3‐Acetyl‐11‐keto‐β‐boswellic acid attenuated oxidative glutamate toxicity in neuron‐like cell lines by apoptosis inhibition. Issue 2 (23rd October 2019)

• Record Type: Journal Article
• Authors: Rajabian, Arezoo; Sadeghnia, Hamid Reza; Hosseini, Azar; Mousavi, Seyed Hadi; Boroushaki, Mohammad Taher
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 2(2020)
• Page Start: 1778
• Page End: 1789
• Publication Date: 2019-10-23
• Subjects: 3‐acetyl‐11‐keto‐β‐boswellic acid (AKBA) -- cytotoxicity -- DNA injury -- glutamate -- neuroprotection -- programmed cell death; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29413
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: 3‐Acetyl‐11‐keto‐β‐boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate‐induced neuronal injury. To investigate the effects of AKBA (2.5‐10 µM) on glutamate injury in neuron‐like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a ( P < .001). However, AKBA (2.5‐10 µM) enhanced the cell viability in both treatment regimens ( P < .001). Also co‐ and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury ( P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen ( P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate‐induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl‐2 and cleaved‐caspase‐3 proteins, concentration‐dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate‐induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death. Abstract : 1. Glutamate neurotoxicity was accompanied by intracellular reactive oxygen species elevation. 2. 3‐Acetyl‐11‐keto‐β‐boswellic acid (AKBA) could protect the neuronal cells against oxidative injury and apoptosis. 3. AKBA attenuated apoptosis through restoring the Bax/Bcl2 and caspase‐3. 4. AKBA potentially possesses neuroprotective activity against glutamate toxicity. 5. Protective efficacy of AKBA in neurodegeneration.