Pilose antler proteins attenuate cyclophosphamide-induced myelosuppression in mice and bone marrow mesenchymal stem...

Traditional Chinese medicine holds that pilose antler can strengthen kidney yang, replenish essence and blood, fortify bones and muscles, as well as enhance immune function and promote hematopoiesis. However, studies on its potential to treat myelosuppression remain limited, and the underlying mechanisms and active components still require further investigation.

This study aimed to evaluate the therapeutic potential of PAPs against myelosuppression and to elucidate the underlying protective mechanisms.

The protein composition of PAPs was identified by LC-MS/MS, and network pharmacology was then applied to predict the mechanisms that may underlie its effects. The protective effects of PAPs against the cytotoxic effects of CTX on bone marrow mesenchymal stem cells (BMSCs) were evaluated in terms of apoptosis, ROS level, cell cycle, cell senescence, and osteogenic differentiation in vitro. Meanwhile, the ameliorative effects of PAPs in myelosuppressed mice were observed by measuring peripheral blood routine parameters and bone marrow histopathology in vivo.

In vitro, PAPs dose-dependently inhibited CTX-induced excessive ROS accumulation, restored SOD activity and reduced MDA content, alleviated apoptosis and senescence, and enhanced the osteogenic differentiation capacity of injured BMSCs. Immunofluorescence analysis further revealed that CTX upregulated Bax (by approximately 9.4-fold) and caspase-3 (by approximately 14.8-fold), and downregulated Bcl-2 (to approximately 0.34-fold). PAPs treatment reversed these changes, with the high-dose group reducing Bax to 0.18-fold and caspase-3 to 0.12-fold, and increasing Bcl-2 to 2.21-fold. In vivo, PAPs significantly elevated WBC, RBC, and PLT counts, as well as HGB levels, restored serum levels of SCF, TPO, EPO, and GM-CSF (to 0.69-0.80-fold of the control), and ameliorated severe bone marrow histopathological damage induced by CTX exposure.

These findings suggest that PAPs alleviate chemotherapy-induced myelosuppression by activating the PI3K/AKT pathway, reducing BMSC injury and oxidative stress, improving peripheral blood parameters, and ameliorating bone marrow histopathological damage. This study not only provides modern scientific evidence supporting the traditional use of deer antler for "nourishing essence and replenishing marrow", but also provides a solid experimental basis for the further development and utilization of PAPs.