Resveratrol, the most important ingredient extracted from Polygonum cuspidatum, exerts cytoprotective effects via anti-inflammatory actions in vitro. In this study, we investigated this effect of resveratrol on the lipopolysaccharide (LPS)-induced inflammatory response and its underlying molecular mechanism of action in RAW264.7 murine macrophages. Results showed that resveratrol down-regulated the expression of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6), therefore, suppressed the production of nitric oxide and the secretion of IL-6 in LPS-stimulated RAW264.7 cells in a dose-dependent manner. Resveratrol also inhibited the translocation of highmobility group box 1 (HMGB1) from the nucleus to the cytoplasm and of nuclear transcription factor kappa-B (NF-κB) p65 from the cytoplasm to the nucleus; it suppressed the phosphorylation of IκBα. Furthermore, these actions were mediated by suppressing the phosphorylation of signal transducer and activator of transcription (STAT)-1 and -3. In conclusion, these data indicate that resveratrol exerts anti-inflammatory effects, at least in part by reducing the release of HMGB1 and modulating the NF-κB and Janus kinase/STAT signaling pathways. Resveratrol could potentially be developed as a useful agent for the chemoprevention of inflammatory diseases.

Resveratrol is a polyphenolic compound extracted from grapes and the Chinese herb, Polygonum cuspidatum. In the present study, in order to elucidate the molecular mechanisms of action of resveratrol in host immune cells, we examined the effects of resveratrol on the inflammatory response in lipopolysaccharide (LPS)‑stimulated RAW264.7 murine macrophages. The cells were treated with resveratrol prior to stimulation with LPS (1 µg/ml). Resveratrol downregulated the expression of inflammatory markers, such as tumor necrosis factor (TNF)-α and interleukin (IL)‑6, induced by LPS, and inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT)1/STAT3. Resveratrol also upregulated the production of suppressor of cytokine signaling 1 (SOCS1; a STAT inhibitor) and suppressed the expression of miR‑155, which plays an essential role in the innate and adaptive immune response. Given the elevated levels of SOCS1 in LPS-induced inflammation, our results suggest that resveratrol exerts anti-inflammatory effects due to the upregulation of SOCS1, which is a potential target of miR‑155, as well as of miR‑155 mimics and inhibitors. These findings suggest the benefits of resveratrol, which are derived from its regulation of SOCS1 expression via the inhibition of miR‑155, and indicate that resveratrol may be developed as a useful agent for the treatment of inflammatory diseases.

Objective: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms. Methods: Healthy male Sprague-Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model + NF-kB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes of intestine/lung tissues were observed by H&E and TUNEL staining. Serum IKBα, p-IKBα, SP-A and TLR4 levels were examined using ELISA. RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by western blot. Results: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury. Conclusion: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

Fluid balance (FB) is associated with poor sepsis outcomes; however, it cannot accurately reflect the dynamic fluid accumulation status. Here, we explored a new index, the FB to fluid intake ratio (FB/FI), for evaluating dynamic fluid accumulation in sepsis. FB/FI values within 48 hours were recorded. Their association with in-hospital mortality was investigated using logistic regression and mediation analyses of data from 7,839 patients. In extended logistic models, a linear association was found between FB and mortality (odds ratio [OR]: 1.05-1.08, p < 0.001). However, this association became non-significant after the adjustment of FB/FI (OR: 1.00, 95% confidence interval [CI]: 0.98-1.02). For FB/FI and mortality, a cut-off value of 0.25 was defined. In the spline function logistic model, FB/FI > 0.25 was significantly associated with increased mortality (OR: 4.46, 95% CI: 2.92-6.80), whereas FB/FI ≤ 0.25 was not. For the FB/FI > 0.25 subgroup, mediation analysis was used to clarify the relationship between FB, FB/FI, and mortality. We observed that the direct effect of FB was non-significant (adjusted coefficient: −0.001, 95% CI: −0.005 to 0.002) while the indirect effect was significant (adjusted coefficient: 0.009, 95% CI: 0.006-0.011). In the FB/FI ≤ 0.25 subgroup, both the FB volume (0.9 ± 0.7 vs. −2.0 ± 1.9, p < 0.001) and the FB/FI ratio (0.14 ± 0.07 vs. −0.77 ± 1.60, p < 0.001) were significantly higher in patients with FB > 0 than those with FB ≤ 0. However, both the crude and adjusted comparisons of hospital mortality were non-significant. Similar associations were observed in septic shock patients. FB/FI > 0.25 is a significant risk factor for mortality in sepsis, while FB/FI ≤ 0.25 is not. The association between FB and mortality is completely mediated by this new fluid accumulation index. More comprehensive indices are required for evaluating dynamic fluid status in sepsis.

QDHX decoction is an effective traditional Chinese medicine that has been used to treat ALI, a disease characterized by pulmonary edema and inflammation. In this study, the aim is to elucidate the molecular mechanisms of QDHX decoction on improving the alveolar-capillary membrane permeability and alleviating inflammatory response. The BALB/c mice were divided into five groups including the control group, ALI group, ALI + low-dose QDHX decoction, ALI + high-dose QDHX decoction, and ALI + dexamethasone. When the animals were sacrificed, the pathology and wet/dry of lung tissue were tested and confirmed Ali model, the LDH and nucleated cells in BALF, and TNF-α and IL-1β in serum; α-ENaC and AQP-1 in lung tissue were examined. In the results, QDHX decoction downregulated the cytokine such as TNF-α and IL-1β, reduced the nucleated cells, and some biochemical parameters of the BALF. It also ameliorated the ENaC-α and AQP-1 expression induced by LPS in primary epithelial cells. These findings may provide new insights into the application of QDHX decoction for the prevention and treatment of LPS-related ALI.