Shatavarin IV, a Bioactive Constituent of Asparagus racemosus , Exerts Antioxidant and Anti-Inflammatory Effects in LPS-Treated Cultured SH-SY5Y Cells via TrkB-BDNF Axis

Objective Shatavarin IV, a steroidal saponin in Asparagus racemosus, is a traditionally recognized phytotherapeutic for the treatment of cognitive ailments. In the present study, the neuroprotective action of shatavarin IV was investigated in cultured SH-SY5Y cells.Methods Cells were treated with shatavarin IV (10 ng/ml) or proprietary ethanolic extract of shatavari root extract (SheVari4®) containing 5% w/v shatavarin IV (100 ng/ml) in presence and absence of lipopolysaccharide (LPS) (1 µg/ml), an inducer of inflammatory response, brain-derived neurotrophic factor (BDNF), a neurotrophin, and K252a, an inhibitor of receptor tyrosine kinase. Proinflammatory cytokines IL-6 and TNF-α and anti-inflammatory cytokines IL-10 and TGF-β were assessed by qPCR. LPS induced oxidative stress was assessed through reactive oxygen species (ROS) and nitric oxide (NO) levels. Molecular docking was carried out to investigate the binding of shatavarin IV to tropomysin receptor kinase B (TrkB) and BDNF.Results In LPS-induced cells treated with shatavarin IV, IL6 and TNFα levels were reduced by 46% and 50%, respectively, and those of IL-10 and TGF-β were upregulated by 2.74 and 4.4 times with significant reductions in ROS and NO levels. Similar results were observed in presence of SheVari4®. Addition of BDNF resulted in further augmentation of shatavarin IV-mediated protection. Administration of K-252a dampened this effect, which indicated that shatavarin IV exerted its effect in the TrkB-BDNF axis. The results also suggested that shatavarin IV probably exerted its effect by salvaging the endogenous BDNF with subsequent docking to TrkB as a BDNF-shatavarin IV complex. In silico docking of shatavarin IV-BDNF complex with TrkB resulted in a considerably strong binding energy of −10.3 kcal/mole, whereas that of shatavarin IV alone was comparatively weaker at −6.9 kcal/mole.Conclusion The results suggested that the primary bioactive component of Asparagus racemosus, shatavarin IV, exerted its neuroprotective effects on SH-SY5Y cell line via the TrkB-BDNF axis.