Duan Hong, Wang Wei, Shi Ying, Wang Li, Khan Ghulam Jilany, Luo Mengmeng, Zhou Jing, Yang Jianhua, He Chenghui, Li Fei, Hu Henggui, Zhai Kefeng
College of Pharmacy, Xinjiang Medical University, Urumqi, 830000, China; School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou, Anhui, 234000, China.
School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou, Anhui, 234000, China; Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, Ourense E-32004, Spain.
Phytomedicine. 2025 Mar;138:156370. doi: 10.1016/j.phymed.2025.156370. Epub 2025 Jan 6.
The therapeutic and prognostic outcomes for colorectal cancer (CRC) remain unsatisfactory. Among multiple reported bioactive functionalities of Glycyrrhiza uralensis Fisch. one vital recently reported activity is its therapeutic role against numerous cancers but limited information is available related to its underlying key mechanisms and therapeutically active ingredients, especially against CRC treatment.
The aim of current study aims is to reconnoiter G. uralensis pharmacological basis and primary molecular mode of action in treating CRC.
For examining the G. uralensis active ingredients and underlying mechanism investigation against CRC including, potential anti-CRC phytochemicals, targets, and related signaling pathways, HPLC and Network-pharmacology analysis techniques was employed, respectively. Whereas, for binding capabilities of active components to their targets, molecular-docking, molecular dynamic simulation technique employed and cell proliferation assays screened the best anti-CRC components, followed by biological function experiments on SW480 cells for verification. Finally, the SW480-xenograft model and subsequent related experiments further confirmed the effect of Liquiritin on CRC.
Seven compounds were identified from G. uralensis through HPLC. Network pharmacology and molecular docking results indicated that G. uralensis components exhibited significant anti-cancer effects. These effects were mediated through cancer and MAPK-related signaling pathways, targeting TP53, SRC, STAT3, and PIK3CA proteins. In-vitro experiments showed that liquiritin had better anti-CRC effects compared to other components as it significantly repressed the SW480 propagation, development of colony, relocation, and invasion. Additionally, liquiritin has been shown to significantly reduce tumor size in tumor-bearing mice by targeting p53 and inhibiting the p38 MAPK pathway.
In G. uralensis, main API is liquiritin that target CRC tumorigeneses via inhibition of p53 and p38 MAPK, thus can be used for CRC therapy. The findings provide a solid pharmacological basis and potential therapeutic targets for G. uralensis in the treatment of CRC.
结直肠癌（CRC）的治疗和预后结果仍不尽人意。在已报道的甘草的多种生物活性功能中，最近报道的一项重要活性是其对多种癌症的治疗作用，但关于其潜在关键机制和治疗活性成分的信息有限，尤其是针对CRC治疗。
本研究旨在探究甘草治疗CRC的药理基础和主要分子作用模式。
为研究甘草抗CRC的活性成分和潜在机制，包括潜在的抗CRC植物化学物质、靶点和相关信号通路，分别采用了高效液相色谱（HPLC）和网络药理学分析技术。而对于活性成分与其靶点的结合能力，采用分子对接、分子动力学模拟技术，并通过细胞增殖试验筛选出最佳抗CRC成分，随后在SW480细胞上进行生物学功能实验进行验证。最后，通过SW480异种移植模型及后续相关实验进一步证实了甘草苷对CRC的作用。
通过HPLC从甘草中鉴定出7种化合物。网络药理学和分子对接结果表明，甘草成分具有显著的抗癌作用。这些作用是通过癌症和丝裂原活化蛋白激酶（MAPK）相关信号通路介导的，靶向TP53、SRC、信号转导和转录激活因子3（STAT3）和磷脂酰肌醇-3-激酶催化亚基α（PIK3CA）蛋白。体外实验表明，与其他成分相比，甘草苷具有更好的抗CRC作用，因为它能显著抑制SW480的增殖、集落形成、迁移和侵袭。此外，甘草苷已被证明通过靶向p53并抑制p38 MAPK通路，可显著减小荷瘤小鼠的肿瘤大小。
在甘草中，主要活性成分是甘草苷，其通过抑制p53和p38 MAPK靶向CRC肿瘤发生，因此可用于CRC治疗。这些发现为甘草治疗CRC提供了坚实的药理基础和潜在治疗靶点。
