Effects of total saikosaponins on CYP3A4 and CYP1A2 in HepaRG cells

Tang,Yunyan; Li,Hongfang; Tang,Jianhua; Hu,Lei; Ma,Feifei; Liu,Yanmiao; Tang,Fushan

doi:10.3892/etm.2024.12505

Effects of total saikosaponins on CYP3A4 and CYP1A2 in HepaRG cells

Authors:
- Yunyan Tang
- Hongfang Li
- Jianhua Tang
- Lei Hu
- Feifei Ma
- Yanmiao Liu
- Fushan Tang
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Affiliations: Department of Pharmacy, Affiliated Meitan People's Hospital of Zunyi Medical University, Zunyi, Guizhou 564100, P.R. China, The Key Laboratory of Clinical Pharmacy of Zunyi City, Zunyi Medical University, Zunyi, Guizhou 563006, P.R. China, Faculty of Biology, Medicine and Health, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, SK10 4TG, UK
Published online on: March 21, 2024 https://doi.org/10.3892/etm.2024.12505
Article Number: 217
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Total saikosaponins (TSS) form a group of chemically and biologically active components that can be extracted from Bupleurum, with reported antidepressive, anti‑inflammatory, antiviral, antiendotoxin, antitumor, anti‑pulmonary fibrosis and anti‑gastric ulcer effects. Bupleurum or TSS is frequently utilized in clinical practice alongside other medications (such as entecavir, lamivudine, compound paracetamol and amantadine hydrochloride capsules), leading to an increased risk of drug‑drug interactions. The cytochrome P450 (CYP) family serves a critical role in the metabolism of numerous essential drugs (such as tamoxifen, ibuprofen and phenytoin), where the majority of drug interactions involve CYP‑mediated metabolism. It is therefore essential to understand the effects of key components of Bupleurum on CYPs when administering combination therapies containing TSS or Bupleurum. The present study aimed to investigate the effects of TSS on the mRNA and protein expression of CYP3A4 and CYP1A2 in HepaRG cells. The effects of TSS on the survival of HepaRG cells was investigated using the Cell Counting Kit‑8 (CCK‑8) method. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot (WB) analysis were used to assess the effects of different concentrations of TSS (0, 5, 10 and 15 µg/ml) on CYP3A4 and CYP1A2 mRNA and protein expression in HepaRG cells. Based on the CCK‑8 assay results, it was observed that the cell viability remained above 80% when treated with 1, 5, 10 and 15 µg/ml TSS. Although there was a statistically significant reduced cell viability at TSS concentrations of 10 and 15 µg/ml compared with the control group, the findings indicated that TSS did not exhibit notable cytotoxic effects at these concentrations. Furthermore, RT‑qPCR results revealed that compared with those in the control group, TSS at concentrations of 10 and 15 µg/ml reduced CYP3A4 mRNA expression but increased CYP1A2 mRNA expression in HepaRG cells at concentrations of 15 µg/ml. WB analysis found that TSS at concentrations of 10 and 15 µg/ml downregulated CYP3A4 protein expression in HepaRG cells while increasing CYP1A2 protein expression at concentrations of 15 µg/ml. Results in the present study suggest that TSS can inhibit CYP3A4 mRNA and protein expression, but exerts opposite effects on their CYP1A2 counterparts. These findings suggest that it is necessary to consider drug interactions between clinical preparations containing TSS or Bupleurum and drugs metabolized by CYP3A4 and CYP1A2 to avoid potential adverse drug reactions in clinical practice.

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