Anti-apoptotic mechanism of Bacoside rich extract against reactive nitrogen species induced activation of iNOS/Bax/caspase 3 mediated apoptosis in L132 cell line

Abstract

Nitric oxide is a highly reactive free radical gas that reacts with a wide range of biomolecules to produce reactive nitrogen species and exerts nitrative stress. Bacopa monniera is a traditional folk and ayurvedic medicine known to alleviate a variety of disorders. Aim of the present study is to evaluate the protective propensity of Bacopa monniera extract (BME) through its oxido-nitrosative and anti-apoptotic mechanism to attenuate sodium nitroprusside (SNP)-induced apoptosis in a human embryonic lung epithelial cell line (L132). Our results elucidate that pre-treatment of L132 cells with BME ameliorates the mitochondrial and plasma membrane damage induced by SNP as evidenced by MTT and LDH leakage assays. BME pre-treatment inhibited NO generation by down-regulating inducible nitric oxide synthase expression. BME exhibited potent antioxidant activity by up-regulating the antioxidant enzymes. SNP-induced damage to cellular, nuclear and mitochondrial integrity was also restored by BME, which was confirmed by ROS estimation, comet assay and mitochondrial membrane potential assays respectively. BME pre-treatment efficiently attenuated the SNP-induced apoptotic biomarkers such as Bax, cytochrome-c and caspase-3, which orchestrate the proteolytic damage of the cell. By considering all these findings, we report that BME protects L132 cells against SNP-induced toxicity via its free radical scavenging and anti-apoptotic mechanism.

Comparative evaluation of four triterpenoid glycoside saponins of bacoside A in alleviating sub-cellular oxidative stress of N2a neuroblastoma cells

“…Moreover, increases in the intensity of Rh‐123 in different cells, post treatment with bacoside, were also observed indicating its ability to restore mitochondrial membrane potential. Role of bacoside A and its components on restoring mitochondrial membrane potential (MMP) is scantily documented . The study is even more important in the light of significance of bacoside A and its components and absence of any detailed analysis on the role of individual bacoside in regulating MMP.…”

“…Amongst four individual bacoside and their mixture, bacoside A3 and bacopaside II have shown around 2‐fold increased cell viability compare with stressed cells (Figure ). Previous studies have reported cytoprotective activity of bacosides rich extract against H 2 O 2 ‐induced cell mortality . Collectively, this study suggests that bacoside A components and bacoside mixture may be used as a neuroprotective compound with optimized dose having bacoside of specified concentration.…”

“…Role of bacoside A and its components on restoring mitochondrial membrane potential (MMP) is scantily documented. [18,19] The study is even more important in the light of significance of bacoside A and its components and absence of any detailed analysis on the role of individual bacoside in regulating MMP. Further, effect of bacoside A components on intracellular ROS was compared and all four bacoside and their mixture responded differently at 0.4 mg/ml concentration on H 2 O 2 stressed neuronal cell line.…”

“…superoxide dismutase, catalase and glutathione peroxidases in the neuronal cells . Bacosides‐rich extracts were evaluated for their anti‐apoptotic and cytoprotective properties on neuronal and lung epithelial cell lines . Existing studies had provided extensive documents on nootropic properties of B. monnieri but lack information on the role of four different bacoside A components in alleviating progression of neuronal diseases .…”

“…[16,17] Bacosides-rich extracts were evaluated for their anti-apoptotic and cytoprotective properties on neuronal and lung epithelial cell lines. [18,19] Existing studies had provided extensive documents on nootropic properties of B. monnieri but lack information on the role of four different bacoside A components in alleviating progression of neuronal diseases. [20] The lack of validation guidelines in most of the countries including developing nations like India also necessitates the need of analysing the role of bacoside A components for better efficacy towards neurological disorder.…”