Anti-inflammatory effect and mechanism of ethanol extract from Saposhnikoviae Radix in LPS-induced inflammation mouse model / 中国中药杂志

This paper aimed to explore the anti-inflammatory effect of ethanol extract from Saposhnikoviae Radix in a lipopolysaccharide(LPS)-induced inflammation mouse model and its regulation of TLR4/NF-κB signaling pathway. The ethanol extract from Saposhnikoviae Radix was separated and purified on the macroporous adsorption resin and its main chemical components were identified by UPLC-QE/MS. The identification results showed that the top ten components of ethanol extract from Saposhnikoviae Radix were mainly chromones and coumarins. A mouse model of inflammation induced by intraperitoneal injection of LPS was used to investigate the anti-inflammatory effects of ethanol extract from Saposhnikoviae Radix after intragastric administration for seven successive days. Mice in all groups except for the control group were treated with intraperitoneal injection of LPS(0.015 g·kg~(-1)) one hour after the last administration, and twelve hours later, the blood was sampled and separated and the broncoalveolar lavage fluid(BALF) was collected. The levels of nitric oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) in mouse serum and BALF were detected by ELISA. The harvested lung tissue was stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by the detection of protein expression levels of related molecules in TLR4/NF-κB signaling pathway by Western blotting. The results showed that the ethanol extract from Saposhnikoviae Radix significantly ameliorated the pathological conditions in lung tissue of model mice, reversed the increase in NO, TNF-α, IL-6, and IL-1β levels of mouse serum and BALF, down-regulated the protein expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor(MyD88), and phosphorylated nuclear transcription factor κB-p65/nuclear transcription factor κB-p65(P-NF-κB p65/NF-κB p65), and up-regulated the NF-κB inhibitory protein α(IκBα). The ethanol extract from Saposhnikoviae Radix exhibited a good anti-inflammatory effect in the LPS-induced acute inflammation muse model, which might be related to the inhibition of the activation of TLR4/NF-κB inflammatory signaling pathway. Chromones and coumarins have been proved to be the active components for its anti-inflammatory effects.

Molecular mechanism of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair against sepsis based on integrative pharmacology platform of traditional Chinese medicine / 中国中药杂志

Guizhi Decoction is a resolving agent,which is a classic prescription for traditional Chinese medicine. It is effective in the treatment of sepsis in clinical practice. However,due to the complexity of the prescription,its anti-sepsis mechanism is difficult to be clarified. The " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair,as the classic compatibility for medicinal and medicinal herbs,is the core of Guizhi Decoction. In this study,Cinnamomi Ramulus-Paeoniae Radix Alba drug pair was used as the research object and the molecular mechanism of its treatment of sepsis was investigated by analyzing the chemical compositions with integrative pharmacology platform( TCMIP,http://www.tcmip.cn/),predicting disease target,analyzing gene function and pathway of " Cinnamomi Ramulus-Paeoniae Radix Alba" in treatment of sepsis,and establishing a multi-dimensional network relationship of " Chinese medicine-chemical components-core targets-key pathways". The prediction results of " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair showed that its anti-sepsis effect was associated with 45 active components,and the active components played an anti-sepsis role through multiple targets and pathways,involving inflammatory targets such as PF4,MyD88,TLR4,BDKRB2,CD14,and NOS3. The sepsis was relieved mainly by regulating Toll like signaling pathway,Fox O signaling pathway,chemokines signaling pathway,thyroid and insulin endocrine signaling pathways and biological processes. This study provides a scientific basis for further development of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair and Guizhi Decoction against sepsis.

Study on mechanism of essential oils of schizonepeta tenuifolia briq. In endotoxin poisoning mice via NLRP3 inflammasome pathway / 中国药理学通报

Aim: To explore the mechanism of the antiinflammatory effect of essential oils of Schizonepeta tenuifolia Briq. (EOST) by investigating the regulatory effect on NLRP3 inflammasome pathway. Methods: EOST (0. 226, 0. 452 g · kg-1) were continuously administered for five days. Thirty minutes after the last administration, the mice were intraperitoneally injected with LPS (0.015 g · kg-1, 10 mL · kg-1) to construct endotoxin poisoning, and relevant indicators for sample determination were taken 12 h after modeling. Determination of NO level in lung tissues by Griess method was performed. The expressions of NLRP3, ASC, caspase-1, IL-1β, iNOS and p65 mRNA in lung tissues were detected by qPCR. The expressions of P2X7R and Cathepsin B protein in lung tissues were assessed using immunohistochemistry. The NLRP3, caspase-1(p20), Pro-caspase-1, COP-1 protein ex pressions were detected by Western blot. Results: 0.226 g · kg-1 EOST could down-regulate the expressions of Cathepsin B and NLRP3 proteins in lung tissues of mice; 0.452 g · kg-1 EOST significantly reduced NO level, the expressions of NLRP3, iNOS, p65, IL-1β mRNA and P2X7R protein in lung tissues of mice; EOST (0.226, 0.452 g · kg-1) markedly reduced the. caspase-1 (p20) protein level and significantly increased COP1 protein level. Conclusions: The protective effect of EOST on endotoxin poisoning mice is closely related to its anti-inflammatory effects, which involves the inhibition of activation of NLRP3 inflammasome.