Protective effect of coconut water concentrate and its active component shikimic acid against hydroperoxide mediated oxidative stress through suppression of NF-κB and activation of Nrf2 pathway

Abstract Ethnopharmacological relevance Conventionally coconut water has been used as an ‘excellent hydrating’ drink that maintain the electrolyte balance and help in treating diverse ailments related to oxidative stress including liver function. The present study was aimed to elucidate whether and how the coconut water concentrate (CWC) and its major active phytoconstituent shikimic acid (SA) can effectively protect murine hepatocytes from the deleterious effect of hydroperoxide-mediated oxidative stress. Materials and methods Bioactivity guided fractionation of CWC resulted in the isolation of a couple of known compounds. Freshly isolated murine hepatocytes were exposed to hydrogen peroxide (H 2 O 2 ) (1 and 3 mM) in the presence or absence of CWC (200 and 400 μg/ml) and SA (40 μM) for the determination of antioxidative, DNA protective, cellular ROS level by modern methods, including immunoblot and flowcytometry to find out the possible mechanism of action. Results Pre-treatment of hepatocyte with CWC and SA showed significant prevention of H 2 O 2 -induced intracellular ROS generation, nuclear DNA damage along with the formation of hepatic TBARS and cellular nitrite. Further, the H 2 O 2 induced cell death was arrested in the presence of CWC through the inhibition of CDC42 mediated SAPK/JNK pathways and activation of other molecules of apoptotic pathways, including Bax and caspase3. Moreover, CWC and SA help in maintaining the GSH level and endogenous antioxidants like Mn-SOD, to support intracellular defense mechanisms, probably through the transcriptional activation of Nrf2; and inhibition of nuclear translocation of NF-κB. Conclusion CWC and its active components SA reversed the H 2 O 2 induced oxidative damage in hepatocytes, probably through the inhibition of NF-κB, with the activation of PI3K/Akt/Nrf2 pathway and reduction of apoptosis by interfering the SAPK/JNK/Bax pathway.