The Extracts of Angelica sinensis and Cinnamomum cassia from Oriental Medicinal Foods Regulate Inflammatory and Autophagic Pathways against Neural Injury after Ischemic Stroke

Abstract

The study indicates inflammation and autophagy are closely related to neural apoptosis in the pathology of ischemic stroke. In the study, we investigate the effects and mechanisms of the extracts of Angelica sinensis and Cinnamomum cassia (AC) from oriental medicinal foods on inflammatory and autophagic pathways in rat permanent middle cerebral artery occlusion model. Three doses of AC extract were, respectively, administered for 7 days. It suggests that AC extract treatment ameliorated scores of motor and sensory functions and ratio of glucose utilization in thalamic lesions in a dose-dependent manner. Expression of Iba1 was decreased and CD206 was increased by immunofluorescence staining, western blotting results showed expressions of TLR4, phosphorylated-IKKβ and IκBα, nuclear P65, NLRP3, ASC, and Caspase-1 were downregulated, and Beclin 1 and LC3 II were upregulated. Low concentrations of TNF-α, IL-1β, and IL-6 were presented by ELISA assay. Additionally, caspase 8 and cleaved caspase-3 expressions and the number of TUNEL positive cells in ipsilateral hemisphere were decreased, while the ratio of Bcl-2/Bax was increased. Simultaneously, in LPS-induced BV2 cells, it showed nuclear P65 translocation and secretion of proinflammatory cytokines were suppressed by AC extract-contained cerebrospinal fluid, and its intervened effects were similar to TLR4 siRNA treatment. Our study demonstrates that AC extract treatment attenuates inflammatory response and elevates autophagy against neural apoptosis, which contributes to the improvement of neurological function poststroke. Therefore, AC extract may be a novel neuroprotective agent by regulation of inflammatory and autophagic pathways for ischemic stroke treatment.

Molecular mechanisms underlying the therapeutic effects of Linggui Zhugan decoction in stroke: Insights from network pharmacology and single-cell transcriptomics analysis

“…[ 29 ] Studies have demonstrated that extracts derived from Cinnamomum cassia possess the ability to modulate inflammatory and autophagic pathways subsequent to ischemic stroke. [ 30 ] Additionally, Glycyrrhiza uralensis, commonly referred to as Licorice, exhibits diverse pharmacological activities including neuroprotective, antifungal, and anticaries effects. Pretreatment with Licorice has been found to regulate apoptosis-related proteins, thereby conferring protection against cerebral ischemic injury in mice.…”

Gut-brain axis: Mechanisms and potential therapeutic strategies for ischemic stroke through immune functions

“…Lipid A and core LPS signals have been observed at the blood-brain interface, and co-localization of LPS with CD14/TLR4 receptors and lipoprotein receptors [including SR-BI and lowdensity lipoprotein (LDL) receptor], suggesting that LPS enters the brain under physiological conditions, possibly through a lipoprotein transport mechanism (Janova et al, 2016;Leláková et al, 2020). A study in which an LPS injection was administered to pigs supported the general idea that LPS affects cytokine and neurotransmitter levels; the LPS injection was found to increase expression of several 10.3389/fnins.2023.1081347 pro-inflammatory cytokines (IL-1 receptor agonists, IL-6, TNF-α, and IFN-γ) and decrease norepinephrine levels in the cortex of the hypothalamus, hippocampus, and frontal lobe (Dickinson et al, 2009)Another study reported that compared with control mice, LPS exposure increased the expression of TNF-α, COX-2, NOS-2 and IL-1β, activated TLR4 and NF-κB signaling, and induced neuroinflammation in the cortex and hippocampus of adult mice (Luo et al, 2021;Xian et al, 2021). Other studies have confirmed that LPS can induce neuronal degeneration by increasing Bax/Bcl2 levels, decreasing cytochrome-c, and decreasing the expression of poly ADP-ribose polymerase-1 (Iványi et al, 2003).…”

Biomarkers and the outcomes of ischemic stroke

“…The levels of TNF-a in CSF have been found to be increased in patients at 24 h, 1 week, and 2 weeks after stroke, and correlate with infarct volume and severity of neurological impairment ( Shang et al, 2020 ; Deng et al, 2021 ). Real-time PCR analysis in rats after t-MCAO has revealed that the mRNA levels for TNF-a, IL-1b, IL-6, E-selectin, and ICAM-1 are increased 3 h after stroke that persist for 24 h in the hemisphere ipsilateral to occlusion ( Elango and Devaraj, 2010 ; Luo et al, 2021 ).…”