The effects of hydro-ethanolic extract of Capparis spinosa (C. spinosa) on lipopolysaccharide (LPS)-induced inflammation and cognitive impairment: Evidence from in vivo and in vitro studies

Abstract

Ethnopharmacological relevance: Capparis spinose (C. spinosa) belonging to Capparaeae, originates from dry areas in the west or central Asia and Mediterranean basin. For thousands of years, C. spinosa has been reported to be used as a therapeutic traditional medicine to relieve various ailments including rheumatism, pain and inflammatory diseases.

Aim of the study: There are several studies mentioning that systemic inflammation results in learning and memory impairments through the activation of microglia. The objective of this study was to investigate the effect of C. spinosa on both in vivo and in vitro models of neuroinflammation and cognitive impairment using lipopolysaccharide (LPS).

Materials and methods: In vivo: 40 male rats were used in the present study. Cognitive impairment was induced using LPS (1 mg/kg/d; i.p.) for 4 weeks. Treatment with C. spinosa (100 and 300 mg/kg/d; p.o.) was performed 1 h before LPS administration. At the end of the experiment, rats were undergone for behavioral and biochemical analysis. In vitro: Primary microglia isolated from mouse was used in the present study. The cells were pretreated with C. spinosa extract (10-300 μg/ml) and then stimulated with LPS (1 μg/ml). The expression levels of inflammatory and anti-inflammatory cytokines were elucidated using Real-Time PCR and ELISA methods.

Results: The escape latency in the Morris water maze test in the LPS group was significantly greater than the control group (p < 0.001), while, in extract-treated groups, it was less than the LPS group (p < 0.001). Additionally, we found that the levels of IL-1β, TNF-α, and iNOS/Arg-1 ratio was also significantly lower in extract-treated groups than the LPS group (p < 0.001). The results revealed that C. spinosa extract significantly reduced the levels of TNF-α, iNOS, COX-2, IL-1β, IL-6, NO and PGE2, and the ratios of iNOS/Arg-1 and NO/urea, following the LPS-induced inflammation in microglia (p < 0.001).

Conclusions: Our finding provides evidence that C. spinosa has a neuroprotective effect, and might be considered as an effective therapeutic agent for the treatment of neurodegenerative diseases that are accompanied by microglial activation, such as AD.

Keywords: Capparis spinosa; Cognitive impairment; Inflammation; LPS; M1/M2; Microglia.