ABSTRACT
The present study examined the potential neuroprotective effects of aloe-emodin (AE) nanoparticles on the cerebral stroke-associated target protein myeloperoxidase (MPO). We investigated the binding interactions between AE and MPO through molecular docking and molecular dynamics simulations. Molecular docking results indicated that AE exhibited a binding energy of -6.9 kcal/mol, whereas it was -7.7 kcal/mol for 2-{[3,5-bis(trifluoromethyl)benzyl]amino}-n-hydroxy-6-oxo-1,6-dihydropyrimidine-5-carboxamide (CCl). Furthermore, molecular dynamics studies demonstrated that AE possesses a stronger binding affinity (-57.137 ± 13.198 kJ/mol) than does CCl (-22.793 ± 30.727 kJ/mol), suggesting that AE has a more substantial inhibitory effect on MPO than does CCl. Despite the therapeutic potential of AE for neurodegenerative disorders, its bioavailability is limited within the body. A proposed hypothesis to enhance the bioavailability of AE is its conversion into aloe-emodin nanoparticles (AENP). The AENPs synthesized through a fabrication method were spherical with a consistent diameter of 104.4 ± 7.9 nm and a polydispersity index ranging from 0.525 to 0.586. In rats experiencing cerebral stroke, there was a notable increase in cerebral infarction size; abnormalities in electrocardiogram (ECG) and electroencephalogram (EEG) patterns; a decrease in brain and cardiac antioxidant activities; and an increase in myeloperoxidase levels compared to those in normal rats. Compared with AE treatment, AENP treatment significantly ameliorated cerebral infarction, normalized ECG and EEG patterns, enhanced brain and cardiac antioxidant activities, and reduced MPO levels in stroke rats. Histopathological evaluations revealed pronounced alterations in the rat hippocampus, with pyknotic nuclei, disarray and loosely packed cells, deterioration of cardiac muscle fibers, and extensive damage to cardiac myocytes, in contrast to those in normal rats. AENP treatment mitigated these pathological changes more effectively than AE treatment in both brain and cardiac cells. These findings support that AENP provides considerable protection against stroke-associated myocardial infarction.
ABSTRACT
The Kisspeptin1 (KISS1)/neurokinin B (NKB)/Dynorphin (Dyn) [KNDy] neurons in the hypothalamus regulate the reproduction stage in human beings and rodents. KNDy neurons co-expressed all KISS1, NKB, and Dyn peptides, and hence commonly regarded as KISS1 neurons. KNDy neurons contribute to the "GnRH pulse generator" and are implicated in the regulation of pulsatile GnRH release. The estradiol (E2)-estrogen receptor (ER) interactions over GnRH neurons in the hypothalamus cause nitric oxide (NO) discharge, in addition to presynaptic GABA and glutamate discharge from respective neurons. The released GABA and glutamate facilitate the activity of GnRH neurons via GABAA-R and AMPA/kainate-R. The KISS1 stimulates MAPK/ERK1/2 signaling and cause the release of Ca2+ from intracellular store, which contribute to neuroendocrine function, increase apoptosis and decrease cell proliferation and metastasis. The ageing in women deteriorates KISS1/KISS1R interaction in the hypothalamus which causes lower levels of GnRH. Because examining the human brain is so challenging, decades of clinical research have failed to find the causes of KNDy/GnRH dysfunction. The KISS1/KISS1R interactions in the brain have a neuroprotective effect against Alzheimer's disease (AD). These findings modulate the pathophysiological role of the KNDy/GnRH neural network in polycystic ovarian syndrome (PCOS) associated with ageing and, its protective role in cancer and AD. This review concludes with protecting effect of the steroid-derived acute regulatory enzyme (StAR) against neurotoxicity in the hippocampus, and hypothalamus, and these measures are fundamental for delaying ageing with PCOS. StAR could serve as novel diagnostic marker and therapeutic target for the most prevalent hormone-sensitive breast cancers (BCs).