Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury?

Abstract

Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining) and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

“…To investigate whether tan IIA treatment ameliorates learning and memory deficits in APP/PS1 mice, open-field test, Y-maze test, and MWM test were performed. The open-field test is mostly used to evaluate the exploration and anxiety-related behaviors in laboratory animals [ 31 ]. Compared with the WT group, APP/PS1 mice showed anxiety and less movement in exploring the central zone as indicated by less time spent in the center, fewer numbers of central entries, and shorter distance in the center.…”

Modulation of Nerve Cell Differentiation: Role of Polyphenols and of Contactin Family Components

“…On a mechanistic ground, these effects may be related to the polyphenols antioxidant activity (Lalkovièová and Danielisová, 2016), thus supporting the ability of such compounds and of the downstream pathways to exert neurotrophic effects (Moosavi et al, 2015). In this respect, a typical example is provided by grape seed polyphenols (GSP), whose ability to promote neural regeneration has been demonstrated in different studies (He et al, 2017; Renno et al, 2017; Ruzicka et al, 2018), as specifically shown in the case of the developmental events of cochlear hair cells (Gu et al, 2015). The polyphenol antioxidant activity may therefore represent a relevant and appropriate therapeutic tool toward the mentioned conditions (Abolhassani et al, 2017; Ahmed et al, 2017; Aguilera et al, 2018).…”

AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function

“…The open field test measures novelty-induced locomotion and anxiety-like behavior ( Ruzicka et al, 2018 ). In this test, mice injected with shRNA-TRPC6 showed a significant increase in the distance traveled compared to mice in the shRNA-control group ( Figures 5A,B,E ), suggesting that mice injected with shRNA-TRPC6 display increased levels of novelty-induced locomotion.…”