Inhibition of Nitric Oxide Production in BV2 Microglial Cells by Triterpenes from Tetrapanax papyriferus

Abstract

Abstract:It is well known that activated microglia produce nitric oxide (NO), which has an important role in the pathophysiology of several neurodegenerative diseases such as Alzheimer's disease. In the course of searching for novel therapeutic agents from medicinal plants against neuroinflammatory diseases, the methanolic extract of Tetrapanax papyriferus was found to have significant NO inhibitory activity in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Nine oleanane-type triterpenes, including two new compounds, epipapyriogenin C-3-O-β-D-glucopyranoside (6) and 11-O-butylpapyrioside LIIc (9), were isolated from the leaves and stems of Tetrapanax papyriferus. The structures of these compounds were elucidated with 1D-and 2D-NMR and MS data. Among these ∆ 11,13 oleanane-type triterpenes, compound 3 showed significant NO inhibitory activity in BV-2 cells, reducing the LPS-induced expression of COX-2 and pro-inflammatory cytokines such as TNF-α and IL-6. Compounds 7 and 9 also showed NO inhibitory activities among the ∆ 12 oleanane-type triterpene saponins. These results show that oleanane-type triterpenes isolated from T. papyriferus could be a potential natural resource of NO inhibitors used in the treatment of neurodegenerative disorders.

Oleanolic Acid Exerts a Neuroprotective Effect Against Microglial Cell Activation by Modulating Cytokine Release and Antioxidant Defense Systems

“…Papyriogenin D, an oleanane-type triterpene isolated from Tetrapanax papyriferus, showed significant NO inhibitory activity in BV2 cells, reducing the LPS-induced expression of COX-2 and proinflammatory cytokines, such as TNF-α and IL-6 [60]. Likewise, Liu et al [61] reported that pretreatment of BV2 cells with paroxetine significantly inhibited the LPS-induced production of NO, as well as TNF-α and IL-1β.…”

Pyridine alkaloids with activity in the central nervous system

“…Nitric oxide (NO) is a membrane-permeable gas that acts as a neuromodulator at the synaptic junctions. 135 High levels of NO will result in oxidative stress and hence neuronal inflammation in the CNS, a condition thought to play a role in neurodegenerative diseases (e.g. AD and Parkinson’s disease).…”

“…AD and Parkinson’s disease). 135 The neuroprotective properties of euphorbialoids A–J and analogues 1 – 2 were investigated by evaluating their inhibitory activity on lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells. 133 Euphorbialoids A–J and their unnamed congeners 1 and 2 inhibited the production of NO to varying degrees in microglial BV-2 cells when compared with 2-methyl-2-thiopseudourea sulfate (positive control; 13.2 µM), 133 suggesting that these alkaloids represent therapeutic leads for the treatment of neurodegenerative diseases.…”

Therapeutic Effect of Tetrapanax papyriferus and Hederagenin on Chronic Neuropathic Pain of Chronic Constriction Injury of Sciatic Nerve Rats Based on KEGG Pathway Prediction and Experimental Verification

“…ere is a series of related studies about these two drugs. Namki found that triterpenes from Tetrapanax papyriferus reduced the LPSinduced expression of proinflammatory cytokines, such as TNF-α and IL-6, and could be a potential natural resource of NO inhibitors used in the treatment of neurodegenerative disorders [10]. Kim showed increased expression of the apoptosis-associated protein, Bcl-2, and decreased expression of Bax and p53 after treatment with hederagenin, and hederagenin treatment attenuated ethanol-induced increases in activated p38 MAPK and increased the levels of phosphorylated AKT and ERK [11].…”