Protective effects of Forsythiae fructus and Cassiae semen water extract against memory deficits through the gut-microbiome-brain axis in an Alzheimer’s disease model

Fruits of Forsythia suspensa Vahl (Oleaceae) and seeds of Cassia obtusifolia Linne (Caesalpinaceae) have been used to treat inflammation in Asia.We examined the alleviation of memory function in Alzheimer's disease (AD) rats fed Forsythiae Fructus (FF) and Cassiae Semen water extracts (CS) and investigated the mechanisms responsible for the effects.Thirty Sprague-Dawley male rats had hippocampal infusions of amyloid-β(25-35) (AD rats; memory deficit), and ten rats were infused with amyloid-β(35-25) (non-AD rats; no memory deficit). For eight weeks, all rats freely consumed high-fat diets (43% lard) incorporated with 200 mg/kg body weight assigned aqueous herbal extracts: AD-FF, AD-CS, or without extracts AD-CON (control), non-AD (normal-control).Memory impairment was prevented in the AD-FF (0.54 ± 0.06-fold) and the AD-CS rats (0.33 ± 0.04-fold) compared to the AD-CON by inhibiting amyloid-β deposition to the levels less than one-fourth of the AD-CON group. The hippocampal pAkt→pGSK-3β→pFOXO1 pathway was attenuated by approximately 3.25-fold in the AD-CON, while AD-FF prevented the attenuation better than AD-CS. The relative intensity of hippocampal tau protein based on β-actin was suppressed with AD-FF (0.68 ± 0.09) and AD-CS (0.96 ± 0.81), compared to AD-CON (1.19 ± 0.13). AD decreased the abundance of Bacteroidales by 34.2% and Lactobacillales by 23.8% and increased Clostridiales by 181% while the AD-FF, but not the AD-CS, normalised the gut microbiota changes to be similar to the non-AD.FF improved memory deficits better than CS in an AD-induced rat model. The potential neuroprotective benefits of FF against AD may be applicable to human AD therapy with additional clinical research.