Sophoridine is a common quateracyclic quinolizidine alkaloid, which can induce apoptosis [1]. Sophoridine ameliorates cardiac Ca2+-induced Ca2+ transients through the up-regulation of the L-type Ca2+ channels (LTCCs) and recovery of the sarcoplasmic reticulum calcium capacity by upregulating SERCA2a expression in cardiomyocytes [2]. Sophoridine has been widely used to inhibit the proliferation of various cancer cells and induce DNA breaks [3].
In vitro, Sophoridine treatment for 48 hours significantly inhibited the viability of PANC-1 cells, Miapaca-2 cells, and HepG2 cells, with IC50 values of 19.23µM, 22.65µM, and 26.78µM, respectively[4]. Treatment with 1mg/ml of Sophoridine for 24 hours induced cell cycle arrest in U87MG cells, promoted cell apoptosis, and led to an increase in reactive oxygen species (ROS) production and a decrease in glutathione content[5]. Treatment with 20μg/ml Sophoridine for 24 hours significantly inhibited the migration of NCI-H446 cells and activated the p53 signaling pathway and the Hippo pathway[6].
In vivo, Sophoridine treatment via intragastric administration at a dose of 25mg/kg daily for 25 days significantly inhibited tumor growth in the Lewis tumor-bearing mouse model, with no obvious organ toxicity [7]. Oral administration of 12.15mg/kg/day of Sophoridine for 5 consecutive days significantly reduced paw edema in mice induced by carrageenan, and inhibited the levels of TNF-α, IL-6, PGE2, and IL-8[8].
References:
[1] Tang Q, Liu Y, Peng X, et al. Research progress in the pharmacological activities, toxicities, and pharmacokinetics of sophoridine and its derivatives[J]. Drug Design, Development and Therapy, 2023: 191-212.
[2] Song T, Hao Y, Wang M, et al. Sophoridine manifests as a leading compound for anti-arrhythmia with multiple ion-channel blocking effects[J]. Phytomedicine, 2023, 112: 154688.
[3] ur Rashid H, Rasool S, Ali Y, et al. Anti-cancer potential of sophoridine and its derivatives: Recent progress and future perspectives[J]. Bioorganic chemistry, 2020, 99: 103863.
[4] Xu Z, Zhang F, Bai C, et al. Sophoridine induces apoptosis and S phase arrest via ROS-dependent JNK and ERK activation in human pancreatic cancer cells[J]. Journal of Experimental & Clinical Cancer Research, 2017, 36(1): 124.
[5] Wang W X, Sun Z H, Chen H M, et al. Role and mechanism of Sophoridine on proliferation inhibition in human glioma U87MG cell line[J]. International journal of clinical and experimental medicine, 2015, 8(1): 464.
[6] Zhu L, Huang S, Li J, et al. Sophoridine inhibits lung cancer cell growth and enhances cisplatin sensitivity through activation of the p53 and Hippo signaling pathways[J]. Gene, 2020, 742: 144556.
[7] Zhao B, Hui X, Zeng H, et al. Sophoridine inhibits the tumour growth of non-small lung cancer by inducing macrophages M1 polarisation via MAPK-mediated inflammatory pathway[J]. Frontiers in Oncology, 2021, 11: 634851.
[8] Huang X, Li B, Shen L. Studies on the anti‐inflammatory effect and its mechanisms of sophoridine[J]. Journal of analytical methods in chemistry, 2014, 2014(1): 502626.