| In vitro: |
| J Pharm Pharmacol. 2018 Nov;70(11):1531-1540. | | Comparative evaluation of four triterpenoid glycoside saponins of bacoside A in alleviating sub-cellular oxidative stress of N2a neuroblastoma cells.[Pubmed: 30073654 ] | To examine the neuroprotective property of triterpenoid glycoside saponins of Bacopa monnieri (L.) Wettst. bacoside A and its components against H2 O2 -induced oxidative stress on neuronal (N2a) cells.
METHODS AND RESULTS:
The cytoprotective effects of individual bacoside A components were evaluated towards oxidative stressed neuronal cells. Bacoside A was screened for neuronal cell viability (MTT assay) and change in intracellular reactive oxygen species (ROS), anti-apoptotic properties and mitochondrial membrane potential (MMP) using fluorescence microscopy.
Different bacoside A components showed decrease in N2a cell viability below 100 (%) after bacoside A concentration of 0.4 mg/ml. Further, cytoprotective effect of optimized dose of bacoside A was analysed for alleviating oxidative stressed, apoptosis and MMP in H2 O2 stressed neuronal cells. Results showed increase in MMP, and decrease in apoptotic induction, without much change in nuclear integrity in stressed neuronal cells. Results showed bacoside A3 and bacopaside II have comparatively higher cytoprotective ability whilst isomer of bacopasponin C, bacopasaponin C and mixture showed comparatively less response.
CONCLUSIONS:
Amongst four different bacoside A components, bacoside A3 and bacopaside II showed comparatively higher neuroprotective response analysed as higher cell viability and decreased intracellular ROS, suggesting better regulation of cyto-(neuronal) protection of N2a cells. | | Nat Prod Bioprospect. 2014 Aug;4(4):251-5. | | Molecular docking of bacosides with tryptophan hydroxylase: a model to understand the bacosides mechanism.[Pubmed: 25089244] | Tryptophan hydroxylase (TPH) catalyses l-tryptophan into 5-hydroxy-l-tryptophan, which is the first and rate-limiting step of serotonin (5-HT) biosynthesis. Earlier, we found that TPH2 up-regulated in the hippocampus of postnatal rats after the oral treatment of Bacopa monniera leaf extract containing the active compound bacosides. However, the knowledge about the interactions between bacosides with TPH is limited.
METHODS AND RESULTS:
In this study, we take advantage of in silico approach to understand the interaction of bacoside-TPH complex using three different docking algorithms such as HexDock, PatchDock and AutoDock. All these three algorithms showed that bacoside A and bacoside A3 well fit into the cavity consists of active sites. Further, our analysis revealed that major active compounds bacoside A3 and A interact with different residues of TPH through hydrogen bond. Interestingly, Tyr235, Thr265 and Glu317 are the key residues among them, but none of them are either at tryptophan or BH4 binding region. However, its note worthy to mention that Tyr 235 is a catalytic sensitive residue, Thr265 is present in the flexible loop region and Glu317 is known to interacts with Fe. Interactions with these residues may critically regulate TPH function and thus serotonin synthesis.
CONCLUSIONS:
Our study suggested that the interaction of bacosides (A3/A) with TPH might up-regulate its activity to elevate the biosynthesis of 5-HT, thereby enhances learning and memory formation. |
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Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
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ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
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Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)
