Transcutaneous auricular vagus nerve stimulation was recently reported to have a therapeutic potential for functional dyspepsia (FD). This study aimed to explore the integrative effects and mechanisms of auricular vagus nerve stimulation (aVNS) in a rodent model of FD. Methods: We evaluated the effects of aVNS on visceral hypersensitivity, gastric motility and open field test (OFT) activity in iodoacetamide (IA)-treated rats. The autonomic function was assessed; blood samples and tissues were collected and analyzed by an enzyme-linked immunosorbent assay and western blot. Vagotomy was performed to investigate the role of vagal efferent nerve. Results: aVNS reduced the electromyography response to gastric distension, improved gastric emptying and increased the horizontal and vertical motion scores of the OFT in IA-treated rats. The sympathovagal ratio was increased in IA-treated rats but normalized with aVNS. The serum cytokines TNF-α, IL-6, IL-1β and NF-κBp65 were increased in IA-treated rats and decreased with aVNS. The hypothalamus–pituitary–adrenal axis was hyperactive in IA-treated rats but inhibited by aVNS. The expression of duodenal desmoglein 2 and occludin were all decreased in IA-treated rats and increased with aVNS but not sham-aVNS. Vagotomy abolished the ameliorating effects of aVNS on gastric emptying, horizontal motions, serum TNF-α and duodenal NF-κBp65. Conclusion: aVNS improves gastric motility and gastric hypersensitivity probably by anti-inflammatory mechanisms via the vago-vagal pathways. A better understanding on the mechanisms of action involved with aVNS would lead to the optimization of the taVNS methodology and promote taVNS as a non-pharmacological alternative therapy for FD.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treating major depressive disorder (MDD). We aimed to explore the modulating effect of prolonged longitudinal taVNS on the striatal subregions’ functional connectivity (FC) in MDD patients. Methods: Sixteen MDD patients were enrolled and treated with taVNS for 8 weeks. Sixteen healthy control subjects (HCs) were recruited without intervention. The resting-state FC (rsFC) based on striatal subregion seed points and the Hamilton Depression Scale (HAMD) were evaluated in the MDD patients and HCs at baseline and after 8 weeks. A two-way ANCOVA test was performed on each rsFC metric to obtain the (group-by-time) interactions. Results: The rsFC values between the left ventral caudate (vCa) and right ventral prefrontal cortex (vPFC), and between the right nucleus accumbens (NAc) and right dorsal medial prefrontal cortex (dmPFC) and ventrolateral prefrontal cortex (vlPFC) are lower in the MDD patients compared to the HCs at baseline, and increase following taVNS; the rsFC values between the left vCa and right, superior occipital gyrus (SOG), and between the left dorsal caudate (dCa) and right cuneus are higher in MDD patients and decrease following taVNS. Conclusions: Prolonged longitudinal taVNS can modulate the striatum rsFC with the prefrontal cortex, occipital cortex, temporal cortex, and intra-striatum, and these changes partly underlie any symptomatic improvements. The results indicate that prolonged longitudinal taVNS may produce beneficial treatment effects by modulating the cortical striatum circuitry in patients with MDD.

This study aimed to investigate the protective effects of Qiliqiangxin capsule (QLQX) against cognitive impairment in rats with heart failure (HF), as well as the underlying mechanisms. Heart failure was induced in rats by LAD ligation. The animals were randomized into four groups (sham, model, QLQX [0.6 g/kg/d], and valsartan [13.3 mg/kg/d]) and received treatment for 60 days. Cardiac function was evaluated by echocardiography, while cognitive function was assessed using the Morris water maze. Myocardial and hippocampal morphology were examined by HE and Nissl staining, respectively. Hippocampal levels of Ang II, Aβ₄₂, and ROS were quantified via ELISA and DHE staining. Finally, Western blot analysis was performed to measure the expression of AT1R, NF-κB, P-gP, RAGE, and the tight junction proteins (Claudin-5, Occludin). Echocardiographic assessments revealed that QLQX significantly improved cardiac function in rats with HF-induced cognitive impairment. The Morris water maze test demonstrated that, compared with the model group, QLQX treatment enhanced the targeting of swimming path and increased the number of platform crossings-consistently indicating alleviation of cognitive dysfunction. Histological analysis using HE staining confirmed that QLQX preserved myocardial structural integrity. Nissl staining further demonstrated that QLQX mitigated neuronal damage in the hippocampus. Additionally, QLQX reduced the levels of Ang II, AT1R, ROS, and Aβ_42. It also downregulated the expression of NF-κB and P-gP while upregulating that of Claudin-5 and Occludin. QLQX improves cardiac function and mitigates cognitive decline in rats with heart failure. These protective effects likely involve the reduction of Ang II, AT1R, and ROS levels, alongside inhibition of the NF-κB pathway. Furthermore, QLQX upregulates the tight junction proteins Claudin-5 and Occludin, which helps preserve blood-brain barrier (BBB) integrity. This cascade of events ultimately reduces cerebral Aβ deposition.