Tangzhiqing Decoction (TZQD), a patented Chinese herbal formula for diabetes, has been shown to improve cognitive function. However, the precise mechanisms linking the gut-brain axis and the TLR4/NF-κB/NLRP3 signaling pathway remain to be elucidated. This study investigated the neuroprotective effects of TZQD on type 2 diabetic (T2DM) mice and explored whether its mechanism involves the modulation of gut microbiota and suppression of the TLR4/NF-κB/NLRP3 inflammatory pathway. UPLC-Q-TOF-MS/MS and network pharmacology were used to determine the active components and therapeutic targets of TZQD. Following 8 weeks of intervention with different doses of TZQD or metformin in T2DM mice, behavioral tests, histological staining, immunofluorescence, ELISA, 16S rDNA sequencing, short-chain fatty acid measurement, and Western blot analysis were performed. Additionally, research employing fecal microbiota transplantation (FMT) was conducted to validate the contribution of gut microbiota to the amelioration of diabetic cognitive dysfunction (DCD) mediated by TZQD. TZQD significantly improved learning and memory, reduced fasting blood glucose, and restored gut microbiota balance and SCFA levels. Furthermore, TZQD treatment alleviated systemic and neuroinflammation and repaired intestinal/blood-brain barrier damage. These effects were associated with the suppression of the TLR4/NF-κB/NLRP3 pathway. Notably, FMT from TZQD-treated mice replicated these protective effects, confirming the essential role of gut microbiota. TZQD alleviates DCD by modulating the gut-brain axis and inhibiting the TLR4/NF-κB/NLRP3 signaling pathway, highlighting its potential as a therapeutic strategy for diabetic complications.
Guan et al. (Fri,) studied this question.