Down-regulation of interlinked inflammatory signalling cascades by ethanolic extract of Suaeda fruticosa Forssk. ex J.F. Gmel. attenuated in vivo inflammatory and nociceptive responses

Abstract

Juice and decoction of leaves of Suaeda fruticosa, a halophytic medicinal plant of Cholistan desert, is traditionally used to treat rheumatism. The current study was carried out to probe into in vivo anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of the whole plant of S. fruticosa (Et-SF) and its bioactive molecules. GC-MS screening of Et-SF revealed presence of various bioactive compounds including phytol, thymol, n-hexadecanoic acid, farnesol, and 1-heptacosanol. DPPH in vitro radical scavenging assay demonstrated moderate antioxidant potential of Et-SF. Safety evaluation of Et-SF confirmed no lethal effects in female albino rats up to the single oral dose of 5000 mg/kg. In all in vivo models, Et-SF was administered in three doses (125, 250, and 500 mg/kg) and a single dose of flurbiprofen (FP) (10 mg/kg). Et-SF significantly (p < 0.05) attenuated acute inflammation in carrageenan, histamine, and serotonin-induced rat paw oedema models in a time-dependent manner. Et-SF alleviated oedema, restored haematological parameters, and reduced severe pannus formation, inflammatory cell infiltration, and fibrous tissue proliferation in the paws of CFA-induced arthritic rats. Moreover, treatment with thymol, farnesol and n-hexadecanoic acid alone and in combination also attenuated the arthritic progression in the arthritic rats indicating involvement of these compounds towards anti-arthritic potential of Et-SF. Et-SF and FP significantly (p < 0.05) down-regulated IL-1β, TNF-α, IL-6, NF-κB, and COX-2 mRNA expression, and up-regulated IL-4 and IL-10 mRNA expression in arthritic rats. Hot plate and acetic acid-induced writhing models results indicated the analgesic attributes of Et-SF in mice models. This study suggests that S. fruticosa ethanol extract may regulate the expression of inflammatory markers involved in nociceptive, inflammatory, and arthritic disorders. Its phytochemicals could target multiple phases of these conditions at cellular and subcellular levels. Further research is needed to confirm this hypothesis.

Keywords: Suaeda fruticosa; Arthritic disorder; Complete Freund’s adjuvant; Flurbiprofen; GC–MS; Nocioceptive responses.