The Protective Effect of Ultrasonicated Processing Ginseng Berry Extract (UGBE) on Liver Injury Models In Rats
Authors: Sohn Uy Dong , Nam Yoonjin , Jeong Ji Hoon , Ko Sung Kwon 
Published: November 2023

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 InformationThis research was supported by High Value‐added Food Technology Development Program, Ministry of Agriculture, Food and Rural Affairs (113021–03).
Composition ratio of GBE and UGBE (%, w/w).

Ginsenoside
GBE
UGBE

Rb1
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±0.137

Data represent mean ± S.E.M.
P < 0.05 increased composition ratio of UGBE compared to same ginsenoside in GBE.

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.

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.

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.

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.

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.