Neuroprotective Effect of Swertiamain on Cerebral Ischemia/Reperfusion Injury by Inducing the Nrf2 Protective Pathway

Abstract

Oxidative stress plays a vital role in the development of cerebral ischemic/reperfusion (I/R). Targeting oxidative stress is proposed to be an effective strategy to treat cerebral I/R injury. Gentiana macrophylla Pall is reported to have a potential protective effect against stroke. Swertiamarin (Swe), an active secoiridoid glycoside compound isolated from Gentiana macrophylla Pall, has been reported to possess antioxidative potential. This study is to explore whether Swe could prevent brain from I/R injury, and the related mechanisms of oxidative stress are also elucidated using mice middle cerebral artery occlusion (MCAO) model and primary hippocampal neurons oxygen-glucose deprivation/reperfusion (OGD/R) model. Swe (25, 100, or 400 mg/kg) was pretreated intraperitoneally for 7 days until establishment of the MCAO model, while hippocampal neurons were maintained in Swe (0.1, 1, or 10 μM) in the entire process of reoxygenation. The results indicated that Swe pretreatment markedly decreased infarct volume, apoptotic neurons, and oxidative damage and promoted neurologic recovery in vivo. It also decreased reactive oxygen species (ROS) and increased cell viability in vitro. Western blot analyses and immunofluorescence staining demonstrated that Swe pretreatment promoted Nrf2 nuclear translocation from Keap1-Nrf2 complex and enhanced the expressions of NAD­(P)­H: quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) both in vivo and in vitro, while the expressions could be reversed by a Nrf2 inhibitor. The binding mode of Keap1 with Swe was also proposed by covalent molecular docking. Collectively, Swe could be considered as a promising protective agent against cerebral I/R injury through suppressing oxidative stress by activation of the Nrf2 protective pathway.

Protective effect of microRNA‑340‑5p against oxygen‑glucose deprivation/reperfusion in PC12 cells through targeting neuronal differentiation 4

“…in the present study, Pc12 cells that received oGd/r served as the cellular model, which has been used in numerous previous studies (24,25,34,35). consistent with the previous studies, the cell apoptotic rate, the inflammatory status and NO levels were increased following oGd/r induction, indicating that the cellular model was successfully established (36,37). in a previous study, the expression levels of mir-340-5p were rapidly decreased in the peripheral blood of patients who had suffered from an acute ischemic stroke, which indicated a potentially protective role for mir-340-5p in ischemic stroke (22).…”

Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC

“…The results obtained for catalposide are similar to those reported by Moon et al Catalpol, another glycosylated iridoid, showed a protective effect against oxidative stress induced by H 2 O 2 in a primary astrocyte culture 58 . Wang et al evaluated the Nrf2-mediated neuroprotective capacity of swertiamarin, a glycosylated secoiridoid, and reported increases in the levels of the antioxidant proteins NQO1 and HMOX-1 in addition to an increase in the Nrf2 protein at the nuclear level 59 . The only report of the protective effects of specioside was made by Asthana et al, in which the ability of the compound to modulate antioxidant enzymes such as CAT and SOD was evaluated in a Caenorhabditis elegans model 60 .…”

Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC

“…The results obtained for catalposide are similar to those reported by Moon et al Catalpol, another glycosylated iridoid, showed a protective effect against oxidative stress induced by H 2 O 2 in a primary astrocyte culture 60 . Wang et al evaluated the Nrf2-mediated neuroprotective capacity of swertiamarin, a glycosylated secoiridoid, and reported increases in the levels of the antioxidant proteins NQO1 and HMOX-1 in addition to an increase in the Nrf2 protein at the nuclear level 61 . The only report of the protective effects of specioside was made by Asthana et al, in which the ability of the compound to modulate antioxidant enzymes such as CAT and SOD was evaluated in a Caenorhabditis elegans model 62 .…”