Inhibition of CYP2C9 by natural products: insight into the potential risk of herb-drug interactions

Wang, Kai; Gao, Qing; Zhang, Tingting; Rao, Jinqiu; Ding, Lei; Qiu, Feng

doi:10.1080/03602532.2020.1758714

Cited by 28 publications

(16 citation statements)

References 116 publications

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“…More and more herbs and related formulations are being used globally as medicines and/or dietary supplements, while worries about their safety have greatly attracted worldwide attention 1 . For instance, Bupleurum was documented in the Chinese and Japanese Pharmacopoeia, which is widely applied as the treatment of various cancers, inflammations and infectious diseases in Eurasia and North Africa 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Effects of saikosaponin‐d on CYP3A4 in HepaRG cell and protein‐ligand docking study

Tang

Wei

et al. 2021

Basic Clin Pharma Tox

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Saikosaponin‐d (SSd) is a major bioactive triterpenoid saponin extracted from Bupleurum, which has anti‐inflammatory, anticancer, antioxidative and anti‐hepatic fibrosis effects. Due to the effects of Bupleurum‐related formulations on cytochrome P450 (CYPs) expression still remain unclear, the combination therapies involved formulations containing Bupleurum may sometimes lead to unexpected drug‐drug interactions in clinical practice. These interactions can limit the clinical applications of related formulations. In this study, we tried to explore the effects of SSd on CYP3A4 mRNA, protein expression and the enzyme activity in HepaRG cells by real‐time quantitative reverse transcription polymerase chain reaction (RT‐qPCR), Western blot (WB) and HPLC method, respectively. The interaction between SSd and CYP3A4 was analysed by molecular docking. HepaRG cells were cultured with different concentrations of SSd (0.5, 1, 5 and 10 μmol/L) for 72 hours. It is revealed that SSd can inhibit CYP3A4 mRNA and its protein expression, and also the enzyme activity. Molecular docking study demonstrated that SSd can bind to several key active sites of amino acid residues of CYP3A4 protein with hydrogen bonds and hydrophobic interactions. Thus, drug‐drug interactions resulted by SSd inhibiting CYP3A4 need attention when formulations containing SSd or Bupleurum are co‐administrated with drugs metabolized by CYP3A4.

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Section: Introductionmentioning

confidence: 99%

Effects of saikosaponin‐d on CYP3A4 in HepaRG cell and protein‐ligand docking study

Tang

Wei

et al. 2021

Basic Clin Pharma Tox

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“…Furthermore, detailed pharmacokinetic studies with phenytoin failed to identify a significant difference in total body clearance among obese as compared with normal body weight subjects (Abernethy and Greenblatt, 1985). The inhibitory effect of fruit juice as well as multiple spices and herbal substances on the enzymatic activity of cytochrome P450 isoforms including CYP2C9 is well documented (Hidaka et al, 2008;Kimura et al, 2010;Wang et al, 2020). The possibility that regular consumption of spices or herbs which are part of the traditional Ethiopian diet might inhibit the activity of CYP2C9 cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibitory effect of fruit juice as well as multiple spices and herbal substances on the enzymatic activity of cytochrome P450 isoforms including CYP2C9 is well documented ( Hidaka et al., 2008 ; Kimura et al., 2010 ; Wang et al., 2020 ). The possibility that regular consumption of spices or herbs which are part of the traditional Ethiopian diet might inhibit the activity of CYP2C9 cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Comparison of CYP2C9 Activity in Ethiopian and Non-Ethiopian Jews Using Phenytoin as a Probe

et al. 2020

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The pharmacokinetics of CYP2C9 substrates is characterized by substantial interethnic variability. The objective of the study was to compare CYP2C9 activity by using Phenytoin Metabolic Ratio (PMR) between Ethiopian and non-Ethiopian Jews. PMR was derived from the ratio of p-HPPH in 24 h urine collection to plasma phenytoin, 12 h (PMR24/12) or 24 h (PMR24/24) after the administration of 300 mg phenytoin. Analysis of CYP2C9*2, *3, *5, *6, *8, and *11 was carried by direct sequencing. PMR was significantly correlated with CYP2C9 genotype in both groups (p < 0.002). Mean PMR values were similar among Ethiopians and non-Ethiopians despite the fact that the fraction of non-carriers of CYP2C9 variant alleles was significantly different (85 vs. 53%, respectively, p < 0.001). However, among non-carriers of CYP2C9*2, *3, *5, *6, *8, and *11 variant alleles, PMR24/12 and PMR24/24 values were 30 and 34% greater respectively in the non-Ethiopians group (p < 0.001). In conclusion-CYP2C9 activity as measured by PMR is similar in Ethiopian and non-Ethiopian Jews. However, among non-carriers of CYP2C9 variant alleles accounting for 85% of Ethiopian Jews, CYP2C9 activity is decreased by approximately one third as compared with non-Ethiopian Jews. Unique genetic CYP2C9 polymorphisms occurring only in Ethiopians may account for this difference.

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“…The well-known anti-inflammatory and anticancer agent berberine acts as a noncompetitive inhibitor of P450 CYP1 family enzymes. Linderane and thujopsene terpenoids show an irreversible inhibition of CYP2 enzymes, while methylenedioxyphenyl lignans act as an irreversible inhibitor of CYP34A [ 214 , 215 , 216 ]. Resveratrol exhibits various P450 inhibitory mechanisms such as it inhibits human P450 CYP1A1 activity in a mixed-type inhibition (competitive–noncompetitive), while also acting as a noncompetitive inhibitor against P450 CYP1B1 and a mechanism-based inhibitor of cytochrome P450 CYP3A4 [ 214 ].…”

Section: Role Of Natural Products In Cyp450 Inhibitionmentioning

confidence: 99%

Role of Phytochemicals in Cancer Chemoprevention: Insights

2021

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Cancer is a condition where the body cells multiply in an uncontrollable manner. Chemoprevention of cancer is a broad term that describes the involvement of external agents to slow down or suppress cancer growth. Synthetic and natural compounds are found useful in cancer chemoprevention. The occurrence of global cancer type varies, depending on many factors such as environmental, lifestyle, genetic etc. Cancer is often preventable in developed countries with advanced treatment modalities, whereas it is a painful death sentence in developing and low-income countries due to the lack of modern therapies and awareness. One best practice to identify cancer control measures is to study the origin and risk factors associated with common types. Based on these factors and the health status of patients, stage, and severity of cancer, type of treatment is decided. Even though there are well-established therapies, cancer still stands as one of the major causes of death and a public health burden globally. Research shows that most cancers can be prevented, treated, or the incidence can be delayed. Phytochemicals from various medicinal plants were reported to reduce various risk factors associated with different types of cancer through their chemopreventive role. This review highlights the role of bioactive compounds or natural products from plants in the chemoprevention of cancer. There are many plant based dietary factors involved in the chemoprevention process. The review discusses the process of carcinogenesis and chemoprevention using plants and phytocompounds, with special reference to five major chemopreventive phytocompounds. The article also summarizes the important chemopreventive mechanisms and signaling molecules involved in the process. Since the role of antioxidants in chemoprevention is inevitable, an insight into plant-based antioxidant compounds that fight against this dreadful disease at various stages of carcinogenesis and disease progression is discussed. This will fill the research gap in search of chemopreventive natural compounds and encourage scientists in clinical trials of anticancer agents from plants.

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Inhibition of CYP2C9 by natural products: insight into the potential risk of herb-drug interactions

Cited by 28 publications

References 116 publications

Effects of saikosaponin‐d on CYP3A4 in HepaRG cell and protein‐ligand docking study

Effects of saikosaponin‐d on CYP3A4 in HepaRG cell and protein‐ligand docking study

Comparison of CYP2C9 Activity in Ethiopian and Non-Ethiopian Jews Using Phenytoin as a Probe

Role of Phytochemicals in Cancer Chemoprevention: Insights

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