alpha-Cyperone

Vet Immunol Immunopathol. 2014 May 15;159(1-2):50-7.

Inhibitory effects of α-cyperone on adherence and invasion of avian pathogenic Escherichia coli O78 to chicken type II pneumocytes.[Pubmed: 24629766]

METHODS AND RESULTS:
Avian pathogenic Escherichia coli (APEC) are extra-intestinal pathogenic E. coli, and usually cause avian septicemia through breaching the blood-gas barrier. Type II pneumocytes play an important role of maintaining the function of the blood-gas barrier. However, the mechanism of APEC injuring type II pneumocytes remains unclear. α-cyperone can inhibit lung cell injury induced by Staphylococcus aureus. In order to explore whether α-cyperone regulates the adherence and invasion of APEC-O78 to chicken type II pneumocytes, we successfully cultured chicken type II pneumocytes.
CONCLUSIONS:
The results showed that α-cyperone significantly decreased the adherence of APEC-O78 to chicken type II pneumocytes. In addition, α-cyperone inhibited actin cytoskeleton polymerization induced by APEC-O78 through down regulating the expression of Nck-2, Cdc42 and Rac1. These results provide new evidence for the prevention of colibacillosis in chicken.

J Microbiol Biotechnol. 2012 Aug;22(8):1170-6.

α-cyperone alleviates lung cell injury caused by Staphylococcus aureus via attenuation of α-hemolysin expression.[Pubmed: 22713997]

METHODS AND RESULTS:
In this study, we aimed to evaluate the effect of α- cyperone on S. aureus. We used a hemolysin test to examine the hemolytic activity in supernatants of S. aureus cultured with increasing concentrations of α- cyperone. In addition, we evaluated the production of α- hemolysin (Hla) by Western blotting. Real-time RT-PCR was performed to test the expression of hla (the gene encoding Hla) and agr (accessory gene regulator). Furthermore, we investigated the protective effect of α- cyperone on Hla-induced injury of A549 lung cells by live/ dead and cytotoxicity assays. We showed that in the presence of subinhibitory concentrations of α-cyperone, Hla production was markedly inhibited. Moreover, α- cyperone protected lung cells from Hla-induced injury.
CONCLUSIONS:
These findings indicate that α-cyperone is a promising inhibitor of Hla production by S. aureus and protects lung cells from this bacterium. Thus, α-cyperone may provide the basis for a new strategy to combat S. aureus pneumonia.

J Ethnopharmacol . 2016 Dec 24;194:219-227.

α-Cyperone of Cyperus rotundus is an effective candidate for reduction of inflammation by destabilization of microtubule fibers in brain[Pubmed: 27353867]

Abstract Ethnopharmacological relevance: Cyperus rotundus L. (Cyperaceae), commonly known as purple nutsedge or nut grass is one of the most invasive and endemic weeds in tropical, subtropical and temperate regions. This plant has been extensively used in traditional medicine for anti-arthritic, antidiarrheal and antiplatelet properties as well as treatment for several CNS disorders such as epilepsy, depression and inflammatory disorders. Inflammation is evidently occurring in pathologically susceptible regions of the Alzheimer's disease (AD) brain as well as other disorders. Many cellular processes are responsible in chronic inflammation. Microtubule-based inflammatory cell chemotaxis is a well-recognized process that influences production of cytokines and phagocytosis. The effect of α-Cyperone, one of main ingredients of Cyperus rotundus on microtubule assembly and dynamics has not been examined and is the purpose of this investigation. Materials and methods: Microtubules and tubulin were extracted in order to explore their interaction with α-Cyperone by utilization of turbidimetric examinations, intrinsic fluorescence and circular dichroism spectroscopy (CD) studies. The molecular docking analysis was executed in order to facilitate a more detail and stronger evidence of this interaction. The BINding ANAlyzer (BINANA) algorithm was used to evaluate and further substantiate the binding site of α-Cyperone. Results: It was demonstrated that α-Cyperone had a pronounced influence on the tubulin structure, decreased polymerization rate and reduced concentration of polymerized tubulin in vitro. The CD deconvolution analysis concluded that significant conformational changes occurred, demonstrated by a drastic increase in content of β-strands upon binding of α-Cyperone. The fluorescence spectroscopy revealed that a static type of quenching mechanism is responsible for binding of α-Cyperone to tubulin. Upon characterization of various biophysical parameters, it was further deduced that ligand binding was spontaneous and a single site of binding was confirmed. Transmission electron microscopy revealed that upon binding of α-Cyperone to microtubule the number and complexity of fibers were noticeably decreased. The computational analysis of docking suggested that α-Cyperone binds preferably to β-tubulin at a distinct location with close proximity to the GTP binding and hydrolysis site. The ligand interaction with β-tubulin is mostly hydrophobic and occurs at amino acid residues that are exclusively on random coil. The BINANA 1.2.0 algorithm which counts and tallies close molecular interaction by performing defined set of simulations revealed that amino acid residues Arg 48 and Val 62 have registered the highest scores and are possibly crucial in ligand-protein interaction. Conclusion: α-Cyperone binds and interacts with tubulin and is capable of distinctly destabilizing microtubule polymerization. The effect of this interaction could result in reduction of inflammation which would be highly beneficial for treatment of inflammatory diseases such as AD. Keywords: ATP (PubChem CID: 5957); GTP (PubChem CID: 6830); Microtubule polymerization; Molecular docking; Rhizomes of Cyperus rotundus; Tubulin; α-Cyperone; α-Cyperone (PubChem CID: 6452086).

J Ethnopharmacol. 2013 May 2;147(1):208-14.

α-Cyperone, isolated from the rhizomes of Cyperus rotundus, inhibits LPS-induced COX-2 expression and PGE2 production through the negative regulation of NFκB signalling in RAW 264.7 cells.[Pubmed: 23500883]

The rhizomes of Cyperus rotundus (Cyperaceae) have been used in Asian traditional medicine for the treatment of several inflammatory diseases. However, the anti-inflammatory effects of α-cyperone, a major active compound of Cyperus rotundus, are poorly understood.
METHODS AND RESULTS:
PGE2 and cytokines released from cells were measured using an EIA assay kit. The expression of iNOS, COX-2, TNF-α, and IL-6 was measured by real-time RT-PCR and/or Western blot analysis. A luciferase assay was performed to measure the effect of α-cyperone on NFκB activity. The n-hexane fraction of the 80% EtOH extract from the rhizomes of Cyperus rotundus was found to inhibit both NO and PGE2 production in RAW 264.7 cells. α-Cyperone isolated from the n-hexane fraction significantly inhibited PGE2 production by suppressing the LPS-induced expression of inducible COX-2 at both the mRNA and the protein levels. In contrast, α-cyperone had little effect on NO production and iNOS expression. Additionally, α-cyperone downregulated the production and mRNA expression of the inflammatory cytokine IL-6. Moreover, treatment with α-cyperone suppressed the transcriptional activity of NFκB and the nuclear translocation of the p65 NFκB subunit in LPS-induced RAW 264.7 cells.
CONCLUSIONS:
The anti-inflammatory activity of α-cyperone is associated with the down-regulation of COX-2 and IL-6 via the negative regulation of the NFκB pathway in LPS-stimulated RAW 264.7 cells.

Immunopharmacol Immunotoxicol. 2013 Apr;35(2):215-24.

Xiang-Qi-Tang and its active components exhibit anti-inflammatory and anticoagulant properties by inhibiting MAPK and NF-κB signaling pathways in LPS-treated rat cardiac microvascular endothelial cells.[Pubmed: 23171279 ]

Xiang-Qi-Tang (XQT) is a Chinese herbal formula containing Cyperus rotundus, Astragalus membranaceus and Andrographis paniculata. alpha-Cyperone (CYP), astragaloside IV (AS-IV) and andrographolide (AND) are the three major active components in this formula. XQT may modulate the inflammatory or coagulant responses. We therefore assessed the effects of XQT on lipopolysaccharide (LPS)-induced inflammatory model of rat cardiac microvascular endothelial cells (RCMECs).
METHODS AND RESULTS:
XQT, CYP, AS-IV and AND inhibited the production of tumor necrosis factor alpha (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1), and up-regulated the mRNA expression of Kruppel-like factor 2 (KLF2). XQT and CYP inhibited the secretion of tissue factor (TF). To further explore the mechanism, we found that XQT, or its active components CYP, AS-IV and AND significantly inhibited extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 phosphorylation protein expression as well as decreased the phosphorylation levels of nuclear factor κB (NF-κB) p65 proteins in LPS-stimulated RCMECs. These results suggested that XQT and its active components inhibited the expression of inflammatory and coagulant mediators via mitogen-activated protein kinase (MAPKs) and NF-κB signaling pathways.
CONCLUSIONS:
These findings may contribute to future research on the action mechanisms of this formula, as well as therapy for inflammation- or coagulation-related diseases.