Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice

Abstract

Type 2 diabetes (T2D) and Alzheimer’s disease (AD) share several common pathophysiological features. Huperzine A (Hup A), a Lycopodium alkaloid extracted from the Chinese herb moss Huperzia serrata , is a specific and reversible inhibitor of acetylcholinesterase, which is clinically used for the treatment of AD. In this study, we investigated whether Hup A improved the metabolic and cognitive functions in the high fat-induced (HFD) obese mice and genetic ob/ob mice. HFD and ob/ob mice were treated with Hup A (0.1, 0.3 mg · kg −1 · d −1 , ig) for 3 months. Body weight was monitored and glucose tolerance tests were performed. Novel object recognition test and Morris water maze assay were conducted to evaluate the cognitive functions. We found that the Hup A treatment had no significant effect on peripheral metabolism of obese mice, whereas Hup A (0.1, mg · kg −1 · d −1 ) improved both the abilities of object recognition and spatial memory in HFD-fed mice, but not in ob/ob mice. Furthermore, Hup A treatment significantly upregulated the insulin and phosphorylated Akt levels in the cortex of HFD-fed mice, but not ob/ob mice. In addition, Hup A (0.3, mg · kg −1 · d −1 ) significantly decreased cortical β-secretase (BACE1) expression. In conclusion, these results demonstrate that treatment with Hup A (0.1, mg · kg −1 · d −1 ) can effectively improve the cognitive functions, at least in diet-induced obese mice.

Amaryllidaceae, Lycopodiaceae Alkaloids and Coumarins—A Comparative Assessment of Safety and Pharmacological Activity

“…Similarly, in vivo studies showed that Lycopodium selago extract, administered to zebrafish (Danio rerio) with cognitive impairment caused by scopolamine, alleviates cognitive deficits, inter alia, by regulating ACHE activity [46]. Another study confirmed that treatment with HupA improved cognition in mice with diet-induced obesity [49]. Other studies showed that angelica polysaccharide ameliorates memory impairment in animal models of cognitive disorders, although the exact mechanisms have not yet been understood [50][51][52][53].…”

Deletion of ghrelin alters tryptophan metabolism and exacerbates experimental ulcerative colitis in aged mice

“…Novel object recognition test (NORT) was carried out as described, with slight modification. 30,31 On the first day, each mouse was subjected to a 5-min trial to acclimatize to the arena (40 cm × 40 cm × 30 cm) without objects. Twenty-four hours after acclimatization session, each mouse was given 5 min to explore (defined as sniffing or touching) identical objects (F1 and F2), placed in fixed adjacent corners.…”

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment

“…kamtschaticus (EFAD) and Huperzine A (Hup A) are both extracts of TCM, which can improve cerebral insulin resistance and cognitive impairment in AD animals. Both of them can increase Ach and decrease AchE and improve synaptic function ( 152 , 153 ). Polyphenol rich frankincense(BS) gum has been proven to have anti-inflammatory, anticancer and anti-apoptotic effects.…”

“…ACF treatment can significantly increase pIRS, PI3K, and pAkt, restrain GSK3β overactivation, thus reducing Aβ deposition ( 156 ). Catechins, proanthocyanidins A1, A2 in Lychee seed and Huperzine A can inhibit hyperphosphorylated Tau through A similar pathway ( 153 , 157 ). Ginseng has many active components against AD.…”