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Molecular Mechanism of Natural Compounds in Neuroinflammation

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 11951

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Special Issue Editor

Dr. Anne Vejux

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Guest Editor

Team “Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism”, Université de Bourgogne, 21000 Dijon, France
Interests: oxysterols; very-long-chain fatty acids; lipid metabolism; diet, peroxisomes; biotherapies; inflammation; cancer; cell cycle and apoptosis; autophagy; biological membranes; oxidative damage; biomarkers; neurodegenerative diseases
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Special Issue Information

Dear Colleagues,

Neuroinflammation corresponds to inflammatory cascades that occur in both the peripheral nervous system (PNS) and the central nervous system (CNS), involving both the immune and nervous systems, complicating its characterization.

From a pathological point of view, in the CNS, neuroinflammation is related to damage resulting from direct penetrating physical injury: traumatic brain injury (TBI), spinal cord injury (SCI) for example, or biochemical disorders such as neurodegenerative pathologies Multiple Sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), tumors (gliomas) or aging. These conditions have a significant impact on the health care system, on patients' lives and require rehabilitation therapies and support services. This neuroinflammation involves pro and anti-inflammatory responses involving among others soluble factors such as cytokines but also different cell types such as microglia, oligodendrocytes, or even astrocytes. Neuroinflammation is a physiological process which when uncontrolled leads to the deterioration of healthy tissue, limiting the physiological functions of these tissues. Even though there are some points like the cause-and-effect interaction between neuroinflammation and neurodegeneration, the involvement of each molecular pathological event in the disease which are not fully known, it is useful to research and develop solutions to slow down or suppress this neuroinflammation. One of the possible solutions is the use of natural molecules to control this neuroinflammation and open more natural therapeutic perspectives. More broadly, studies to investigate the impact of diet/nutrition on the activation of nervous system cells involved in neuroinflammation in a physiological or pathological context may also provide important information (for example the study of role of chronic neuroinflammation in neuroplasticity and cognitive function in relationship with natural molecules).

Dr. Anne Vejux
Guest Editor

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Keywords

neuroinflammation
natural molecules
microglia
cytokines
feeding
immune system

Published Papers (5 papers)

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Research

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21 pages, 4250 KiB

Open AccessArticle

Identification of Anti-Neuroinflammatory Bioactive Compounds in Essential Oils and Aqueous Distillation Residues Obtained from Commercial Varieties of Cannabis sativa L.

by Maria Cristina Barbalace, Michela Freschi, Irene Rinaldi, Eugenia Mazzara, Tullia Maraldi, Marco Malaguti, Cecilia Prata, Filippo Maggi, Riccardo Petrelli, Silvana Hrelia and Cristina Angeloni

Int. J. Mol. Sci. 2023, 24(23), 16601; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242316601 - 22 Nov 2023

Viewed by 1849

Abstract

Neuroinflammation, which is mainly triggered by microglia, is a key contributor to multiple neurodegenerative diseases. Natural products, and in particular Cannabis sativa L., due to its richness in phytochemical components, represent ideal candidates to counteract neuroinflammation. We previously characterized different C. sativa commercial varieties which showed significantly different chemical profiles. On these bases, the aim of this study was to evaluate essential oils and aqueous distillation residues from the inflorescences of three different hemp varieties for their anti-neuroinflammatory activity in BV-2 microglial cells. Cells were pretreated with aqueous residues or essential oils and then activated with LPS. Unlike essential oils, aqueous residues showed negligible effects in terms of anti-inflammatory activity. Among the essential oils, the one obtained from ‘Gorilla Glue’ was the most effective in inhibiting pro-inflammatory mediators and in upregulating anti-inflammatory ones through the modulation of the p38 MAPK/NF-κB pathway. Moreover, the sesquiterpenes (E)-caryophyllene, α-humulene, and caryophyllene oxide were identified as the main contributors to the essential oils’ anti-inflammatory activity. To our knowledge, the anti-neuroinflammatory activity of α-humulene has not been previously described. In conclusion, our work shows that C. sativa essential oils characterized by high levels of sesquiterpenes can be promising candidates in the prevention/counteraction of neuroinflammation. Full article

(This article belongs to the Special Issue Molecular Mechanism of Natural Compounds in Neuroinflammation)

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15 pages, 4447 KiB

Open AccessArticle

The Mechanism of Two Benzaldehydes from Aspergillus terreus C23-3 Improve Neuroinflammatory and Neuronal Damage to Delay the Progression of Alzheimer’s Disease

by Minqi Chen, Jinyue Liang, Yi Liu, Yayue Liu, Chunxia Zhou, Pengzhi Hong, Yi Zhang and Zhong-Ji Qian

Int. J. Mol. Sci. 2023, 24(2), 905; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24020905 - 04 Jan 2023

Cited by 2 | Viewed by 1704

Abstract

Alzheimer’s disease (AD), a neurodegenerative disease, is the most common cause of dementia in humans worldwide. Although more in-depth research has been carried out on AD, the therapeutic effect of AD is not as expected, and natural active substances are increasingly sought after by scientists. In the present study, we evaluated two benzaldehydes from a coral-derived Aspergillus terreus strain C23-3, their anti-neuroinflammatory activity in microglia (BV-2), and their neuroprotective activity and mechanisms in hippocampal neuronal cells (HT-22). These include the protein expression of iNOS, COX-2, MAPKs pathways, Tau protein-related pathways, caspases family-related signaling pathways. They also include the levels of TNF-α, IL-6, IL-18 and ROS, as well as the level of mitochondrial oxidative stress and neuronal cell apoptosis. The results showed that both benzaldehydes were effective in reducing the secretion of various inflammatory mediators, as well as pro-inflammatory factors. Among these, benzaldehyde 2 inhibited mitochondrial oxidative stress and blocked neuronal cell apoptosis through Tau protein-related pathways and caspases family-related signaling pathways, thereby inhibiting β-amyloid (Aβ)-induced neurological damage. This study reveals that benzaldehyde 2 has potential as a therapeutic agent for Alzheimer’s disease, and offers a new approach to the high-value use of marine natural products. Full article

(This article belongs to the Special Issue Molecular Mechanism of Natural Compounds in Neuroinflammation)

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19 pages, 5717 KiB

Open AccessArticle

Imperatorin Improves Obesity-Induced Cardiac Sympathetic Nerve Injury Mediated by P2X4 Receptor in Stellate Sympathetic Ganglion

by Mingming Zhang, Yuqing Wen, Peiwen Liang, Changsen Yang, Hongcheng Tu, Jingyi Wei, Junpei Du, Ting Zhan, Shangdong Liang, Guodong Li and Yun Gao

Int. J. Mol. Sci. 2023, 24(1), 783; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010783 - 02 Jan 2023

Cited by 3 | Viewed by 1522

Abstract

Obesity can activate the inflammatory signal pathway, induce in the body a state of chronic inflammation, and increase the excitability of the sympathetic nervous system, which may induce sympathetic neuropathic injury. The stellate sympathetic ganglia (SG) can express the P2X4 receptor, and the abnormal expression of the P2X4 receptor is related to inflammation. Imperatorin (IMP) is a kind of furan coumarin plant which has anti-inflammatory effects. This project aimed to investigate whether IMP can affect the expression of P2X4 receptors in the SG of obese rats to display a protective effect from high-fat-triggered cardiac sympathetic neuropathic injury. Molecular docking through homology modelling revealed that IMP had good affinity for the P2X4 receptor. Our results showed that compared with the normal group, the administration of IMP or P2X4 shRNA decreased sympathetic excitement; reduced the serum levels of triglyceride, total cholesterol, and lactate dehydrogenase; downregulated the expression of P2X4 receptors in SG; and inhibited the expression of inflammatory factors in the SG and serum of obese rats significantly. In addition, the expression of factors associated with the cell pyroptosis GSDMD, caspase-1, NLRP-3, and IL-18 in obese rats were significantly higher than those of the normal rats, and such effects were decreased after treatment with IMP or P2X4 shRNA. Furthermore, IMP significantly reduced the ATP-activated currents in HEK293 cells transfected with P2X4 receptor. Thus, the P2X4 receptor may be a key target for the treatment of obesity-induced cardiac sympathetic excitement. IMP can improve obesity-induced cardiac sympathetic excitement, and its mechanism of action may be related to the inhibition of P2X4 receptor expression and activity in the SG, suppression of cellular pyroptosis in the SG, and reduction of inflammatory factor levels. Full article

(This article belongs to the Special Issue Molecular Mechanism of Natural Compounds in Neuroinflammation)

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12 pages, 1675 KiB

Open AccessArticle

Coffee Polyphenol, Chlorogenic Acid, Suppresses Brain Aging and Its Effects Are Enhanced by Milk Fat Globule Membrane Components

by Keiko Unno, Kyoko Taguchi, Tadashi Hase, Shinichi Meguro and Yoriyuki Nakamura

Int. J. Mol. Sci. 2022, 23(10), 5832; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105832 - 23 May 2022

Cited by 7 | Viewed by 3000

Abstract

Mice feed with coffee polyphenols (CPP, chlorogenic acid) and milk fat globule membrane (MFGM) has increased survival rates and helps retain long-term memory. In the cerebral cortex of aged mice, CPP intake decreased the expression of the proinflammatory cytokine TNF-α, and lysosomal enzyme cathepsin B. The suppression of inflammation in the brain during aging was thought to result in the suppression of the repressor element 1-silencing transcription factor (REST) and prevention of brain aging. In contrast, CPP increased the expression of REST, cAMP-responsive element binding (CREB) and transforming growth factor β1 (TGF-β1) in the young hippocampus. The increased expression of these factors may contribute to the induction of neuronal differentiation and the suppression of memory decline with aging. Taken together, these results suggest that CPP increases CREB in the young hippocampus and suppresses inflammation in the old brain, resulting in a preventive effect on brain aging. The endotoxin levels were not elevated in the serum of aged mice. Although the mechanism of action of MFGM has not yet been elucidated, the increase in survival rate with both CPP and MFGM intake suggests that adding milk to coffee may improve not only the taste, but also the function. Full article

(This article belongs to the Special Issue Molecular Mechanism of Natural Compounds in Neuroinflammation)

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Review

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30 pages, 1265 KiB

Open AccessReview

Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut–Brain Axis

by Humna Liaqat, Amna Parveen and Sun-Yeou Kim

Int. J. Mol. Sci. 2022, 23(23), 14968; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314968 - 29 Nov 2022

Cited by 8 | Viewed by 3114

Abstract

Modern neurological approaches enable detailed studies on the pathophysiology and treatment of depression. An imbalance in the microbiota–gut–brain axis contributes to the pathogenesis of depression. This extensive review aimed to elucidate the antidepressive effects of brain-derived neurotrophic factor (BDNF)-targeting therapeutic natural products and their derivatives on the gut–brain axis. This information could facilitate the development of novel antidepressant drugs. BDNF is crucial for neuronal genesis, growth, differentiation, survival, plasticity, and synaptic transmission. Signaling via BDNF and its receptor tropomyosin receptor kinase B (TrkB) plays a vital role in the etiopathogenesis of depression and the therapeutic mechanism of antidepressants. This comprehensive review provides information to researchers and scientists for the identification of novel therapeutic approaches for neuropsychiatric disorders, especially depression and stress. Future research should aim to determine the possible causative role of BDNF-TrkB in the gut–brain axis in depression, which will require further animal and clinical research as well as the development of analytical approaches. Full article

(This article belongs to the Special Issue Molecular Mechanism of Natural Compounds in Neuroinflammation)

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