picroside-ii and Inflammation

Ulcerative colitis (UC) is a common acute or chronic intestinal disease with an imbalance of inflammation. Picroside II (P-II) exerts a protective role in various inflammation-related diseases. However, the effect of P-II on UC is still unclear.. To explore the effect of P-II on UC and its potential mechanism.. Human monocytic leukemia cell line THP-1 was treated with phorbol ester (PMA) to differentiate into a macrophage. The differentiated THP-1 cells were hatched with LPS combined with ATP or Nigericin to activate the NLRP3 inflammasome. The maximum nontoxic concentration of P-II on THP-1 cells was 60 μM. LPS combined with ATP or Nigericin stimulated the production of IL-1β, which was antagonized by P-II treatment. Meanwhile, P-II administration interfered with the aggregation of ASC and the assembly of NLRP3 inflammasomes. Also, P-II treatment reduced the LPS and ATP-induced elevation of the relative protein expression of NLRP3, pro-caspase-1, IL-1β and p-p65/p65, and the concentration of TNF-α and IL-6. Besides, the NF-κB specific inhibitor BAY-117082 notably repressed the LPS together with ATP-enhanced the relative protein expression of NLRP3, caspase-1 and IL-1β. Moreover,. P-II alleviated DSS-induced UC by repressing the production of NLRP3 inflammasomes

Topics: Adenosine Triphosphate; Animals; Caspase 1; Cinnamates; Colitis, Ulcerative; Dextran Sulfate; Inflammasomes; Inflammation; Iridoid Glucosides; Lipopolysaccharides; Mice; NF-kappa B; Nigericin; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction

Picroside II (P-II), one of the main active components of scrophularia extract, which have anti-oxidative, anti-inflammatory effects, but its effect on hyperhomocysteinemia (HHcy) induced endothelial injury remains to be determined. Here, we test whether P-II protects HHcy-induced endothelial dysfunction against oxidative stress, inflammation and cell apoptosis. In vitro study using HUVECs, and in hyperhomocysteinemia mouse models, we found that HHcy decreased endothelial SIRT1 expression and increased LOX-1 expression, subsequently causing reactive oxygen species generation, up-regulation of NADPH oxidase activity and NF-κB activation, thereby promoting pro-inflammatory response and cell apoptosis. Blockade of Sirt1 with Ex527 or siRNASIRT1 increased LOX-1 expression, whereas overexpression of SIRT1 decreased LOX-1 expression markedly. P-II treatment significantly increased SIRT1 expression and reduced LOX-1 expression, and protected against endothelial cells from Hcy-induced oxidative injury, inflammation and apoptosis. However, blockade of SIRT1 or overexpression of LOX-1 attenuated the therapeutic effects of P-II. In conclusion, our results suggest that P-II prevents the Hcy induced endothelial damage probably through regulating the SIRT1/LOX-1 signaling pathway.

Topics: Animals; Antioxidants; Apoptosis; Cell Line; Cinnamates; Endothelium; Human Umbilical Vein Endothelial Cells; Humans; Hyperhomocysteinemia; Inflammation; Iridoid Glucosides; Mice; Mice, Inbred C57BL; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Sirtuin 1; Up-Regulation

Reactive astrocyte-mediated neuroinflammatory responses in the spinal dorsal horn have been reported to play a pivotal role in pathological pain. Chronic constriction injury (CCI) enhances the activation of nuclear factor kappa B (NF-κB), which is involved in neuropathic pain (NP). Picroside II (PII), a major active component of Picrorhiza scrophulariiflora, has been investigated for its anti-oxidative, anti-inflammatory, and anti-apoptotic activities. Here, we explored the analgesic effects of PII on a model of CCI-induced NP and investigated the levels of the GFAP protein and the mRNA and protein levels of pro-inflammatory cytokines in the spinal cord, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). CCI significantly induced mechanical allodynia and thermal hyperalgesia. Intraperitoneal administration of PII remarkably reversed the CCI-induced mechanical allodynia and thermal hyperalgesia and reduced the mRNA and protein levels of IL-1β, IL-6, and TNF-α in the spinal cord. Additionally, according to the in vitro data, the PII treatment inhibited LPS-induced increases in the mRNA and protein levels of IL-1β, IL-6, and TNF-α and suppressed the NF-κB pathway by inhibiting the phosphorylation of NF-κB/p65 and the degradation of inhibitor of NF-κB (IκB) in astrocytes without toxicity to astrocytes. Overall, the analgesic effect of PII correlated with the inhibition of spinal reactive astrocyte-mediated neuroinflammation through the NF-κB pathway in rats with NP.

Topics: Analgesics; Animals; Astrocytes; Cells, Cultured; Cinnamates; Constriction, Pathologic; Cytokines; Glial Fibrillary Acidic Protein; Hyperalgesia; Inflammation; Iridoid Glucosides; Male; Neuralgia; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord

Picroside II is the main active ingredient in the root department of Chinese medicine Picrorhiza scrophulariiflora which has been proved to have beneficial effects on health, such as ameliorating the cerebral ischemia and protecting the liver. However, its effects on acute lung injury remain unclear. The purpose of the study was to evaluate the effects of picroside II on acute lung injury in mice and the inflammation in A549 cells which are lipopolysaccharide (LPS) induced. We evaluated the levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6) in vivo and vitro by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qRT-PCR). Results showed picroside II significantly decreased the concentrations of TNF-α, IL-1β, and IL-6 in cells and mice. In addition, Western blot and immunofluorescence analysis indicated that picroside II suppressed the activation of p65 NF-κB signaling pathway compared with LPS stimulation. In the acute lung injury model of mice, after picroside II treatment, the pathologic changes of lung tissues had been alleviated and lung wet/dry weight ratio was decreased. In summary, picroside II showed the promising effects of anti-inflammation in cells and animals.

Topics: A549 Cells; Acute Lung Injury; Animals; Cinnamates; Humans; Inflammation; Iridoid Glucosides; Lipopolysaccharides; Lung; NF-kappa B; Protective Agents; Rats