Abstract
Pancreatic inflammation and fibrosis are typical pathological features in chronic pancreatitis (CP). Activated pancreatic stellate cells (PSCs) have been regarded as the core event in the development of pancreatic fibrosis and are considered to be the key target for treatment of CP. Baicalin (C21H18O11), the main chemical composition of Baikal skullcap in the traditional Chinese medicines Dachaihu decoction (DCHD) and Xiaochaihu decoction (XCHD), has shown significant effects in the treatment of pancreatic fibrosis in CP mice; however, whether baicalin can inhibit the activation of PSCs and its underlying mechanism remain unclear. In this study, the influence of baicalin on activated PSCs in vitro and in vivo was investigated, and the results showed that Baicalin could significantly ameliorate the degree of pancreatic inflammation and fibrosis, while decreasing the levels of alpha-smooth muscle actin (α-SMA), F4/80 (surface markers of mouse macrophages), nuclear factor kappa-B (NF-κB), monocyte chemotactic protein 1 (MCP-1), and collagen type I alpha 1 (COL1A1)in the pancreas. Moreover, NF-κB and α-SMA were co-expressed in the pancreas of CP mice. Baicalin treatment markedly reduced the expression of co-location of α-SMA and NF-κB. In vitro, the protein expression levels of transforming growth factor-β receptor 1 (TGF-βR1), phosphorylated TGF-β activated kinase 1 p-TAK 1, and NF-κBp65 in PSCs were all remarkably reduced after treatment with baicalin. In addition, baicalin could inhibit MCP-1 mRNA expression in supernatant of activated PSCs, as well as the excessive migration of macrophages. Taken together, our findings indicated that baicalin could inhibit the TGF-β1/TGF-βR1/TAK1/NF-κB signaling pathway of activated PSCs, reduce the secretion of MCP-1, and further decrease the infiltration of macrophages and inflammation cells of the local microenvironment of the pancreas. Thus, this study provides a reliable experimental basis for baicalin in the prevention and treatment of CP.
Highlights
Chronic pancreatitis (CP) is characterized by progressive and irreversible injury in the pancreas caused by various etiologic factors, leading to endocrine and exocrine dysfunction (Chari 2016)
The results showed that more positive staining ratio and higher expression of COL1A1 were observed in the pancreas with the development of chronic pancreatitis (CP) (p < 0.01), but the level of COL1A1 expression were significantly downregulated after treatment with baicalin (p < 0.01) compared with that in the CP group at the same timepoint (Figures 2C,D)
The results demonstrated that baicalin can inhibit the pancreatic stellate cells (PSCs) activation induced by TGF-β1 (Figure 4D)
Summary
Chronic pancreatitis (CP) is characterized by progressive and irreversible injury in the pancreas caused by various etiologic factors, leading to endocrine and exocrine dysfunction (Chari 2016). Pancreatic fibrosis has been considered a common pathological feature and the core event in the progression of CP, as well as the key target for treatment (Conti et al, 2018; Xu et al, 2018). The CP treatment has concentrated on some supportive therapies for helping patients to alleviate clinical symptoms, correct complications, and improve life quality. It was reported that classical Chinese prescriptions, such as Dachaihu decoction (DCHD) and Xiaochaihu decoction (XCHD), have shown significant clinical benefits for CP patients (Liu C. et al, 2019; Cui et al, 2017; Shi et al, 2020), such as improving the digestive manifestation of patients. Our previous experiments confirmed that DCHD could remarkably reduce the degree of pancreatic fibrosis in L-arginine-induced CP mice (Xu et al, 2016; Duan et al, 2017)
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