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. 2021 Jul 27:2021:9945149.
doi: 10.1155/2021/9945149. eCollection 2021.

Picroside II Improves Severe Acute Pancreatitis-Induced Hepatocellular Injury in Rats by Affecting JAK2/STAT3 Phosphorylation Signaling

Xuehua Piao  1 , Xiaodan Sui  2 , Baohai Liu  3 , Tingfang Cui  3 , Zinan Qi  3
Affiliations

Picroside II Improves Severe Acute Pancreatitis-Induced Hepatocellular Injury in Rats by Affecting JAK2/STAT3 Phosphorylation Signaling

Xuehua Piao et al. Biomed Res Int. .

Abstract

Picroside II is an important ingredient agent in Traditional Chinese medicine and hoped to reduce hepatocellular injury caused by severe acute pancreatitis (SAP). An SAP-induced hepatocellular injury model was established in rats by using pentobarbital sodium. 27 rats were divided into 3 groups: the sham group (SG), model group (MG), and Picroside groups (PG). SAP-induced hepatocellular injury was assessed using hematoxylin and eosin staining. We measured hepatocellular enzymes (amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)), oxidative stress factors (superoxidase dismutase (SOD) and malondialdehyde (MDA)), and inflammatory factors (tumor necrosis factor α (TNF-α), interleukin- (IL-) 6, and IL-10), apoptotic factors (BAX and cleaved caspase 3), and inflammatory signaling (Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), p-JAK2, and p-STAT3) in hepatocellular tissues. The SAP-induced hepatocellular injury model was successfully established. Picroside II treatment repaired hepatocellular injury by reducing the activities of AMY, ALT, and AST; reducing the levels of MDA, TNF-α, IL-1, IL-6, p-JAK2, p-STAT3, BAX, and cleaved caspase 3; and increasing the levels of SOD and IL-10. Picroside II exerted protective function for the SAP-induced hepatocellular injury model. Picroside II improved SAP-induced hepatocellular injury and antioxidant and anti-inflammatory properties by affecting JAK2/STAT3 phosphorylation signaling.

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Conflict of interest statement

The authors declare there are no conflicts of interest.

Figures

Figure 1
Figure 1
The effects of Picroside II on the liver injury. (a) The time flowchart on the biochemical analysis. (b) Amylase (AMY). (c) ALT. (d) AST. (e) Hematoxylin and Eosin (H&E) staining analysis of the effects of Picroside II on serious acute pancreatitis (SAP) and disease scores at 6 hours. (f) Disease scores at 12 hours. (g) Disease scores at 24 hours. (h) Hematoxylin and Eosin (H&E) staining analysis of the effects of Picroside II on serious acute pancreatitis- (SAP-) induced hepatocellular injury. Disease scores at 6 hours. (i) Disease scores at 12 hours. (j) Disease scores at 24 hours. All rats were divided into 3 groups, the sham group (SG), the model group (MG), and the Picroside II group (PG). The arrows show the inflammatory cells. n = 3 for each group. Scale bar = 30 μm. ∗P < 0.05 vs. the MG group.
Figure 2
Figure 2
The total bile acid (TBA) levels. (a) Serum levels of TBA among different groups. (b) TBA levels in the liver among different groups. n = 3 for each group.
Figure 3
Figure 3
The effects of Picroside II on the levels of oxidative stress markers. (a) Superoxide dismutase (SOD) activity at 6 hours. (b) Malondialdehyde (MDA) concentration at 6 hours. ∗P < 0.05 vs. the MG group. n = 3 for each group.
Figure 4
Figure 4
The effects of Picroside II on the serum levels of inflammatory cytokines. (a) Tumor nuclear factor- (TNF-) α level at 6 hours. (b) Interleukin-6 (IL-6) level at 6 hours. (c) Interleukin-10 (IL-10) level at 6 hours. ∗P < 0.05 vs. the MG group. n = 3 for each group.
Figure 5
Figure 5
The functional mechanism of Picroside II. Picroside II may exert its function by affecting JAK2/STAT3 phosphorylation signaling, which results in the increase in antioxidant, anti-inflammatory, and antiapoptotic activities.
Figure 6
Figure 6
The effects of Picroside II on the levels of apoptotic factors and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) in hepatocellular tissues. (a) Relative mRNA levels of BAX. (b) Relative mRNA levels of caspase 3. (c) Relative mRNA levels of JAK2. (d) Relative mRNA levels of STAT3. (e) Relative protein levels of BAX. (f) Relative protein levels of caspase 3. (g) Relative protein levels of p-JAK2. (h) Relative protein levels of JAK2. (i) Relative protein levels of STAT3. (j) Relative protein levels of p-STAT3. (k) The expression of BAX. (l) The expression of caspase 3. (m) The expression of JAK2. (n) The expression of p-JAK2. (o) The expression of STAT3. (p) The expression of p-STAT3. Scale bar = 30 μm. ∗P < 0.05 vs. the MG group. n = 3 for each group.
Figure 7
Figure 7
Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on the effects of Picroside II on the hepatocellular apoptosis (magnification 400x). Scale bar = 30 μm. ∗P < 0.05 vs. the MG group. n = 3 for each group.
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