Hepatoprotective effect of protocatechuic acid against type 2 diabetes-induced liver injury

Abstract

Context

Protocatechuic acid (PCA) has a protective effect on alcoholic liver injury, but the role of PCA in type 2 diabetes-induced liver injury is not well known.

Objectives

This study explores the therapeutic effect and potential mechanism of PCA on type 2 diabetes-induced liver injury.

Materials and methods

An insulin resistance/type 2 diabetic (IR/D) model was established by high-fat diet for 4 weeks + streptozotocin (35 mg/kg; i.p) in male Wistar rats pretreated with or without PCA (15 or 30 mg/kg for 6 d).

Results

PCA at 15 and 30 mg/kg significantly upregulated the levels of body weight (BW; 230.2, 257.8 g), high density lipids (22.68, 34.78 mg/dL), glutathione (10.24, 16.21 nmol/mg), superoxide dismutase (21.62, 29.34 U/mg), glucagon-like peptide-1, glucose transporter-4, Wnt1, and β-catenin, while downregulating those of liver weight (LW; 9.4, 6.7 g), BW/LW (4.1, 2.6%), serum glucose (165, 120 mg/dL), serum insulin (13.46, 8.67 μIU/mL), homeostatic model assessment of insulin resistance (5.48, 2.57), total cholesterol (68.52, 54.31 mg/dL), triglycerides (72.15, 59.64 mg/dL), low density lipids (42.18, 30.71), aspartate aminotransferase (54.34 and 38.68 U/L), alanine aminotransferase (42.87, 29.98 U/L), alkaline phosphatase (210.16, 126.47 U/L), malondialdehyde (16.52, 10.35), pro-inflammatory markers (tumor necrosis factor α (TNF-α (149.67, 120.33 pg/mg)) , IL-6 (89.79, 73.69 pg/mg) and IL-1β (49.67, 38.73 pg/mg)), nuclear factor kappa B (NF-κB), and interleukin-1β, and ameliorated the abnormal pathological changes in IR/D rats.

Discussion and conclusion

PCA mitigates the IR, lipid accumulation, oxidative stress, and inflammation in liver tissues of IR/D rats by modulating the NF-κB and Wnt1/β-catenin pathways.

Keywords:

• NF-κB pathway
• Wnt1/ β-catenin pathway
• oxidative stress
• inflammation
• lipid accumulation

Authors contributions

Substantial contributions to conception and design: Kaixia Xu, Guang Lu. Data acquisition, data analysis and interpretation: Qianjin Feng, Shuangchao Chen, Yonghui Wang. Drafting the article or critically revising it for important intellectual content: Kaixia Xu, Guang Lu. Final approval of the version to be published: All authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: all authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China Youth Program [No. 81903951] and Shanxi Provincial Department of Human Resources and Social Security, Shanxi Province Overseas Students Scientific and Technological Activities Selective Funding Project [No. 20210047].