Danshen protects endothelial progenitor cells from oxidized low-density lipoprotein induced impairment.
In this study, we examined the protective effects of Danshen both on endothelial progenitor cells (EPCs) in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers. In the clinical study, we randomly divided 24 subjects with hypercholesterolemia into two groups (the control group and the Danshen-treated group). At the end of two weeks of treatment, the EPC cellular functions of both groups were tested. The results indicated that, compared to the control group, EPCs in the Danshen-treated group showed significantly better cellular functions, which was manifested in the cloning number, the proliferation capacity, the number of EPC adhesions, and cell migration. In the subsequent in-vitro experiments, EPCs were treated with vehicle, oxidized low-density lipoprotein (Ox-LDL, 100 microg/ml), or Ox-LDL (100 microg/ml) plus different concentrations of Danshen (Danshensu 2, 10, or 50 microg/ml, respectively) for 24 h. The results showed that Danshen treatments can prevent the detrimental effects of Ox-LDL on EPC cellular functions measured by proliferation capacity (0.24+/-0.08, 0.37+/-0.11, 0.30+/-0.04 vs. 0.13+/-0.02, P<0.05, P<0.01, and P<0.01, respectively), and adhesion ability (63.00+/-11.60, 70.00+/-10.80, 85.50+/-11.41 vs. 40.50+/-6.85, all P<0.01). Compared to the group treated with Ox-LDL alone, Danshen treatment significantly decreased the lipid peroxidation end product malondialdehyde (MDA) [(4.34+/-0.54), (3.98+/-0.47), (3.46+/-0.31) vs. (5.57+/-0.64) nmol/ml, all P<0.01], increased the production of superoxide dismutase (SOD) [(29.74+/-0.71), (31.09+/-0.83), (30.41+/-0.65) vs. (14.76+/-3.99) U/ml, all P<0.01], and lowered the expression of interleukin-6 (IL-6) [(24.62+/-7.69), (27.04+/-3.14), (33.38+/-18.86) vs. (230.67+/-33.53) pg/ml, all P<0.01] and tumor necrosis factor-alpha (TNF-alpha) [(41.72+/-6.10), (17.02+/-6.82), (3.73+/-2.26) vs. (228.71+/-41.53) pg/ml, all P<0.01] in Ox-LDL treated EPCs. These results suggest that Danshen may exert a protective effect through its antioxidant and anti-inflammatory features.
Ji
Kang-ting
KT
Department of Cardiology, the Second Affiliated Hospital, Wenzhou Medical College, China.
Chai
Jun-de
JD
Xing
Cheng
C
Nan
Jin-liang
JL
Yang
Peng-lin
PL
Tang
Ji-fei
JF
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008516:Medicine, Chinese Traditional; D010100:Oxygen / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013234:Stem Cells / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008077:Lipoproteins, LDL; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D010100:Oxygen