College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China
Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Biosci Rep. 2018 Jul 12;38(4). doi: 10.1042/BSR20180429. Print 2018 Aug 31.
The combined administration between Radix Hook F (LGT) and Herba Hance (JQC) belongs to mutual detoxication compatibility of seven emotions in traditional Chinese medicine (TCM) theory. However, until now, the compatibility detoxication mechanisms remain unknown. The present study was undertaken to observe detoxication mechanisms of LGT through compatibility with JQC in tumor-bearing mice by involving NF-E2-related factor 2 (Nrf2)-mediated antioxidant defenses. In addition, influence of compatibility on antitumor activity was also investigated here. Our results demonstrated that compatibility with JQC administration significantly reversed LGT-elevated serum alanine/aspartate transaminase (ALT/AST) levels and alleviated hepatocytes' swelling or degeneration damage, and at the ratio 2/1 (LGT/JQC) produced the strongest detoxication effect. Besides, compatibility with JQC administration reversed not only LGT-elevated hepatic malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) but also the LGT lowered GSH, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and interleukin (IL)-10 levels. Furthermore, compatibility with JQC administration significantly up-regulated protein expression of Nrf2 and mRNA expression of it regulated downstream antioxidant genes such as heme oxygenase-1 (), NAD(P)H: quinone oxidoreductase-1 (), and glutamate cysteine ligase catalytic subunit (). In addition, compatibility with JQC further decreased LGT-decreased tumor weight and at the ratio 2/1 (LGT/JQC) also exerted the strongest synergistic effect. Collectively, through compatibility with JQC exerted detoxication effect on LGT-induced hepatotoxicity and the mechanisms could be at least partly attributed to up-regulation of Nrf2 and its downstream signals, thereby enhancing antioxidant defenses, and inhibiting lipid peroxidation, oxidative stress, and inflammation. Additionally, at the ratio 2/1 (LGT/JQC) exerted the strongest effects on both detoxication and synergism.
钩藤（LGT）与鸡骨草（JQC）联合给药属于中医七情相须解毒范畴。然而，目前为止，这种配伍的解毒机制仍不清楚。本研究旨在通过涉及核因子 E2 相关因子 2（Nrf2）介导的抗氧化防御，观察 LGT 通过与 JQC 配伍在荷瘤小鼠体内的解毒机制。此外，还研究了这种配伍对抗肿瘤活性的影响。研究结果表明，与 JQC 配伍给药可显著逆转 LGT 升高的血清丙氨酸氨基转移酶（ALT/AST）水平，并减轻肝细胞肿胀或变性损伤，且在 2/1 比例（LGT/JQC）时产生最强的解毒作用。此外，与 JQC 配伍给药不仅逆转了 LGT 升高的肝丙二醛（MDA）和肿瘤坏死因子-α（TNF-α），还逆转了 LGT 降低的谷胱甘肽（GSH）、谷胱甘肽-S-转移酶（GST）、谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和白细胞介素（IL）-10 水平。此外，与 JQC 配伍给药显著上调了 Nrf2 蛋白表达和它调节的下游抗氧化基因如血红素加氧酶-1（）、NAD（P）H：醌氧化还原酶-1（）和谷胱甘肽半胱氨酸连接酶催化亚基（）的 mRNA 表达。此外，与 JQC 配伍给药进一步降低了 LGT 降低的肿瘤重量，且在 2/1 比例（LGT/JQC）时也发挥了最强的协同作用。综上所述，通过与 JQC 配伍给药对 LGT 诱导的肝毒性产生解毒作用，其机制至少部分归因于 Nrf2 及其下游信号的上调，从而增强了抗氧化防御能力，抑制了脂质过氧化、氧化应激和炎症。此外，在 2/1 比例（LGT/JQC）时对解毒和协同作用都发挥了最强作用。
