Sinapic Acid Attenuates the Neuroinflammatory Response by Targeting AKT and MAPK in LPS-Activated Microglial Models

Abstract

Sinapic acid (SA) is a phenolic acid that is widely found in fruits and vegetables, which has various bioactivities, such as antidiabetic, anti-in ammatory, anticancer and anxiolytic functions. Overactivated microglial cells play a major role in the development of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The objective of this study was to investigate the effect and mechanism of sinapic acid in microglia-derived neuroin ammatory models. Our results demonstrated that SA inhibited production of the nitric oxide (NO) pro-in ammatory factor, induced nitric oxide synthase (iNOS), induced interleukin (IL)-6 and enhanced the release of IL-10 in a dose-dependent manner. Subsequently, a mechanistic study revealed that SA remarkably attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, administration of SA regulated the production of in ammation-related cytokines and inhibited the phosphorylation of MAPK cascades and Akt in the mouse cerebral cortex. These results suggested that SA may offer a possible treatment for antiin ammatory activity by targeting the AKT/MAPK signaling pathway.

Lysophosphatidic Acid Receptor 1 Plays a Pathogenic Role in Permanent Brain Ischemic Stroke by Modulating Neuroinflammatory Responses

“…These effector pathways are involved in LPA 1 -dependent pathogenesis of transient ischemic stroke ( Gaire et al ., 2019b ). Moreover, activation of MAPKs can contribute to pro-inflammatory responses ( Huang et al ., 2023 ), whereas activation of PI3K/Akt can contribute to anti-inflammatory responses ( Vergadi et al ., 2017 ; He et al ., 2022 ). Therefore, we determined whether these effector pathways of LPA 1 could be involved in LPA 1 -dependent pathogenesis after pMCAO challenge by Western blot analysis.…”

Assessment of Pharmaco-Technological Parameters of Solid Lipid Nanoparticles as Carriers for Sinapic Acid

“…Sinapic acid is abundantly found in different plant species, e.g., strawberries and cranberries, as well as cereals and vegetables; it is one of the most common compounds in the Brassicaceae family. Data found in the literature show that sinapic acid possesses antioxidant and anti-inflammatory properties [3], as well as anticancer [4], hepatoprotective [5], cardioprotective [6], renoprotective [6], neuroprotective [7], antidiabetic [8], anxiolytic [9], and antibacterial activity [10]. A review of the pharmacological and therapeutic applications of sinapic acid was recently published by Pandi et al [11].…”

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders

“…63 In terms of SA's anti-inflammatory properties, studies done in vitro and in vivo showed that it could work as an active substance by blocking the MAPK and AKT signaling pathways to stop LPS-induced inflammation and could be a possible therapeutic choice for treating NDs that are connected to inflammation. 61 The mechanism of SA's neuroprotective activity has also been investigated in connection with GABA, which is the primary inhibitory neurotransmitter for the adult central nervous system, generated by the GABAergic neurons in the hippocampus, thalamus, basal ganglia, hypothalamus, and brainstem, and it reduces neuronal excitability through nerve transmission blockade. For a proper neurologic function, there must be a balance between inhibitory neuronal transmission via GABA and excitatory transmission via glutamate.…”

“…Neuroinflammation happens when cells in the central nervous system, mainly microglia, recognize pathogen endotoxins through Toll-like receptors (TLRs) and start the inflammatory process. They then release cytokines and proinflammatory agents, such as nitric oxide, prostaglandin E2, and ROS. , Moreover, these cells activate downstream proteins, including protein kinase B (AKT) and mitogen-activated protein kinases (MAPKs), by triggering antigen-induced signal transduction pathways. Stimulation by lipopolysaccharide (LPS) leads to the activation of MAPK cascades, with AKT serving as an essential effector kinase downstream of phosphoinositide 3-kinases (PI3K) .…”

“…Stimulation by lipopolysaccharide (LPS) leads to the activation of MAPK cascades, with AKT serving as an essential effector kinase downstream of phosphoinositide 3-kinases (PI3K) . In terms of SA’s anti-inflammatory properties, studies done in vitro and in vivo showed that it could work as an active substance by blocking the MAPK and AKT signaling pathways to stop LPS-induced inflammation and could be a possible therapeutic choice for treating NDs that are connected to inflammation . The mechanism of SA’s neuroprotective activity has also been investigated in connection with GABA, which is the primary inhibitory neurotransmitter for the adult central nervous system, generated by the GABAergic neurons in the hippocampus, thalamus, basal ganglia, hypothalamus, and brainstem, and it reduces neuronal excitability through nerve transmission blockade.…”