Department of Animal Biotechnology, Institute of Tropical Biology, Vietnam Academy of Science and Technology, Ho Chi Minh City, Viet Nam; Faculty of Biotechnology, Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Ha Noi City, Viet Nam.
Department of Animal Biotechnology, Institute of Tropical Biology, Vietnam Academy of Science and Technology, Ho Chi Minh City, Viet Nam.
J Ethnopharmacol. 2022 Feb 10;284:114803. doi: 10.1016/j.jep.2021.114803. Epub 2021 Nov 6.
Curcuma singularis Gagnep is a Vietnamese medicinal plant which has been commonly used as a medicinal remedy in traditional and folk medicines for improving health as well as for treating some diseases, like rheumatoid arthritis, kidney failure. However, pharmacological effects, including anti-cancer activity and the safety of this plant has not been fully investigated.
This study aimed to investigate the in vitro anti-growth activity of an extract derived from Curcuma singularis rhizome extract (CSE) against cell lines as well as determine its phytochemical composition. The other goal of our study was to assess the safety of CSE in rats.
The main constituents in the extract were identified and quantitatively analyzed. The in vitro cytotoxicity of CSE was evaluated in several cancer and normal cell lines. The apoptotic activity of CSE and the expression of the apoptosis-related genes were investigated in AGS cells to clarify the underlying molecular mechanisms. The in vivo toxicity of CSE was assessed via acute and subacute oral studies on Sprague-Dawley rats, respectively according to the guidelines 425 and 407 of the Organization for Economic Cooperation and Development (OECD). The drug-related toxicity signs, mortality, body and organ weights were recoreded during the experimental period. In addition, the selected hematological and biochemical parameters, and histological alterations were determined at the end of the subacute toxicity test.
Germacrone, ar-turmerone, and curcumol were three sesquiterpene components found in the extract. CSE showed cytotoxic effects in different cancer cells, but had minimal effects on normal cells. Apoptosis in AGS cells was caused by CSE in a concentration-dependent pattern through increase of Bax/Bcl-2 ratio, and release of cytochrome c, which leads to activation of caspase-3/-7, caspase-9, as well as cleavage of PARP. In the acute toxicity test, no signs of toxicity and no mortality were recorded in rats at both doses of 1000 and 5000 mg/kg. In the subacute toxicity study, CSE showed no drug-related adverse effects on water and food consumption, body and organ weights. CSE at a dose of 1000 mg/kg slightly increased WBC and platelet values in female rats, while it increased WBC values in male rats in all tested doses. The decrease of total cholesterol and triglyceride levels were found in female rats treated CSE at doses of 250 or 500 mg/kg. In addition, the increase of serum ALT and AST levels in rats treated at the dose of 1000 mg/kg were noted. No significant changes in histopathological structures of kidneys, spleen, heart and lungs, except liver tissue with minor modifications was found.
Our findings indicated that CSE exhibited in vitro anti-proliferative effects on AGS cells by mainly activating the caspase-dependent mitochondrial apoptotic pathway. CSE also showed in vivo toxicity signals at the dose of 1000 mg/kg with proven minor hepatic injuries, which should be avoided the high dose for prolonged use. Curcuma singularis rhizomes may be used as a chemotherapeutic agent for the treatment of gastric cancer with in vitro anti-cancer investigation and in vivo biological safety evaluation.
姜黄奇异是越南的一种药用植物，在传统和民间医学中常被用作改善健康和治疗某些疾病的药物，如类风湿关节炎、肾衰竭。然而，其药理作用，包括抗癌活性和这种植物的安全性尚未得到充分研究。
本研究旨在研究姜黄奇异根茎提取物（CSE）对细胞系的体外生长抑制活性，并确定其植物化学成分。我们研究的另一个目的是评估 CSE 在大鼠中的安全性。
鉴定并定量分析提取物中的主要成分。在几种癌细胞和正常细胞系中评估 CSE 的体外细胞毒性。在 AGS 细胞中研究 CSE 的促凋亡活性和凋亡相关基因的表达，以阐明潜在的分子机制。根据经济合作与发展组织（OECD）的 425 和 407 号准则，分别通过急性和亚急性口服研究评估 CSE 的体内毒性。在实验期间记录药物相关毒性迹象、死亡率、体重和器官重量。此外，在亚急性毒性试验结束时，确定选定的血液学和生化学参数以及组织学改变。
提取物中发现了三种倍半萜成分，即姜烯酮、α-姜黄烯和姜黄素。CSE 在不同的癌细胞中表现出细胞毒性作用，但对正常细胞的影响很小。CSE 通过增加 Bax/Bcl-2 比值和细胞色素 c 的释放，导致 caspase-3/-7、caspase-9 的激活以及 PARP 的裂解，以浓度依赖性方式诱导 AGS 细胞凋亡。在急性毒性试验中，1000 和 5000mg/kg 两个剂量的大鼠均未出现毒性迹象和死亡率。在亚急性毒性研究中，CSE 对水和食物摄入、体重和器官重量没有表现出药物相关的不良影响。CSE 在 1000mg/kg 剂量下略微增加了雌性大鼠的白细胞和血小板值，而在所有测试剂量下均增加了雄性大鼠的白细胞值。在 250 或 500mg/kg 剂量下，雌性大鼠的总胆固醇和甘油三酯水平降低。此外，在 1000mg/kg 剂量下，大鼠的血清 ALT 和 AST 水平升高。除肝脏组织有轻微改变外，肾脏、脾脏、心脏和肺组织的组织学结构没有明显变化。
我们的研究结果表明，CSE 通过主要激活 caspase 依赖性线粒体凋亡途径，对 AGS 细胞表现出体外增殖抑制作用。CSE 在 1000mg/kg 剂量下也表现出体内毒性信号，并有轻微的肝损伤证据，因此应避免高剂量长期使用。姜黄奇异根茎可作为治疗胃癌的化疗药物，具有体外抗癌作用和体内生物安全性评价。
