Effect of kanglaite on rat cytochrome P450

Du, Xiaoxiang; Ye, Huizhou; Zhang, Chunxia; Ye, Lei; Lin, Gen‐Min

doi:10.3109/13880209.2014.952833

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…Cytochrome P450 enzymes (CYP450s) are heme-thiolate proteins that are responsible for the oxidative metabolism of numerous xenobiotics as well as endogenous substrates [ 15 ]. The inhibition against CYP450s has resulted in costly late failures of drug development and withdrawal of drugs on the market [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes

Shi

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Cytochrome p450 (CYP450) enzymes are predominantly involved in Phase I metabolism of xenobiotics. In this study, the CYP450 isoforms involved in xanthotoxol metabolism were identified using recombinant CYP450s. In addition, the inhibitory effects of xanthotoxol on eight CYP450 isoforms and its pharmacokinetic parameters were determined using human liver microsomes. CYP1A2, one of CYP450s, played a key role in the metabolism of xanthotoxol compared to other CYP450s. Xanthotoxol showed stronger inhibition on CYP3A4 and CYP1A2 compared to other isoenzymes with the IC50 of 7.43 μM for CYP3A4 and 27.82 μM for CYP1A2. The values of inhibition kinetic parameters (Ki) were 21.15 μM and 2.22 μM for CYP1A2 and CYP3A4, respectively. The metabolism of xanthotoxol obeyed the typical monophasic Michaelis-Menten kinetics and V max, K m, and CLint values were calculated as 0.55 nmol·min−1·mg−1, 8.46 μM, and 0.06 mL·min−1·mg−1. In addition, the results of molecular docking showed that xanthotoxol was bound to CYP1A2 with hydrophobic and π-π bond and CYP3A4 with hydrogen and hydrophobic bond. We predicted the hepatic clearance (CLH) and the CLH value was 15.91 mL·min−1·kg−1 body weight. These data were significant for the application of xanthotoxol and xanthotoxol-containing herbs.

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Section: Discussionmentioning

confidence: 99%

Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes

Shi

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…The results showed that a single oral dose of Coix seed oil did not affect the pharmacokinetics of the five probe drugs when given as a drug cocktail intravenously; however, when Coix seed oil was administered concomitantly with other drugs, a single oral dose or short-term dosing could increase plasma drug concentrations and enhance intestinal absorption (Yao et al, 2019). Another study also looked at the effect of Kanglaite on the expression of rat CYP enzymes and showed that treatment with multiple doses of Kanglaite (for 7 days via intraperitoneal injection) had an induction effect on rat CYP1A2, whereas CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzyme activities were inhibited (Du et al, 2015). Therefore, it is necessary to take precautions to avoid possible interactions between Coix seed oil and other drugs in future applications.…”

Section: The Pharmacokinetics Of Coicis Semenmentioning

confidence: 99%

Coicis Semen for the treatment of malignant tumors of the female reproductive system: A review of traditional Chinese medicinal uses, phytochemistry, pharmacokinetics, and pharmacodynamics

et al. 2023

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CoicisSemen is an important food product and traditional Chinese medicine (TCM) derived from the dried and mature seeds of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf. An increasing number of studies have investigated its use, either alone or in combination with other botanical drugs, to treat female reproductive system malignancies, and its pharmacological effects have been confirmed clinically. This review aims to provide an overview of Coicis Semen’s historical role in treating female reproductive system malignancies based on TCM theory, to summarize clinical trials results, and to analyze information pertaining to the main phytochemical components, pharmacokinetics, related anti-cancer pharmacological effects, and toxicology of Coicis Semen. Information on Coicis Semen was collected from internationally accepted scientific databases. Seventy-four clinical trials were identified that used Coicis Semen in combination with other Chinese medicine to treat female reproductive system malignancies, most of which demonstrated good anti-tumor efficacy and few adverse reactions. To date, more than 80 individual compounds have been isolated from this botanical drug. In terms of anti-tumor effects, Coix seed oil has been studied the most. Pharmacokinetic data suggest that the active ingredients in Coicis Semen are widely distributed after administration, and Coicis Semen and its active compounds play a beneficial role in treating female reproductive system malignancies. Mechanistically, the anti-cancer effects may be related to inhibition of tumor cell proliferation and promotion of apoptosis, inhibition of tumor angiogenesis, suppression of the chronic inflammatory microenvironment of tumors, modulation of immune function, and regulation of the female reproductive system. Most acute toxicity and genotoxicity studies have shown that Coicis Semen is non-toxic. However, the existing studies have many limitations, and the future research direction should emphasize 1) the relationship between drug concentration and pharmacological action as well as toxicity; 2) the structural modification or the synthesis of analogues led by the active ingredients of Coicis Semen to enhance pharmacological activities and bioavailability; 3) accurately revealing the anti-cancer pharmacological effects of Coicis Semen and its compounds through multi-omics technology. We hope that this review can determine future directions and inform novel drug development for treating female reproductive malignancies.

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“…Polyphenols and polysaccharides are considered as the major active components of Coicis Semen 277 . Kanglaite, an oily substance, has been reported to induce CYP1A2, but it inhibits CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzymatic activities 278 . Ethanolic extract of Coicis Semen downregulates the protein expression of CYP1A1, CYP1A2, CYP2C6, CYP2C11, CYP2D1, CYP2E1, CYP3A1, and CYP3A2 in the rat liver 279 .…”

Section: Tcms For the Treatment Of Covid-19 Infectionsmentioning

confidence: 99%