Objective: To investigate the effect and mechanism of total flavonoids from Psidium guajava leaves (TFPGL) on pancreatic fibrosis in a mouse model of chronic pancreatitis (CP). Method: Fifty male C57BL/6 mice were randomly divided into control group

CP model group

oxidized ATP (oxATP) group

high-dose TFPGL group and low-dose TFPGL group. CP model were built in the latter four groups by intraperitoneally injecting 50 μg·kg-1 cerulein (dissolved in 200 μL of physiological saline) per hour

6 times per day

three times per week

for six consecutive weeks.Six weeks later

oxATP (15 μg·kg-1 per day

dissolved in 200 μL of physiological saline) was given to oxATP group through intraperitoneal injection. And 0.186 g·kg-1 per day and 0.372 g·kg-1 per day TFPGL were given by gavage to high-dose TFPGL group and low-dose TFPGL group for two weeks

respectively. Meanwhile

the control group received 0.9% sterile sodium chloride through intraperitoneal injection at the same frequency and volume of the model group.The degree of pancreatic damage was evaluated by HE staining

and the content of pancreatic tissue collagen was detected by Sirius red staining. The expressions of nucleotide binding oligomerization domain like receptor 3 (NLRP3)

cysteinyl aspartate specific proteinase-1 (Caspase-1) and α-smooth muscle actin (α-SMA) were assessed by immunohistochemical staining. The IL-1β and IL-18 levels in pancreatic tissues were measured by an enzyme-linked immunosorbent assay. Result: Compared with the control group

the pancreatic damage aggravated (P<0.01)

and the levels of Caspase-1

NLRP3

α-SMA

IL-1β and IL-18 increased (P<0.01). After injection with caerulein. Picric acid-sirius red staining in pancreatic tissues showed that the pericellular accumulations of collagen I (Col I) and collagen Ⅲ (Col Ⅲ) (P<0.001)

were increased compared with the control group. Compared with the model group

ameliorated inflammatory injury and fibrosis (P<0.05

P<0.01)

were observed in oxATP and TFPGL groups

which was manifested as decrease in degree of picric acid-sirius red staining and levels of Caspase-1

NLRP3

α-SMA

IL-1β and IL-18. Conclusion: TFPGL can alleviate chronic inflammatory reaction and fibrosis in the model mice of chronic pancreatitis

which related to the inhibition of P2X7R-mediated NLRP3 inflammasome activation.