Effect of Hesperidin on Chronic Unpredictable Mild Stress-Related Depression in Rats through Gut-Brain Axis Pathway.

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.

Updated systematic review and meta-analysis of randomized clinical trials comparing carotid artery stenting and carotid endarterectomy in the treatment of carotid stenosis.

BACKGROUND: To compare carotid artery stenting (CAS) versus carotid endarterectomy (CEA) in the treatment of carotid stenosis, including two recently published, large, prospective, randomized trials of these therapies. METHODS: We searched electronic databases for prospective, randomized, controlled trials involving carotid stenosis patients who underwent CAS or CEA, focusing on studies published in 1995 to 2010. Primary outcomes were death, stroke, and myocardial infarction. RESULTS: Thirteen trials containing 7,501 patients were analyzed, and odds ratios (ORs) were calculated for CAS versus CEA. The risk of stroke or death within 30 days was higher after CAS than CEA (OR = 1.57; 95% confidence interval [CI] = 1.11-2.22), especially in previously symptomatic patients (OR = 1.89; 95% CI = 1.48-2.41). However, the risk of stroke or death within 1 year was comparable (OR = 1.12; 95% CI = 0.55-2.30). In a subgroup analysis, the risk of death and disabling stroke at 30 days did not differ significantly between CEA and CAS (death: OR = 1.43; 95% CI = 0.85-2.40; disabling stroke: OR = 1.28; 95% CI = 0.89-1.83), whereas the rate of nondisabling stroke within 30 days was much higher in the CAS group (OR = 1.87; 95% CI = 1.40-2.50). The risks of myocardial infarction within 30 days and 1 year were significantly less for CAS. CONCLUSION: CAS is inferior to CEA with regard to the incidence of stroke or death for periprocedural outcomes, especially in symptomatic patients. However, CAS was associated with a lower incidence of myocardial infarction. These procedures may be considered complementary rather than competing modes of therapy, each of which can be optimized with careful patient selection.