ecdysterone and Inflammation

20-Hydroxyecdysone (20E) is known to have numerous pharmacological activities and can be used to treat diabetes and cardiovascular diseases. However, the protective effects of 20E against endothelial dysfunction and its targets remain unclear. In the present study, we revealed that 20E treatment could modulate the release of the endothelium-derived vasomotor factors NO, PGI

Topics: Cardiovascular Diseases; Ecdysterone; Endothelial Cells; Humans; Inflammation; Molecular Docking Simulation; NF-kappa B; Sirtuins; Tumor Necrosis Factor-alpha

The roots of Achyranthes bidentata Blume (AB) is commonly used in the treatment of osteoporosis and dementia in traditional Chinese medicine. Pharmacological reports evidenced that AB possessed anti-osteoarthritis effects. However, there is little literature about the anti-dementia activities of AB. The present study was designed to prepare steroid-enriched fraction of AB (ABS) and investigate whether ABS can protect from cognitive dysfunction and neuroinflammation against Aβ 1-40-induced Alzheimer's disease (AD) model in rats. ABS only contained 135.11 ± 4.28 mg of ecdysterone per gram. ABS (50 mg/kg) reversed the dysfunction of exploratory activity and memory function on plus-maze and Morris water maze caused by Aβ 1-40 in rats. ABS (50 mg/kg) also decreased amyloid deposition, neurofibrillary tangle, neural damage, activated astrocyte, and microglial caused by Aβ 1-40. Furthermore, ABS reversed the phenomenon of neural oxidative damage and neuroinflammation, including the higher levels of MDA and cytokines, and the lower activities of antioxidant enzymes and GSH levels caused by Aβ 1-40 in rat cortex and hippocampus. Finally, ABS restored the activation of ERK pathway and decreased NF-κB phosphorylation and translocation altered by Aβ 1-40. ABS alone (50 mg/kg) promoted cognitive function, activated brain antioxidant defense system, and decreased brain TNF-α levels in sham group. Therefore, ABS has the cognition-promoting and antidementia potential. Steroids especial ecdysterone are major active components of AB. The action mechanism is due to decreasing oxidative stress and neuroinflammation through modulating ERK pathway, NF-κB phosphorylation, and translocation in Aβ 1-40-induced AD rat model.

Topics: Acetylcholinesterase; Achyranthes; Amyloid beta-Peptides; Animals; Antioxidants; Astrocytes; Behavior, Animal; Brain; Cognitive Dysfunction; Cytokines; Ecdysterone; Glutathione; Hippocampus; Inflammation; Male; Malondialdehyde; MAP Kinase Signaling System; Maze Learning; Memory; Microglia; Neuroprotective Agents; NF-kappa B; Oleanolic Acid; Peptide Fragments; Rats, Sprague-Dawley; Steroids; Triterpenes; Ursolic Acid

Osteoarthritis (OA) is characterized by a loss of articular cartilage accompanied with inflammation of synovium. β-Ecdysterone (Ecd), a major component of several Chinese herbal medicines, e.g., Achyranthes bidentata BL., has been used for the prevention and treatment of OA. Ecd is an estrogen analog and is likely to have similar pharmacological effects including the effect of protective chondrocytes. This study investigated the effects of Ecd on interleukin-1β (IL-1β)-induced apoptosis and inflammation in rat chondrocytes. Ecd protected chondrocytes from IL-1β-induced injury by inhibiting expression of Bax, p53 phosphorylation, and promoting expression of Bcl-xL . Simultaneously, Ecd reduced caspase 3 activity. IL-1β-induced inflammation and matrix degration were also prevented by Ecd via down-regulation of matrix metalloproteinases MMP 3, MMP 9, and cyclooxygenase-2 expression. Additionally, Ecd inhibited Nuclear Factor Kappa B (NF-κB) p65 phosphorylation, IκBα degradation, and phosphorylation in IL-1β-induced rat chondrocytes. These results suggested Ecd exerted anti-apoptosis and anti-inflammation in IL-1β-induced rat chondrocytes, which might be related to NF-κB signal pathway.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Apoptosis Regulatory Proteins; Cell Survival; Cells, Cultured; Chondrocytes; Ecdysterone; I-kappa B Proteins; Inflammation; Interleukin-1beta; Male; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; NF-KappaB Inhibitor alpha; Rats, Sprague-Dawley; Signal Transduction; Transcription Factor RelA; Tumor Suppressor Protein p53

Beyond their role in cell metabolism, development, and reproduction, hormones are also important modulators of the immune system. In the context of inflammatory disorders, systemic administration of pharmacological doses of synthetic glucocorticoids (GCs) is widely used as an anti-inflammatory treatment [1, 2]. However, not all actions of GCs are immunosuppressive, and many studies have suggested that physiological concentrations of GCs can have immunoenhancing effects [3-7]. For a more comprehensive understanding of how steroid hormones regulate immunity and inflammation, a simple in vivo system is required. The Drosophila embryo has recently emerged as a powerful model system to study the recruitment of immune cells to sterile wounds [8] and host-pathogen dynamics [9]. Here we investigate the immune response of the fly embryo to bacterial infections and find that the steroid hormone 20-hydroxyecdysone (20-HE) can regulate the quality of the immune response and influence the resolution of infection in Drosophila embryos.

Topics: Animals; Drosophila melanogaster; Drosophila Proteins; Ecdysterone; Embryo, Nonmammalian; Escherichia coli; Immunity, Humoral; Inflammation; Micrococcus luteus; Pectobacterium carotovorum; Real-Time Polymerase Chain Reaction; Signal Transduction

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature