Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis

Abstract

AIMTo explore the role of macrophages in chronic pancreatitis (CP) and the effect of Dachaihu decoction (DCHD) on pancreatic fibrosis in mice.METHODSKunMing mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine (3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6 (IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas.RESULTSCompared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α mRNA, and fibronectin levels were reduced.CONCLUSIONThe dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.

Baicalin Ameliorates Pancreatic Fibrosis by Inhibiting the Activation of Pancreatic Stellate Cells in Mice with Chronic Pancreatitis

“…Yet, it has been gradually realized that some traditional Chinese herbal medicines, such as DCHD and XCHD, show significant clinical benefits in the treatment of CP, which could remarkably improve the clinical symptoms of CP patients ( Liu C. et al, 2019 ; Cui et al, 2017 ; Shi et al, 2020 ). Moreover, similar effects have been confirmed in some animal experiments ( Xu et al, 2016 ; Duan et al, 2017 ; Zhang et al, 2017 ). Our previous study found that DCHD can alleviate the degree of pancreatic inflammation and fibrosis in several mouse models of CP ( Xu et al, 2016 ; Duan et al, 2017 ).…”

“…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. Moreover, 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 ).…”

Effects of Gyeongshingangjeehwan 18 on Pancreatic Fibroinflammation in High-Fat Diet-Fed Obese C57BL/6J Mice

“…Our previous study suggested that GGEx18 curtails impaired glucose metabolism and pancreatic fat accumulation by regulating pancreatic genes that govern lipid metabolism and by improving insulin sensitivity (submitted). Based on report that showed an association between visceral obesity and ectopic fat accumulation in different organs (e.g., liver, pancreas, skeletal muscle, and heart) (Smith, 2015) and that pancreatic steatosis may cause pancreatic inflammation and subsequent fibrosis (Acharya et al, 2014;Noel et al, 2016;Duan et al, 2017), we hypothesized that GGEx18 can regulate pancreatic fibroinflammation in HFD-fed obese mice.…”

“…It has been reported that fatty pancreas in obese individuals exaggerates pancreatic inflammation, resulting in pancreatitis (Acharya et al, 2014;Noel et al, 2016). Macrophages also play an important role in the development of pancreatic fibrosis, as evidenced by the observation that inhibition of macrophage infiltration and inflammatory factor secretion ameliorates pancreatic fibrosis (Duan et al, 2017). Original Article asthma, edema, diabetes, steatosis, gastrointestinal disease, and chronic renal failure (Chen, 1928;Yen, 1996;Greenway et al, 2004;Wang et al, 2009;Yang et al, 2016).…”

Drug discovery and formulation development for acute pancreatitis

“…Sheng-Jiang powder ameliorated obesity-induced pancreatic inflammatory injury in rats (Miao et al., 2018 ). Dachaihu Decoration could ameliorated the L-arginine-induced pancreatitis via inhibiting the infiltration of macrophages and decreasing the gene expression of macrophage inflammatory protein 1α (MIP-1α), IL-6 and monocyte chemoattractant protein-1 (MCP-1) (Duan et al., 2017 ).…”