Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM)

Xiaobing Yang; Di Lu; Yanfei Sun; Tiandi Wei; Dulegeqi Man; Anbin Chen; Tao Luo; Feihu Zhao; Xuemeng Liu; Bo Cheng; Xu Wang; Peng Zhao; Donghai Wang; Xingang Li

doi:10.3389/fonc.2023.1255164

Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM)

Front Oncol. 2023 Sep 5:13:1255164. doi: 10.3389/fonc.2023.1255164. eCollection 2023.

Authors

Xiaobing Yang^{1

2}, Di Lu^{1

2}, Yanfei Sun^{1

2}, Tiandi Wei³, Dulegeqi Man⁴, Anbin Chen⁵, Tao Luo^{6

7}, Feihu Zhao^{1

2}, Xuemeng Liu^{1

2}, Bo Cheng^{1

2}, Xu Wang^{1

2}, Peng Zhao^{1

2}, Donghai Wang^{1

2}, Xingang Li^{1

2}

Affiliations

¹ Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
² Jinan Microecological Biomedicine Shandong Laboratory and Shandong Key Laboratory of Brain Function Remodeling, Jinan, China.
³ State Key Laboratory of Microbial Technology, Microbial Technology, Institute, Shandong University, Qingdao, China.
⁴ International Mongolia Hospital of Inner Mongolia, Hohhot, China.
⁵ Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁶ School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.
⁷ Department of Emergency, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.

Abstract

Introduction: Safranal is an active component of the traditional Tibetan medicine (TTM) saffron, which has potential anticancer activity.

Methods and results: Here, we studied the therapeutic effect and mechanism of safranal on GBM. CCK-8, GBM-brain organoid coculture experiments and 3D tumour spheroid invasion assays showed that safranal inhibited GBM cell proliferation and invasion in vitro. Network pharmacology, RNA-seq, molecular docking analysis, western blotting, apoptosis, and cell cycle assays predicted and verified that safranal could promote GBM cell apoptosis and G2/M phase arrest and inhibit the PI3K/AKT/mTOR axis. In vivo experiments showed that safranal could inhibit GBM cell growth alone and in combination with TMZ.

Conclusion: This study revealed that safranal inhibits GBM cell growth in vivo and in vitro, promotes GBM cell apoptosis and G2/M phase arrest, inhibits the PI3K/AKT/mTOR axis and cooperate with TMZ.

Keywords: Akt; glioma; network pharmacology; safranal; traditional tibetan medicine.

Grants and funding

The Department of Science & Technology of Shandong Province (2020CXGC010903 and ZR2019ZD33), the Clinical Research Center of Shandong University (2020SDUCRCB002), Research Project of Jinan Microecological Biomedicine Shandong Laboratory (JNL-2022003A) and the Shandong Research Institute of Industrial Technology.