Spica Prunellae attenuates ER stress via GRP78/IRE1α/JNK pathway in CCL₄-induced acute liver injury in mice.
- 1School of Food and Biological Engineering, Hezhou University/Guangxi Key Laboratory of Healthcare Food Science and Technology, Hezhou, China.
- 2School of Basic Medicine, Heilongjiang University of Chinese Medicine, Harbin, China.
- 3School of Materials and Chemistry, Hezhou University, Hezhou, China.
Abstract
Objective
To evaluate the effects of Spica Prunellae (SP) on CCl₄-induced acute liver injury (ALI) in mice and its regulation of the endoplasmic reticulum stress pathway.Methods
In the toxicity test, ICR mice were administered SP decoction (2 g/kg, crude herb/mouse weight) by gavage for 10 days. Liver and kidney tissues were collected for H&E staining, and serum levels of liver function (AST, ALT) and renal (BUN, SCR) function indicators were measured. After confirming safety, 48 ICR mice were randomly assigned to normal, model, high-, medium-, and low-dose SP, and positive control groups (n = 8 per group). All mice, except the normal group, received a 10% CCl₄/peanut oil intraperitoneal injection to induce ALI. The normal and model groups received saline; the positive control group received bifendate; and the SP groups received corresponding SP doses by daily gavage for 10 days. Body weight, liver, spleen, and thymus indices were recorded; ELISA measured serum ALT and AST, and liver MDA and SOD; liver histopathology was assessed by H&E staining; hepatocyte ultrastructure was examined via transmission electron microscopy; and ER stress-related proteins (GRP78, IRE1α, and JNK) expressions were determined by Western blot.Results
SP caused minimal damage to hepatic and renal tissues in mice at 2 g/kg, with no significant changes in liver (ALT, AST) or renal (BUN, SCR) function indicators (p > 0.05). In the ALI model vs. model group, SP-treated groups demonstrated improved organ indices (p < 0.05), reduced serum ALT and AST levels (p < 0.05), increased SOD levels (p < 0.05), and significantly decreased MDA levels (p < 0.01). Histopathological analysis revealed clear attenuation of liver tissue damage, with mild nuclear deformation. Endoplasmic reticulum degranulation was alleviated, showing an organized arrangement and preserved cellular structure. Compared to the model group, GRP78 and IRE1α expression were significantly declined in the positive control and SP-treated groups (p < 0.01, p < 0.05), and JNK expression was downregulated (p < 0.05).Conclusion
These findings suggest the involvement of the GRP78/IRE1α/JNK signaling pathway in the hepatoprotective action of SP against CCl₄-induced ALI.
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BibTeX
@article{wang2026spica,
title = {{Spica Prunellae attenuates ER stress via GRP78/IRE1α/JNK pathway in CCL₄-induced acute liver injury in mice.}},
author = {Yanjie Wang and Jiaping Hao and Jinfeng Yang and Qiaomei Dai and Zhimin Chen and Feifei Han and Yiwen Zhang and Huijun Zhang},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1909409},
url = {https://europepmc.org/article/MED/42898186},
note = {CC BY},
}
RIS
TY - JOUR
TI - Spica Prunellae attenuates ER stress via GRP78/IRE1α/JNK pathway in CCL₄-induced acute liver injury in mice.
AU - Yanjie Wang
AU - Jiaping Hao
AU - Jinfeng Yang
AU - Qiaomei Dai
AU - Zhimin Chen
AU - Feifei Han
AU - Yiwen Zhang
AU - Huijun Zhang
PY - 2026
DA - 2026/10/05
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1909409
UR - https://europepmc.org/article/MED/42898186
AB - Objective To evaluate the effects of Spica Prunellae (SP) on CCl₄-induced acute liver injury (ALI) in mice and its regulation of the endoplasmic reticulum stress pathway.Methods In the toxicity test, ICR mice were administered SP decoction (2 g/kg, crude herb/mouse weight) by gavage for 10 days. Liver and kidney tissues were collected for H&E staining, and serum levels of liver function (AST, ALT) and renal (BUN, SCR) function indicators were measured. After confirming safety, 48 ICR mice were randomly assigned to normal, model, high-, medium-, and low-dose SP, and positive control groups (n = 8 per group). All mice, except the normal group, received a 10% CCl₄/peanut oil intraperitoneal injection to induce ALI. The normal and model groups received saline; the positive control group received bifendate; and the SP groups received corresponding SP doses by daily gavage for 10 days. Body weight, liver, spleen, and thymus indices were recorded; ELISA measured serum ALT and AST, and liver MDA and SOD; liver histopathology was assessed by H&E staining; hepatocyte ultrastructure was examined via transmission electron microscopy; and ER stress-related proteins (GRP78, IRE1α, and JNK) expressions were determined by Western blot.Results SP caused minimal damage to hepatic and renal tissues in mice at 2 g/kg, with no significant changes in liver (ALT, AST) or renal (BUN, SCR) function indicators (p > 0.05). In the ALI model vs. model group, SP-treated groups demonstrated improved organ indices (p < 0.05), reduced serum ALT and AST levels (p < 0.05), increased SOD levels (p < 0.05), and significantly decreased MDA levels (p < 0.01). Histopathological analysis revealed clear attenuation of liver tissue damage, with mild nuclear deformation. Endoplasmic reticulum degranulation was alleviated, showing an organized arrangement and preserved cellular structure. Compared to the model group, GRP78 and IRE1α expression were significantly declined in the positive control and SP-treated groups (p < 0.01, p < 0.05), and JNK expression was downregulated (p < 0.05).Conclusion These findings suggest the involvement of the GRP78/IRE1α/JNK signaling pathway in the hepatoprotective action of SP against CCl₄-induced ALI.
SN - 1663-9812
ER -