Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, U.P, India.
Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, U.P, India.
J Ethnopharmacol. 2021 Jun 28;274:114060. doi: 10.1016/j.jep.2021.114060. Epub 2021 Mar 23.
Epidemiological studies promote the inclusion of natural-products in diet due to their inhibitory effects on various types of cancer. Among them, Achyranthes aspera L. (Family Amaranthaceae) is a medicinal plant in Ayurvedic pharmacopeia, found in India, Southeast Asia, America, and Sub-Saharan Africa. It is endowed with anti-inflammatory, anti-oxidant, and anti-cancer activities. However, its potential effect on Non-Hodgkin lymphomas (NHLs), has not yet been clarified.
In the present study, we aimed to investigate the effect of Achyranthes aspera L. leaf extracts on highly aggressive murine NHL called Dalton's Lymphoma (DL) in vitro and in vivo.
GC-HRMS analysis was carried out for the identification of compounds present in A. aspera leaf extract. The cytotoxicity of various A. aspera leaf extracts was evaluated on DL cells by MTT assay. Chromatin condensation, nuclear fragmentation, and morphological changes were observed by microscopy technique. Flow cytometry was used to measure the changes in mitochondrial membrane potential (ΔΨm) and apoptosis. In addition, the expressions of apoptosis-related proteins were detected by western blotting. Meanwhile, the in vivo anti-tumor effect of leaf extract was tested in DL induced Balb/c mice.
GC-HRMS analysis of A. aspera methanolic leaf extract (AAML) revealed the presence of ten pharmacologically active compounds. The results showed that AAML suppressed cell proliferation, decreased mitochondrial membrane potential, changed the morphological structure, and induced apoptosis. Moreover, AAML could promote the release of cytochrome c by regulating Bcl-2 family proteins and then activated caspase-9/ -3 to triggered cell apoptosis. At the same time in DL cells treated with AAML, the protein kinase Cα (PKCα) pathway was inhibited in a concentration-dependent manner. Remarkably, in vivo, AAML mediated suppression of DL growth in Balb/c mice was accompanied by attenuation of the PKCα pathway and induction of apoptosis. Our result suggested that AAML promotes mitochondrial apoptotic cascade in DL cells by suppressing the PKCα signaling pathway.
The study suggests that AAML could potently suppress DL progression by promoting apoptosis via mitochondrial-cascade and attenuation of the PKCα signaling pathway.
流行病学研究因天然产物对各种类型癌症的抑制作用而促进将其纳入饮食。其中，牛膝（苋科）是印度、东南亚、美洲和撒哈拉以南非洲的阿育吠陀药理学中的一种药用植物。它具有抗炎、抗氧化和抗癌作用。然而，其对非霍奇金淋巴瘤（NHLs）的潜在影响尚未得到明确。
本研究旨在研究牛膝叶提取物对高度侵袭性的鼠类 NHL 即道尔顿淋巴瘤（DL）的体外和体内作用。
通过 GC-HRMS 分析鉴定牛膝叶提取物中的化合物。通过 MTT 测定法评估各种牛膝叶提取物对 DL 细胞的细胞毒性。通过显微镜技术观察染色质浓缩、核片段化和形态变化。流式细胞术用于测量线粒体膜电位（ΔΨm）和凋亡的变化。此外，通过 Western 印迹检测凋亡相关蛋白的表达。同时，在 DL 诱导的 Balb/c 小鼠中测试了叶提取物的体内抗肿瘤作用。
牛膝甲醇叶提取物（AAML）的 GC-HRMS 分析显示存在十种具有药理活性的化合物。结果表明，AAML 抑制细胞增殖、降低线粒体膜电位、改变形态结构并诱导细胞凋亡。此外，AAML 可以通过调节 Bcl-2 家族蛋白来促进细胞色素 c 的释放，然后激活 caspase-9/-3 来触发细胞凋亡。同时，在 AAML 处理的 DL 细胞中，蛋白激酶 Cα（PKCα）途径呈浓度依赖性抑制。值得注意的是，体内，AAML 介导的对 Balb/c 小鼠中 DL 生长的抑制伴随着 PKCα 途径的减弱和细胞凋亡的诱导。我们的结果表明，AAML 通过抑制 PKCα 信号通路在 DL 细胞中促进线粒体凋亡级联反应。
该研究表明，AAML 通过促进线粒体级联反应和减弱 PKCα 信号通路诱导细胞凋亡，从而有力地抑制 DL 的进展。
