Neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease are characterized by the progressive loss of
neurons. One of the contributing factors for these diseases is oxidative stress, characterized by the imbalance of free
radicals production and antioxidant defense mechanisms. In the present study, the neuroprotective effects of Ocimum
basilicum var. thyrsiflora against hydrogen peroxide (H2
O2
)-induced oxidative stress in SK-N-SH neuroblastoma cells
were evaluated. The exposure of SK-N-SH cells to 50 µM H2
O2
for 24 h induced cytotoxicity and apoptosis as measured
by cell viability and flow cytometry, respectively. Pretreatment with ethyl acetate (ObEA) fraction at 3.1-25 µg/mL showed
the highest protection against H2
O2
-induced cell death compared to other fractions and crude extract by increasing cell
viability and reducing apoptosis. The evaluation of antioxidant capacity via 1, 1-diphenyl-2-picrylahydrazyl (DPPH)
and ferric reducing/antioxidant power (FRAP) assays showed ObEA possessed the highest antioxidative properties. The
intracellular reactive oxygen species (ROS) production of H2
O2
in untreated cells increased by 2.39-fold compared to the
control and was significantly attenuated by the 2 h pre-treatment of O. basilicum (p<0.05). The reduction in intracellular
superoxide dismutase (SOD) induced by H2
O2
was also abrogated by the pretreatment of O. basilicum. These findings
suggested that O. basilicum is potentially neuroprotective against oxidative damage in neuronal cells by scavenging free
radicals, restoring SOD activities and eventually prevent cell death.
Acquired paclitaxel (PTX) chemoresistance in triple-negative breast cancer (TNBC) can be inferred from the overexpression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) proteins and the activation of the TLR4/MyD88 cascading signalling pathway. Finding a new inhibitor that can attenuate the activation of this pathway is a novel strategy for reducing PTX chemoresistance. In this study, a series of small molecule compounds were synthesised and tested in combination with PTX against TNBC cells. The trimethoxy-substituted compound significantly decreased MyD88 overexpression and improved PTX activity in MDA-MB-231TLR4+ cells but not in HCCTLR4- cells. On the contrary, the trifluoromethyl-substituted compound with PTX synergistically improved the growth inhibition in both TNBC subtypes. The fluorescence titrations indicated that both compounds could bind with MD2 with good and comparable binding affinities. This was further supported by docking analysis, in which both compounds fit perfectly well and form some critical binding interactions with MD2, an essential lipid-binding accessory to TLR4 involved in activating the TLR-4/MyD88-dependent pathway.