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Nrf2 参与了炮制技术降低 Radix 对 S180 荷瘤小鼠毒性和增强抗肿瘤作用的机制。

Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix to S180-bearing mice by herbal-processing technology.

机构信息

a College of Pharmacy , Henan University of Chinese Medicine , Zhengzhou , China.

b Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province , Henan University of Chinese Medicine , Zhengzhou , China.

出版信息

Pharm Biol. 2019 Dec;57(1):437-448. doi: 10.1080/13880209.2019.1634106.

Abstract

Radix Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Thunb. (Caprifoliaceae) (JYH), Radix Pall. (Ranunculaceae) (BS), Herba Hance (Primulaceae) (JQC), Radix et Rhizoma Fisch. (Fabaceae) (GC) and Seed L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). 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. Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED 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 -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 and . Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED 12.2 μg/kg. Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.

摘要

钩藤(Celastraceae)(LGT)具有显著的疗效;然而,其副作用包括高毒性,特别是肝毒性和肾毒性。为了通过分别用包括金银花(Caprifoliaceae)(JYH)、白头翁(Ranunculaceae)(BS)、瞿麦(Primulaceae)(JQC)、甘草(Fabaceae)(GC)和莱菔子(Fabaceae)(LD)这几种草药对 LGT 进行炮制来研究其解毒机制,我们将 S180 荷瘤小鼠用核因子(erythroid-derived 2)样 2(Nrf2)进行了实验。LGT 生品和炮制品以 60mg/kg 的剂量连续口服给药给接种 S180 肿瘤细胞的 KM 雄性小鼠 14 天,取血、肿瘤、肝和肾,观察解毒作用和生物学机制。炮制工艺显著减弱了 LGT 引起的肝毒性和肾毒性,各炮制药物中转化的雷公藤内酯醇的 ED 分别为血清丙氨酸转氨酶、天冬氨酸转氨酶、肌酐和尿素氮的 9.3、16.6、2.5 和 4.2μg/kg,肝谷胱甘肽、谷胱甘肽转移酶、过氧化氢酶、肿瘤坏死因子-α和白细胞介素-10 的 114.9、67.8、134.1、7.7、4171.6μg/kg,肾 21.9、20.5、145.0、529.7、19.4μg/kg。此外,炮制工艺促进了 Nrf2 进入细胞核,并上调了 和 的 mRNA 表达。此外,炮制工艺提高了肿瘤抑制率,ED 为 12.2μg/kg。炮制工艺提高了 LGT 在癌症治疗中的安全性和有效性,未来的研究可能集中在 Nrf2 相关分子上。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76a/6691819/c18981d5f341/IPHB_A_1634106_F0001_B.jpg

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