echinacoside and Inflammation

The activation of NLRP3 inflammasome, which initiates an inflammatory cascade and triggers inflammatory death, plays a crucial role in the pathogenesis of spinal cord injury (SCI). Echinacoside (ECH) is a phenylethanoid glycoside possessing prominent anti-inflammatory effects and various neuroprotective properties in the central nervous system, but the effect of ECH on SCI was rarely studied. Therefore, the purpose of this experiment was to look into the therapeutic effects of ECH on SCI and the underlying mechanisms.. Basso-Beattie-Bresnahan (BBB) locomotion scale, Nissl staining, and hematoxylin-eosin (HE) staining was employed to examine the therapeutic effects of ECH on SCI. In addition, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) in BV-2 cells stimulated with lipopolysaccharides and adenosine 5'-triphosphate were examined. The expression levels of proteins involving NLRP3 inflammasome-related pathway were measured.. The in vivo experiment indicated that administration of ECH significantly enhanced the BBB scores, reduced the neuron loss, and ameliorated the tissue architecture after SCI. Additionally, ECH dramatically inhibited NLRP3 inflammasome activation in the rat SCI model. In vitro study indicated that ECH significantly reduced ROS level, improved the MMP, blocked activation of NF-κB, and inhibited the NLRP3 inflammasome signaling pathway. The effect of ECH on inhibition of NLRP3 inflammasome signaling pathway was partially governed by suppression of the generation of ROS and activation of NF-κB.. ECH can accelerate motor function recovery in rats following SCI by inhibiting NLRP3 inflammasome-related signaling pathway, suggesting that ECH may serve as a potential therapeutic agent for treating SCI.

Topics: Animals; Glycosides; Inflammasomes; Inflammation; Locomotion; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Recovery of Function; Signal Transduction; Spinal Cord Injuries

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition of colon and small intestine. Echinacoside (ECH) is a phenylethanoid glycoside that possesses various activities, including anti-inflammatory effect. However, the role of ECH in IBD is unknown. The present study aimed to evaluate the effect of ECH on LPS-induced rat intestine epithelial cells and the potential mechanisms. The results showed that LPS inhibited cell viability in time- and dose-dependent manners. ECH treatment attenuated the inhibition effect of LPS on cell viability. ECH alleviated LPS-induced apoptosis of rat intestine epithelial cells. ECH attenuated LPS-induced secretion and mRNA expression of TNF-α and IL-6, but enhanced LPS-induced secretion and mRNA expression of IL-10 and TGF-β1 in IEC-6 cells. The mTOR/STAT3 pathway was activated by LPS, while the activation was inhibited by ECH. Rapamycin, an inhibitor of mTOR, reversed the effect of LPS on rat intestine epithelial cells. In summary, this work suggested that ECH attenuated LPS-induced inflammation and apoptosis in rat intestine epithelial cells via suppressing the mTOR/STAT3 pathway. The findings indicated that ECH might be considered as a potential strategy for the treatment of IBD.

Topics: Animals; Apoptosis; Cell Survival; Epithelial Cells; Glycosides; Inflammation; Interleukin-10; Intestinal Mucosa; Intestines; Lipopolysaccharides; Rats; Signal Transduction; Sirolimus; STAT3 Transcription Factor; TOR Serine-Threonine Kinases; Transforming Growth Factor beta1

Echinacoside is a major compound of Cistanche Herb and has glutamate release-inhibiting activity in the brain. Given the involvement of excitotoxicity caused by massive glutamate in the pathophysiology of epilepsy, we explored the antiepileptic effect of echinacoside on kainic acid-induced seizures in rats. The rats were intraperitoneally administrated echinacoside for 30 min prior to intraperitoneal injection with kainic acid. The results showed that kainic acid induced seizure-like behavioral patterns, increased glutamate concentrations, caused neuronal loss and microglial activation, and stimulated proinflammatory cytokine gene expression in the hippocampus. These kainic acid-induced alternations were found to be attenuated by echinacoside pretreatment. Furthermore, decreased Akt and glycogen synthase kinase 3β (GSK3β) phosphorylation as well as Bcl-2 expression in the hippocampus was reversed by the echinacoside pretreatment. These results demonstrate that echinacoside exert its antiepileptic and neuroprotective actions in a kainic acid rat model through suppressing inflammatory response and activating the Akt/GSK3β signaling. Therefore, the present study suggests that echinacoside is the potentially useful in the prevention of epilepsy.

Topics: Animals; Brain; Cistanche; Cytokines; Disease Models, Animal; Epilepsy; Glutamic Acid; Glycogen Synthase Kinase 3 beta; Glycosides; Inflammation; Kainic Acid; Male; Microglia; Neuroprotective Agents; Neurotoxicity Syndromes; Phosphorylation; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Seizures; Signal Transduction

This study aimed to investigate the protective effects of echinacoside, one of the phenylethanoids isolated from the stems of Cistanche salsa, a Chinese herbal medicine, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced acute liver injury in mice.. We administered GalN (650 mg/kg) together with LPS (30 μg/kg) to mice by intraperitoneal injection to induce acute liver damage. Echinacoside (60 mg/kg) was given intraperitoneally to mice at 1 h prior to GalN/LPS exposure. Mice were sacrificed at different time points following GalN/LPS treatment, and the liver and blood samples were collected for future analysis.. It showed that GalN/LPS treatment produced severe hepatic injury, evidenced by significantly elevated plasma alanine aminotransferase (ALT) levels and abnormal histological changes such as hepatocyte necrosis or apoptosis, hemorrhage, fatty degeneration, and neutrophil infiltration. Notably, pretreatment with echinacoside remarkably improved the survival rate of GalN/LPS-treated mice and attenuated acute hepatotoxicity, as demonstrated by decreased ALT levels and improved histological signs. Echinacoside shows both anti-apoptotic and anti-inflammatory properties, characterized by a substantial inhibition of hepatocyte apoptosis and a significant reduction in the inflammatory markers, including myeloperoxidase, extracellular nucleosomes, high-mobility group box 1, and inflammatory cytokines in the plasma of mice, which may be important mechanisms related to its protective effect.. Our results suggest that echinacoside can provide a pronounced protection against GalN/LPS-induced acute liver injury in mice, which may complement the available strategies for management of acute liver damage in clinical settings.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Apoptosis; Biomarkers; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Galactosamine; Glycosides; Hepatocytes; Inflammation; Injections, Intraperitoneal; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Treatment Outcome