Panigrahi Gati Krushna, Ch Ratnasekhar, Mudiam Mohana K R, Vashishtha Vipin M, Raisuddin S, Das Mukul
†Food, Drug and Chemical Toxicology Group, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Post Box 80, Lucknow 226001, India.
∥Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi 110062, India.
Chem Res Toxicol. 2015 Jun 15;28(6):1120-32. doi: 10.1021/acs.chemrestox.5b00056. Epub 2015 May 14.
Our prior studies have shown an association between the deaths of children and consumption of Cassia occidentalis (CO) seeds. However, the chemicals responsible for the CO poisoning are not known. Therefore, the present study was designed to identify the key moieties in CO seeds and their cytotoxicity in rat primary hepatocytes and HepG2 cells. Activity-guided sequential extraction and fractionation of the seeds followed by GC-MS analysis identified the toxic compounds in the CO seeds. These identified compounds were subsequently detected and quantified in blood and urine samples from CO-exposed rats and CO poisoning human study cases. GC-MS analysis of different fractions of methanol extracts of CO seeds revealed the presence of five anthraquinones (AQs), viz. physcion, emodin, rhein, aloe-emodin, and chrysophanol. Interestingly, these AQs were detected in serum and urine samples from the study cases and CO-exposed rats. Cytotoxicity analysis of the above AQs in rat primary hepatocytes and HepG2 cells revealed that rhein is the most toxic moiety, followed by emodin, aloe-emodin, physcion, and chrysophanol. These studies indicate that AQ aglycones are responsible for producing toxicity, which may be associated with symptoms of hepatomyoencephalopathy in CO poisoning cases.
我们之前的研究表明儿童死亡与决明子种子的食用之间存在关联。然而,导致决明子中毒的化学物质尚不清楚。因此,本研究旨在确定决明子种子中的关键成分及其对大鼠原代肝细胞和HepG2细胞的细胞毒性。通过活性导向的种子连续提取和分馏,随后进行气相色谱-质谱分析,确定了决明子种子中的有毒化合物。随后,在暴露于决明子的大鼠和决明子中毒人体研究病例的血液和尿液样本中检测并定量了这些已鉴定的化合物。决明子种子甲醇提取物不同馏分的气相色谱-质谱分析显示存在五种蒽醌(AQs),即大黄素甲醚、大黄素、大黄酸、芦荟大黄素和大黄酚。有趣的是,在研究病例和暴露于决明子的大鼠的血清和尿液样本中检测到了这些蒽醌。上述蒽醌对大鼠原代肝细胞和HepG2细胞的细胞毒性分析表明,大黄酸是毒性最大的成分,其次是大黄素、芦荟大黄素、大黄素甲醚和大黄酚。这些研究表明,蒽醌苷元是产生毒性的原因,这可能与决明子中毒病例中的肝脑脊髓病症状有关。