Singh Salam Asbin, Singh Asem Robinson, Singh Atom Rajiv, Devi Anoubam Sujita, Korimayum Minhaz, Singh Lisam Shanjukumar
Department of Biotechnology, Manipur University, Canchipur, Manipur, 795003, India.
Department of Chemistry, Manipur University, Canchipur, Manipur, 795003, India.
Anticancer Agents Med Chem. 2025;25(8):563-573. doi: 10.2174/0118715206364530241128044041.
As the number of new cancer cases increases every year, there is a necessity to develop new drugs for the treatment of different types of cancers. Plants' resources are considered to be huge reservoirs for therapeutic agents in nature. Among all the medicinal plants, is one of the most widely used medicinal plants in India, China, and Southeast Asian countries. Combinatorial drug treatment, on the other hand, is favored over single drug treatment in order to target multiple biomolecular moieties that help in the growth and development of cancer. Therefore, combinatorial drug treatment using a co-crystal of multiple drugs gives researchers an idea of the development of a new type of drug for targeting multiple targets. In this study, a new co-crystal of chrysin and oroxylin A was isolated from the leaves of , and its anticancer properties were studied in cervical cancer cells HeLa.
This study was conducted with the aim of identifying new anticancer compounds from the leaves of and studying the anticancer properties of the isolated compound.
In this study, we elucidated the structure of a new co-crystal compound, which was isolated from the leaf extract of . The apoptosis induction mechanism of the newly discovered co-crystal in HeLa cells was also studied.
A crystal compound from the chloroform extract of leaves of was isolated by solvent fractionation and chromatographic methods involving HPLC. The molecular structure of the isolated crystal was elucidated by Single Crystal-XRD, FT-IR analysis, and further determined by LC-MS. The antiproliferative activity was carried out using an MTT assay and fluorescence microscopy, and the mechanism of apoptosis was determined using Western blotting techniques.
The novel co-crystal consists of two active pharmaceutical ingredients (APIs) in a 1:1 ratio, i.e., oroxylin A and chrysin. The isolated new co-crystal induced death in HeLa cells with a very low IC50 value of 8.49 μM. It induced caspase-dependent apoptosis in HeLa cells by activation of Caspase-3 through inhibition of ERKs and activation of p38 of MAPK cell signalling pathway.
This study presents the first report on the discovery of a naturally occurring co-crystal of chrysin and oroxylin A and the involvement of ERKs and p38 of MAPK pathways in the induction of apoptosis in HeLa cells by the co-crystal. Our study sheds light on the development of a co-crystal of chrysin and oroxylin A in a specific ratio of 1:1 for combination therapy of the two APIs. The purified co-crystal was found to be more efficient compared to the compounds present individually. Further analysis of the physiochemical properties and molecular mechanisms of the isolated co-crystal in different cancer cells is warranted for its application in therapeutics.
随着每年新增癌症病例数量的增加，开发用于治疗不同类型癌症的新药变得很有必要。植物资源被认为是自然界中治疗剂的巨大宝库。在所有药用植物中，[植物名称]是印度、中国和东南亚国家使用最广泛的药用植物之一。另一方面，为了靶向有助于癌症生长和发展的多个生物分子部分，联合药物治疗比单一药物治疗更受青睐。因此，使用多种药物的共晶体进行联合药物治疗，让研究人员有了开发一种新型靶向多种靶点药物的思路。在本研究中，从[植物名称]的叶子中分离出一种白杨素和木犀草素A的新型共晶体，并在宫颈癌HeLa细胞中研究了其抗癌特性。
本研究旨在从[植物名称]的叶子中鉴定新的抗癌化合物，并研究分离出的化合物的抗癌特性。
在本研究中，我们阐明了从[植物名称]叶提取物中分离出的一种新型共晶体化合物的结构。还研究了新发现的共晶体在HeLa细胞中的凋亡诱导机制。
通过溶剂分级分离和包括高效液相色谱（HPLC）在内的色谱方法，从[植物名称]叶子的氯仿提取物中分离出一种晶体化合物。通过单晶X射线衍射（Single Crystal-XRD）、傅里叶变换红外光谱（FT-IR）分析阐明分离出的晶体的分子结构，并通过液相色谱-质谱联用（LC-MS）进一步确定。使用MTT法和荧光显微镜进行抗增殖活性检测，并使用蛋白质免疫印迹技术确定凋亡机制。
该新型共晶体由两种活性药物成分（API）以1:1的比例组成，即木犀草素A和白杨素。分离出的新型共晶体在HeLa细胞中诱导死亡，IC50值极低，为8.49μM。它通过抑制细胞外调节蛋白激酶（ERK）和激活丝裂原活化蛋白激酶（MAPK）细胞信号通路的p38，激活Caspase-3，从而在HeLa细胞中诱导依赖Caspase的凋亡。
本研究首次报道了天然存在的白杨素和木犀草素A共晶体的发现，以及MAPK途径的ERK和p38参与该共晶体诱导HeLa细胞凋亡的过程。我们的研究为以1:1的特定比例开发白杨素和木犀草素A的共晶体用于这两种API的联合治疗提供了思路。发现纯化的共晶体比单独存在的化合物更有效。有必要进一步分析分离出的共晶体在不同癌细胞中的物理化学性质和分子机制，以便将其应用于治疗。
