Chemical Biology Lab (ASK-II-409), School of Chemical and Biotechnology (SCBT), SASTRA Deemed University, Thanjavur, Tamilnadu, India.
Medicinal Chemistry and Immunology Lab (ASK-II-406), School of Chemical and Biotechnology (SCBT), SASTRA Deemed University, Thanjavur, Tamil Nadu, India.
J Ethnopharmacol. 2020 Apr 6;251:112527. doi: 10.1016/j.jep.2019.112527. Epub 2019 Dec 28.
In search of safe and effective therapeutic agents as alternative to synthetic chemotherapeutics for the treatment of leukemia, the herbal drugs (Leaf of Madhuca longifolia, leaf of Prosopis cineraria and bark of Flacourtia indica) with long traditional use in West Bengal have received our attention.
Present work was conducted to isolate and identify the active compounds of the selected herbal drugs using bio-assay guided fractionation and also to investigate their anticancer mechanism in leukemia cell lines.
Bio-assay guided fractionation was used for the isolation of active constituents such as myricitrin, vitexin and vanillin from the aqueous extracts of M. longifolia, P. cineraria and F. indica, respectively using liquid partitioning and column chromatography and the compounds were characterized by HPLC, MS and NMR. Dose and time-dependent cytotoxicity of isolated compounds were studied against leukemia cells and their anticancer mechanism such as cell wall damage, nuclear damage, ROS and NO generation, SOD level, LDH release and lipid peroxidation were investigated.
Aqueous extract of M. longifolia, P. cineraria and F. indica exhibited maximum anti-proliferative activity against HL-60 (Acute myeloid leukemia, AML, 72.06%), K-562 (Chronic myeloid leukemia, CML, 42.14%) and Jurkat (Acute lymphoblastic leukemia, ALL, 51.71%) cells. Myricitrin, vitexin and vanillin exhibited dose-dependent (IC-50 values 164.4, 147 & 29.22 μg/ml) and time-dependent activity with maximum cytotoxicity at 48 h. All these three compounds caused apoptosis in leukemia cells by inducing free radicals such as ROS (1.33-2.65 Arbitrary units) and NO (11.17-18.53 μM), cell membrane damage and nuclear condensation which were evidenced by increased release of LDH (1326-1439 U/L), improved lipid peroxidation (10.19-14.41 nM/mg protein) and reduced SOD level (6.2-9.21 U/mg protein) in leukemia cells.
Based on anti-proliferative activity, the isolated phyto-compounds myrcitrin, vitexin and vanillin from M. longifolia, P. cineraria and F. indica could be developed as natural drugs for treating AML, CML and ALL leukemia types, respectively.
为了寻找安全有效的治疗白血病的治疗药物，替代合成化疗药物，我们关注了在西孟加拉邦长期使用的草药（长叶芒果叶、金合欢叶和印度使君子树皮）。
本研究采用生物测定指导的分步分离方法，从芒果叶、金合欢叶和印度使君子树皮的水提物中分离和鉴定活性化合物，并研究其在白血病细胞系中的抗癌机制。
采用液-液分配和柱层析法从芒果叶、金合欢叶和印度使君子树皮的水提物中分离出活性成分，如杨梅素、荭草苷和香草醛，用 HPLC、MS 和 NMR 对化合物进行了表征。研究了分离得到的化合物对白血病细胞的剂量和时间依赖性细胞毒性及其抗癌机制，如细胞壁损伤、核损伤、ROS 和 NO 生成、SOD 水平、LDH 释放和脂质过氧化。
芒果叶、金合欢叶和印度使君子树皮的水提取物对 HL-60（急性髓系白血病，AML，72.06%）、K-562（慢性髓系白血病，CML，42.14%）和 Jurkat（急性淋巴细胞白血病，ALL，51.71%）细胞表现出最大的增殖抑制活性。杨梅素、荭草苷和香草醛表现出剂量依赖性（IC-50 值分别为 164.4、147 和 29.22μg/ml）和时间依赖性活性，在 48h 时表现出最大的细胞毒性。这三种化合物均通过诱导 ROS（1.33-2.65 任意单位）和 NO（11.17-18.53μM）等自由基、细胞膜损伤和核固缩，导致白血病细胞凋亡，这可以通过 LDH 释放增加（1326-1439U/L）、脂质过氧化增强（10.19-14.41nM/mg 蛋白）和 SOD 水平降低（6.2-9.21U/mg 蛋白）来证明。
基于增殖抑制活性，从芒果叶、金合欢叶和印度使君子树皮中分离出的植物化合物杨梅素、荭草苷和香草醛，可分别开发成治疗 AML、CML 和 ALL 白血病的天然药物。
