Major compounds of red ginseng oil attenuate Aβ_25–35-induced neuronal apoptosis and inflammation by modulating MAPK/NF-κB pathway

Abstract

β-Amyloid (Aβ)-induced neuronal toxicity in Alzheimer's disease (AD) is associated with complex mechanisms. Thus, a multi-target approach might be suitable for AD treatment. Following our previous study on the neuroprotective effects of red ginseng oil extract, its major compounds, including linoleic acid (LA), β-sitosterol (BS), and stigmasterol (SS), were examined to elucidate the mechanism of anti-apoptosis and anti-inflammation in Aβ25-35-stimulated PC12 cells. The results showed that the three compounds mitigated Aβ25-35 toxicity by regulating oxidative stress, apoptotic responses, and pro-inflammatory mediators. LA and SS strongly regulated intrinsic apoptosis markers, such as mitochondrial membrane potential, intracellular Ca2+, Bax/Bcl-2 ratio, and caspases-9, -3, and -8. However, BS blocked only the intrinsic apoptotic pathway, particularly by suppressing Ca2+ accumulation. Furthermore, all three compounds downregulated iNOS and phospho-nuclear factor-κB, but only LA and SS inhibited the expression of cyclooxygenase-2 and phospho-IκB. In assays to evaluate MAPK expression for confirming upstream signal pathways, BS decreased the phosphorylation of p38 and ERK, but not JNK, while SS markedly decreased the phosphorylation of all three MAPKs, and LA clearly decreased the phosphorylation of ERK and JNK, but not p38. These results indicate that LA, BS, and SS act as neuroprotectives against Aβ25-35-induced injury by distinct molecular mechanisms, indicating their preventive and/or therapeutic potential to treat AD.

Integrated meta-analysis, network pharmacology, and molecular docking to investigate the efficacy and potential pharmacological mechanism of Kai-Xin-San on Alzheimer's disease

“…Stigmasterol is a terpenoid that reduce production of Ab thereby protecting the nerves in vivo (Burg et al 2013). Moreover, it has been reported to down-regulate inducible nitric oxide synthase and phosphorylation of factor-jB as well as exert anti-apoptotic and anti-inflammatory effects (Lee et al 2018). In the same line, fumarine has been reported to inhibit acetylcholinesterase activity and reduce memory impairment (Kim et al 1999).…”

Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection

“…Red ginseng oil extract is composed mainly of linoleic acid, β-sitosterol and stigmasterol. These three compounds inhibit the toxicity induced by Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) by regulating oxidative stress, apoptosis and inflammation but using different molecular mechanisms in PC12 cells [95]. For example, at the level of cell death, linoleic acid and stigmasterol regulate mitochondrial membrane potential; intracellular calcium; Bax/Bcl-2 ratio and caspases-9, -3 and -8, while β-sitosterol blocks only the intrinsic apoptotic pathway [95].…”

<p>Anti-Inflammatory Activity of Sanjie Zhentong Capsule Assessed By Network Pharmacology Analysis of Adenomyosis Treatment </p>

“…For instance, oxidation products of stigmasterol interfered with the female sex hormone 17β-estradiol in human breast and endometrium cells. 30 Stigmasterol itself decreased inflammation by modulating the MAPK/NF-κB ROCK1 pathway, 31 combined stigmasterols achieved more obvious anti-proliferation in Caco-2 cells than a single stigmasterol, 32 and reduced TNF-ɑ and VEGFR-2 signaling by affecting phosphorylated Src, Akt, PCL, and FAK. 33 It can be inferred that our approach is reliable and the screened active compounds act synergistically in the treatment of AM.…”