Background. Picroside II exerts anti-inflammatory and antidiarrheal effects for treating the diseases associated with oxidative injury. However, its function on pancreatitis-induced intestinal barrier injury remains unclear. Hypothesis/Purpose. We hypothesized that picroside II will have protective effects against pancreatitis-induced intestinal barrier injury by affecting oxidative and inflammatory signaling (Toll-like receptor 4- (TLR4-) dependent phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and nuclear factor kappa B (NF-κB)). Study Design and Methods. A Sprague-Dawley (SD) rat model with severe acute pancreatitis (SAP) was induced via the injection of sodium taurocholate (4% wt/vol; 1 mL/kg). All rats were divided into 3 groups: sham (CG), SAP-induced intestinal barrier injury (MG), and picroside II (PG) groups. Intestinal barrier injury was assessed by scanning electron microscopy (SEM), hematoxylin and eosin staining, and pathological scores. We measured the levels of pancreatitis biomarkers (amylase and lipase), oxidative and inflammatory signaling (TLR4-dependent PI3K/AKT/NF-κB), oxidative stress marker (superoxidase dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx), and malondialdehyde), and inflammatory markers (tumor necrosis factor α (TNFα), interleukin- (IL-) 1, IL-6, and IL-10) in serum and/or gut tissues. Gut microbiota composition in feces was measured by using 16S rRNA sequencing. Results. SEM showed that intestinal barrier injury was caused with the loss of intestinal villi and mitochondria destruction, and pathological scores were increased in the MG group. The levels of amylase, lipase, malondialdehyde, TNFα, IL-1, IL-6, TLR4, PI3K, AKT, and NF-κB were increased, and the levels of SOD, GPx, CAT, and IL-10 was reduced in the MG group when compared with CG group (P<0.05). Picroside II treatment inhibited the symptoms in the MG group and showed antioxidant and anti-inflammatory activities. The serum levels of picroside II had strong correlation with the levels of inflammatory and oxidative stress biomarkers (P<0.05). Picroside II treatment increased the proportion of Lactobacillus and Prevotella and decreased the proportion of Helicobacter and Escherichia_Shigella in the model. Conclusions. Picroside II improved the SAP-induced intestinal barrier injury in the rat model by inactivating oxidant and inflammatory signaling and improving gut microbiota.

Background: Polygonum cuspidatum Siebold & Zucc. (PCS) has antibacterial properties and may prevent Ulcerative colitis (UC) but related molecular mechanism remains unknown. NF-κB signaling pathway is associated with inflammatory responses and its inactivation may be critical for effective therapy of UC.Methods: UC mouse (C57BL/6J) model was established by using dextran sulfate sodium (DSS). The extract of PCS (PCSE) was prepared by using ethanol and its main ingredients were measured by HPLC. Thirty-two UC mice were evenly assigned into DG (received vehicle control), LG (0.1 g/kg PCSE daily), MG (0.2 g/kg PCSE daily) and HG (0.4 g/kg PCSE daily) groups. Meanwhile, 8 healthy mice were assigned as a control group (CG). Serum pharmacokinetics of PCS was measured by using HPLC. After 8-day treatment, weight, colon length and disease activity index (DAI) were measured. Inflammatory cytokines and oxidant biomarkers were measured by ELISA kits. The levels of cytokines, and key molecules in NF-κB pathway, were measured by using Western Blot. The effects of main ingredients of PCSE on cytokines and NF-κB signaling pathway were explored by using intestinal cells of a mouse UC model. The normality criterion was evaluated using the Saphiro–Wilk test. The quantitative variables were compared using the paired Student’s-t test.Results: The main ingredients of PCSE were polydatin, resveratrol and emodin. Polydatin may be transformed into resveratrol in the intestine of the mice. PCSE prevented DSS-caused weight loss and colon length reduction, and improved histopathology of UC mice (P < 0.05). PCSE treatment increased the serum levels of IL-10 and reduced the levels of IL-1 beta, IL-6 and TNF-α (P < 0.05). PCSE increased the activities of SOD, CAT, GPX and reduced the level of MDA, BCL-2, beta-arrestin, NF-κB p65 and the activity of MPO (P < 0.05). The combination of polydatin, resveratrol or emodin, and or PCSE exhibited higher inhibitory activities for cytokines and NF-κB signaling related molecules than any one of the three ingredients with same concentration treatment.Conclusion: Oral administration of PCSE suppressed NF-κB signaling pathway and exerts its anti-colitis effects via synergistic effects of polydatin, resveratrol or emodin.

Gastric ulcer (GU) is a main threat to public health. 1-Deoxynojirimycin (DNJ) has antioxidant and anti-inflammatory properties and may prevent GU but related mechanism remains unclear. DNJ was extracted from the supernatants of Bacillus subtilis by using ethanol and purified by using CM-Sepharose chromatography. A GU mouse model was induced by indomethacin. The functional role of DNJ in GU mice was explored by measuring the main molecules in the NF-KappaB pathway. After the model establishment, 40 GU mice were evenly assigned into five categories: IG (received vehicle control), LG (10 μg DNJ daily), MG (20 μg DNJ daily), HG (40 μg DNJ daily), and RG (0.5 mg ranitidine daily). Meanwhile, eight healthy mice were assigned as a control group (CG). After 1-month therapy, weight and gastric volume were investigated. The levels of serum inflammatory cytokines (IL-6 and TNF-α), antioxidant indices [superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)], and oxidant biomarker malondialdehyde (MDA) were examined via ELISA. Meanwhile, inflammatory cytokine (IL-6 and TNF-α) levels, and key molecules (NF-κB p65), cyclooxygenase 1 (COX-1 and COX2) involved in NF-κB pathway, were analyzed by using Western Blot. COX-1 and COX-2 levels were further measured by immunohistochemistry. The effects of DNJ on gastric functions were explored by measuring the changes of Motilin (MOT), Substance P (SP), Somatostatin (SS), and Vasoactive intestinal peptide (VIP) in GU mouse models with ELISA Kits. The results indicated that DNJ prevented indomethacin-caused increase of gastric volume. DNJ improved histopathology of GU mice when compared with the mice from IG group (P < 0.05). DNJ consumption decreased the levels of IL-6 and TNF-α (P < 0.05). DNJ increased antioxidant indices of GU mice by improving the activities of SOD, CAT and reduced GSH, and reduced MDA levels (P < 0.05). DNJ increased the levels of prostaglandin E2, COX-1, COX2, and reduced the levels of and NF-κB p65 (P < 0.05). DNJ showed protection for gastric functions of GU mice by reducing the levels of MOT and SP, and increasing the levels of SS and VIP. DNJ treatment inactivates NF-κB signaling pathway, and increases anti-ulceration ability of the models.

Hydrostatin-SN1 (peptide sequence, DEQHLETELHTLTSVLTANGFQ), a kind of peptides extracted from snake venom, has been reported to have anti-inflammatory effect, but its truncated mutant hydrostatin-SN10 (peptide sequence, DEQHLETELH) on pancreatitis-induced acute lung injury has not been well documented. Interleukin- (IL-) 6-induced Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway is involved with inflammatory and oxidative stress activities and may be associated with the pathogenesis of lung injury, and related molecules were measured. Taurocholate-induced pancreatitis associated with acute lung injury was established and treated with hydrostatin-SN10. Pancreatitis was confirmed by measuring the serum levels of amylase, lipase, and trypsinogen and urinary amylase. Lung injury was determined by histologically assessing acinar cell changes. The related molecules of IL-6-induced JAK2/STAT3-associated inflammation and oxidative stress were quantitated by real time-PCR, Western blot, and/or immunochemical assay. Hydrostatin-SN10 reduced the levels of serum amylase, lipase, and trypsinogen and urinary amylase when compared with the model group (p < 0.05). Hydrostatin-SN10 significantly inhibited the IL-6-stimulated JAK2/STAT3 pathway and reduced the number of apoptotic cells via the downregulation of caspase 3 and BAX (proapoptotic) and upregulation of Bcl2 (antiapoptotic) (p < 0.05). IL-6 induced the increase in the levels of JAK2 and STAT3, which was reversed by hydrostatin-SN10 treatment (p < 0.05). In addition, hydrostatin-SN10 reduced the expression of IL-6 and TNF- (tumor necrosis factor-) α and increased the level of IL-10 (p < 0.05). On the other hand, hydrostatin-SN10 treatment increased the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) and the levels of malondialdehyde (MDA) and alanine aminotransferase (ALT) (p < 0.05). These results suggest that hydrostatin-SN10 may inhibit pancreatitis-induced acute lung injury by affecting IL-6-mediated JAK2/STAT3 pathway-associated inflammation and oxidative stress.

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.