Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix <i>Tripterygium wilfordii</i> to S180-bearing mice by herbal-processing technology

Abstract

<b>Context:</b> Radix <i>Tripterygium wilfordii</i> Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. <b>Objective:</b> To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower <i>Lonicera japonica</i> Thunb. (Caprifoliaceae) (JYH), Radix <i>Paeonia lactiflora</i> Pall. (Ranunculaceae) (BS), Herba <i>Lysimachia christinae</i> Hance (Primulaceae) (JQC), Radix et Rhizoma <i>Glycyrrhiza uralensis</i> Fisch. (Fabaceae) (GC) and Seed <i>Phaseolus radiatus</i> L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). <b>Materials and methods:</b> LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. <b>Results:</b> Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED₅₀ of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 μg/kg, for liver glutathione, glutathione <i>S</i>-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 μg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 μg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of <i>Nrf2</i> and <i>heme oxygenase-1</i>. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED₅₀ 12.2 μg/kg. <b>Discussion and conclusions:</b> Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.