Effects and mechanism of extracts rich in phenylpropanoids-polyacetylenes and polysaccharides from Codonopsis Radix on improving scopolamine-induced memory impairment of mice

Alzheimer's disease (AD) is a progressive developmental neurodegenerative disease that primarily develops in old age. Memory impairment is an important manifestation of AD. It has been demonstrated that inflammation and oxidative stress are important mediators in the development and progression of AD. Codonopsis Radix (CR) has a long history of consumption, exhibiting lots of beneficial health effects, including anti-ageing, antioxidant, and anti-inflammatory properties. However, studies on the effects of CR on scopolamine-induced amnesia have rarely been reported.The aim of this study was to investigate the ameliorative effect of macromolecular portion (polysaccharides, POL) and small molecule portion (fine extract rich in phenylpropanoids-polyacetylenes, EPP) from CR on improving scopolamine-induced memory impairment and to elucidate the potential mechanism of action.C57BL/6 mice were pretreated with EPP (0.2, 0.4, and 0.6 g/kg), POL (0.3, 0.6, and 0.9 g/kg), and donepezil (5 mg/kg) by gavage for 7 days, followed by intraperitoneal injection of scopolamine (1 mg/kg) to induce memory impairment. The 16S rRNA gene sequencing, histopathological, western blotting, and biochemical analysis (various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation) were performed to further elucidate the mechanism of action. Moreover, the acetylcholinesterase (AChE) inhibitory activities of POL, EPP, and its main compounds tangshenoside I, lobetyol, lobetyolin, and lobetyolinin were evaluated.Experiments have confirmed that both POL and EPP from CR could improve scopolamine-induced spatial learning memory deficits. Both of them could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities. They also could enhance antioxidant defense via increasing the activities of superoxide dismutase and glutathione peroxidase, and anti-inflammatory function through suppressing inflammatory factors (nitric oxide, TNF-α, and IL-6) and regulating gut flora. Besides, in vitro experiments demonstrated that four monomeric compounds and EPP, except POL, exhibited inhibition of AChE activity.EPP and POL from CR exert a beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. CR may be a promising medicine for preventing and improving learning memory.