Terminalia chebula Extract Protects OGD-R Induced PC12 Cell Death and Inhibits LPS Induced Microglia Activation

Abstract

Abstract:Terminalia chebula, native to Southeast Asia, is a popular medicinal plant in Ayurveda. It has been previously reported to have strong antioxidant and anti-inflammatory efficacy. In this study, we aimed to investigate if fruit extract from T. chebula might protect neuronal cells against ischemia and related diseases by reduction of oxidative damage and inflammation in rat pheochromocytoma cells (PC12) using in vitro oxygen-glucose deprivation followed by reoxygenation (OGD-R) ischemia and hydrogen peroxide (H 2 O 2 ) induced cell death. Cell survival was evaluated by a 2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Free radical scavenging, lipid peroxidation and nitric oxide inhibition were measured by diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid (TBA) and Griess reagent, respectively. We found that T. chebula extract: (1) increases the survival of cells subjected to OGD-R by 68%, and H 2 O 2 by 91.4%; (2) scavenges the DPPH free radical by 96% and decreases malondialdehyde (MDA) levels from 237.0 ± 15.2% to 93.7 ± 2.2%; (3) reduces NO production and death rate of microglia cells stimulated by lipopolysaccharide (LPS). These results suggest that T. chebula extract has the potential as a natural herbal medicine, to protect the cells from ischemic damage and the possible mechanism might be the inhibition of oxidative and inflammatory processes.

Evaluation of Terminalia chebula Extract for Anti-Arthritic Efficacy and Safety in Osteoarthritic Dogs

“…Chebulagic acid and chebulinic acid are the major constituents and their chemical structures are shown in Figure 6. In experimental and human studies, TCE and its components have been shown to exert antioxidant, anti-inflammatory and analgesic activities, thereby exerting anti-arthritic effects [72][73][74][75][76][77][78][79][80][81][82]. Das et al [83] demonstrated that gallic acid in TCE inhibited NF-κB activity, suggesting its potential for anti-inflammatory activity.…”

Polyphenol Ellagic Acid-Targeting To Brain: A Hidden Treasure

“…T. Chebula extract has protective effectsagainst in-vitro experiment where oxygen-glucose deprivation followed by reoxygenation (OGD-R) ischemia and hydrogen peroxide (H2O2) induced cell death on PC12 cells. T. chebula extract showed the diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and reduced H2O2-induced MDA production where DPPH radical scavenging activity of T. chebula is mostly related to the hydroxyl group in ellagic acid [91]. Moreover, Ellagitannins produces hexa-hydroxydiphenic acid (HHDP) on ester bonds hydrolysis with acids or bases, which rearranges spontaneously to produce Ellagic acid [45] .…”

“…The activation of the primary microglia is one of the major reasons of cellular inflammation in ischemic condition. Terminalia chebula extract reduced LPS induced cell death and inhibited the production of NO by BV2 cellsin Lipopolysaccharide activated microglia cells (BV2 cell) and reduce cellular inflammation [91] . Pomegranates extract feeding improved behavioral performance in APP/PS1 mice, which correlated with decreased microgliosis, nuclear factor of activated T-cell c2 (NFATc2) activity, and brain TNF-α concentration.…”

“…The association between inflammation and AD manifests itself through (1) the presence of activated microglia surrounding senile plaques and (2) higher levels of inflammatory mediators in the brains of AD patients versus age-matched controls [5,101,102] . Oxidative damage due to the ROS/RNS play the vital role to initiate a wide range of intracellular stress signaling processes that culminate in excessive cytokine such as inducible COX-2 and iNOS and adhesion molecule as intracellular adhesion molecule (ICAM)-1 and E-andP-selectins upregulation [91,103] . Neuroinflammatory processes have been shown to have a fundamental role in the pathogenesis of neurodegenerative disorders like Alzheimer's disease (AD) [104] .…”

Pharmacological screening of Polygonaceae species and isolation of biologically active compounds from Rumex aquaticus L. and Rumex thyrsiflorus Fingerh.

“…This model is a robust and validated model for preliminary screening of neuroprotective agents. [150][151][152] Plant-derived flavonoids belong to the broader class of polyphenolic compounds, which are purported to have salutary effects in various disease states. 153 What makes flavonoids a fascinating class of molecules is that, in addition to their chemical diversity and abundance in natural sources, their pharmacological effects are also multi-faceted.…”