Suppression of P2X7/NF-κB pathways by Schisandrin B contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury

Abstract

The aim of the present study was to assess the effects and mechanisms of Schisandrin B (SchB) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg), and SchB (25, 50, and 75 mg/kg) was injected 1 h before LPS challenge by gavage. After 12 h, bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected. Histological studies demonstrated that SchB attenuated LPS-induced interstitial edema, hemorrhage, and infiltration of neutrophils in the lung tissue. SchB pretreatment at doses of 25, 50, and 75 mg/kg was shown to reduce LPS-induced lung wet-to-dry weight ratio and lung myeloperoxidase activity. In addition, pretreatment with SchB lowered the number of inflammatory cells and pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. The mRNA and protein expression levels of nuclear factor kappa B (NF-κB) signaling-related molecules activated by P2X7 were investigated to determine the molecular mechanism of SchB. The findings presented here suggest that the protective mechanism of SchB may be attributed partly to the decreased production of pro-inflammatory cytokines through the inhibition of P2X7/NF-κB activation.

Schisandrin B ameliorated chondrocytes inflammation and osteoarthritis via suppression of NF-κB and MAPK signal pathways

“…chinensis , has been reported to exhibit anti-inflammatory properties in inflammatory bowel disease, neuroinflammatory damage, and acute lung injuries. 14 – 16 For the first time, to the best of our knowledge, we report the protective effect of Schisandrin B on cartilage degeneration via suppression of NF-κB and MAPK pathways in this study.…”

“…Studies focusing on the molecular mechanism revealed that Schisandrin B could effectively reduce the activation of inflammatory signal pathways including nuclear factor-κB (NF-κB) pathway and MAPK/extracellular signal-regulated kinase (Erk)/p38/c-Jun amino-terminal kinase (Jnk) pathway. 10 – 13 Several in vivo studies have also demonstrated the protective role of Schisandrin B in inflammatory bowel disease, 14 neuroinflammatory damage, 15 acute lung injuries, 16 etc. However, the effect of Schisandrin B on chondrocyte inflammation and OA progression has not been reported yet.…”

P2 Purinergic Signaling in the Distal Lung in Health and Disease

“…There is compelling evidence from KO experiments and pharmacological interferences that P2X 7 is relevant for the pathogenesis of ARDS [ 98 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 204 , 205 ] ( Figure 2 ). A hallmark of ARDS is excessive invasion and activation of neutrophils (PMN) in the alveolar space.…”

Protective effects of P2X7R antagonist in sepsis‐induced acute lung injury in mice via regulation of circ_0001679 and circ_0001212 and downstream Pln, Cdh2, and Nprl3 expression

“…Extracellular adenosine triphosphate activates P2X 7 R and then the NLRP3 inflammasome, followed by caspase-1 activation, which releases mature interleukin (IL)-1β, thereby promoting inflammation. 13 P2X 7 R is involved in the process of proinflammatory cytokine production, 12,14 the cell cycle, 15 apoptosis, autophagy induction 12,16 and host defenses against infectious pathogens. 17 Additionally, P2X 7 R plays a vital role in immune responses to infections, including sepsis.…”