Ashwagandha ( Withania somnifera) supercritical CO 2 extract derived withanolides mitigates Bisphenol A induced mitochondrial toxicity in HepG2 cells

Abstract

Bisphenol A (BPA) safety aspects on human health are debated extensively for long time. In the present study, we have studied the toxicity induced by BPA at no observed adverse effect level (NOAEL) using HepG2 cells. We report that BPA at 100 nM induced cytotoxicity to HepG2 cells as determined by MTT assay at 0–72 h. The toxicity was result of reduced oxygen consumption and reduced mitochondrial membrane potential associated with decreased ATP production. The BPA treatment resulted in increase of malondialdehyde (MDA) content with decreased glutathione and other antioxidant enzymes. BPA derived toxicity is a concern to human health and alternative non-toxic natural products/derivatives or adjuvants that serve as antidote will be relevant. In this context, Ashwagandha (Withania somnifera) a widely used herb to treat arthritis, rheumatism and to improve longevity for time immemorial is investigated for its antidote effect. Ashwagandha supercritical CO2 extract derived Withanolides (ADW) at 100 μg/ml protect HepG2 cells from BPA induced toxicity by suppressing mitochondrial damage and increased ATP production. Further, cellular MDA content was significantly suppressed with increased non-enzymic and antioxidant enzyme activities. These findings derived from the present study suggest the beneficial effect of ADW in mitigating BPA induced mitochondrial toxicity in HepG2 cells.

Neuroprotective effects of Withania somnifera in the SH-SY5Y Parkinson cell model

“…Interestingly, pre-treatment of SH-SY5Y cells with KSM-66 followed by 6-OHDA treatment was able to lower protein glutathionylation within the cells ( Figure 7 ). These results are in agreement with earlier reports on Ashwagandha extract mediated inhibition of glutathionylation formation in in vitro and in vivo studies ( Sood et al., 2018 ; Vidyashankar et al., 2014 ). It has been reported that a mechanism for Ashwagandha protection of neuronal cells was through activation of the Nrf2 pathway ( Hybertson et al., 2019 ; Priyandoko et al., 2011 ).…”

“…Whereas, post-treatment of KSM-66 restored peroxidase activity at 0.5 and 1 mg/ml ( Figure 5 D) showing that KSM-66 increased peroxidase activity in neuronal cells under oxidative stress. In agreement with previous reports in HepG2 and striatum cells, glutathione peroxidase activities were replenished by Ashwagandha under oxidative stress ( Ahmad et al., 2005 ; Vidyashankar et al., 2014 ).…”

“…Cell viability increased in SH-SY5Y cells treated with 6-OHDA for both post and pre-treatment with KSM-66 ( Figure 3 C and F) suggesting that KSM-66 had both protective and therapeutic effects in cells exposed to oxidative stress. The results obtained from this study supported previous reports showing the neuroprotective effects of Ashwagandha extract in both in vitro and in vivo studies ( Prakash et al., 2014 ; Saykally et al., 2017 ; Vidyashankar et al., 2014 ). Root extract of Ashwagandha decreased Bisphenol A (BPA) toxicity in HepG2 cells and increased ATP production ( Vidyashankar et al., 2014 ).…”

“…The results obtained from this study supported previous reports showing the neuroprotective effects of Ashwagandha extract in both in vitro and in vivo studies ( Prakash et al., 2014 ; Saykally et al., 2017 ; Vidyashankar et al., 2014 ). Root extract of Ashwagandha decreased Bisphenol A (BPA) toxicity in HepG2 cells and increased ATP production ( Vidyashankar et al., 2014 ). Alcoholic extract and water extract of Ashwagandha increased human neuroblastoma and rat glioblastoma cell viability exposed to H 2 O 2 by 20–30%.…”

“…catalase, ascorbate peroxidase, peroxidase, glutathione transferase, glutathione peroxidase, monodehydroascorbate reductase in vivo and in vitro ( Ahmed et al., 2018 ; Mishra et al., 2014 ; Sabina et al., 2013 ). W. somnifera has also been reported to inhibit mitochondrial damage and increase ATP production ( Vidyashankar et al., 2014 ). The use of W. somnifera extracts demonstrated the neuroprotective effects of W. somnifera against 6-hydroxydopamine (6-OHDA) induced Parkinsonism in rats ( Ahmad et al., 2005 ).…”