Bioassay directed isolation of a novel anti-inflammatory cerebroside from the leaves of Aerva sanguinolenta

This paper attempts to evaluate the anti-inflammatory potential and the possible mechanism of action of the leaf extracts and isolated compound(s) of Aerva sanguinolenta (Amaranthaceae), traditionally used in ailments related to inflammation. The anti-inflammatory activity of ethanol extract (ASE) was evaluated by acute, subacute and chronic models of inflammation, while a new cerebroside (‘trans’, ASE-1), isolated from the bioactive ASE and characterized spectroscopically, was tested by carrageenan-induced mouse paw oedema and protein exudation model. To understand the underlying mechanism, we measured the release of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin (PG)E2, along with the cytokines like tumour necrosis factor (TNF)-α, and interleukins(IL)-1β, IL-6 and IL-12 from lipopolysaccharide (LPS)-stimulated peritoneal macrophages. The results revealed that ASE at 400 mg/kg caused significant reduction of rat paw oedema, granuloma and exudative inflammation, while the inhibition of mouse paw oedema and exudative inflammation by ASE-1 (20 mg/kg) was comparable to that of the standard drug indomethacin (10 mg/kg). Interestingly, both ASE and ASE-1 showed significant inhibition of the expressions of iNOS2 and COX-2, and the down-regulation of the expressions of IL-1β, IL-6, IL-12 and TNF-α, in LPS-stimulated macrophages, via the inhibition of COX-2-mediated PGE2 release. Thus, our results validated the traditional use of A. sanguinolenta leaves in inflammation management.