Effects of Danggui and Its Component Ferulic Acid On Hematopoiesis and Platelet Production.

Abstract 3509

Poster Board III-446

Chinese herbs have been used for the treatment of myelosuppression and thrombocytopenia for centuries and some herb mixtures have been shown to have favorable effects in cancer patients with myelosuppression. Our recent publication has shown that Danggui Buxue Tong, a traditional Chinese medicine decoction containing Radix Angelicae Sinensis (Danggui) and Radix Astragali (Huangqi), promotes hematopoiesis and thrombopoiesis in mouse model (Yang et al, J Ethnopharm, 2009). However, reports about the pharmacological effects of each herb ingredient have been scanty. The root of Danggui is an important ingredient of many commonly used prescriptions in Chinese herbs for promoting blood production. The chemical constituents and the pharmacological action of Danggui have been investigated using modern scientific methods at the beginning of this century. The objective of this study was to compare the effect of Danggui and TPO on hematopoiesis and platelet production in radiation-induced hematocytopenic mouse model. Danggui extracts (10 mg/kg/day) and TPO (10 ug/kg/day) were given by injection daily for 21 days starting from the day after radiotherapy. Peripheral blood platelet, WBC and RBC from Danggui, TPO and water control groups were analyzed at different time-points. On day 21, the mouse was sacrificed and bone marrow cells were harvested for CFU-MK and CFU-GM assays using the plasma clot and methylcellulose methods. The results showed that both Danggui and TPO significantly enhanced the recovery of platelet and WBC count, as well as CFU-MK and CFU-GM formation (n=6). Morphological examination of bone marrow also showed that Danggui treatment significantly increased the recovery of hematopoietic progenitor cells and megakaryocytic cell series. In addition, Danggui also increased the recovery of the body weight and organ weight (liver and spleen) in mouse model. We further analyzed the in vitro effect of Ferulic acid (major component of Danggui) and Astragaloside IV (major component of Huangqi) on hematopoiesis using CFU assay. Ferulic acid plus Astragaloside IV significantly promoted mouse CFU-GEMM formation (n=4). Ferulic acid together with Astragaloside IV also significantly reduced serum free-induced apoptosis in K562 cells by annexin V assay using flow cytometry (n=3). This anti-apoptotic effect can be mediated by reducing the activation of Caspase-3 pathway. In summary, our studies showed that Danggui extracts as well as TPO enhances hematopoiesis and thrombopoiesis in a radiation-induced hematocytopenic mouse model. Ferulic acid, in combination with Astragaloside IV, also has promoting effect on hematopoiesis and anti-apoptotic effect on hematopoietic cells.