Song Ling-Ling, Wang Jun-Ming, Guan Yue-Chen, Wang Yan-Mei, Gong Ming-Zhu, Li Bing-Yin
College of Pharmacy,Henan University of Chinese Medicine Zhengzhou 450046, China.
College of Pharmacy,Henan University of Chinese Medicine Zhengzhou 450046, China Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of China, Henan University of Chinese Medicine Zhengzhou 450046, China.
Zhongguo Zhong Yao Za Zhi. 2022 Feb;47(3):668-675. doi: 10.19540/j.cnki.cjcmm.20210924.301.
This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.
本研究旨在探讨不同炮制方法对雷公藤所致心脏毒性的解毒作用，并通过核因子E2相关因子2（Nrf2）/血红素加氧酶1（HO-1）通路初步探究解毒机制。将雷公藤生品及炮制品[炒制品、金钱草拌炒品（JQC）、赤小豆拌炒品（LD）、白芍拌炒品（BS）、甘草拌炒品（GC）、醋炒品（CZ）]按2 g·kg⁻¹（以生药量计）的剂量灌胃给予小鼠，连续给药28天。末次给药24小时后，检测小鼠血清生化指标以评价解毒效果。此外，通过蛋白质免疫印迹法检测小鼠心脏组织中Nrf2/HO-1通路关键蛋白的表达，并使用相应试剂盒检测部分氧化/抗氧化相关指标以探究解毒机制。雷公藤生品给药后可使小鼠血清肌酸激酶、乳酸脱氢酶及心脏脂质过氧化产物丙二醛水平升高（P<0.01），使Nrf2和HO-1蛋白水平下调（P<0.01），并降低总超氧化物歧化酶、谷胱甘肽、谷胱甘肽过氧化物酶及谷胱甘肽S-转移酶水平（P<0.01）。然而，给予JQC、LD、BS、GC及CZ炮制品后，生品所致上述指标异常均得到恢复（P<0.05或P<0.01）。其中，JQC拌炒品表现最佳。综上所述，JQC、LD、BS、GC及CZ拌炒可减轻雷公藤所致心脏毒性，其中JQC拌炒解毒效果最佳。其机制可能与上调Nrf2介导的心脏抗氧化防御及减轻氧化损伤有关。
