Abstract
Silymarin is a bioactive constituent isolated from milk thistle (Silybum marinum). Since its discovery, silymarin has been considered a gold standard drug in treating ailments related to the liver, resulting from alcohol consumption and viral hepatitis. This hepatoprotective nature of silymarin arises out of antioxidative and tissue-regenerating properties of silymarin. However, several recent studies have established the neuroprotective link of silymarin, too. Thus, the current investigation was aimed at exploring the neuroprotective effect of nanosilymarin (silymarin encapsulated inside collagen-based polymeric nanoparticulate drug delivery system). The study aimed at bringing out the role of nanoparticles in enhancing the therapeutic effect of silymarin against neuronal injury, originating out of oxidative-stress-related brain damages in focal cerebral ischemia. Collagen-based micellar nanoparticles were prepared and stabilized using 3-ethyl carbodiimide-hydrochloride (EDC-Hcl) and malondialdehyde (MDA) as crosslinkers. Nanoparticles were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy techniques, and the size of nanoparticles was found to be around 48 nm. Male albino Wistar rats were pretreated with three different doses of nanosilymarin of 10, 100, and 1,000 μg/kg b.wt and a dose of free silymarin of 100 mg/kg b.wt intraperitoneally (i.p.) for 7 days. Focal cerebral ischemia was induced using the middle cerebral artery occlusion (MCAO) model on the eighth day for 1 h followed by 24 h reperfusion. The animals were then evaluated for neurobehavioral, infarct analysis, biochemical, histopathological, and immunohistochemical studies. All the above parameters showed remarkable improvement in nanosilymarin-treated groups in comparison to the silymarin-treated group. Nanoparticle encapsulation of drug enhanced neuroprotection by increasing drug bioavailability and targeting. Thus, the present study concluded with satisfactory results, showing the critical role played by nanoparticles in improving the neuroprotection at very low drug doses.
Highlights
Stroke has become the second common cause of deaths worldwide at 11.8%, after deaths due to ischemic heart disease at 14.8% (Feigin et al, 2017)
Chemicals acquired from Sigma-Aldrich include silymarin, 2,3,5-triphenyl tetrazolium chloride (TTC), MDA, Dulbecco’s modified Eagle’s medium (DMEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), fetal bovine serum (FBS), and Ovicoll Collagen was acquired from Holista Colltech Limited Australia
This indicates the formation of additional amide (–CONH) bonds, which is further confirmed by the appearance of a broad peak of –NH stretching between 3,100 and 3,500 cm−1
Summary
Stroke has become the second common cause of deaths worldwide at 11.8%, after deaths due to ischemic heart disease at 14.8% (Feigin et al, 2017). The brain damage associated with ischemia might be due to metabolic stress suffered by the neurons, which do not store adenosine triphosphate (ATP) and rely on oxidative metabolism. This results in a lack of proper functioning of the mitochondria, disturbing the delicate redox balance, leading to a series of events following the ischemic cascade resulting in the combined effect of necrotic and apoptotic cell death pathways (Chauhan et al, 2017). Treatment strategies for treating various central nervous system (CNS) disorders require crossing specific barriers possessed by CNS for protecting itself from invading pathogens and neurotoxic molecules These barriers are essential interfaces between CNS and periphery. This reduces drug efficacy and requires the drug to be administered in high doses to achieve desired effects resulting in undesirable side effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
