Danggui Buxue decoction alleviates cyclophosphamide-induced myelosuppression by regulating β-hydroxybutyric acid metabolism and suppressing oxidative stress

CONTEXT: Danggui Buxue Decoction (DBD) is an effective complementary medicine in alleviating myelosuppression after chemotherapy (MAC). However, its mechanism of action is elusive. OBJECTIVE: To illustrate that regulating β-hydroxybutyric acid (β-OHB) metabolism and suppressing oxidative stress could be a potential mechanism of action for DBD in alleviating MAC. MATERIALS AND METHODS: After HPLC quantification and dose testing (3, 6 and 10 g/kg, gavage) of DBD, Sprague-Dawley rats were divided into control, cyclophosphamide (CTX) (30 mg/kg CTX for 5 days, intraperitoneal administration) and CTX + DBD groups (6 g/kg DBD for 14 days, gavage). Blood cell counts, thigh bone histological examination, β-OHB levels, oxidative stress indices and HDAC1 activity were tested. The biological function of β-OHB was verified in vitro (hBMSC cells were incubated in culture mediums that contained 40 μM CTX and β-OHB in 0, 1, 2.5, 5, 10 mM) and in vivo (MAC rat model, 3 g/kg β-OHB for 14 days, gavage). RESULTS: Rats in the CTX + DBD group showed upregulated blood cell counts (118–243%), β-OHB levels (495 nmol/mL in blood, 122 nmol/mg in marrow supernatant) and downregulated HDAC1 activity (59%), and oxidative stress indices (60–85%). In vitro, 5 mM β-OHB improved hBMSC cell migration (123%) and proliferation (131%). In vivo, rats treated with 3 g/kg β-OHB showed upregulated blood cell counts (121–182%) and downregulated HDAC1 activity (64%) and oxidative stress indices (65–83%). DISCUSSION AND CONCLUSIONS: DBD, a traditional Chinese medicine, alleviates MAC by intervening in β-OHB metabolism and oxidative stress.