Wang Songsong, Xiao Xiao, Li Ao, Li Peng
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China.
Evid Based Complement Alternat Med. 2021 Apr 1;2021:5566078. doi: 10.1155/2021/5566078. eCollection 2021.
An-Gong-Niu-Huang Wan (AGNH) has been a well-known cinnabar- and realgar-containing compound recipe for cerebral diseases. Unfortunately, its clinical practice is often restrained by the specific hepatorenal toxicity of cinnabar and realgar (C + R). In previous research studies, we have found that the antioxidative and anti-inflammatory effects of its herbal constituents could mitigate the risks from the toxicity. The underlying detoxification mechanisms are still unsolved. The present study investigated the protective effects of AGNH's herbal constituents on hepatorenal injury induced by C + R. For the mice treated with C + R, the increased expression levels of sensitive biomarkers of metal exposure and hepatorenal toxicity, including metallothionein (MT) in both hepatorenal tissues and kidney induced molecule-1 (KIM-1) in the kidney, were simultaneously reduced when C + R coadministered with other herbal medicines. In addition, the contents of trivalent As (As), pentavalent As (As), and mercury (Hg) in hepatorenal tissues of mice were also significantly reduced benefiting from the herbal constituents in AGNH. Further mechanism studies showed that the herbal constituents in AGNH could downregulate the expressions of uptake transporters (AQP9 and OAT1) and upregulate the expressions of efflux transporters (P-gp, MRP2, and MRP4) in mice intoxicated by C + R. Our results suggested that AGNH's herbal constituents protect the body against C + R-induced hepatorenal toxicity and accumulations of Hg and As, which could be associated with the reestablishment of heavy metal homeostasis and the detoxification system.
安宫牛黄丸（AGNH）是一种著名的含朱砂和雄黄的复方制剂，用于治疗脑部疾病。不幸的是，其临床应用常常受到朱砂和雄黄（C+R）特定肝肾毒性的限制。在先前的研究中，我们发现其草药成分的抗氧化和抗炎作用可以减轻毒性风险。潜在的解毒机制仍未解决。本研究调查了AGNH草药成分对C+R诱导的肝肾损伤的保护作用。对于用C+R处理的小鼠，当C+R与其他草药联合给药时，肝肾组织中金属暴露和肝肾毒性敏感生物标志物（包括金属硫蛋白（MT））以及肾脏中肾损伤分子-1（KIM-1）的表达水平升高同时降低。此外，受益于AGNH中的草药成分，小鼠肝肾组织中三价砷（As）、五价砷（As）和汞（Hg）的含量也显著降低。进一步的机制研究表明，AGNH中的草药成分可以下调C+R中毒小鼠摄取转运体（AQP9和OAT1）的表达，并上调外排转运体（P-gp、MRP2和MRP4）的表达。我们的结果表明，AGNH的草药成分可保护机体免受C+R诱导的肝肾毒性以及Hg和As的蓄积，这可能与重金属内稳态和解毒系统的重建有关。
