Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

Abstract

Centella asiatica (CA) herb is a traditional medicine, long reputed to provide cognitive benefits. We have reported that CA water extract (CAW) treatment improves cognitive function of aged Alzheimer’s disease (AD) model Tg2576 and wild-type (WT) mice, and induces an NRF2-regulated antioxidant response in aged WT mice. Here, CAW was administered to AD model 5XFAD female and male mice and WT littermates (age: 7.6 +/ − 0.6 months), and object recall and contextual fear memory were tested after three weeks treatment. CAW’s impact on amyloid-β plaque burden, and markers of neuronal oxidative stress and synaptic density, was assessed after five weeks treatment. CAW antioxidant activity was evaluated via nuclear transcription factor (erythroid-derived 2)-like 2 (NRF2) and NRF2-regulated antioxidant response element gene expression. Memory improvement in both genders and genotypes was associated with dose-dependent CAW treatment without affecting plaque burden, and marginally increased synaptic density markers in the hippocampus and prefrontal cortex. CAW treatment increased Nrf2 in hippocampus and other NRF2 targets (heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase catalytic subunit). Reduced plaque-associated SOD1, an indicator of oxidative stress, was observed in the hippocampi and cortices of CAW-treated 5XFAD mice. We postulate that CAW treatment leads to reduced oxidative stress, contributing to improved neuronal health and cognition.

Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression

“…All these findings indicate that HO-1 upregulation could be noxious for the brain. However, there are many other studies that favor HO-1 induction as a therapeutic strategy for AD and other neurodegenerative diseases [45][46][47][48][49]. Actually, there are other CNS-related diseases, such as multiple sclerosis, where HO-1 is found downregulated and this has been hypothesized to be related with relapses of the disease [50].…”

“…On one hand, in the earlier stages of AD, when HO-1 is still not up-regulated, its induction could have neurotherapeutic effects due to its antioxidant and anti-inflammatory properties derived from its end products biliverdin/bilirubin and CO. Therefore, strategies aiming to induce HO-1, such as hemin, or CO releasers, could be of interest [45][46][47][48][49]. In fact, therapies with multitarget compounds combining Nrf2 activators and CO-releasers have provided promising results in inflammatory-related diseases, such as EAE [18][19][20].…”

Caffeoylquinic Acids in Centella asiatica Reverse Cognitive Deficits in Male 5XFAD Alzheimer’s Disease Model Mice

“…The cognitive and neurological benefits of CA have been widely studied in preclinical and clinical investigations [ 2 ]. For example, we demonstrated that a CA water extract (CAW) dose-dependently reversed memory deficits in novel object recognition and conditioned fear response (CFR) in both male and female 5XFAD transgenic mice, an amyloid-β-driven model of Alzheimer’s disease (AD) [ 3 ]. The identification of active compounds of CA is important, both to understand the mode of action of this botanical, and for possible standardization of herbal preparations of CA for memory enhancement.…”

Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model

“…A large number of antioxidant based strategies focusing on ascorbic acid, deferoxamine, cucurmin etc has been investigated for management of the PD symptoms but without any translatable benefits 47,48 ; thus requiring elucidation of better alternatives with robust antioxidant capabilities to promote neuronal health in PD. Natural derivatives have been increasingly appreciated for their potency in prevention and management of neurodegenerative diseases 35,49,50 . Convolvulus pluricaulis extract is one of the most widely used neuropharmacological agent that significantly improved learning and memory in experimental models 34,51,52 .…”