Jasminoidin and ursodeoxycholic acid exert synergistic effect against cerebral ischemia-reperfusion injury via Dectin-1-induced NF-κB activation pathway.

BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review.

Gastric cancer (GC) is a common gastrointestinal tumor. Gastric precancerous lesions (GPL) are the last pathological stage before normal gastric mucosa transforms into GC. However, preventing the transformation from GPL to GC remains a challenge. Traditional Chinese medicine (TCM) has been used to treat gastric disease for millennia. A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL. This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC, especially focusing on anti-inflammatory, anti-angiogenesis, proliferation, and apoptosis. This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Protective action of aspirin and its against endothelial Nlrp3 inflammasome activation in response to LPS stimuli / 中国药理学与毒理学杂志

OBJECTIVE Recent studies have demonstrated that the Nlrp3 inflammasome serve as a central role in the pathogenesis of cardiovascular diseases and endothelial dysfunction occurs in association with several cardiovascular risk factors. Given the demonstrated anti-inflammatory effects of aspirin, the present study was designed to test whether aspirin diminish NLRP3 inflammasome activation and prevent endothelium injury and associated coronary artery damage during LPS. METHODS Mouse carotid arterial endothelial cells (CAECs) were cultured and treated with 0.1-3 mmol·L-1 of aspirin in response to LPS (2 μg·mL-1) stimuli. After 24 h, the Nlrp3 inflammasome complexes consist of varied proteins were analyzed by WB. NO and T-AOC in the supernatant was detected by ELISA. Intracellular reactive oxygen species (ROS) generation for 24 h was observed by DCF fluorescence. The mice were treated with aspirin (12.5 mg·kg-1 per day, 62.5 mg·kg-1 per day, 125 mg·kg-1 per day) and dexametha?sone (0.0182 mg · kg- 1 per day) for 7 d. The level of IL- 1β,IL- 18 protein was detected by ELISA. RESULTS Immunofluorescence results showed the colocalization of Nlrp3 with ASC or caspase 1 decrease in a concentration- dependent manner. Meanwhile, the expression of Nlrp3 and caspase 1 protein was decreased with the concentration of aspirin, but no changes the expression of ASC protein. Nlrp3 protein levels in CAECs were 0.33- 0.8- fold and cle- caspase 1 protein levels in CAECs were 0.48-1-fold compared to those in LPS stimulation when treated with 0.1-3 mmol·L-1 aspirin for 24 h (P<0.01). Aspirin significantly antagonized the effect of LPS on NO (1.22-1.91-fold that of LPS stimulation, P<0.01) and T-AOC expression (1.02-1.90-fold that of LPS stimulation, P<0.01). As the different concentration of aspirin treated, the generation of ROS was 0.51-1.10-fold that of LPS stimulation (P<0.01). In vivo data shown the level of IL-1β, IL-18 protein from serum are in concordance with the level of Nlrp3 inflammasome activation. CONCLUSION We conclude that aspirin has anti- inflammatory properties, protecting CAECs from LPS-induced injury by inhibition of NLRP3 inflammasome activation through ROS pathway.