Drugs exhibiting anti-inflammatory and analgesic properties have been clinically used in the management of pain and impairment of joint functions in arthritis. In view of available studies on the beneficial effect of artesunate in various inflammatory conditions, the present study was carried out to evaluate its efficacy in ameliorating functional limitations of arthritis and to understand the underlying mechanisms. The study was carried out in rat model of Freund's complete adjuvant-induced monoarthritis where artesunate was found to produce a dose-dependent reduction in joint inflammation, improvement in functional parameters like stair climbing ability, motility, and suppression of mechanical allodynia at the doses of 50 and 150 mg/kg. Our study shows that protection afforded by artesunate was brought about by decreasing the levels of nitric oxide, influx of neutrophils, maintenance of oxidative homeostasis, inhibition of COX-2 expression, and apoptosis. Further, histological analysis of the arthritic joints also substantiated the anti-inflammatory property of artesunate. Thus, our study shows that artesunate has a potential for use in the treatment of arthritis.
Purpose
Detailed understanding of host pathogen interaction in tuberculosis is an important avenue for identifying novel therapeutic targets. Small extracellular vesicles (EVs) like exosomes that are rich in proteins, nucleic acids and lipids, act as messengers and may show altered composition in disease conditions.
Experimental design
In this case control study, small EVs are isolated from serum of 58 subjects (all male, 33 (15–70) in years) including drug naïve active tuberculosis (ATB: n = 22), non‐tuberculosis (NTB: n = 18), and healthy subjects (n = 18). Serum small EVs proteome analysis is carried out using isobaric tag for relative and absolute quantification (iTRAQ) experiments and an independent sample (n = 36) is used for validation.
Results
A set of 132 and 68 proteins are identified in iTRAQ‐I (ATB/Healthy) and iTRAQ‐II (ATB/NTB) experiments, respectively. Four proteins (KYAT3, SERPINA1, HP, and APOC3) show deregulation (log2‐fold change > ±0.48, p < 0.05) in ATB with respect to healthy controls and Western blot data corroborated mass spectrometry findings.
Conclusions and clinical relevance
These important proteins, involved in neutrophil degranulation, plasma heme scavenging, kynurenine, and lipid metabolism, show deregulation in ATB patients. Identification of such a protein panel in circulating small EVs besides providing novel insights into their role in tuberculosis may prove to be useful targets to develop host‐directed therapeutic intervention.
BackgroundYukyung karne (YK) is a traditional Tibetan formulation used for many centuries for the treatment of ovarian cancer. However, the pharmacological basis of its anticancer property is not well understood. In the present study, the anticancer property of YK was investigated in cell culture.MethodsThe growth inhibitory property of YK was evaluated in SKOV6, IHH, HepG2 and HEK293 cell lines using MTT assay. The pro-apoptotic activity of drug was analyzed by terminal deoxynuleotidyl transferase dUTP nick end labeling (TUNEL) and DNA fragmentation assays. Confocal microscopy was used to show the release of cytochrome c and its co-localization with mitochondria with the help of dsRed mitotracker in SKOV6 cells. The inhibition in cell proliferation was also visualized by confocal microscopy after BrDU incorporation. The activation of tumor suppressor p53 was evaluated by Western blotting while VEGF levels in culture supernatant were measured by a colorimetric method.ResultsYK specifically and efficiently induced apoptotic killing of the human ovarian cancer SKOV6 cells as indicated by increased DNA fragmentation and nick end DNA labeling. Confocal microscopy suggested inhibition of cell proliferation and increase in cytochrome c release via perturbation in mitochondrial membrane potential (Δψm). Further, YK up-regulated the expression of tumor suppressor p53 and key cyclin-dependent kinase inhibitor p21, and inhibited VEGF secretion by cells. Interestingly, YK also exhibited a synergy with paclitaxel which is a well-known anti-cancer therapeutic drug.ConclusionsThe pharmacological properties of YK to impose growth arrest and trigger pro-apoptotic death in cells amply justify its usage in primary as well as adjunct therapy for ovarian cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-380) contains supplementary material, which is available to authorized users.
BackgroundIn Traditional Tibetan medicine, Yukyung Karne has been used for the treatment of ovarian cancer. Though Yukyung Karne has been reported to be clinically effective, the molecular mechanism of its anti-metstatic action remains elusive.MethodsThe cytotoxic property of Yukyung Karne was evaluated by crystal violet staining while its ability to induce ceramide production was analyzed by sphingomyelinase assay. The anti-metastatic property was investigated using adhesion, invasion, migration and colony formation assays. The effect of Yukyung Karne on the expression of extracellular matrix components, and epithelial and mesenchymal markers were evaluated by confocal microscopy and western blotting.ResultsYukyung Karne exhibited a strong anti-metastatic property by significantly reducing the invasion, migration and colony formation ability of ovarian cancer cells. Besides it inhibited the levels of biomarkers involved in epithelial to mesenchymal transition such as down-regulation of vimentin and N-cadherin and up-regulation of epithelial E-cadherin. Yukyung Karne also induced the neutral sphingomyelinase II (nSMNaseII) enzyme activity that is known to hydrolyze sphingomyelins into pro-apoptotic intracellular molecule ceramide.ConclusionsThe study provides some compelling evidences supporting the anti-metastatic potential of Yukyung Karne which strongly suggests its possible usage as a promising alternative medicine. Thus, Yukyung Karne may be used as an anticancer and anti-metastatic agent along with other conventional anticancer therapeutics to increase their efficacy.
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