Saikosaponin D

Saikosaponin D is a triterpene saponin isolated from Bupleurum, with anti-inflammatory, anti-bacterial, anti-tumor, and anti-allergic activities; Saikosaponin D inhibits selectin, STAT3 and NF-kB and activates estrogen receptor-β. IC50 & Target: Selectin^[1], STAT3, NF-kB^[2], Estrogen receptor-β^[3] In Vitro: Saikosaponin D (Compound 3) is a triterpene saponin, which inhibits E-selectin, L-selectin and P-selectin binding to THP-1 cells, with IC₅₀s of 1.8 µM, 3.0 µM and 4.3 µM, and such effects are not due to cytotoxic action. Saikosaponin D (1, 5, 10 µM) dose-dependently inhibits the THP-1 adhesion to the HUVECs monolayer activated by TNF-α. Saikosaponin D (30 μM) also inhibits the expression of P-selectin ligand (CD162) in THP-1 cells^[1]. Saikosaponin D (5 μM) suppresses the proliferation of HSC-T6 cells induced by H₂O₂ treatment, reduces the expression levels of α-SMA, TGF-β1, Hyp, COL1 and TIMP-1, and increases MMP-1 expressioon, thus inhibiting H₂O₂-induced excessive extracellular matrix (ECM) formation, with similar effects to estradiol (E2), and these effects are blocked by ER antagonists. Saikosaponin D also inhibits oxidative stress-induced ROS generation and down reduates MAPK signaling pathway, and the inhibition is also suppressed by ER antagonists^[3]. In Vivo: Saikosaponin D (2 mg/kg/day, i.p.) shows a protective effect on overdose of acetaminophen (APAP)-induced liver injury of mice. Saikosaponin D affects APAP metabolism, increases GSH levels but does not alter PPARα activation. Saikosaponin D (2 mg/kg/day, i.p.) also suppresses APAP-induced increases in the expression of STAT3 target genes and pro-inflammatory cytokines and inhibits APAP-induced activation of STAT3 and NF-kB^[2].