Meng Jingjing, Zhang Xiangqi, Xiang Danfeng, Liang Hanlu, Zhao Shuai, Xu Lingyan, Yang Jiao, Chen JunJun, Zhang Jingxian, Han Yonglong
Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.
Chin Med. 2025 Aug 5;20(1):120. doi: 10.1186/s13020-025-01179-x.
Huachansu injection (HCSI) shows effective medicinal functions against osteosarcoma. This study aimed to reveal the underlying mechanisms of HCSI against osteosarcoma by integrating metabolomics, network pharmacology and bioinformatics.
Metabolomics was used to identify different metabolites and pathways. Network pharmacology was utilized to predict the potential targets of HCSI against osteosarcoma. Differentially expressed lncRNAs and miRNAs were screened and the corresponding lncRNAs-miRNAs-mRNAs network were constructed through the GEO database and miRcode database. Machine learning and immune infiltration analysis were performed on the key target obtained from the intersection of network pharmacology and bioinformatics. The binding affinity between active compounds of HCSI and potential targets was evaluated by molecular docking. The underlying mechanisms were further validated by RT-qPCR and immunoblotting.
Lipid metabolism pathways were obtained by non-target metabolomics enrichment. A total of 44 HCSI targets associated with osteosarcoma were collected by network pharmacology. Intersection of the mRNAs obtained from ceRNA network with the above 44 targets yielded eight common targets. The main target HMGCR were obtained by machine learning and RT-qPCR. The BCYRN1-miR-27a-3p-HMGCR axis was subsequently screened as the primary ceRNA regulatory network in HSCI against osteosarcoma. Molecular docking also showed an excellent affinity between the active compounds of HCSI and HMGCR. In vitro experiments demonstrated that HCSI down-regulated HMGCR, thereby reduced intracellular cholesterol levels, and ultimately promoting osteosarcoma cell apoptosis.
HCSI could inhibit osteosarcoma progression by regulating lipid metabolism through BCYRN1-miR-27a-3p-HMGCR axis, indicating that HCSI may provide insights for developing herbal medicine injection-based therapies for osteosarcoma.
华蟾素注射液（HCSI）对骨肉瘤显示出有效的药用功能。本研究旨在通过整合代谢组学、网络药理学和生物信息学来揭示HCSI抗骨肉瘤的潜在机制。
采用代谢组学鉴定不同的代谢物和途径。利用网络药理学预测HCSI抗骨肉瘤的潜在靶点。筛选差异表达的lncRNAs和miRNAs，并通过GEO数据库和miRcode数据库构建相应的lncRNAs - miRNAs - mRNAs网络。对从网络药理学和生物信息学交叉点获得的关键靶点进行机器学习和免疫浸润分析。通过分子对接评估HCSI活性化合物与潜在靶点之间的结合亲和力。通过RT - qPCR和免疫印迹进一步验证潜在机制。
通过非靶向代谢组学富集获得脂质代谢途径。通过网络药理学收集了总共44个与骨肉瘤相关的HCSI靶点。从ceRNA网络获得的mRNA与上述44个靶点的交集产生了8个共同靶点。通过机器学习和RT - qPCR获得主要靶点HMGCR。随后筛选出BCYRN1 - miR - 27a - 3p - HMGCR轴作为HSCI抗骨肉瘤的主要ceRNA调控网络。分子对接还显示HCSI的活性化合物与HMGCR之间具有良好的亲和力。体外实验表明，HCSI下调HMGCR，从而降低细胞内胆固醇水平，并最终促进骨肉瘤细胞凋亡。
HCSI可通过BCYRN1 - miR - 27a - 3p - HMGCR轴调节脂质代谢来抑制骨肉瘤进展，表明HCSI可能为开发基于中药注射液的骨肉瘤治疗方法提供思路。
