Abstract
Pancreatic fibrosis is a pathological characteristic of chronic pancreatitis (CP) and pancreatic cancer. Chaihu Guizhi Ganjiang Decoction (CGGD) is a traditional Chinese medicine, which is widely used in the clinical treatment of digestive diseases. However, the potential anti-fibrosis mechanism of CGGD in treating CP remains unclear. Here, we conducted a series of experiments to examine the effect of CGGD on the CP rat model and primary isolated pancreatic stellate cells (PSCs). The results revealed that CGGD attenuated pancreatic damage, decreased collagen deposition, and inhibited PSC activation in the pancreas of CP rats. However, compared with the CP group, CGGD had no effect on body weight and serum amylase and lipase. In addition, CGGD suppressed autophagy by downregulating Atg5, Beclin-1, and LC3B and facilitated phosphorylation of mTOR and JNK in pancreatic tissues and PSCs. Moreover, the CGGD-containing serum also decreased LC3B or collagen I expression after rapamycin (mTOR inhibitor) or SP600125 (JNK inhibitor) treatment in PSCs. In conclusion, CGGD attenuated pancreatic fibrosis and PSC activation, possibly by suppressing autophagy of PSCs through the JNK/mTOR signaling pathway.
Highlights
Chronic pancreatitis (CP) is a progressive pathological change in the pancreas, characterized by glandular atrophy and fibrosis, which leads to endocrine and exocrine dysfunction (Witt et al, 2007)
We investigated the anti-fibrotic effects of Chaihu Guizhi Ganjiang Decoction (CGGD) on DBTC-induced chronic pancreatitis (CP) rats and isolated Pancreatic stellate cells (PSCs)
The results revealed CGGD treatment decreased pancreatic damage, restrained PSC activation, and reduced the deposition of extracellular matrix (ECM)
Summary
Chronic pancreatitis (CP) is a progressive pathological change in the pancreas, characterized by glandular atrophy and fibrosis, which leads to endocrine and exocrine dysfunction (Witt et al, 2007). The underlying pathogenesis of CP is still unclear, and there is lack of specific therapeutic drugs for pancreatic fibrosis. Pancreatic fibrosis is caused by the imbalance in the production and degradation of extracellular matrix (ECM). A large number of fibers replace the parenchyma of the pancreas, resulting in impaired pancreatic function and many other complications such as diabetes. PSCs only account for a small proportion in the pancreas and are inactivated. When pancreatic tissues are damaged, PSCs differentiate into myofibroblast-like cells, proliferate rapidly, and secrete a large amount of ECM including alpha-
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