Gypsophila elegans isoorientin-2″-O-α-l-arabinopyranosyl ameliorates porcine serum-induced immune liver fibrosis by inhibiting NF-κB signaling pathway and suppressing HSC activation.

The present study was to investigate the inhibitory effect of Gypsophila elegans isoorientin-2″-O-α-l-arabinopyranosyl (GEI) on hepatic stellate cells (HSCs), to reveal the underlying mechanism of GEI against hepatic fibrosis. Our study showed that GEI significantly alleviated liver injury induced by porcine serum (PS) in rats; it notably alleviated collagen accumulation as evidenced by a significant decrease in the levels of collagen biomarkers including hyaluronic acid, laminin, hydroxyproline and procollagen III N-terminal peptide. Moreover, GEI treatment markedly decreased the secretion of inflammatory cytokines by inhibiting the NF-κB pathway and significantly inhibited the generation of excessive extracellular matrix (ECM) components by restoring the balance between matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs). Additionally, the cell experiments in vitro showed that GEI strongly inhibited HSC proliferation, migration and clonogenicity and markedly induced HSC apoptosis. Moreover, GEI caused cell cycle arrest at G2 phase. In conclusion, our study demonstrates that GEI significantly alleviates PS-induced hepatic fibrosis by inhibiting the NF-κB pathway, restoring the balance between MMPs and TIMPs, and suppressing HSC activation.

Evaluation of novel saponins from Psammosilene tunicoides and their analogs as immunomodulators.

Two original oleanane-type triterpenoid saponins, tunicosaponin A (TSA) and tunicosaponin E (TSE) were isolated from the roots of Psammosilene tunicoides. Four semi-synthetic saponin derivatives, TSA1, TSA2, TSA3, and TSA4, were synthesized from TSA; two derivatives TSE1 and TSE2 were prepared from TSE. Through comparing their hemolytic activity and effects on ovalbumin (OVA)-induced IgG response with those of Quil A, TSA2 was selected as a lead candidate to evaluate acute and hepatotoxic toxicities and adjuvant potentials on the cellular and humoral immune responses of ICR mice against OVA. TSA2 had lower hemolytic activity than Quil A and TSA (P<0.001). Furthermore, TSA2 did not cause any mortality and side effects when mice were administered subcutaneously at a dose up to 1.6 mg. Moreover, no significant hepatotoxic effect was observed in TSA2 groups in doses ranging from 0.05 mg to 0.8 mg. The Con A-, LPS-, and OVA-induced splenocyte proliferation, OVA-specific antibody levels (IgG, IgG1, IgG2a and IgG2b) and IFN-γ, TNF-α, IL-2, IL-4 and IL-5 in serum were significantly enhanced by TSA2 (25 µg/mouse). The present study of structure-activity relationship indicates that the hydrophobicity of the ester/amide chains bonds to the carboxyl group of the glucuronic acid residue at position C-3 of the triterpene aglycone and the type of sugar chain at C-28 position of saponin could affect the potential of toxicity and adjuvant. Our findings demonstrate that TSA2 possesses higher adjuvant activities with less adverse effects and should be further explored as an immunomodulator for immune responses.