Diosgenin inhibits superoxide generation in FMLP-activated mouse neutrophils via multiple pathways. (December 2014)

• Record Type: Journal Article
• Authors: Lin, Y.; Jia, R.; Liu, Y.; Gao, Y.; Zeng, X.; Kou, J.; Yu, B.
• Is Part Of: Free radical research. Volume 48:Number 12(2014:Dec.)
• Page Start: 1485
• Page End: 1493
• Publication Date: 2014-12
• Subjects: Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.3109/10715762.2014.966705
• Languages: English
• ISSNs: 1071-5762

Abstract

<abstract> <title>Abstract</title> <p>Diosgenin possesses anti-inflammatory and anticancer properties. Activated neutrophils produce high concentrations of the superoxide anion which is involved in the pathophysiology of inflammation-related diseases and cancer. In the present study, the inhibitory effect and possible mechanisms of diosgenin on superoxide generation were investigated in mouse bone marrow neutrophils. Diosgenin potently and concentration-dependently inhibited the extracellular and intracellular superoxide anion generation in Formyl-Met-Leu-Phe (FMLP)- activated neutrophils, with IC<sub>50</sub> values of 0.50 ± 0.08 μM and 0.66 ± 0.13 μM, respectively. Such inhibition was not mediated by scavenging the superoxide anion or by a cytotoxic effect. Diosgenin inhibited the phosphorylation of p47phox and membrane translocation of p47phox and p67phox, and thus blocking the assembly of nicotinamide adenine dinucleotide phosphate oxidase. Moreover, cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were also effectively increased by diosgenin. It attenuated FMLP-induced increase of phosphorylation of cytosolic phospholipase A (cPLA<sub>2</sub>), p21-activated kinase (PAK), Akt, p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK). Our data indicate that diosgenin exhibits inhibitory effects on superoxide anion production through the blockade of cAMP, PKA, cPLA<sub>2</sub>, PAK, Akt and MAPKs signaling pathways. The results may explain the clinical implications of diosgenin in the treatment of inflammation-related disorders.</p> </abstract>