ABSTRACT
The prevalence of Alzheimer's disease and other forms of dementia is increasing worldwide, and finding effective treatments for these conditions is a major public health challenge. Natural bioactive drugs have been identified as a promising source of potential treatments, due to their ability to target multiple pathways and their low toxicity. This paper reviews the current state of research on natural bioactive drugs used in the treatment of Alzheimer's disease and other dementias. The paper summarizes the findings of studies on various natural compounds, including curcumin, resveratrol, caffeine, genistein, quercetin, GinkoBiloba, Withaniasomnifera, Ginseng Brahmi, Giloy, and huperzine, and their effects on cognitive function, neuroinflammation, and amyloid-beta accumulation. In this review, we discuss the mechanism of action involved in the treatment of Alzheimer's disease. The paper also discusses the challenges associated with developing natural bioactive drugs for dementia treatment, including issues related to bioavailability and standardization. Finally, the paper suggests directions for future research in this area, including the need for more rigorous clinical trials and the development of novel delivery systems to improve the efficacy of natural bioactive drugs. Overall, this review highlights the potential of natural bioactive drugs as a promising avenue for the development of safe and effective treatments for Alzheimer's disease and other dementias.
ABSTRACT
Salinomycin (Sal) is a potent veterinary antibiotic known to offer significant toxicity to the variety of neoplastic cells. Its therapeutic utility is limited due to its higher lipophilicity (logP 7.5) and poor hydrophilicity. Liquid crystalline nanoparticles (LCNPs) known to offer a suitable delivery platform for these kinds of drugs. The overexpressed nucleolin receptor on the cell surface and cytoplasm, could be selected as a target in cancer therapy. The present study involves the development and characterization of the F3 peptide functionalized LCNPs for delivering Sal (F3-Sal-NPs) for selectively targeting to the nucleolin receptor. The optimized LCNPs were characterized for particle size, zeta potential, surface morphology, drug release kinetics and stability. The LCNPs have a structure similar to nematic phases. In vitro drug release studies revealed sustained drug release characteristics (89.5 ± 1.5% at 120 h) with F3-Sal-NPs. The cytotoxicity results demonstrated that F3-Sal-NPs were 4.8, 2.6 and 5.5 folds more effective than naïve drug in MDA-MB-468, MDA-MB-231 and MCF-7 cells, respectively and the cell cycle was arrested in the S and G2/M phases. The expression of the gene responsible for the stemness (CD44 gene), apoptosis (BAX/Bcl-2 ration) and angiogenesis (LCN-2) was reduced by F3-Sal-NPs treatment. Ex vivo hemolytic toxicity was reduced (6.5 ± 1.5%) and the pharmacokinetics and bioavailability of Sal was improved with F3-Sal-NPs. The in vivo antitumor efficacy was tested in EAC bearing mice, where F3-Sal-NPs significantly reduced the tumor growth by 2.8-fold compared to pure Sal and induced necrosis of tumor cells. The results clearly demonstrate the outstanding performance of F3 peptide functionalized LCNPs for delivering Sal against breast cancer.
