Pinoresinol diglucoside activates Nrf2 pathway to improve osteoporosis in mice / 中华内分泌外科杂志

ABSTRACT

Objective:Rosin alcohol two glycosidase (pinores inoldiglucoside, PDG) effect on the improvement of the osteoporosis in mice and the possible mechanism of action.Methods:A mouse model of osteoporosis was established by removing bilateral ovaries. According to the random number table method, 50 mice were divided into model (MOD) group (equal volume of normal saline), positive control (PC) group (0.2 mg/kg estradiol), PDG-low dose (L) group (5 mg/kg) PDG), PDG-high dose (H) group (10 mg/kg PDG by gavage) and PDG-H+ML385 group (10 mg/kg PDG by gavage after intramuscular injection of 30 mg·kg-1 ML385), 10 mice in each group; Another 10 mice without any ovarian treatment were selected as sham group (intragastric administration of the same amount of normal saline). After 3 weeks of drug intervention, the serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), interleukin-6 (IL-6) and tumor necrosis factor were detected by enzyme-linked immunosorbent assay (ELISA) -α (TNF-α). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by dual energy X-ray. The mRNA and protein expression levels of nuclear factor related factor 2 (Nrf2), oxidase heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot, respectively.Results:The serum ALP levels in Sham, MOD, PC, PDG-L, PDG-H and PDG-H + ML385 groups were (25.88±3.42), (47.42±5.32), (36.20±3.37), (38.95±3.24), (29.66±2.64), (39.57±2.06) U/dL, respectively; The serum trap levels were (2.18±0.40), (4.69±0.83), (3.58±0.38), (3.67± 0.48), (2.93±0.26), (3.81±0.49) U/L, respectively; BMD (153.04±12.96), (86.25±6.71), (126.53±8.99), (119.77±8.84), (139.18±15.94), (92.09±4.17) mg/cm 2; The expression levels of Nrf2 mRNA were 1.00±0.00, 0.35±0.04, 0.67±0.05, 0.54±0.03, 0.82±0.08 and 0.48±0.04, respectively; The expression levels of HO-1 mRNA were 1.00±0.00, 0.25±0.03, 0.56±0.03, 0.47± 0.03, 0.71±0.04 and 0.37±0.04, respectively; The expression levels of nqo1mrna were 1.00±0.00, 0.38± 0.02, 0.63±0.03, 0.58±0.04, 0.79±0.05 and 0.44±0.03, respectively; Nrf2 protein expression levels were 0.98±0.08, 0.26±0.04, 0.52 ±0.06, 0.46±0.03, 0.86±0.07, 0.45±0.05. HO-1 protein expression levels were 0.39±0.02, 0.09±0.01, 0.15 ±0.03, 0.17±0.03, 0.26±0.03, 0.12±0.02. NQO1 protein expression levels were 0.53±0.03, 0.21±0.02, 0.38±0.04, 0.29±0.02, 0.55±0.03, 0.24±0.04, respectively; The levels of serum IL-6 were (104.25±11.35), (515.38±74.48), (351.78± 65.12), (364.73±36.64), (246.18±17.52), (408.93±32.56) pg/ml, respectively; The levels of serum TNF-α were (33.79±3.55), (170.11±19.24), (76.09±8.99), (84.95±6.12), (66.98±3.73), (119.04±9.75) pg/mL, respectively; The serum SOD levels were (258.47±19.25), (72.15±8.12), (187.60±14.63), (152.61±12.36), (204.22±19.65), (138.01±13.62) U/mL, respectively; The serum MDA levels were (2.02±0.27), (4.75±0.73), (3.19±0.46), (3.7±0.49), (2.91±0.42), (4.10 ±0.25) μmol/L respectively. There were significant differences between MOD group and Sham group, or PC, PDG-L, PDG-H, PDG-H+ML385 group and MOD group,or PDG-H+ML385 group and PDG-H ( P<0.05) . Conclusion:PDG can reduce bone inflammation and oxidative stress by activating Nrf2 pathway and improve the state of osteoporosis.