Acori Tatarinowii Rhizoma inhibited neuroinflammation in Alzheimer's disease rats by modulating the intestinal flora.

Alzheimer's disease (AD) is a degenerative disorder causing neuronal loss and cognitive deficits, which is associated with intestinal flora dysbiosis. Acori Tatarinowii Rhizoma (ATR) is the dried rhizome of Acorus tatarinowii Schott., and exhibits neuroprotective effects. We aimed to investigate the therapeutic mechanism of ATR in AD. AD rat models were constructed by intracerebroventricular injection of Aβ1-42, with gavage of ATR water extract (5, 10, and 20 mg/kg) for 21 days. Behavior tests, HE staining, immunohistochemistry, ELISA, immunofluorescence, and 16S rRNA sequencing were performed. In AD rats, ATR improved cognitive dysfunction and brain histopathological damage, with reduced Aβ1-42, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, malondialdehyde, ionized calcium binding adaptor molecule, and glial fibrillary acidic protein expression, and higher superoxide dismutase activity, indicating inhibition of neuroinflammation by ATR. Moreover, Ruminococcus was strongly associated with ATR treatment for AD, which mainly enriched in Carbohydrate metabolism, Amino acid metabolism, and Lipid metabolism. Meanwhile, Dorea was negatively correlated with behavioural indicators and positively correlated with inflammatory factors, whereas g_Adlercreutzia showed the opposite trend. These findings suggested that ATR may attenuate neuroinflammation and improved AD by modulating intestinal flora and inhibiting microglia and astrocyte activation, providing a scientific basis for its clinical application in AD.