Caesalpinia mimosoides Leaf Extract Promotes Neurite Outgrowth and Inhibits BACE1 Activity in Mutant APP-Overexpressing Neuronal Neuro2a Cells

Abstract

Alzheimer’s disease (AD) is implicated in the imbalance of several proteins, including Amyloid-β (Aβ), amyloid precursor protein (APP), and BACE1. APP overexpression interferes with neurite outgrowth, while BACE1 plays a role in Aβ generation. Medicinal herbs with effects on neurite outgrowth stimulation and BACE1 inhibition may benefit AD. This study aimed to investigate the neurite outgrowth stimulatory effect, along with BACE1 inhibition of Caesalpinia mimosoides (CM), using wild-type (Neuro2a) and APP (Swedish mutant)-overexpressing (Neuro2a/APPSwe) neurons. The methanol extract of CM leaves stimulated neurite outgrowth in wild-type and APP-overexpressing cells. After exposure to the extract, the mRNA expression of the neurite outgrowth activation genes growth-associated protein-43 (GAP-43) and teneurin-4 (Ten-4) was increased in both Neuro2a and Neuro2a/APPSwe cells, while the mRNA expression of neurite outgrowth negative regulators Nogo receptor (NgR) and Lingo-1 was reduced. Additionally, the extract suppressed BACE1 activity in the APP-overexpressing neurons. Virtual screening demonstrated that quercetin-3′-glucuronide, quercetin-3-O-glucoside, clausarinol, and theogallin were possible inhibitors of BACE1. ADMET was analyzed to predict drug-likeness properties of CM-constituents. These results suggest that CM extract promotes neurite outgrowth and inhibits BACE1 activity in APP-overexpressing neurons. Thus, CM may serve as a source of drugs for AD treatment. Additional studies for full identification of bioactive constituents and to confirm the neuritogenesis in vivo are needed for translation into clinic of the present findings.

Polyherbal formulation exerts wound healing, anti-inflammatory, angiogenic and antimicrobial properties: Potential role in the treatment of diabetic foot ulcers

“…The real-time PCR assay was performed using AccuPower 2X GreenStar™ qPCR Master Mix (Bioneer) in Exicycler™ 96 (Bioneer) using gene-specific primers ( Table 3 ). The mRNA expression level was calculated via the delta-delta Ct method using GAPDH as an internal control ( Rangsinth et al, 2021 ).…”

Thunbergia laurifolia Leaf Extract Inhibits Glutamate-Induced Neurotoxicity and Cell Death through Mitophagy Signaling

“…Co-crystal structures of Kelch-like ECH-associated protein 1 (KEAP1) complexed with 2-[[4-[2-hydroxy-2-oxoethyl-(4-methoxyphenyl)sulfonyl-amino]-3-phenylmethoxy-phenyl]-(4-methoxyphenyl)sulfonyl-amino]ethanoic acid (GX8) (PDB ID: 6HWS, , accessed on 23 August 2021) and PTEN-induced kinase 1 (PINK1) complexed with ubiquitin (PDB ID: 6EQI, , accessed on 23 August 2021) [ 24 ], and E3 ubiquitin–protein ligase parkin (PDB ID: 5C1Z, , accessed on 23 August 2021) [ 25 ] were obtained from RCSB Protein Data Bank. Protein and compound files were prepared following the previous procedure [ 26 ]. Briefly, the proteins were prepared by removing all waters and original ligands, as well as adding missing hydrogen atoms and Kollman charges using the AutoDockTools-1.5.6 program.…”

“…[24], and E3 ubiquitin-protein ligase parkin (PDB ID: 5C1Z, https://www.rcsb.org/structure/5C1Z, accessed on 23 August 2021) [25] were obtained from RCSB Protein Data Bank. Protein and compound files were prepared following the previous procedure [26]. Briefly, the proteins were prepared by removing all waters and original ligands, as well as adding missing hydrogen atoms and Kollman charges using the AutoDockTools-1.5.6 program.…”

Effect of Thai medicinal plants Acanthus ebracteatus Vahl. Carthamus tinctorius L. and Streblus asper Lour. on neurite outgrowth activity in Neuro-2A cells

“…Many studies with herbal extracts have identified increased neurite outgrowth 10 as a potential feature of the herb's neuroprotective properties. 11,12 Thai medicinal herb Streblus asper Lour. (SA) Has previously been shown to protect against photoaging and provide neuroprotection in C.elegans.…”