To investigate the toxicity, protective effects, and action mechanism of
gallotannin-enriched extracts isolated from
Galla Rhois (GEGR) against
carbon tetrachloride (CCl₄)-induced hepatotoxicity in Institute for
Cancer Research (ICR) mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related
proteins, and
liver fibrosis regulating factors were measured in mice pretreated with GEGR for five days before CCl₄ injection. The GEGR/CCl₄ treated group showed decreased levels of three
serum marker enzymes (ALP, AST, and ALT) representing liver toxicity, although LDH levels remained constant. Necrotic area indicating hepatic cell death significantly inhibited, while
malondialdehyde (MDA) concentration and
superoxide dismutase (SOD) expression were dramatically recovered in the GEGR preadministrated group. In mechanism analyses of GEGR, the formation of active
caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the GEGR/CCl₄ treated group. The level of pro-inflammatory
cytokines, TNF-α and
IL-6, as well as the phosphorylation of p38 and JNK in the TNF-α downstream signaling pathway was rapidly recovered in the GEGR/CCl₄ treated group, while anti-inflammatory
cytokine (IL-10) increased slightly in the same group. Furthermore, the GEGR/CCl₄ treated group showed a significant decrease in
collagen accumulation results from alleviation of MMP-2 expression, TGF-β1 secretion and the phosphorylation of Smad2/3. Taken together, these results suggest that GEGR may induce remarkable protective effects against hepatic injury induced by CCl₄ treatment through upregulation of the anti-inflammatory and
antioxidant system.