linezolid metabolism in pooled human liver microsomes was evaluated to provide estimates of the relative fractional contributions of these enzymes to linezolid metabolism. These experiments suggest that CYP2J2 and CYP4F2 contribute about 50% each to linezolid hepatic metabolism. It is proposed that the oxidative metabolic clearance of linezolid is primarily catalyzed by these two unusual P450 enzymes and that this explains the lack of observation of meaningful effects of common perpetrators of drug interactions on linezolid pharmacokinetics. SIGNIFICANCE STATEMENTLinezolid is an important antibacterial drug, but the enzymes involved in its oxidative metabolism were unknown. In this paper, evidence is shown that supports an important role for two enzymes not frequently associated with the metabolism of drugs: CYP2J2 and CYP4F2. These observations offer insight to understand the results of clinical drug-drug interaction studies conducted on linezolid.

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Section: Discussionmentioning

confidence: 99%

Linezolid Metabolism Is Catalyzed by Cytochrome P450 2J2, 4F2, and 1B1

Obach

2022

Drug Metab Dispos

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“…The potential for interactions of sesamin with drugs metabolized by CYP2C9 in humans is not well characterized and warrants additional monitoring. Furthermore, there is evidence that sesamin can inhibit the activities of cytochrome P450 3A4 and cytochrome P450 4F2 12,55,159–161 . Inhibition of CYP3A4 is associated with increased plasma concentrations of γ-tocopherol.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, there is evidence that sesamin can inhibit the activities of cytochrome P450 3A4 and cytochrome P450 4F2. 12,55,[159][160][161] Inhibition of CYP3A4 is associated with increased plasma concentrations of γ-tocopherol. CYP3A4 also participates in the metabolism of a wide variety of substrates including retinoic acid, bile acid, testosterone, estrogen, cholesterol, dietary chemicals, and environmental toxins, as well as drugs such as acetaminophen, codeine, and cyclosporin A and the novel heart rate-lowering agent, ivabradine.…”

Section: Safetymentioning

confidence: 99%

Sesame

Singletary¹

2022

Nutr Today

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Sesame (Sesamum indicum L.) is an annual plant whose seeds are purported to be one of the oldest oilseeds used by humans. Although originating in Africa and India, this plant currently is cultivated in diverse regions worldwide from semiarid tropics to temperate areas. This edible seed oil has many routine and diverse uses in food preparation and cooking, and the dehulled seed is included in the preparation of numerous food products, condiments, and confectionaries, imparting a distinctive savory, nutty, roasted flavor. Sesame has a long history of use in traditional medicines for treatment of wounds, asthma, blurred vision, abdominal pain and ulcers, toothaches and gum disease, and migraine, to name a few. More recently, sesame constituents have demonstrated antioxidant and anti-inflammatory properties that may alleviate conditions such as atherosclerosis, diabetes, hypertension, and pain. The current narrative summarizes human studies evaluating sesame seeds, oil, and constituents for improving diverse human disorders, and provides suggestions for future research. Nutr Today 2022;57(5):271-287 S esame (Sesamum indicum L., family Pedaliaceae), also known as sesamum, gingelly, til, goma, ajonjoli, and benniseed, is an annual plant (Figure 1). The seeds are purported to be one of the oldest oilseeds used by humans. The seed colors of this plant vary considerably including white, yellow, gray, brown, and black, depending on the variety and strain of S indicum. Black sesame seeds and white sesame seeds are the most available worldwide.Although the chemical differences among the various colored sesame seeds are not well characterized, it has been reported that the contents of indole-3-carboxylic acid, hesperidin, 2-methoxycinnamic acid, vitamin B2, and hyoscyamine are significantly higher in black seeds compared with white seeds. However, at least for sesame lignans, seed color and content of these bioactives are unrelated. 1,2 Although apparently originating in Africa and India, this plant is currently cultivated in diverse regions worldwide from semiarid tropics to temperate areas, and India, China, Tanzania, Sudan, and Myanmar are considered the major producers. Because of the high content of oil, sesame seed is called the queen of oilseeds. Its major use is the production of a notably oxidative rancidity-resistant oil. This oil has numerous uses such as a solvent, a hydrophobic vehicle for drug delivery, and a skin softener, and in the preparation of soaps and margarines. [2][3][4][5][6][7] In cosmetics, it can function as a binder, emulsifier, and viscosity-increasing agent. 8 As an edible seed oil, it has many routine and diverse uses in food preparation. It has widespread use globally in salads, and in Asia, the seed and oil are routinely used in cooking. Some Europeans substitute it for olive oil in cooking. The dehulled seed is included in the preparation of numerous food products, condiments, and confectionaries, imparting a distinctive savory, nutty, roasted flavor. For example, besides being sprinkled on ...

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“…A recent meta-analysis indicated that intake of sesamin can decrease blood pressure. The antihypertensive effect of sesamin may be related to the sesamin-mediated inhibition of CYP4F2-catalyzed 20-hydroxyl eicosaenoic acid production [ 72 ]. Sesamin can also effectively decrease serum and liver fat levels [ 73 ].…”

Section: Functions and Activities Of Sesame Protein And Sesame Lignansmentioning

confidence: 99%

Byproducts of Sesame Oil Extraction: Composition, Function, and Comprehensive Utilization

Yuan

Zhou

Zhao

et al. 2023

Foods

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Sesame is principally used to generate oil, which is produced by chemical refining or pressing. Sesame meal, as a main byproduct of sesame oil extraction, is usually discarded, causing resource waste and economic loss. Sesame meal is rich in sesame protein and three types of sesame lignans (sesamin, sesamolin, and sesamol). Sesame protein extracted via a physical method and an enzymic method has balanced amino acid composition and is an important protein source, and thus it is often added to animal feed and used as a human dietary supplement. Extracted sesame lignan exhibits multiple biological activities such as antihypertensive, anticancer, and cholesterol-lowering activities, and therefore it is used to improve the oxidative stability of oils. This review summarizes the extraction methods, functional activities, and comprehensive utilization of four active substances (sesame protein, sesamin, sesamolin, and sesamol) in sesame meal with the aim to provide theoretical guidance for the maximum utilization of sesame meal.

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<i>In Vitro</i> Inhibitory Effects of Sesamin on CYP4F2 Activity

Cited by 8 publications

References 22 publications

Linezolid Metabolism Is Catalyzed by Cytochrome P450 2J2, 4F2, and 1B1

Linezolid Metabolism Is Catalyzed by Cytochrome P450 2J2, 4F2, and 1B1

Sesame

Byproducts of Sesame Oil Extraction: Composition, Function, and Comprehensive Utilization

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