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Special Issue "Role of Natural Compounds in Inflammation and Inflammatory-Related Diseases"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 31 July 2019

Special Issue Editor

Guest Editor
Prof. Francesco Maione

Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
Website | E-Mail
Interests: inflammation, immuno-pharmacology, pharmacology of natural compounds and nutraceuticals

Special Issue Information

Dear Colleagues,

Inflammation is a complex biological response to injury as a result of different stimuli such as pathogens, damaged cells, or irritants. Inflammatory injuries induce the release of a variety of systemic mediators, cytokines and chemokines that orchestrate the cellular infiltration that consequentially bring about the resolution of inflammatory responses and the restoration of tissue integrity. However, persistent inflammatory stimuli or the disregulation of mechanisms of the resolution phase can lead to chronic inflammation and inflammatory-based diseases.

Nowadays, commercially approved anti-inflammatory drugs are represented by nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids (SAID), and in some cases immunosuppressant and/or biological drugs. These agents are effective for the relief of the main inflammatory symptoms. However, they induce severe side effects, and most of them are inadequate for chronic use.

Starting from these premises, the demand for new effective and safe anti-inflammatory drugs has furthered research into new therapeutic approaches. The recent and emerging scientific community slant is oriented towards natural products/compounds that could represent a treasure for the discovery of new active molecules and for the development of new drugs and potentially useful therapeutic agents in different inflammatory-related diseases.

We hope that this Special Issue will stimulate the interest of the scientific community involved in studying the effects of natural products/compounds on different fields of interests such as acute and chronic inflammation, inflammatory pain, inflammatory-related diseases (such as autoimmune disease) and other.

The papers published here will contribute to proposing new insights into the mechanisms of several conditions, as well as suggesting new diagnostic alternatives and therapeutic targets in widespread pathologies. The discovery of the new is, as always, anchored in recourse to the old.

Prof. Francesco Maione
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Inflammation
  • Inflammatory-based diseases
  • Natural compounds
  • Natural products
  • Nutraceuticals

Published Papers (9 papers)

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Research

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Open AccessArticle
Inhibitory Effects on NO Production and DPPH Radicals and NBT Superoxide Activities of Diarylheptanoid Isolated from Enzymatically Hydrolyzed Ehthanolic Extract of Alnus sibirica
Molecules 2019, 24(10), 1938; https://doi.org/10.3390/molecules24101938
Received: 16 April 2019 / Revised: 5 May 2019 / Accepted: 17 May 2019 / Published: 20 May 2019
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Abstract
Alnus sibirica (AS) is geographically distributed in Korea, Japan, Northeast China, and Russia. Various anti-oxidant, anti-inflammation, anti-atopic dermatitis and anti-cancer biological effects of AS have been reported. Enzymatic hydrolysis decomposes the sugar bond attached to glycoside into aglycone which, generally, has a superior [...] Read more.
Alnus sibirica (AS) is geographically distributed in Korea, Japan, Northeast China, and Russia. Various anti-oxidant, anti-inflammation, anti-atopic dermatitis and anti-cancer biological effects of AS have been reported. Enzymatic hydrolysis decomposes the sugar bond attached to glycoside into aglycone which, generally, has a superior biological activity, compared to glycoside. Enzymatic hydrolysis of the extract (EAS) from AS was processed and the isolated compounds were investigated—hirsutanonol (1), hirsutenone (2), rubranol (3), and muricarpon B (4). The structures of these compounds were elucidated, and the biological activities were assessed. The ability of EAS and the compounds (14) to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and Nitroblue tetrazolium (NBT) superoxide, and to inhibit NO production was evaluated in vitro. EAS showed more potent antioxidant and anti-inflammatory activity than AS. All investigated compounds showed excellent antioxidant and anti-inflammatory activities. Full article
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Open AccessArticle
Polyphenols-Rich Fruit (Euterpe edulis Mart.) Prevents Peripheral Inflammatory Pathway Activation by the Short-Term High-Fat Diet
Molecules 2019, 24(9), 1655; https://doi.org/10.3390/molecules24091655
Received: 2 April 2019 / Revised: 24 April 2019 / Accepted: 26 April 2019 / Published: 27 April 2019
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Abstract
Juçara berry is a potential inflammatory modulator, rich in dietary fiber, fatty acids, and anthocyanins. Considering this, we evaluated the high-fat diet (HFD) intake supplemented with different doses of freeze-dried juçara pulp on the TLR4 pathway. Twenty-seven male Wistar rats with ad libitum [...] Read more.
Juçara berry is a potential inflammatory modulator, rich in dietary fiber, fatty acids, and anthocyanins. Considering this, we evaluated the high-fat diet (HFD) intake supplemented with different doses of freeze-dried juçara pulp on the TLR4 pathway. Twenty-seven male Wistar rats with ad libitum access to food and water were divided into four experimental groups: control standard chow group (C); high-fat diet control group (HFC); high-fat diet juçara 0.25% group (HFJ0.25%); and high-fat diet juçara 0.5% group (HFJ0.5%). The inflammatory parameters were analyzed by ELISA and Western blotting in liver and retroperitoneal adipose tissue (RET). The HFJ0.25% group had the energy intake, aspartate transaminase (AST) levels, and liver triacylglycerol accumulation reduced; also, the tumor necrosis factor α (TNF-α) and TNF receptor-associated factor 6 (TRAF6) expression in RET were reduced. However, there were no changes in other protein expressions in liver and adipose tissue. Adiposity and pNFκBp50 had a positive correlation in HFC and HFJ0.5%, but not in the C group and HFJ0.25%. The necrosis hepatic score did not change with treatment; however, the serum (AST) levels and the hepatic triacylglycerol were increased in HFC and HFJ0.5%. These results demonstrated that one week of HFD intake triggered pro-inflammatory mechanisms and liver injury. Additionally, 0.25% juçara prevented inflammatory pathway activation, body weight gain, and liver damage Full article
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Open AccessArticle
Antineuroinflammatory Activities and Neurotoxicological Assessment of Curcumin Loaded Solid Lipid Nanoparticles on LPS-Stimulated BV-2 Microglia Cell Models
Molecules 2019, 24(6), 1170; https://doi.org/10.3390/molecules24061170
Received: 12 December 2018 / Revised: 11 March 2019 / Accepted: 19 March 2019 / Published: 25 March 2019
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Abstract
Curcumin, which is a potential antineuroinflammatory and neuroprotective compound, exhibits poor bioavailability in brain cells due to its difficulty in crossing the blood–brain barrier and its rapid metabolism during circulation, which decreases its efficacy in treating chronic neuroinflammatory diseases in the central nervous [...] Read more.
Curcumin, which is a potential antineuroinflammatory and neuroprotective compound, exhibits poor bioavailability in brain cells due to its difficulty in crossing the blood–brain barrier and its rapid metabolism during circulation, which decreases its efficacy in treating chronic neuroinflammatory diseases in the central nervous system. The bioavailability and potential of curcumin can be improved by using a nanodelivery system, which includes solid lipid nanoparticles. Curcumin-loaded solid lipid nanoparticles (SLCN) were efficiently developed to have a particle size of about 86 nm and do not exhibit any toxicity in the endothelial brain cells. Furthermore, the curcumin-loaded solid lipid nanoparticles (SLCN) were studied to assess their efficacy in BV-2 microglial cells against LPS-induced neuroinflammation. The SLCN showed a higher inhibition of nitric oxide (NO) production compared to conventional curcumin in a dose-dependent manner. Similarly, the mRNA and proinflammatory cytokine levels were also reduced in a dose-dependent manner when compared to those with free curcumin. Thus, SLCN could be a potential delivery system for curcumin to treat microglia-mediated neuroinflammation. Full article
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Open AccessArticle
Theaflavins Improve Memory Impairment and Depression-Like Behavior by Regulating Microglial Activation
Molecules 2019, 24(3), 467; https://doi.org/10.3390/molecules24030467
Received: 8 January 2019 / Revised: 26 January 2019 / Accepted: 27 January 2019 / Published: 28 January 2019
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Abstract
Inflammation in the brain is associated with various disorders including Alzheimer’s disease and depression. Thus, inflammation has received increasing attention regarding preventive approaches to such disorders. Epidemiological investigations have reported that drinking tea reduces the risk of dementia and depression. Theaflavins, a polyphenol [...] Read more.
Inflammation in the brain is associated with various disorders including Alzheimer’s disease and depression. Thus, inflammation has received increasing attention regarding preventive approaches to such disorders. Epidemiological investigations have reported that drinking tea reduces the risk of dementia and depression. Theaflavins, a polyphenol found in black tea, are known to have anti-oxidative and anti-inflammation effects, but the effects of theaflavins on cognitive decline and depression induced by inflammation have not been investigated. To address this research gap, the present study assessed whether theaflavins could protect synapses and dendrites damaged by inflammation and prevent concomitant memory impairment and depression-like behavior in mice. Intracerebroventricular injection with lipopolysaccharide (LPS) induces neural inflammation associated with reduced spontaneous alternations in the Y-maze test and increased immobility in the tail suspension test, indicating impaired spatial memory and depression-like behavior, respectively. Oral administration with theaflavins prevented these behavioral changes induced by LPS. Theaflavins also suppressed productions of inflammatory cytokines and prevented dendritic atrophy and spine loss in the brain. Notably, theaflavins have a stronger anti-inflammatory effect than other polyphenols such as catechin, chlorogenic acid, and caffeic acid. These results suggest that theaflavins can suppress neural inflammation and prevent the symptoms of inflammation-related brain disorders. Full article
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Open AccessArticle
20-Hydroxy-3-Oxolupan-28-Oic Acid Attenuates Inflammatory Responses by Regulating PI3K–Akt and MAPKs Signaling Pathways in LPS-Stimulated RAW264.7 Macrophages
Molecules 2019, 24(3), 386; https://doi.org/10.3390/molecules24030386
Received: 19 December 2018 / Revised: 18 January 2019 / Accepted: 21 January 2019 / Published: 22 January 2019
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Abstract
20-Hydroxy-3-oxolupan-28-oic acid (HOA), a lupane-type triterpene, was obtained from the leaves of Mahonia bealei, which is described in the Chinese Pharmacopeia as a remedy for inflammation and related diseases. The anti-inflammatory mechanisms of HOA, however, have not yet been fully elucidated. Therefore, [...] Read more.
20-Hydroxy-3-oxolupan-28-oic acid (HOA), a lupane-type triterpene, was obtained from the leaves of Mahonia bealei, which is described in the Chinese Pharmacopeia as a remedy for inflammation and related diseases. The anti-inflammatory mechanisms of HOA, however, have not yet been fully elucidated. Therefore, the objective of this study was to characterize the molecular mechanisms of HOA in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. HOA suppressed the release of nitric oxide (NO), pro-inflammatory cytokine tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 macrophages without affecting cell viability. Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) analysis indicated that HOA also suppressed the gene expression of inducible NO synthase (iNOS), TNF-α, and IL-6. Further analyses demonstrated that HOA inhibited the phosphorylation of upstream signaling molecules, including p85, PDK1, Akt, IκBα, ERK, and JNK, as well as the nuclear translocation of nuclear factor κB (NF-κB) p65. Interestingly, HOA had no effect on the LPS-induced nuclear translocation of activator protein 1 (AP-1). Taken together, these results suggest that HOA inhibits the production of cytokine by downregulating iNOS, TNF-α, and IL-6 gene expression via the downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs), and the inhibition of NF-κB activation. Our findings indicate that HOA could potentially be used as an anti-inflammatory agent for medical use. Full article
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Open AccessFeature PaperArticle
Anti-Inflammatory and Anti-Oxidant Activity of Portulaca oleracea Extract on LPS-Induced Rat Lung Injury
Molecules 2019, 24(1), 139; https://doi.org/10.3390/molecules24010139
Received: 16 December 2018 / Revised: 26 December 2018 / Accepted: 26 December 2018 / Published: 1 January 2019
Cited by 2 | PDF Full-text (1854 KB) | HTML Full-text | XML Full-text
Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are classified as two lung complications arising from various conditions such as sepsis, trauma, and lung inflammation. Previous studies have shown that the extract of the leaves of Portulaca oleracea (PO) possesses anti-inflammatory [...] Read more.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are classified as two lung complications arising from various conditions such as sepsis, trauma, and lung inflammation. Previous studies have shown that the extract of the leaves of Portulaca oleracea (PO) possesses anti-inflammatory and anti-oxidant activities. In the present study, the effects of PO (50–200 mg/kg) and dexamethasone (Dexa; 1.5 mg/kg) on lipopolysaccharide (LPS)-induced ALI were investigated. Subsequentially, the lung wet/dry ratio; white blood cells (WBC); levels of nitric oxide (NO); myeloperoxidase (MPO); malondialdehyde (MDA); thiol groups formation; super oxide dismutase (SOD) and catalase (CAT) activities; and levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-10, prostaglandin E2 (PGE2), and transforming growth factor (TGF)-β in the broncho alveolar lavage fluid (BALF) were evaluated in order to demonstrate the anti-oxidant and anti-inflammatory activity of PO. Our results show that PO suppresses lung inflammation by the reduction of IL-β, IL-6, TNF-α, PGE2, and TGF-β, as well as by the increase of IL-10 levels. We also found that PO improves the level of WBC, MPO, and MDA, as well as thiol group formation and SOD and CAT activities, compared with the LPS group. The results of our investigation also show that PO significantly decreased the lung wet/dry ratio as an index of interstitial edema. Taken together, our findings reveal that PO extract dose-dependently displays anti-oxidant and anti-inflammatory activity against LPS-induced rat ALI, paving the way for rational use of PO as a protective agent against lung-related inflammatory disease. Full article
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Open AccessArticle
Iso-α-Acids, the Bitter Components of Beer, Suppress Microglial Inflammation in rTg4510 Tauopathy
Molecules 2018, 23(12), 3133; https://doi.org/10.3390/molecules23123133
Received: 15 November 2018 / Revised: 27 November 2018 / Accepted: 27 November 2018 / Published: 29 November 2018
Cited by 2 | PDF Full-text (2057 KB) | HTML Full-text | XML Full-text
Abstract
Due to the growth in aging populations, prevention for cognitive decline and dementia are in great demand. We previously demonstrated that the consumption of iso-α-acids (IAA), the hop-derived bitter compounds in beer, prevents inflammation and Alzheimer’s disease pathology in model mice. However, the [...] Read more.
Due to the growth in aging populations, prevention for cognitive decline and dementia are in great demand. We previously demonstrated that the consumption of iso-α-acids (IAA), the hop-derived bitter compounds in beer, prevents inflammation and Alzheimer’s disease pathology in model mice. However, the effects of iso-α-acids on inflammation induced by other agents aside from amyloid β have not been investigated. In this study, we demonstrated that the consumption of iso-α-acids suppressed microglial inflammation in the frontal cortex of rTg4510 tauopathy mice. In addition, the levels of inflammatory cytokines and chemokines, including IL-1β and MIP-1β, in the frontal cortex of rTg4510 mice were greater than those of wild-type mice, and were reduced in rTg4510 mice fed with iso-α-acids. Flow cytometry analysis demonstrated that the expression of cells producing CD86, CD68, TSPO, MIP-1α, TNF-α, and IL-1β in microglia was increased in rTg4510 mice compared with wild-type mice. Furthermore, the expression of CD86- and MIP-1α-producing cells was reduced in rTg4510 mice administered with iso-α-acids. Moreover, the consumption of iso-α-acids reduced the levels of phosphorylated tau in the frontal cortex. Collectively, these results suggest that the consumption of iso-α-acids prevents the inflammation induced in tauopathy mice. Thus, iso-α-acids may help in preventing inflammation-related brain disorders. Full article
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Open AccessArticle
Nuciferine Inhibits Proinflammatory Cytokines via the PPARs in LPS-Induced RAW264.7 Cells
Molecules 2018, 23(10), 2723; https://doi.org/10.3390/molecules23102723
Received: 29 September 2018 / Revised: 17 October 2018 / Accepted: 21 October 2018 / Published: 22 October 2018
Cited by 1 | PDF Full-text (2360 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Inflammation is important and has been found to be an underlying cause in many acute and chronic human diseases. Nuciferine, a natural alkaloid containing an aromatic ring, is found in the nelumbo nucifera leaves. It has been shown to have potential anti-inflammatory activities, [...] Read more.
Inflammation is important and has been found to be an underlying cause in many acute and chronic human diseases. Nuciferine, a natural alkaloid containing an aromatic ring, is found in the nelumbo nucifera leaves. It has been shown to have potential anti-inflammatory activities, but the molecular mechanism has remained unclear. In this study, we found that nuciferine (10 μM) significantly inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokine IL-6 and TNF-α production in RAW 264.7 cells. In addition, the luciferase reporter assay results of different subtypes of the peroxisome proliferator-activated receptor (PPAR) showed that nuciferine dose-dependently activated all the PPAR activities. Specific inhibitors of PPARα and PPARγ significantly abolished the production of inflammatory cytokines as well as IκBα degradation. However, PPARδ inhibitor did not show this effect. Our results suggested a potential molecular mechanism of the anti-inflammatory effects of nuciferine in LPS-induced inflammation, at least in part, by activating PPARα and PPARγ in RAW 264.7 cells. Full article
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Review

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Open AccessReview
Therapeutic Approaches of Resveratrol on Endometriosis via Anti-Inflammatory and Anti-Angiogenic Pathways
Molecules 2019, 24(4), 667; https://doi.org/10.3390/molecules24040667
Received: 2 January 2019 / Revised: 8 February 2019 / Accepted: 11 February 2019 / Published: 13 February 2019
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Abstract
Endometriosis represents a severe gynecological pathology, defined by implantation of endometrial glands and stroma outside the uterine cavity. This pathology affects almost 15% of women during reproductive age and has a wide range of consequences. In affected women, infertility has a 30% rate [...] Read more.
Endometriosis represents a severe gynecological pathology, defined by implantation of endometrial glands and stroma outside the uterine cavity. This pathology affects almost 15% of women during reproductive age and has a wide range of consequences. In affected women, infertility has a 30% rate of prevalence and endometriosis implants increase the risk of ovarian cancer. Despite long periods of studies and investigations, the etiology and pathogenesis of this disease still remain not fully understood. Initially, endometriosis was related to retrograde menstruation, but new theories have been launched, suggesting that chronic inflammation can influence the development of endometriosis because inflammatory mediators have been identified elevated in patients with endometriosis, specifically in the peritoneal fluid. The importance of dietary phytochemicals and their effect on different inflammatory diseases have been highlighted, and nowadays more and more studies are focused on the analysis of nutraceuticals. Resveratrol is a phytoestrogen, a natural polyphenolic compound with antiproliferative and anti-inflammatory actions, found in many dietary sources such as grapes, wine, peanuts, soy, berries, and stilbenes. Resveratrol possesses a significant anti-inflammatory effect via inhibition of prostaglandin synthesis and it has been proved that resveratrol can exhibit apoptosis-inducing activities. From the studies reviewed in this paper, it is clear that the anti-inflammatory effect of this natural compound can contribute to the prevention of endometriosis, this phenolic compound now being considered a new innovative drug in the prevention and treatment of this disease. Full article
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