Mitolactol

Danggui Buxue Decoction (DBD) is an effective complementary medicine in alleviating myelosuppression after chemotherapy (MAC). However, its mechanism of action is elusive.

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.

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).

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%).

DBD, a traditional Chinese medicine, alleviates MAC by intervening in β-OHB metabolism and oxidative stress.

As a major risk factor for cardiovascular diseases (CVD), Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). Recent studies indicated that the increased cardiovascular risk in patients with OSA may be mediated by accelerated vascular senescence. Danggui-Buxue decoction (DBD) has been used for treating cardiovascular diseases, but its mechanism of vascular senescence regulation is still unclear.

To investigate the effect of DBD on vascular senescence in mice exposed to CIH and to explore the role of the Nrf2/HO-1 pathway.

C57BL/6N mice were randomly divided into Normoxia control group (CON), CIH (21%-5% O₂, 20 times/h, 8 h/d) exposed group (CIH), and DBD treatment group (intragastrically treated with 2.34, 4.68, or 9.36 g/kg/day of DBD separately for 12 weeks as DBL, DBM, or DBH). Blood pressure, cardiac and vascular function, vascular senescence, inflammation response, oxidative stress, and Nrf2/HO-1 expression were determined.

DBD (4.68 and 9.36 g/kg) significantly decreased Tail-cuff blood pressure, increased left ventricular systolic function, and alleviated arterial stiffness and vasorelaxation dysfunction in mice exposed to CIH. DBD treatment reduced SA-β-gal activity, decreased p16 (0.68-fold, 0.62-fold), P21 (0.58-fold, 0.52-fold), and p53 expressions (0.67-fold, 0.65-fold), and increased SIRT1 expression (2.22-fold, 2.98-fold) in the aortic. DBD treatment decreased IL-6, NF-κB, and TNF-α expressions, decreased MDA but increased SOD levels, and increased Nrf2 (1.8-fold, 1.89-fold) and HO-1 (2.25-fold, 2.43-fold) expression.

DBD could attenuate vascular senescence accelerated by CIH exposure through inhibiting inflammatory response and oxidative stress by activating the Nrf2/HO-1 pathway.