Although Salvia miltiorrhiza has been reported to have anti-cancer mechanisms, such as caspase activation, cell cycle arrest, an anti-angiogenesis effect, and Bcl-2 family regulation, its underlying mechanism of endoplasmic reticulum (ER) stress-mediated apoptosis has never been demonstrated. Thus, in this current study, ER stress-related apoptosis via miR-216b of the ethanol extract of Salvia miltiorrhiza (SM) is elucidated for the first time. SM treatment inhibited the viability of U266 and U937 cells in a concentration-dependent manner. However, SM-exposed Raw264.7 cells were intact compared to U266 or U937 cells. Treatment with SM significantly elevated the generation of reactive oxygen species (ROS). The anti-proliferative effect of SM was reversed by pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), compared to cells treated only with SM. Also, SM treatment increased the ER stress by elevation of phosphorylated activating transcription factor 4 (p-ATF4), phosphorylated eukaryotic Initiation Factor 2 (p-eIF2), and phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK) expression. Caspase-3 and Poly (ADP-ribose) polymerase (PARP) were cleaved and CCAAT-enhancer-binding protein homologous protein (CHOP) was activated by SM treatment. PARP cleavage and CHOP activation were attenuated by NAC pretreatment. Furthermore, SM increased the tumor suppressor, miR-216b, and suppressed its target, c-Jun. miR-216b inhibitor attenuated the apoptotic effect of SM. Taken together, SM treatment induced apoptosis through regulation of miR-216b and ROS/ER stress pathways. SM could be a potential drug for treatment of multiple myeloma and myeloid leukemia.
Objectives: To investigate the effects of acupuncture at GV20 and EX-HN1 on cerebral blood flow (CBF) velocity and cerebrovascular reactivity (CVR) in the middle cerebral arteries (MCA) and anterior cerebral arteries (ACA) and to compare the effects to acupuncture at GV20.Methods: The study was a randomized, crossover trial that included 10 healthy men aged 20 to 29 years who underwent acupuncture treatment four times with a washout period of one week. The CBF velocity and CVR were measured by transcranial Doppler sonography (TCD) on both MCAs at the first and second visits, and both ACAs at the third and fourth visits. Participants were randomly assigned to one of two groups (A and B) before the first and third visits. Group A received two phases of acupuncture intervention at a single GV20 point and a combination of GV20 and EX-HN1 acupoints. Group B received the same interventions, but in the reverse order.Results: The increase in CO2 reactivity was significantly higher for the combination acupoints of GV20 and EX-HN1 than for the GV20 single acupoint in both MCAs (Right: 136 to 178, p=0.017; Left: 127 to 191, p=0.017) and ACAs (Right: 133 to 158, p=0.013; Left: 122 to 168, p=0.025). No significant change was noted in the corrected velocity at PETCO2 40 mmHg, blood pressure, or heart rate.Conclusions: The findings suggest that improvement of the CBF in the MCA and ACA after GV20 acupuncture increases when acupuncture is also performed at EX-HN1. These results clinically support the combined use of EX-HN1 and GV20 to treat disorders of MCA and ACA circulation.
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