Abstract Background Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus, an important brain region for memory processes, is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin, a carotenoid pigment found in marine organisms, has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. Methods In this study, we utilized a rat model of VaD induced by CCH to investigate the therapeutic potential of astaxanthin. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Results Our results demonstrated that astaxanthin significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that astaxanthin modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, astaxanthin exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. Conclusions These findings provide valuable insights into the potential therapeutic effects of astaxanthin in VaD. By elucidating the mechanisms underlying the actions of astaxanthin, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. Further research is warranted to fully understand the therapeutic potential of astaxanthin and its application in the clinical treatment of VaD.
Lung cancer is a kind of malignant tumor with high morbidity and metastasis tendency. Gambogic acid (GA) has demonstrated significant antitumor activity in vitro, but its poor water-solubility and adverse effects restrict its application in vivo and in clinic. In this study, a passive-targeting GA delivery system was prepared for orthotopic Lewis lung carcinoma model mice. Besides the ∼7 μm size distribution, slow and steady in vitro drug release in a week, high targeting effect to lung, effective restoration of histomorphological abnormalities in lung, maintaining on bodyweight, and prolongation on survival time, excellent improvements of the GA-loaded particles on physiological and psychological statuses and obvious inhibition on tumor metastasis to liver have also been observed, through the measurements of Porsolt forced swim, hypoxic tolerance time, ultrastructure of pulmonary capillary, pulmonary vascular permeability, and hepatic histological change. These results suggest that this GA-loaded particle may be an ideal approach to achieve satisfactory therapeutic function on lung cancer.
Abstract Alhagi honey (AH) is produced in arid and hot areas of Central Asia, and its polysaccharides (AP) are widely known for their activity in the treatment of intestinal diseases such as diarrhea. However, the therapeutic potential and mechanism of AP in ulcerative colitis (UC) remain unclear. Here, AH polysaccharide‐2 (AP2), a polysaccharide with the highest content in AP, was isolated and evaluated for its effects on dextran sulfate sodium (DSS)‐induced UC in mice. AP2 was found to alleviate UC symptoms and regulate gut microbiota dysbiosis by decreasing Helicobacter levels and increasing Lactobacillus levels. Analysis of PICRUSt2 predicted that AP2 may regulate carbohydrate and amino acid metabolism, and metabolomic analysis confirmed that AP2 promotes the metabolism of tryptophan to produce kynurenic acid (kyna). Moreover, kyna acted as an aryl hydrocarbon receptor (AhR) ligand, which activated AhR to increase the expression of the tight junction proteins claudin‐1 and occludin. Interestingly, AP2 showed similar effects in protecting the intestinal barrier and alleviating colitis as the AhR agonist 6‐formylindolo[3,2‐ b ]carbazole, and the AhR antagonist CH223191 partially blocked the therapeutic effect of AP2 in UC mice, indicating that the anti‐UC effect of AP2 was AhR dependent. These findings demonstrate that AP2 alleviates UC by regulating the gut microbiota and promoting tryptophan metabolism to generate kyna‐activated AhR. The insights gained from this study could help in the future development of AP2 as a drug candidate or functional food for the treatment of UC.
Vascular dementia (VaD) is the second most common type of dementia worldwide. Although there are five FDA-approved drugs for the treatment of Alzheimerâs disease (AD), none of them have been applied to treat VaD. Adalimumab is a TNF-α inhibitor that is used for the treatment of autoimmune diseases such as rheumatoid arthritis. In a recent retrospective case-control study, the application of adalimumab for rheumatoid or psoriasis was shown to decrease the risk of AD. However, whether adalimumab can be used for the treatment of VaD is not clear. In this study, we used 2VO surgery to generate a VaD rat model and treated the rats with adalimumab or vehicle. We demonstrated that VaD rats treated with adalimumab exhibited significant improvements in memory. In addition, adalimumab treatment significantly alleviated neuronal loss in the hippocampi of VaD rats. Moreover, adalimumab significantly reduced microglial activation and reversed M1/M2 polarization in VaD rats. Furthermore, adalimumab treatment suppressed the activity of NF-κB, an important neuroinflammatory transcription factor. Finally, adalimumab displayed a protective role against oxidative stress in VaD rats. Our results indicate that adalimumab may be applied for the treatment of human patients with VaD.
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