Protective effects of sea buckthorn polysaccharide extracts against LPS/d-GalN-induced acute liver failure in mice via suppressing TLR4-NF-κB signaling.
BACKGROUND
Sea buckthorn (Hippophae rhamnoides L.) berries have been traditionally used to treat gastric disorders, cardiovascular problems, and liver injuries in oriental medicinal system. This study aimed to explore the protective effects and mechanisms of the polysaccharide extracts of Sea buckthorn (HRP) berries against lipopolysaccharide (LPS) and d-galactosamine hydrochloride (d-GalN)-induced acute liver failure in mice.


METHODS
HRP was isolated by hot-water extraction and characterized by HPLC and infrared spectrum analysis. The total carbohydrate, uronic acid and protein contents of HRP were measured by a spectrophotometric method. Mice were orally administrated with HRP (50, 100, 200mg/kg) once daily for 14 consecutive days prior to the challenge with LPS (50 μg/kg) and d-GalN (300 mg/kg). Animals of positive control group were intraperitoneally injected with dexamethasone (10mg/kg). Mice were sacrificed at 8h after LPS/d-GalN injection.


RESULTS
Pretreatment with HRP significantly inhibited LPS/d-GalN-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which were accompanied by alleviated liver injuries and reduced production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). HRP was also found to reduce malondialdehyde (MDA) content and to restore superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities. Furthermore, HRP supplementation dose-dependently inhibited the expression of Toll-like receptor 4 (TLR4), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated mitogen activated protein kinase 38 (p-p38 MAPK) in the liver of LPS/d-GalN challenged mice. Pretreatment with HRP also inhibited LPS/d-GalN-induced activation and translocation of nuclear factor-κB (NF-κB).


CONCLUSIONS
This study indicates that pretreatment with HRP protects against LPS/d-GalN-induced liver injury in mice via suppressing the TLR4-NF-κB signaling pathway. Sea buckthorn may be a hopeful drug for prevention of acute live injury.
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Huan
H
Liu
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Wei
W
Zhang
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Shichao
S
Dong
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Liang
L
Song
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Shimin
S
Zhao
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Chunyan
C
Wu
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Xue
X
Wang
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Fang
F
Liu
Clinical Laboratory, Hospital of Inner Mongolia, Hohhot 010010, PR China.
Jiming
J
Xie
College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, PR China.
Jinling
J
Wang
College of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, PR China. Electronic address: wangyuzhen817@126.com.
Yuzhen
Y
Wang
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D005638:Fruit; D005688:Galactosamine; D031281:Hippophae; D053583:Interleukin-1beta / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D011134:Polysaccharides / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D053583:Interleukin-1beta; D016328:NF-kappa B; D010936:Plant Extracts; D011134:Polysaccharides; D020011:Protective Agents; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
Acute liver failure; Dexamethasone (PubChem CID: 5743); Galactosamine hydrochloride (PubChem CID: 2723866); Hippophae rhamnoides; Lipopolysaccharide (PubChem CID: 11970143); MAPK; NF-κB; Polysaccharide; TLR4