Cudratricusxanthone A Protects Mouse Hippocampal Cells against Glutamate-Induced Neurotoxicity via the Induction of Heme Oxygenase-1

Abstract

Cudratricusxantone A (CTXA), isolated from the roots of Cudrania tricuspidata Bureau (Moraceae), has potent hepatoprotective, antiproliferative, and monoamine oxidase inhibitory effects. In this study, we examined whether CTXA could protect HT22-immortalized hippocampal cells against glutamate-induced oxidative stress through the induction of heme oxygenase (HO)-1 expression. CTXA induced the expression of HO-1 and increased HO activity dose- and time-dependently. CTXA also suppressed glutamate-induced ROS generation in HT22 cells. Interestingly, treatment of neuronal cells with CTXA enhanced cellular resistance to glutamate oxidative stress. The protective effect of CTXA was abrogated by tin protoporphyrin IX, an HO inhibitor. In addition, treatment with the HO-1 inducer, cobalt protoporphyrin IX, and bilirubin, one of the enzymatic products of HO-1, produced comparable protection. These results demonstrate that CTXA protects neuronal cells from glutamate-induced oxidative stress via the induction of HO-1.

Sauchinone Suppresses Pro-inflammatory Mediators by Inducing Heme Oxygenase-1 in RAW264.7 Macrophages

“…(Saururaceae) has been traditionally used for the treatment of various diseases such as beriberi, pneumonia, urinary disorders, jaundice and gonorrhea. In Korea this plant is a known folk medicine, used for the treatment of edema.11) Sauchinone, a biologically active lignan isolated from the roots of S. chinensis, exibits various pharmacological activities, including hepatoprotective, antiinflammatory, cytoprotective and immunosuppressive effects.12-16) Moreover, several published studies demonstrate the inhibitory effect of sauchinone on LPS-induced expression of iNOS, iNOS-derived nitric oxide, TNF-a and COX-2 in murine macrophages.12,17) As a part of our ongoing research to identify phytochemicals isolated from natural sources that can induce HO-1 in vitro, 18,19) sauchinone was shown significantly induce the levels of HO-1 in RAW264.7 macrophages. In this study, we demonstrate that the effects of sauchinone on lipopolyscharride (LPS)-induced PGE 2 , NO, TNF-a and IL-1b production were partially reversed by the HO-1 inhibitor tin protoporphyrin.…”

“…12,17) As a part of our ongoing research to identify phytochemicals isolated from natural sources that can induce HO-1 in vitro, 18,19) sauchinone was shown significantly induce the levels of HO-1 in RAW264.7 macrophages. In this study, we demonstrate that the effects of sauchinone on lipopolyscharride (LPS)-induced PGE 2 , NO, TNF-a and IL-1b production were partially reversed by the HO-1 inhibitor tin protoporphyrin.…”

“…[12][13][14][15][16] Moreover, several published studies demonstrate the inhibitory effect of sauchinone on LPS-induced expression of iNOS, iNOS-derived nitric oxide, TNF-a and COX-2 in murine macrophages. 12,17) As a part of our ongoing research to identify phytochemicals isolated from natural sources that can induce HO-1 in vitro, 18,19) sauchinone was shown significantly induce the levels of HO-1 in RAW264.7 macrophages. In this study, we demonstrate that the effects of sauchinone on lipopolyscharride (LPS)-induced PGE 2 , NO, TNF-a and IL-1b production were partially reversed by the HO-1 inhibitor tin protoporphyrin.…”

Cytoprotective Constituents of the Heartwood of <i>Caesalpinia sappan</i> on Glutamate-Induced Oxidative Damage in HT22 Cells

“…HO-1, an important enzyme that contributes to the cytoprotective response, is considered to be an adaptive and protective response against oxidative insult in a wide variety of cells, 24,26) including neuronal cells such as HT22. 11,27) In addition, nuclear translocation of Nrf2 is required for expression of HO-1, a phase 2 detoxifying and antioxidant enzyme. 28,29) Furthermore, it has previously been reported that the MAPK pathways play a regulatory role in HO-1 gene expression.…”

“…Several studies have reported that the activation of the MAPK pathways contributes to the induction of HO-1. 26,27) Therefore, we examined the effect of compound 2 on activation of MAPKs in HT22 cells. Cells were exposed to compound 2, total protein was harvested, and then Western blots were performed using anti-phospho-c-Jun NH 2 -terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 antibodies.…”