Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration

Abstract

Oxidative stress (OS) and c-Jun N-terminal kinase (JNK) are both key indicators implicated in neuro-inflammatory signalling pathways and their respective neurodegenerative diseases. Drugs targeting these factors can be considered as suitable candidates for treatment of neuronal dysfunction and memory impairment. The present study encompasses beneficial effects of a naturally occurring triterpenoid, friedelin, against scopolamine-induced oxidative stress and neurodegenerative pathologies in mice models. The treated animals were subjected to behavioural tests i.e., Y-maze and Morris water maze (MWM) for memory dysfunction. The underlying mechanism was determined via western blotting, antioxidant enzymes and lipid profile analyses. Molecular docking studies were carried out to predict the binding modes of friedelin in the binding pocket of p-JNK protein. The results reveal that scopolamine caused oxidative stress by (1) inhibiting catalase (CAT), peroxidase enzyme (POD), superoxide dismutase (SOD), and reduced glutathione enzyme (GSH); (2) the up-regulation of thiobarbituric acid reactive substances (TBARS) in mice brain; and (3) affecting the neuronal synapse (both pre- and post-synapse) followed by associated memory dysfunction. In contrast, friedelin administration not only abolished scopolamine-induced oxidative stress, glial cell activation, and neuro-inflammation but also inhibited p-JNK and NF-κB and their downstream signaling molecules. Moreover, friedelin administration improved neuronal synapse and reversed scopolamine-induced memory impairment accompanied by the inhibition of β-secretase enzyme (BACE-1) to halt amyloidogenic pathways of amyloid-β production. In summary, all of the results show that friedelin is a potent naturally isolated neuro-therapeutic agent to reverse scopolamine-induced neuropathology, which is characteristic of Alzheimer’s disease.

Optimizing extraction conditions and isolation of bound phenolic compounds from corn silk (Stigma maydis) and their antioxidant effects

“…13 C NMR (151 MHz, CDCl 3 ) δ 213.31, 59.48, 58.24, 53.11, 42.79, 42.16, 41.54, 41.29, 39.70, 39.26, 38.30, 37.45, 36.01, 35.63, 35.35, 35.03, 32.77, 32.42, 32.09, 31.78, 30.51, 30.00, 29.71, 28.18, 22.29, 20.26, 18.67, 18.24, 17.95, 14.66, 6.83 are shown in Figure 5. The NMR data from compound 1 matched those from the literature (Atewolara‐Odule et al., 2020; Mujawah et al., 2023; Sandhu et al., 2022), so this compound was identified as friedelin compound 2 (( E )−4‐(4‐hydroxy‐3‐methoxyphenyl) but‐3‐en‐2‐one) (Y1).…”

“…22.29, 20.26, 18.67, 18.24, 17.95, 14.66, 6.83 are shown in Figure 5. The NMR data from compound 1 matched those from the literature (Atewolara-Odule et al, 2020;Mujawah et al, 2023;Sandhu et al, 2022), so this compound was identified as friedelin compound 2 ((E)−4-(4-hydroxy-3methoxyphenyl) but-3-en-2-one) (Y1).…”

Genetic deletion of astrocytic calcineurin B1 prevents cognitive impairment and neuropathology development in acute and chronic mouse models of Alzheimer's disease

“…Because of a persistent loop of mutual activation between astrocytes and microglia, subsequently influencing neuronal activity and memory, it is likely that ACN inhibition might be sufficient to interrupt such a vicious cycle, preserving neuronal function. Reduced neuroinflammation can be, indeed, positively associated with the preservation of cognitive abilities we observed both in the AβO‐induced and in indACNKO‐AD mice, because of the strong association described between glial activation, neuroinflammation, and synaptic plasticity and memory (Al‐Onaizi et al, 2022; Amirahmadi et al, 2022; Balducci et al, 2017; Hong et al, 2016; Morris et al, 2013; Sandhu et al, 2022; Zhang et al, 2022).…”

Ranuncoside’s attenuation of scopolamine-induced memory impairment in mice via Nrf2 and NF-ĸB signaling

“…Group I (Control group or C), Group II (Scopolamine treated group or SCOP), Group III (Scopolamine plus Ranuncoside treated group or SCOP + R) and Group IV (Ranuncosid treated group or R). Mice of group 1 received normal saline (0.9%) on daily basis as described in previous literature ( Naseer et al, 2014 , Jahan et al, 2022 ), group II received injection of scopolamine (1 mg/kg/day) for a period of three weeks, according to the protocol described in previous literature ( Yadang et al, 2020 , Noroozi et al, 2022 , Sandhu et al, 2022 , Syed et al, 2022 ), group III was subjected injections of scopolamine (1 mg/kg/day) for three weeks, along with ranuncoside (10 mg/kg) administered every other day for a duration of two weeks while group IV was treated with ranuncoside (10 mg/kg) after a gap of every fifth day. The injections were delivered intraperitoneally with great care on the specified days.…”