Medicinal Herbs and Their Derived Ingredients Protect against Cognitive Decline in In Vivo Models of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) has pathological hallmarks including amyloid beta (Aβ) plaque formation. Currently approved single-target drugs cannot effectively ameliorate AD. Medicinal herbs and their derived ingredients (MHDIs) have multitarget and multichannel properties, engendering exceptional AD treatment outcomes. This review delineates how in in vivo models MHDIs suppress Aβ deposition by downregulating β- and γ-secretase activities; inhibit oxidative stress by enhancing the antioxidant activities and reducing lipid peroxidation; prevent tau hyperphosphorylation by upregulating protein phosphatase 2A expression and downregulating glycogen synthase kinase-3β expression; reduce inflammatory mediators partly by upregulating brain-derived neurotrophic factor/extracellular signal-regulated protein kinase 1/2-mediated signaling and downregulating p38 mitogen-activated protein kinase (p38 MAPK)/c-Jun N-terminal kinase (JNK)-mediated signaling; attenuate synaptic dysfunction by increasing presynaptic protein, postsynaptic protein, and acetylcholine levels and preventing acetylcholinesterase activity; and protect against neuronal apoptosis mainly by upregulating Akt/cyclic AMP response element-binding protein/B-cell lymphoma 2 (Bcl-2)-mediated anti-apoptotic signaling and downregulating p38 MAPK/JNK/Bcl-2-associated x protein (Bax)/caspase-3-, Bax/apoptosis-inducing factor-, C/EBP homologous protein/glucose-regulated protein 78-, and autophagy-mediated apoptotic signaling. Therefore, MHDIs listed in this review protect against Aβ-induced cognitive decline by inhibiting Aβ accumulation, oxidative stress, tau hyperphosphorylation, inflammation, synaptic damage, and neuronal apoptosis in the cortex and hippocampus during the early and late AD phases.

Cognitive decline in Sprague–Dawley rats induced by neuroplasticity changes after occlusal support loss

“…AKT is recruited on the cell membrane to trigger cell proliferation, inhibit cell apoptosis, and play a neurotrophic and protective role. [61][62][63][64] As for the AKT expression, same dropping trend was found in YL and OL groups when compared to YC and OC groups, respectively. But no statistical significance in WB was found between OL group and OC group.…”

“…Among others, AKT pathway plays an important role in promoting cell proliferation and apoptosis. AKT is recruited on the cell membrane to trigger cell proliferation, inhibit cell apoptosis, and play a neurotrophic and protective role 61–64 . As for the AKT expression, same dropping trend was found in YL and OL groups when compared to YC and OC groups, respectively.…”

Isoimperatorin therapeutic effect against aluminum induced neurotoxicity in albino mice

“…Inflammatory mediators are also regulated by mitogen-activated protein kinases (MAPKs), including c-Jun NH2terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 in mammals (Zhou et al, 2018;Ji et al, 2021;Zong et al, 2021;Mehrbeheshti et al, 2022). Related to that, the phosphorylation events caused by AlCl3 stimulation can activate JNK, ERK, and p38 (Mehrbeheshti et al, 2022;Tsai et al, 2022). Al exposure and it subsequent accumulation in the brain was shown to be associated with neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease (AD) (Dalla Torre et al, 2019;McLachlan et al, 2019;McLachlan et al, 2020;Bondy and Campbell, 2021;Hassan and Kadry, 2021;Kawahara et al, 2021;Zeng et al, 2021;Abbas et al, 2022).…”