Effects of mulberry leaf extracts on activity and mRNA expression of five cytochrome P450 enzymes in rat

Sheng, Chenming; Shi, Xiaoyan; Ze-Xian, Ding; Chen, Yunna; Shi, Xiaoqian; Wu, Yongkang; Zhang, Wenjing; Chen, Weidong

doi:10.1590/s2175-97902020000x181059

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…CYP1A2 accounts for 13% of the total CYP content and is involved in the metabolism of 8–10% of the drugs on the market [ 36 , 37 , 38 ]. This enzyme is well confirmed as a potential cancer-promoting agent in colorectal, breast, and lung cancers [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Lysiphyllum strychnifolium (Craib) A. Schmitz Extracts Moderate the Expression of Drug-Metabolizing Enzymes: In Vivo Study to Clinical Propose

et al. 2023

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Lysiphyllum strychnifolium (Craib) A. Schmitz (LS) has been traditionally used as a medicinal herb by folk healers in Thailand with rare evidence-based support. Hepatic cytochrome P450s (CYPs450) are well known as the drug-metabolizing enzymes that catalyze all drugs and toxicants. In this study, we investigated the mRNA levels of six clinically important CYPs450, i.e., CYP1A2, 3A2, 2C11, 2D1, 2D2, and 2E1, in rats given LS extracts. Seventy Wistar rats were randomized into seven groups (n = 10). Each group was given LS stem ethanol (SE) and leaf water (LW) extracts orally at doses of 300, 2000, and 5000 mg/kg body weight (mg/kg.bw) for twenty-eight consecutive days. After treatment, the expression of CYPs450 genes was measured using quantitative real-time PCR. The results revealed that SE and LW, which contained quercetin and gallic acid, promoted the upregulation of all CYPs450. Almost all CYPs450 genes were downregulated in all male LW-treated rats but upregulated in female-treated groups, suggesting that CYP gene expressions in LS-treated rats were influenced by gender. Moderate and high doses of the LS extracts had a tendency to induce six CYP450s’ transcription levels in both rat genders. CYP2E1 gene showed a unique expression level in male rats receiving SE at a dose of 2000 mg/kg.bw, whereas a low dose of 300 mg/kg.bw was found in the LW-treated female group. As a result, our findings suggest that different doses of LS extracts can moderate the varying mRNA expression of clinically relevant CYP genes. In this study, we provide information about CYP induction and inhibition in vivo, which could be a desirable condition for furthering the practical use of LS extracts in humans.

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Section: Discussionmentioning

confidence: 99%

Lysiphyllum strychnifolium (Craib) A. Schmitz Extracts Moderate the Expression of Drug-Metabolizing Enzymes: In Vivo Study to Clinical Propose

et al. 2023

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“…In a previous study, the Chinese traditional medicine formulation BuChang NaoXinTong, which contains MA twig and some other herbs, was shown to induce the expression of CYP2C19 in human primary hepatocytes and HepG2 cells via activation of PXR (Sun et al, 2016). Similarly, an aqueous extract of mulberry leaves increased CYP3A4 activity, while an ethanol extract of mulberry leaves reduced CYP1A2, CYP2D6, and CYP2C19 activity in a rat model (Sheng et al, 2021). Therefore, there are several other factors such as the part of the MA plant being used, the extraction method employed, and the combination of MA with other compounds and plants that could affect the regulatory profiles of CYP expression.…”

Section: Effect Of Combinations Of Ma Fruit and Common Drugs On Phase...mentioning

confidence: 99%

Impact of Morus alba L. on the expression of drug-metabolizing enzymes and transporters in Caco-2 cells

Chatuphonprasert¹,

Wattanathorn²,

Tukum-mee³

et al. 2022

j app pharm sci

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Morus alba (MA) L. (mulberry) fruit has been consumed for a long time as a food and a source of vitamin C, anthocyanins, flavonoids, and alkaloids. The effects of MA fruit extract on drug-metabolizing genes and drug transporters were investigated in human colorectal adenocarcinoma cells. Cells treated with MA or its major bioactive constituents, rutin, and cyanidin-3-O-glucoside (C3G), were assessed for cell viability, production of reactive oxygen species (ROS), and alanine aminotransferase (ALT) and aspartate transaminase (AST) levels. The mRNA expression of target metabolic genes was determined using real-time polymerase chain reaction. Cell viability remained higher than 80%, and ROS levels were unchanged by all treatments. MA, C3G, and rutin did not alter the ALT and AST levels or expression of CYP2D6 and sulfotransferase 1A1 (SULT1A1). However, MA, C3G, and rutin down-regulated the expression of CYP2C19, CYP3A4, uridine diphosphate-glucuronosyltransferase 1A6 (UGT1A6), N-acetyltransferase 1, and organic anion transporting polypeptide 1B1 (OATP1B1), and MA elevated the expression of CYP1A2. In addition, MA induced CYP1A2 and CYP2C19 expression in combination with aspirin, caffeine, and simvastatin and upregulated expression of UGT1A6 and SULT1A1 in combination with paracetamol. Therefore, consumption of MA fruit or its supplements poses a risk for drug interactions via its modulation of cytochrome P450 and conjugation enzyme-associated metabolism and OATP1B1-mediated drug transport.

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Effects of mulberry leaf extracts on activity and mRNA expression of five cytochrome P450 enzymes in rat

Cited by 2 publications

References 21 publications

Lysiphyllum strychnifolium (Craib) A. Schmitz Extracts Moderate the Expression of Drug-Metabolizing Enzymes: In Vivo Study to Clinical Propose

Lysiphyllum strychnifolium (Craib) A. Schmitz Extracts Moderate the Expression of Drug-Metabolizing Enzymes: In Vivo Study to Clinical Propose

Impact of Morus alba L. on the expression of drug-metabolizing enzymes and transporters in Caco-2 cells

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