Abstract
Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP), and pancreatic stellate cells (PSCs) are considered to be the key cells. Puerarin is the most important flavonoid active component in Chinese herb Radix Puerariae, and it exhibited anti-fibrotic effect in various fibrous diseases recently. However, the impact and molecular mechanism of puerarin on CP and pancreatic fibrosis remain unknown. This study systematically investigated the effect of puerarin on CP and pancreatic fibrosis in vivo and in vitro. H&E staining, Sirius Red staining, qRT-PCR and Western blotting analysis of fibrosis and inflammation related genes of pancreatic tissues showed that puerarin notably ameliorated pancreatic atrophy, inflammation and fibrosis in a model of caerulein-induced murine CP. Western blotting analysis of pancreatic tissues showed the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2 and p38 MAPK) significantly increased after modeling of cerulein, while puerarin could inhibit their phosphorylation levels to a certain extent. We found that puerarin exerted a marked inhibition on the proliferation, migration and activation of PSCs, determined by CCK-8 assay, transwell migration assay, scratch wound-healing assay and expression levels of α-SMA, Fibronectin, Col1α1 and GFAP. Western blotting result demonstrated that puerarin markedly inhibited the phosphorylation of MAPK family proteins (JNK1/2, ERK1/2 and p38 MAPK) of PSCs in a dose-dependent manner whether or not stimulated by platelet-activating factor. In conclusion, the present study showed that puerarin could be a potential therapeutic candidate in the treatment of CP, and the MAPK pathway might be its important target.
Highlights
Chronic pancreatitis (CP) is a persistent and progressive inflammatory disease, which often leads to destruction of the pancreatic parenchyma, infiltration of inflammatory cells and pancreatic calcification
Serum TGF-β1 levels were significantly increased in the Cae group due to repeated caerulein injections, while the level was markedly ameliorated by additional puerarin administration (Figure 2C)
The current study is the first study to investigate the treatment effect of puerarin on caeruleininduced murine CP, and the result illustrated that puerarin could ameliorate the pancreatic inflammation and fibrosis by reducing proliferation, migration and activation of pancreatic stellate cells (PSCs)
Summary
Chronic pancreatitis (CP) is a persistent and progressive inflammatory disease, which often leads to destruction of the pancreatic parenchyma, infiltration of inflammatory cells and pancreatic calcification. Inhibiting the proliferation, migration and activation of PSCs may become a potential effective method for the treatment of CP, which is the hot spot of basic research in recent years (Ulmasov et al, 2016; Zeng et al, 2019; Che et al, 2020; Wang et al, 2020). Puerarin has a wide range of pharmacological effects, including inhibiting platelet aggregation, anti-oxidative, antiinflammatory, diuresis, regulating blood pressure, blood glucose and blood lipid, protecting myocardium, etc. It has been tolerated and approved that puerarin exhibited anti-fibrotic effect in various fibrous diseases such as liver, lung, renal and cardiac fibrosis (Zhou et al, 2017; Hu et al, 2019; Zhang et al, 2019; Li et al, 2020). The impact of puerarin on CP and pancreatic fibrosis remains unknown and the underlying molecular mechanism is remaining to be well investigated
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