The immunomodulatory effects of ginsenoside derivative Rh2-O on splenic lymphocytes in H22 tumor-bearing mice is partially mediated by TLR4

Purpose: Previously, we reported the octyl ester derivative of ginsenoside Rh2 (Rh2-O) had better antitumor and immunomodulatory effects than Rh2 in H22 tumor-bearing mice. Therefore, this study further explored the effects of Rh2-O on splenic lymphocytes in H22 tumor-bearing mice and the underlying mechanism.

Methods: Wild type and TLR4^-/- mice were selected to establish the H22 tumor-bearing mice model. After the treatment of Rh2-O (10 mg/kg by gavage) for 15 days, the sizes of tumor were measured. Subsequently, the splenic lymphocytes were isolated and the activities (eg. cell proliferation, cytotoxicity and cytokine secretion) were evaluated. Then, the proteins and mRNA expression levels of TRAF6 and NF-ĸB p65 in splenic lymphocytes were examined.

Results: The results showed that Rh2-O administration enhanced the proliferative capacity and cytotoxicity of splenic lymphocytes, and the effects were Tlr4-associated. Compared to WT mice, the up-regulation of cytokines secretion (eg. IFN-γ, IL-2 and IL-4) in isolated splenic lymphocytes after Rh2-O administration was lower in TLR4^-/- mice. Moreover, the results showed Rh2-O increased the expression of TRAF6 and the level of endonuclear NF-ĸB p65, which was inhibited in TLR4^-/- mice (P < 0.05).

Conclusion: Rh2-O could exert immunomodulatory effects on splenic lymphocytes with the partial participation of TLR4 in H22 tumor-bearing mice.