Bushen Yisui Shengxue Formula Restores Bone Marrow Hematopoietic Function in Aplastic Anemia Mice by Modulating Hippo/Yap Pathway

Aplastic anemia (AA) is a severe bone marrow failure disorder, often life-threatening. Current treatments like hematopoietic stem cell transplantation (HSCT) are limited by donor availability, while immunosuppressive therapy (IST) carries risks such as hepatitis B virus (HBV) reactivation in infected patients. This highlights a critical need for alternative or complementary therapies that can restore bone marrow function without these drawbacks. The Hippo/Yes-associated protein (Yap) pathway is a key regulator of organ size, cell proliferation, and apoptosis, making it a potential target for regenerating hematopoietic stem cells and alleviating bone marrow failure in AA.

BALB/c mice were used to establish an aplastic anemia model via X-ray irradiation combined with DBA/2 mouse lymphocyte infusion. After successful modeling, mice were gavaged daily for 14 consecutive days with Bushen Yisui Shengxue Formula or normal saline (control/model groups). Primary endpoints included general condition, peripheral blood cell counts, bone marrow pathology (HE and Wright-Giemsa staining), bone marrow nucleated cell counts, and apoptosis levels (flow cytometry). Molecular analysis involved qPCR for Yap, TEAD, and TERT mRNA expression, and Western blot for their protein levels.

Compared to control, aplastic anemia model mice exhibited significant weight loss, weakness, and lethargy. They also showed reduced peripheral blood cell counts, decreased bone marrow hematopoietic cells, increased adipocyte infiltration, and elevated apoptosis. Bone marrow nucleated cell counts were lower, and mRNA and protein expression of TERT, Yap, and TEAD were downregulated.

Bushen Yisui Shengxue Formula treatment significantly restored body weight, mental state, and physical activity in the AA mice. This suggests a reversal of the disease phenotype, although specific quantitative data for the molecular markers post-treatment were not detailed in the abstract for the BYSF group.