Saikosaponin D is a triterpenoid saponin derivative with antioxidant, antipyretic, and anti-inflammatory properties[1]. Saikosaponin D directly targets fat mass and obesity associated protein (FTO), thereby increasing global m6A RNA methylation, which in turn decreases the stability of downstream gene transcripts, leading to the suppression of relevant pathways and overcoming FTO/m6A-mediated leukemia resistance to tyrosine kinase inhibitors[2]. Saikosaponin D has been widely used in tumor research to inhibit the growth of various cancer cells and angiogenesis[3].
In vitro, Saikosaponin D treatment for 48 hours significantly inhibited the viability of BCAP-37, HepG2, and Hep3B cells, with IC50 values of 10.67µM, 4.88µM and 9.61µM, respectively[4]. Incubation of A549 cells with 20µM Saikosaponin D for 48 hours induced apoptosis, accompanied by increased expression of p53 and p21/WAF1 proteins and DNA fragmentation[5]. Treatment with 1µM Saikosaponin D for 72 hours promoted cell death in HSC-T6 and LX-2 cells, decreased the protein expression of collagen I, collagen III, and α-SMA, induced the translocation of BAX and BAK from the cytoplasm to the mitochondria, and led to inhibition of mitochondrial function and disruption of membrane potential[6].
In vivo, Saikosaponin D treatment via intragastric administration at a dose of 8mg/kg daily for 10 days alleviated dextran sulfate sodium-induced colitis, prevented body weight loss, and attenuated colon shortening in mice [7]. Subcutaneous injection of Saikosaponin D (2mg/kg), twice a week for 6 weeks, mitigated hepatic injury and liver fibrosis induced by CCl4, and reversed mitochondrial dysfunction and prevented activation of the NLRP3 inflammasome[8]. Continuous intraperitoneal injection of Saikosaponin D (2mg/kg/day) for 28 consecutive days reduced the pulmonary inflammation and pulmonary fibrosis induced by bleomycin in mice[9].
References:[1] Manoharan S, Deivendran B, Perumal E. Chemotherapeutic potential of Saikosaponin D: Experimental evidence[J]. Journal of xenobiotics, 2022, 12(4): 378-405.
[2] Sun K, Du Y, Hou Y, et al. Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling[J]. Theranostics, 2021, 11(12): 5831.
[3] Zhou P, Shi W, He X Y, et al. Saikosaponin D: review on the antitumour effects, toxicity and pharmacokinetics[J]. Pharmaceutical biology, 2021, 59(1): 1478-1487.
[4] Li D Q, Wu J, Liu L Y, et al. Cytotoxic triterpenoid glycosides (saikosaponins) from the roots of Bupleurum chinense[J]. Bioorganic & Medicinal Chemistry Letters, 2015, 25(18): 3887-3892.
[5] Hsu Y L, Kuo P L, Lin C C. The proliferative inhibition and apoptotic mechanism of Saikosaponin D in human non-small cell lung cancer A549 cells[J]. Life sciences, 2004, 75(10): 1231-1242.
[6] Chen M F, Huang S J, Huang C C, et al. Saikosaponin d induces cell death through caspase-3-dependent, caspase-3-independent and mitochondrial pathways in mammalian hepatic stellate cells[J]. BMC cancer, 2016, 16(1): 532.
[7] Li P, Wu M, Xiong W, et al. Saikosaponin-d ameliorates dextran sulfate sodium-induced colitis by suppressing NF-κB activation and modulating the gut microbiota in mice[J]. International immunopharmacology, 2020, 81: 106288.
[8] Zhang K, Lin L, Zhu Y, et al. Saikosaponin d alleviates liver fibrosis by negatively regulating the ROS/NLRP3 inflammasome through activating the ERβ pathway[J]. Frontiers in Pharmacology, 2022, 13: 894981.
[9] Wu Y, Zhang J, Wang X, et al. Saikosaponin-d regulates angiogenesis in idiopathic pulmonary fibrosis through angiopoietin/Tie-2 pathway[J]. Acta Histochemica, 2023, 125(8): 152100.