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The Protective Effect of Ultrasonicated Processing Ginseng Berry Extract (UGBE) on Liver Injury Models In Rats
Author(s) -
Sohn Uy Dong,
Nam Yoonjin,
Jeong Ji Hoon,
Ko Sung Kwon
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1192.7
Subject(s) - chemistry , glutathione , superoxide dismutase , nitric oxide , pharmacology , aspartate transaminase , catalase , glutathione peroxidase , liver injury , nitric oxide synthase , lipopolysaccharide , alanine transaminase , antioxidant , biochemistry , medicine , alkaline phosphatase , enzyme , organic chemistry
The Panax ginseng berry extract (GBE) is well known to have antidiabetic effect. The aim of this study is to evaluate and investigate of hepatoprotective effect of UGBE compared to GBE. After ultrasonication process, the composition ratio of ginsenoside in GBE was changed. The component ratio of ginsenoside Rh1, Rg2, Rg5 and F4 in extract were elevated. In this study, we evaluated the protective effect of the newly developed UGBE on two different liver injury models. Silymarin (150 mg/kg) was used for positive control. In D‐galactosamine (D‐GalN)/lipopolysaccharide (LPS)–induced acute rat hepatoxicity model, UGBE (100 mg/kg, 250 mg/kg, 500 mg/kg) were orally administered for 3 weeks before D‐GalN (300 mg/kg)/LPS (30 μg/kg) treatment. The survival rates in UGBE‐treated group were significantly increased compared to D‐GalN/LPS challenged group or GBE‐treated group. The serum alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin levels were reduced significantly in UGBE pretreated group in a dose‐dependent manner. In addition, tumor necrosis factor alpha (TNF‐α), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) levels in liver were also significantly decreased in UGBE pretreated group. Furthermore, the activity of superoxide dismutase (SOD), glutathion peroxidase (GPx), catalase (CAT) and glutathione (GSH) in liver homogenates were increased in UGBE treated group. Hepatic HO‐1 levels were increased dose dependently in UGBE treated group. Additionally, H&E staining results showed an overall decline of liver injury. In EtOH‐induced sub‐acute rat hepatotoxicity model, UGBE (100 mg/kg, 250 mg/kg, 500 mg/kg) was co‐administered with EtOH (30 %) for 5 weeks. The ATL, AST and gamma glutamyl transferase (γGT) level were significantly decreased in UGBE treated group. Also, the LDL, total cholesterol and epididymal fat pad/body weight (F/B) ratio were slightly but significantly attenuated in UGBE treated group, and the HDL level was recovered in UGBE group. The levels of enzymatic markers for oxidative stress and inflammatory cytokine (SOD, GPx, CAT and TNF‐α) were also reduced by UGBE treatment. In enzyme‐linked immunosorbent assays, protein expression of toll‐like receptor 4 (TLR4) was significantly decreased in UGBE treated group compared to only ethanol‐treated group. H&E staining and immunohistochemistry results also showed an overall decline of liver injury. In conclusion, UGBE effectively reduced liver injury induced by D‐GalN/LPS or EtOH and recovered liver function, suggesting that UGBE may have protective effect on liver injury. Support or Funding Information This research was supported by High Value‐added Food Technology Development Program, Ministry of Agriculture, Food and Rural Affairs (113021–03). 1 Composition ratio of GBE and UGBE (%, w/w).Ginsenoside GBE UGBERb1 0.758±0.179 0.072±0.052 Rb2 0.594±0.114 0 Rd 1.534±0.182 0.025±0.007 Re 11.169±0.158 0.288±0.037 Rf 0.330±0.115 0 Rg1 0.567±0.013 0.033±0.004 Rg2 0.801±0.215 2.278±0.368 20S‐Rg3 0 0.432±0.063 20R‐Rg3 0 0.400±0.059 Rg6 0.044±0.026 0.445±0.063 Rh1 0.629±0.095 1.350±0.208 Rh4 0 0.083±0.011 Rk1 0 0.207±0.030 Rk3 0 0.039±0.005 F1 0.193±0.149 0.035±0.017 F4 0.191±0.026 1.210±0.137Data represent mean ± S.E.M. * P < 0.05 increased composition ratio of UGBE compared to same ginsenoside in GBE.2 Serum AST, ALT and T. bilirubin levels in G/L induced liver injury model.AST (IU/L) ALT (IU/L) T. Bilirubin (mg/dL)Control 92.43 ± 10.94 39.29 ± 7.11 0.14 ± 0.04 G/L 3425.917 ± 766.71 *** 2590.3 ± 591.63 *** 1.08 ± 0.3 * G/L + Sil 150 1452.1 ± 236.56 ## 697.6 ± 196.94 ### 0.47 ± 0.1 ## G/L + GBE 250 2478 ± 508.65 1872.6 ± 205.36 0.99 ± 0.1 G/L + UGBE 100 2468.08 ± 912.39 # 1907.33 ± 170.45 0.74 ± 0.14 # G/L + UGBE 250 1706.5 ± 306.76 ## 616.17 ± 237.13 ## 0.54 ± 0.12 ### G/L + UGBE 500 303.571 ± 178.15 ### 203.14 ± 122.79 ### 0.30 ± 0.09 ###Data represent mean ± S.E.M. * P < 0.05, *** P<0.005 compared to control, # P < 0.05, ## P < 0.01, ### P < 0.001 compared to G/L.3 Hepatic SOD, GPx, CAT and GSH activities in G/L induced liver injury model.SOD (U/mg) GPx (U/mg) CAT (U/mg) GSH (ng/mg)Control 83.20 ± 5.99 25.59 ± 5.38 24.81 ± 9.48 10.41 ± 2.84 G/L 15.26 ± 1.92 *** 10.19 ± 2.28 ** 7.85 ± 3.37 *** 3.65 ± 1.54 *** G/L + Sil 150 52.72 ± 11.55 ## 17.73 ± 0.7 ### 17.02 ± 3.89 # 6.44 ± 1.74 # G/L + GBE 250 26.62 ± 9.11 10.94 ± 3.77 6.78 ± 1.27 3.45 ± 1.23 G/L + UGBE 100 37.87 ± 3.63 ## 15.87 ± 0.45 ## 15.77 ± 3.92 # 6.51 ± 2.33 # G/L + UGBE 250 54.62 ± 3.51 ## 19.66 ± 0.4 ### 18.70 ± 3.83 ## 9.41 ± 5.86 # G/L + UGBE 500 71.70 ± 2.08 ### 22.05 ± 1.92 ### 23.45 ± 3.55 ### 9.47 ± 2 ###Data represent mean ± S.E.M. ** P < 0.01, *** P<0.005 compared to control, # P < 0.05, ## P < 0.01, ### P < 0.001 compared to G/L.4 Serum AST, ALT and γ‐GT levels in EtOH induced liver injury model.AST (IU/L) ALT (IU/L) γ‐GT (IU/L)Control 91.14 ± 13.09 41 ± 7.87 0.77 ± 0.28 EtOH 154.375 ± 25.99 *** 108.86 ± 38.72 *** 3.96 ± 0.61 ** EtOH +Sil 150 109.86 ± 16.83 # 71.14 ± 16.94 # 3.26 ± 0.77 EtOH + GBE 250 135.71 ± 36.95 116.83 ± 19.33 3.54 ± 1.83 EtOH + UGBE 100 123.43 ± 27.16 # 70.17 ± 21.94 # 2.89 ± 1.2 EtOH + UGBE 250 116.5 ± 22.81 # 67.33 ± 16.01 # 2.66 ± 0.99 # EtOH + UGBE 500 92.43 ± 15.64 ### 44.86 ± 8.29 ### 1.74 ± 1.01 ##Data represent mean ± S.E.M. ** P < 0.01, *** P<0.005 compared to control, # P < 0.05, ## P < 0.01, ### P < 0.001 compared to EtOH.5 Serum LDL, HDL and T. cholesterol levels in EtOH induced liver injury model.LDL (mg/dL) HDL (mg/dL) T. cholesterol (mg/dL)Control 10.57 ± 1.06 43.5 ± 2.44 65.14 ± 4.26 EtOH 16.25 ± 2.76 * 33.43 ± 6.31 * 90 ± 13.6 * EtOH + Sil 150 15.38 ± 4.42 36.25 ± 2.38 82.5 ± 3.85 EtOH + GBE 250 10.25 ± 2.14 # 41 ± 2.16 # 64.83 ± 8.47 # EtOH + UGBE 100 16 ± 4.16 33.25 ± 2.89 75 ± 8.46 EtOH + UGBE 250 12.14 ± 2.73 # 35.29 ± 4.75 71.6 ± 7.23 # EtOH + UGBE 500 11.13 ± 1.68 # 40.5 ± 2.89 # 63.8 ± 3.11 #Data represent mean ± S.E.M. * P < 0.05 compared to control, # P < 0.05 compared to EtOH.6 Hepatic SOD, GPx and CAT activities in EtOH induced liver injury model.GPx (U/mg) SOD (U/mg) CAT (U/mg)Control 25.51 ± 4.38 83.08 ± 8.46 11.01 ± 1.63 EtOH 12.87 ± 3.35 *** 34.43 ± 3.5 *** 4.12 ± 2.44 * EtOH + Sil 150 16.95 ± 3.87 # 63.31 ± 11.65 # 7.82 ± 2.07 # EtOH + GBE 250 14.47 ± 1.75 51.15 ± 8.85 # 4.04 ± 2.13 EtOH + UGBE 100 18.68 ± 6.12 43.44 ± 7.38 4.99 ± 2.02 EtOH + UGBE 250 19.82 ± 2.85 # 61.43 ± 3.1 ## 7.52 ± 1.96 # EtOH + UGBE 500 23.48 ± 2.54 ### 72.86 ± 5.55 ### 9.93 ± 1.27 ###Data represent mean ± S.E.M. * P < 0.05, *** P<0.005 compared to control, # P < 0.05, ## P < 0.01, ### P < 0.005 compared to EtOH.