Abstract
Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity.Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2).Materials and methods: 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.Results: 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 S-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 Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 μg/kg.Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.
Highlights
Processing (‘Paozhi’ in Chinese Pinyin), as an ancient and classic pharmaceutical technology of traditional Chinese medicine (TCM), is one of the characteristics and advantages of TCM (Wang et al 2012a; Cai et al 2017)
Hepatic and kidney tissues levels of antioxidants including GSH, glutathione s-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and CAT and inflammatory mediators including IL-10 and tumour necrosis factor-alpha (TNF-a) were assayed, respectively, by the commercial kits and according to the manufacturer’s protocols, and the results were all expressed based on tissue protein concentrations which were measured by Bradford Protein Assay
The results showed that administration of LGT raw product reduced the tumour weight with a 17.2% inhibition rate, while treatments of its processedherb products including JYHprocessed LGT (JYHLGT), BS-processed LGT (BSLGT), JQCprocessed LGT (JQCLGT), GC-processed LGT (GCLGT) and LDprocessed LGT (LDLGT) all further reduced LGT-decreased tumour weight (Figure 7), with higher inhibition rates of 27.6, 29.2, 40.4, 20.9 and 35.2%, respectively
Summary
Processing (‘Paozhi’ in Chinese Pinyin), as an ancient and classic pharmaceutical technology of traditional Chinese medicine (TCM), is one of the characteristics and advantages of TCM (Wang et al 2012a; Cai et al 2017). Processed-herb technology, as one of the most common and traditional concocted techniques, is to use some CHMs to concoct other CHMs in order to promote efficacy, attenuate toxicity, prevent the poor bias or influence medicinal properties (Wang et al 2012a; Cai et al 2017).
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