Exploring the antidepressant mechanisms of Guipi pill: A focus on gut-brain axis and immunity modulation

Figure 10  The molecular mechanism by which Guipi pills exerted antidepressant effects through the gut-brain axis. Following Guipi pills intervention, it specifically upregulated GZMA expression in CD8+ NC cells by modulating the intestinal immune microenvironment. GZMA activated the cyclic adenosine monophosphate (cAMP)/protein kinase A/cAMP response element-binding protein signaling pathway by inhibiting phosphodiesterase 4B, thereby promoting GPX4 transcriptional upregulation and enhancing ferroptosis resistance. Concurrently, cAMP response element-binding protein pathway activation further facilitated neuroplasticity. These effects collectively alleviated neuroinflammation, protected neurons, and ultimately ameliorated depressive symptoms. GPP: Guipi pills; cAMP: Cyclic adenosine monophosphate; PKA: Protein kinase A; CREB: Cyclic adenosine monophosphate response element binding protein; PDE4B: Phosphodiesterase 4B.