Alkannin Inhibited Hepatic Inflammation in Diabetic Db/Db Mice.

Abstract

BACKGROUND/AIMS:

The current study was designed to investigate the protective role of alkannin (ALK) on liver injury in diabetic C57BL/KsJ-db/db mice and explore its potential mechanisms.

METHODS:

An oral glucose tolerance test (OGTT) was performed. The levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) were determined by commercial kits. The pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were determined by ELISA. The levels of the ROCK/NF-κB pathway were determined by Western blotting.

RESULTS:

The contents of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were inhibited by ALK, metformin or fasudil in diabetic db/db mice. Further, Western blotting analysis showed that the expression of Rho, ROCK1, ROCK2, p-NF-κBp65, and p-IκBα was significantly reversed by ALK treatment. In human hepatic HepG2 cells, the hepatoprotective effects of ALK were further characterized. With response to palmitic acid-challenge, increased amounts of insulin, ALT, AST, TG, and TC were observed, whereas ALK pretreatment significantly inhibited their leakage in HepG2 cells without appreciable cytotoxic effects. The inflammation condition was recovered with ALK treatment as shown by changes of IL-1β, IL-6 and TNF-α. Further, Western blotting analysis also suggested that ALK improves hepatic inflammation in a Rho-kinase pathway.

CONCLUSION:

The present study successfully investigated the role of Rho-kinase signalling in diabetic liver injury. ALK exhibited hepatoprotective effects in diabetic db/db mice, and it might act through improving hepatic inflammation through the Rho-kinase pathway.

• Authors: Wenhua Xue, Zhirui Fan, Yuanzhe Li, Lifeng Li, Tengfei Zhang, Jingli Lu, Bingjun Ma, Zijia Zhu, Jingyao Lian, Chaoqi Zhang, Xiaoqin Song, Dongxu Sun, Yunkai Zhai, Ruitai Fan, Yang Cao, Xiaoming Deng, Jie Zhao
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 45 Issue 6 Pg. 2461-2470 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29554661 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Naphthoquinones
• alkannin
• rho-Associated Kinases

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Cell Survival (drug effects)
• Cytokines (analysis, immunology)
• Diabetes Complications (blood, drug therapy, immunology, pathology)
• Diabetes Mellitus (blood, drug therapy, immunology, pathology)
• Hep G2 Cells
• Humans
• Inflammation (blood, drug therapy, immunology, pathology)
• Liver (drug effects, immunology, pathology)
• Liver Diseases (blood, drug therapy, immunology, pathology)
• Mice, Inbred C57BL
• Naphthoquinones (therapeutic use)
• Signal Transduction (drug effects)
• rho-Associated Kinases (immunology)