Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Analytical Chemistry Division (Instrumentation), CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India.
Cancer Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India; AcSIR: Academy of Scientific and Innovative Research, Jammu- Campus, Jammu, India.
J Ethnopharmacol. 2018 Jan 30;211:295-310. doi: 10.1016/j.jep.2017.09.034. Epub 2017 Sep 27.
Tinospora cordifolia is a miraculous ayurvedic herb used in the treatment of innumerable diseases such as diabetes, gonorrhea, secondary syphilis, anaemia, rheumatoid arthritis, dermatological diseases, cancer, gout, jaundice, asthma, leprosy, in the treatment of bone fractures, liver & intestinal disorders, purifies the blood, gives new life to the whole body; (rejuvenating herb) and many more. Recent studies have revealed the anticancer potential of this plant but not much work has been done on the anticancer chemical constituents actually responsible for its amazing anticancer effects. This prompted us to investigate this plant further for new potent anticancer molecules.
The present study was designed to isolate and identify new promising anticancer candidates from the aqueous alcoholic extract of T. cordifolia using bioassay-guided fractionation.
The structures of the isolated compounds were determined on the basis of spectroscopic data interpretation and that of new potent anticancer molecule, TC-2 was confirmed by a single-crystal X-ray crystallographic analysis of its corresponding acetate. The in vitro anti-cancer activity of TC-2 was evaluated by SRB assay and the autophagic activity was investigated by immunofluorescence microscopy. Annexin-V FITC and PI dual staining was applied for the detection of apoptosis. The studies on Mitochondrial Membrane potential and ROS (Reactive oxygen species) production were also done.
Bioassay guided fractionation and purification of the aqueous alcoholic stem extract of Tinospora cordifolia led to the isolation of a new clerodane furano diterpene glycoside (TC-2) along with five known compounds i.e. cordifolioside A (β-D-Glucopyranoside,4-(3-hydroxy-1-propenyl)- 2,6-dimethoxyphenyl 3-O-D-apio-β-D-furanosyl) (TC-1), β-Sitosterol(TC-3), 2β,3β:15,16-Diepoxy- 4α, 6β-dihydroxy-13(16),14-clerodadiene-17,12:18,1-diolide (TC-4), ecdysterone(TC-5) and tinosporoside(TC-6). TC-2 emerged as a potential candidate for the treatment of colon cancer.
The overall study on the bioassay guided isolation of T.cordifolia identified and isolated a new clerodane furano diterpenoid that exhibited anticancer activity via induction of mitochondria mediated apoptosis and autophagy in HCT116 cells. We have reported a promising future candidate for treating colon cancer.
三叶鬼针草是一种神奇的顺势疗法草药，用于治疗无数疾病，如糖尿病、淋病、二期梅毒、贫血、类风湿性关节炎、皮肤病、癌症、痛风、黄疸、哮喘、麻风病、骨折治疗、肝脏和肠道疾病、净化血液、赋予全身新的生命；（ rejuvenating herb ）等等。最近的研究揭示了这种植物的抗癌潜力，但对实际负责其惊人抗癌效果的抗癌化学成分的研究还不多。这促使我们进一步研究这种植物，以寻找新的有效的抗癌分子。
本研究旨在通过生物活性指导的分级分离从三叶鬼针草的水醇提取物中分离和鉴定新的有前途的抗癌候选物。
根据光谱数据解释和新的有效抗癌分子 TC-2 的单晶 X 射线晶体学分析，确定分离化合物的结构。TC-2 的体外抗癌活性通过 SRB 测定法进行评估，自噬活性通过免疫荧光显微镜进行研究。用 Annexin-V FITC 和 PI 双重染色法检测细胞凋亡。还进行了线粒体膜电位和 ROS（活性氧）产生的研究。
生物活性指导的三叶鬼针草水醇提取物的分级分离和纯化导致分离出一种新的 clerodane furano 二萜糖苷（TC-2），以及五种已知化合物，即 cordifolioside A（β-D-吡喃葡萄糖苷，4-（3-羟基-1-丙烯基）-2,6-二甲氧基苯基 3-O-D-阿比奥-β-D-呋喃基）（TC-1）、β-谷甾醇（TC-3）、2β,3β：15,16-环氧-4α,6β-二羟基-13(16),14-环二萜-17,12：18,1-二醇内酯（TC-4）、ecdysterone（TC-5）和 tinosporoside（TC-6）。TC-2 是治疗结肠癌的潜在候选药物。
通过生物活性指导的三叶鬼针草分离鉴定出一种新的 clerodane furano 二萜，该化合物通过诱导 HCT116 细胞中线粒体介导的细胞凋亡和自噬发挥抗癌活性。我们报告了一种有前途的治疗结肠癌的候选药物。
