Shikonin derivatives protect immune organs from damage and promote immune responses in vivo in tumour-bearing mice.

Shikonin, a major component of Lithospermum erythrorhizon and Arnebia euchroma, exhibits antiinflammatory, immunomodulatory and antitumour activities. Although many recent studies have focused on the antitumour effects of shikonin, the exact mechanisms underlying its antitumour and immunomodulatory effects in tumour-bearing mice remain unclear. The aim of the present study was to investigate the antitumour and immunomodulatory effects of shikonin derivatives (ShD) in tumour-bearing mice. Swiss mice inoculated with hepatoma HepA(22) or sarcoma 180 (S(180)) cells were treated with ShD or 5-fluorouracil (5Fu). Survival time, immune organs, natural killer cell activity, lymphocytes, lymphocyte transformation and interleukin (IL)-2 production were analysed. ShD significantly prolonged the survival (median survival time prolonged by >7 days) of tumour-bearing mice in a dose-dependent manner, inhibited the growth of transplantable neoplasms (inhibitory rate, > 33%), and recovered (at [ShD] = 2.5 mg/kg/day) or increased (at [ShD] > 5 mg/kg/day) the number of CD3- and CD19-positive cells. ShD also played a role in protecting the immune organs from damage and reversed or enhanced immune responses, as noted by the nearly normal thymic structure; enlarged splenic corpuscles; and improved natural killer cell activity, lymphocyte transformation and IL-2 production in ShD-treated mice. ShD reduced the tumour load of tumour-bearing mice and protected the immune organs against tumour-induced damage and immune function impairment.

Naphthoquinones from Zicao reverses the immunosuppression of transplantable carcinomas / 中国免疫学杂志

Objective:To observe the anti-carcinoma and immuno-regulatory effects of shikonin derivatives.Methods:A water-soluble preparation of shikonin derivatives was prepared (designated as LE)and given by lavage (2.5～10 mg/kg daily for 10 days) to the mice inoculated with either HepA22 or S180 sarcoma. Their survival duration and the in situ tumor mass were observed. Thymus and spleen indexes of the mice were measured. The parameters for immuno-functions were detected by the routine activity assays, which included NK cytotoxicity, ConA-induced lymphocyte transformation and IL-2 production by the splenocytes of the mice. Thymic and splenic morphology of the experimental animals were microscopically examined with HE staining.Results:Both thymic and splenic indexes in the tumor-bearing mice diminished extremely compared to those of the normal control, and the immunological functions analyzed were also found obviously lowered when loaded with the transplantable carcinomas. Under light microscopy, it was surprisingly exhibited that thymus cortex was almost disappeared in the organs of tumor-bearing mice, and the germinal centers of their spleens were visibly shrunk. LE inhibited propagation of the inoculated tumors and at the same time, it amended the immunosuppresive impacts by tumor-bearing, including both structures of immune organs and the bioactivities of spleen cells.Conclusion:LE can reverse the immune damages mediated by carcinomas.