Withania somnifera Extract Protects Model Neurons from In Vitro Traumatic Injury

Abstract

Withania somnifera has been used in traditional medicine for a variety of neural disorders. Recently, chronic neurodegenerative conditions have been shown to benefit from treatment with this extract. To evaluate the action of this extract on traumatically injured neurons, the efficacy of W. somnifera root extract as a neuroprotective agent was examined in cultured model neurons exposed to an in vitro injury system designed to mimic mild traumatic brain injury (TBI). Neuronal health was evaluated by staining with annexin V (an early, apoptotic feature) and monitoring released lactate dehydrogenase activity (a terminal cell loss parameter). Potential mechanisms underlying the observed neuroprotection were examined. Additionally, morphological changes were monitored following injury and treatment. Although no differences were found in the expression of the antioxidant transcription factor nuclear factor erythroid 2-like 2 (Nrf2) or other Nrf2-related downstream components, significant changes were seen in apoptotic signaling. Treatment with the extract resulted in an increased length of neurites projecting from the neuronal cell body after injury. W. somnifera extract treatment also resulted in reduced cell death in the model neuron TBI system. The cell death factor Bax was involved (its expression was reduced 2-fold by the treatment) and injury-induced reduction in neurite lengths and numbers was reversed by the treatment. This all indicates that W. somnifera root extract was neuroprotective and could have therapeutic potential to target factors involved in secondary injury and long-term sequelae of mild TBI.

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

“…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 ).…”

“…Alcoholic extract and water extract of Ashwagandha increased human neuroblastoma and rat glioblastoma cell viability exposed to H 2 O 2 by 20–30%. In addition, upon cell injury by nitrogen gas pulse, root extract from Ashwagandha decreased LDH levels by 20% compared to injured SH-SY5Y controls ( Saykally et al., 2017 ). Apoptotic pathways in dopaminergic neurons of PD mouse model were inhibited by Ashwagandha.…”

Assessment of the Effects of Stretch-Injury on Primary Rat Microglia

“…Phase-contrast imaging showed that stretch-injury signi cantly reduced process length twelve hours after injury, demonstrating that a deformation event alone can rearrange the cytoskeleton. This is consistent with morphological alteration in neurons (53,54), astrocytes (55), and endothelial (56) cells exposed to stretch-injury. The stretch-induced reduction in process length may contribute to the decreased number of cells migrated into the exclusion zone.…”

Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation

“…CM-LPS-treated neuronal cultures with ASH-WEX and FIV supplementation showed high percentage of the viable cells and restoration of neurite outgrowth. A recent report by Saykally et al (2017) also showed that treatment of cultured traumatic brain injury (TBI) model neurons with Withania somnifera root chloroform-methanolic extract protected neurons from TBI injury induced apoptotic cell death along with restoration of neurite length and number [70]. Various active phytochemicals like withaferin A, withanone, withanolide A, withanoside IV and withanoside VI etc.…”