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Anti-Inflammatory Activity of Natural Products
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Anti-Inflammatory Activity of Natural Products

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

Deadline for manuscript submissions: closed (30 November 2019) | Viewed by 118832

Special Issue Editor

Dr. Maria da Graça Costa G. Miguel

E-Mail Website
Guest Editor
Mediterranean Institute for Agriculture, Environment and Development, Faculdade de Ciências e Tecnologia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
Interests: bee products; medicinal plants; essential oils; anthocyanins
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammation involves several steps to respond to harmful stimuli, such as pathogen agents, tissue lesions, irritants, etc., in order to destroy or isolate those agents, remove damaged tissues and restore tissue homeostasis. The first step consists of the recognition of infection and damage, the second step consists of the activation of common signaling pathways and the third step consists of the transcription and translation of genes, that is, the inducible expression of pro-inflammatory cytokines. These molecules, together with chemokines, originate the recruitment of monocytes and neutrophils to a damaged site, passing selectively through endothelial cells with a protein-rich fluid. Whereas, in acute inflammation, there is an immediate and early response to an injurious agent and is quickly resolved, in chronic inflammation the disturbance persists. Chronic inflammation is associated with a variety of cardiovascular, metabolic, and neurodegenerative diseases.

The use of plants, plant products, marine compounds, mushrooms, bee products (honey, propolis, bee pollen) are examples of materials that have been the target of many studies in order to find effective anti-inflammatory compounds or extracts. Such studies include not only the isolation and identification of compounds but also the mechanisms involved in the anti-inflammatory activity.

This Special Issue “Anti-Inflammatory Activity of Natural Products” invites researchers to contribute to original research or review articles related to the anti-inflammatory activity, including mechanisms and pharmacological characterization, of extracts from mushrooms, bee products, marine or plant products, their fractions or purified substances (extraction procedures, isolation, and identification).

Dr. Maria G. Miguel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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
  • anti-inflammatory
  • natural products
  • pharmacology
  • plant
  • marine

Published Papers (24 papers)

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Editorial

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6 pages, 194 KiB  
Editorial
Editorial to Special Issue—Anti-Inflammatory Activity of Natural Products
by Maria Graça Miguel
Molecules 2020, 25(8), 1926; https://doi.org/10.3390/molecules25081926 - 21 Apr 2020
Cited by 2 | Viewed by 1827
Abstract
Inflammation involves several steps to respond to harmful stimuli [...] Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)

Research

Jump to: Editorial, Review

18 pages, 5924 KiB  
Article
Bioaffinity Fishing Procedure Using Secretory Phospholipase A2 for Screening for Bioactive Components: Modulation of Pharmacological Effect Induced by sPLA2 from Crotalus durissus terrificus by Hispidulin from Moquiniastrum floribundum
by Adeilso Bispo dos Santos Junior, Cinthia I. Tamayose, Marcelo J. P. Ferreira, Mariana N. Belchor, Caroline R. C. Costa, Marcos Antonio de Oliveira and Marcos Hikari Toyama
Molecules 2020, 25(2), 282; https://doi.org/10.3390/molecules25020282 - 09 Jan 2020
Cited by 3 | Viewed by 2866
Abstract
Bioaffinity capturing of molecules allows the discovery of bioactive compounds and decreases the need for various stages in the natural compound isolation process. Despite the high selectivity of this technique, the screening and identification methodology depends on the presence of a protein to [...] Read more.
Bioaffinity capturing of molecules allows the discovery of bioactive compounds and decreases the need for various stages in the natural compound isolation process. Despite the high selectivity of this technique, the screening and identification methodology depends on the presence of a protein to capture potential ligands. However, some proteins, such as snake secretory phospholipase A2 (sPLA2), have never been investigated using this approach. The purpose of this study was to evaluate the use of a new method for screening natural compounds using a bioaffinity-guided ultrafiltration method on Crotalus durissus terrificus sPLA2 followed by HPLC-MS to identify the compounds, and this method could be used to discover new anti-inflammatory compounds from the various organisms originating from biodiversity. Different extracts were selected to evaluate their ability to inhibit sPLA2 activity. The extracts were incubated with sPLA2 and the resulting mixture was ultrafiltrated to elute unbound components. The resulting compounds were identified by HPLC-MS. We identified hispidulin as one of the components present in the Moquiniastrum floribundum leaf and evaluated the ability of this isolated compound to neutralize the inflammatory activity of sPLA2 from Crotalus durissus terrificus. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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16 pages, 3091 KiB  
Article
Bioactive Compounds in Moringa oleifera Lam. Leaves Inhibit the Pro-Inflammatory Mediators in Lipopolysaccharide-Induced Human Monocyte-Derived Macrophages
by Thitiya Luetragoon, Rungnapa Pankla Sranujit, Chanai Noysang, Yordhathai Thongsri, Pachuen Potup, Nungruthai Suphrom, Nitra Nuengchamnong and Kanchana Usuwanthim
Molecules 2020, 25(1), 191; https://doi.org/10.3390/molecules25010191 - 02 Jan 2020
Cited by 39 | Viewed by 5106
Abstract
Moringa oleifera (MO) is an important plant for traditional medicine. The present study aimed to identify the MO active phytochemical compounds for their ability against inflamed macrophages. An ethyl acetate extract fraction of MO was fractionation by flash column chromatography. Human macrophages were [...] Read more.
Moringa oleifera (MO) is an important plant for traditional medicine. The present study aimed to identify the MO active phytochemical compounds for their ability against inflamed macrophages. An ethyl acetate extract fraction of MO was fractionation by flash column chromatography. Human macrophages were stimulated by Lipopolysaccharide and then treated with fractions of MO to examine their anti-inflammatory activity and cellular mechanism. The active fractions were analyzed by liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometer (LC-ESI-QTOF-MS). MO treated cells showed a decreased production of pro-inflammatory mediator in response to lipopolysaccharide. This was evident at both mRNA and protein levels. The study revealed that MO suppressed mRNA expression of IL-1, IL-6, TNF-α, PTGS2, NF-κB (P50), and RelA. Furthermore, the extract effectively inhibited the expression of inflammatory mediators, including IL-6, TNF-α, and cyclooxygenase-2. Interestingly, the effect of MO inhibited phosphorylation of IκB-α and the ability to reduce expression of the nuclear factor (NF)-κB p65, suppressing its nuclear translocation. Moreover, LC-ESI-QTOF-MS analysis of the MO active fraction revealed seven compounds, namely 3,4-Methyleneazelaic acid, (2S)-2-phenylmethoxybutane-1,4-diol, (2R)-2-phenylmethoxybutane-1, 4-diol, γ-Diosphenol, 2,2,4,4-Tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, 3-Hydroxy-β-ionone, and Tuberonic acid. Our findings highlight the ability of MO compounds to inhibit inflammation through regulation of the NF-κB pathway. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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14 pages, 3654 KiB  
Article
Chlojaponilactone B Attenuates Lipopolysaccharide-Induced Inflammatory Responses by Suppressing TLR4-Mediated ROS Generation and NF-κB Signaling Pathway
by Shaoxia Ye, Qiyao Zheng, Yang Zhou, Bai Bai, Depo Yang and Zhimin Zhao
Molecules 2019, 24(20), 3731; https://doi.org/10.3390/molecules24203731 - 16 Oct 2019
Cited by 17 | Viewed by 7986
Abstract
The lindenane-type sesquiterpenoid chlojaponilactone B (1), isolated from Chloranthus japonicus, has been reported to possess anti-inflammatory properties. The present study aimed to further explore the molecular mechanisms underlying the anti-inflammatory activity of 1. RNA-seq analyses revealed the significant changes [...] Read more.
The lindenane-type sesquiterpenoid chlojaponilactone B (1), isolated from Chloranthus japonicus, has been reported to possess anti-inflammatory properties. The present study aimed to further explore the molecular mechanisms underlying the anti-inflammatory activity of 1. RNA-seq analyses revealed the significant changes in the expression levels of genes related to multiple inflammatory pathways upon treatment of lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages with 1. Real time PCR (RT-PCR) and Western blotting were used to confirm the modulations in the expression of essential molecules related to inflammatory responses. Compound 1 inhibited toll like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) activation upon LPS stimulation, influencing the expression of NF-κB and pro-inflammatory mediators. Molecular docking studies showed that 1 bound to TLR4 in a manner similar to that of TAK-242, a TLR4 inhibitor. Moreover, our results showed that 1 suppressed inflammatory responses by inhibiting TLR4 and subsequently decreasing reactive oxygen species (ROS) generation, downregulating the NF-κB, thus reducing the expression of the pro-inflammatory cytokines iNOS, NO, COX-2, IL-6 and TNF-α; these effects were similar to those of TAK-242. We proposed that 1 should be considered as a potential anti-inflammatory compound in future research. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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15 pages, 1977 KiB  
Article
Anti-Inflammatory Activity of the Wild Mushroom, Echinodontium tinctorium, in RAW264.7 Macrophage Cells and Mouse Microcirculation
by Sumreen Javed, Wai Ming Li, Mehreen Zeb, Almas Yaqoob, Linda E. Tackaberry, Hugues B. Massicotte, Keith N. Egger, Peter C.K. Cheung, Geoffrey W. Payne and Chow H. Lee
Molecules 2019, 24(19), 3509; https://doi.org/10.3390/molecules24193509 - 27 Sep 2019
Cited by 14 | Viewed by 3919
Abstract
The aim of this study was to investigate the anti-inflammatory activity of a previously un-studied wild mushroom, Echinodontium tinctorium, collected from the forests of north-central British Columbia. The lipopolysaccharide (LPS)-induced RAW264.7 macrophage model was used to study the in vitro anti-inflammatory activity. [...] Read more.
The aim of this study was to investigate the anti-inflammatory activity of a previously un-studied wild mushroom, Echinodontium tinctorium, collected from the forests of north-central British Columbia. The lipopolysaccharide (LPS)-induced RAW264.7 macrophage model was used to study the in vitro anti-inflammatory activity. The crude alkaline extract demonstrated potent anti-inflammatory activity, and was further purified using a “bio-activity-guided-purification” approach. The size-exclusion and ion-exchange chromatography yielded a water-soluble anti-inflammatory polysaccharide (AIPetinc). AIPetinc has an average molecular weight of 5 kDa, and is a heteroglucan composed of mainly glucose (88.6%) with a small amount of galactose (4.0%), mannose (4.4%), fucose (0.7%), and xylose (2.3%). In in vivo settings, AIPetinc restored the histamine-induced inflammatory event in mouse gluteus maximus muscle, thus confirming its anti-inflammatory activity in an animal model. This study constitutes the first report on the bioactivity of Echinodontium tinctorium, and highlights the potential medicinal benefits of fungi from the wild forests of northern British Columbia. Furthermore, it also reiterates the need to explore natural resources for alternative treatment to modern world diseases. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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18 pages, 5096 KiB  
Article
Therapeutic Use of Scoparia dulcis Reduces the Progression of Experimental Osteoarthritis
by Marcus Vinícius Viégas Lima, Abner de Oliveira Freire, Emerson Lucas Frazão Sousa, André Alvares Marques Vale, Alberto Jorge Oliveira Lopes, Cleydlenne Costa Vasconcelos, Mônica Virginia Viégas Lima-Aragão, Humberto Oliveira Serra, Rosane Nassar Meireles Guerra Liberio, Ana Paula Silva de Azevedo dos Santos, Gyl Eanes Barros Silva, Claúdia Quintino da Rocha, Fernando César Vilhena Moreira Lima, Maria do Socorro de Sousa Cartágenes and João Batista Santos Garcia
Molecules 2019, 24(19), 3474; https://doi.org/10.3390/molecules24193474 - 25 Sep 2019
Cited by 7 | Viewed by 3808
Abstract
Pain is recognized as one of the main symptoms in knee osteoarthritis and is the main reason why patients seek medical attention. Scoparia dulcis has been popularly used to relieve discomfort caused by various painful conditions. The objective of the study is to [...] Read more.
Pain is recognized as one of the main symptoms in knee osteoarthritis and is the main reason why patients seek medical attention. Scoparia dulcis has been popularly used to relieve discomfort caused by various painful conditions. The objective of the study is to evaluate the analgesic and anti-inflammatory effect of the crude extract of S. dulcis, in an experimental model of osteoarthritis. The experiment was performed with Wistar rats divided into 4 groups with 5 animals each: healthy, saline, crude extract, and meloxicam groups. Knee osteoarthritis was induced by intra-articular injection of sodium mono-iodoacetate. First, clinical parameters of pain were assessed at days 0, 5, 10, 15, and 20 after induction. Second, the potential cyclooxygenase inhibition was evaluated, and the cytokines of the synovial fluid were quantified. An in silico test and Molecular Docking tests were performed. A histopathological evaluation was made on articular cartilage with safranin O staining. The results showed that a 15-day treatment with crude extract reduced edema, spontaneous pain, peripheral nociceptive activity, and proinflammatory cytokines in the synovial fluid. The highest inhibition of cyclooxygenase 2 in the crude extract occurred at 50 µg/mL. The crude extract of S. dulcis presents therapeutic potential for the treatment of osteoarthritis due to its anti-inflammatory and anti-nociceptive action. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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10 pages, 788 KiB  
Article
Phytochemical Investigation of Tradescantia Albiflora and Anti-Inflammatory Butenolide Derivatives
by Ping-Chen Tu, Han-Chun Tseng, Yu-Chia Liang, Guan-Jhong Huang, Te-Ling Lu, Tzong-Fu Kuo and Yueh-Hsiung Kuo
Molecules 2019, 24(18), 3336; https://doi.org/10.3390/molecules24183336 - 13 Sep 2019
Cited by 5 | Viewed by 2781
Abstract
Phytochemical investigation of the whole plant of Tradescantia albiflora Kunth led to the isolation and characterization of a butanolide, rosmarinosin B (1), that was isolated from natural sources for the first time, a new butenolide, 5-O-acetyl bracteanolide A ( [...] Read more.
Phytochemical investigation of the whole plant of Tradescantia albiflora Kunth led to the isolation and characterization of a butanolide, rosmarinosin B (1), that was isolated from natural sources for the first time, a new butenolide, 5-O-acetyl bracteanolide A (2), and a new apocarotenoid, 2β-hydroxyisololiolide (11), together with 25 known compounds (compounds 3–10 and 12–28). The structures of the new compounds were elucidated by analysis of their spectroscopic data, including MS, 1D, and 2D NMR experiments, and comparison with literature data of known compounds. Furthermore, four butenolides 4a–4d were synthesized as novel derivatives of bracteanolide A. The isolates and the synthesized derivatives were evaluated for their preliminary anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW 264.7 cells. Among them, the synthesized butenolide derivative n-butyl bracteanolide A (4d) showed enhanced NO inhibitory activity compared to the original compound, with an IC50 value of 4.32 ± 0.09 μg/mL. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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12 pages, 1995 KiB  
Article
Anti-Inflammatory Effect of Erinacine C on NO Production Through Down-Regulation of NF-κB and Activation of Nrf2-Mediated HO-1 in BV2 Microglial Cells Treated with LPS
by Li-Yu Wang, Chin-Shiu Huang, Yu-Hsuan Chen, Chin-Chu Chen, Chien-Chih Chen and Cheng-Hung Chuang
Molecules 2019, 24(18), 3317; https://doi.org/10.3390/molecules24183317 - 12 Sep 2019
Cited by 24 | Viewed by 4082
Abstract
Previous studies have revealed the anti-inflammatory and neuroprotective properties of Hericium erinaceus extracts, including the fact that the active ingredient erinacine C (EC) can induce the synthesis of nerve growth factor. However, there is limited research on the use and mechanisms of action [...] Read more.
Previous studies have revealed the anti-inflammatory and neuroprotective properties of Hericium erinaceus extracts, including the fact that the active ingredient erinacine C (EC) can induce the synthesis of nerve growth factor. However, there is limited research on the use and mechanisms of action of EC in treating neuroinflammation. Hence, in this study, the inflammatory responses of human BV2 microglial cells induced by LPS were used to establish a model to assess the anti-neuroinflammatory efficacy of EC and to clarify its possible mechanisms of action. The results showed that EC was able to reduce the levels of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) proteins produced by LPS-induced BV2 cells, in addition to inhibiting the expression of NF-κB and phosphorylation of IκBα (p-IκBα) proteins. Moreover, EC was found to inhibit the Kelch-like ECH-associated protein 1 (Keap1) protein, and to enhance the nuclear transcription factor erythroid 2-related factor (Nrf2) and the expression of the heme oxygenase-1 (HO-1) protein. Taken together, these data suggest that the mechanism of action of EC involves the inhibition of IκB, p-IκBα, and iNOS expressions and the activation of the Nrf2/HO-1 pathway. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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16 pages, 4286 KiB  
Article
Bioactive Constituents from the Roots of Eurycoma longifolia
by Jingya Ruan, Zheng Li, Ying Zhang, Yue Chen, Mengyang Liu, Lifeng Han, Yi Zhang and Tao Wang
Molecules 2019, 24(17), 3157; https://doi.org/10.3390/molecules24173157 - 30 Aug 2019
Cited by 35 | Viewed by 4130
Abstract
Four new phenolic components, eurylophenolosides A (1) and B (2), eurylolignanosides A (3) and B (4), along with twelve known compounds were isolated from the roots of Eurycoma longifolia Jack. The structure of these components [...] Read more.
Four new phenolic components, eurylophenolosides A (1) and B (2), eurylolignanosides A (3) and B (4), along with twelve known compounds were isolated from the roots of Eurycoma longifolia Jack. The structure of these components was elucidated by using various spectral techniques and chemical reactions. Among the known isolates, syringaldehyde (12), 3-chloro-4-hydroxybenzoic acid (13), 3-chloro-4-hydroxyl benzoic acid-4-O-β-d-glucopyranoside (14), and isotachioside (15) were isolated from the Eurycoma genus for the first time. Further, the NMR data of 14 was reported here firstly. Meanwhile, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at 40 μM. As results, piscidinol A (6), 24-epi-piscidinol A (7), bourjotinolone A (10), and scopoletin (16) were found to play important role in suppressing NO levels without cytotoxicity. Furthermore, the Western blot method was used to investigate the mechanism of compounds 6, 7, 10, and 16 by analysing the level of inflammation related proteins, such as inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in LPS-stimulated RAW264.7 cells. Consequently, compounds 6, 7, 10, and 16 were found to significantly inhibit LPS-induced protein expression of IL-6, NF-κB and iNOS in NF-κB signaling pathway. Moreover, it was found that the protein expression inhibitory effects of 6, 7, and 16 exhibited in a dose-dependent manner. The mechanism may be related to the inhibition of the iNOS expressions through suppressing the IL-6-induced NF-κB pathway. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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16 pages, 3915 KiB  
Article
Fangchinoline, a Bisbenzylisoquinoline Alkaloid can Modulate Cytokine-Impelled Apoptosis via the Dual Regulation of NF-κB and AP-1 Pathways
by Young Yun Jung, Muthu K. Shanmugam, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Omar H.M. Shair, Jae-Young Um, Gautam Sethi and Kwang Seok Ahn
Molecules 2019, 24(17), 3127; https://doi.org/10.3390/molecules24173127 - 28 Aug 2019
Cited by 31 | Viewed by 3598
Abstract
Fangchinoline (FCN) derived from Stephaniae tetrandrine S. Moore can be employed to treat fever, inflammation, rheumatism arthralgia, edema, dysuria, athlete’s foot, and swollen wet sores. FCN can exhibit a plethora of anti-neoplastic effects although its precise mode of action still remains to be [...] Read more.
Fangchinoline (FCN) derived from Stephaniae tetrandrine S. Moore can be employed to treat fever, inflammation, rheumatism arthralgia, edema, dysuria, athlete’s foot, and swollen wet sores. FCN can exhibit a plethora of anti-neoplastic effects although its precise mode of action still remains to be deciphered. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) can closely regulate carcinogenesis and thus we analyzed the possible action of FCN may have on these two signaling cascades in tumor cells. The effect of FCN on NF-κB and AP-1 signaling cascades and its downstream functions was deciphered using diverse assays in both human chronic myeloid leukemia (KBM5) and multiple myeloma (U266). FCN attenuated growth of both leukemic and multiple myeloma cells and repressed NF-κB, and AP-1 activation through diverse mechanisms, including attenuation of phosphorylation of IκB kinase (IKK) and p65. Furthermore, FCN could also cause significant enhancement in TNFα-driven apoptosis as studied by various molecular techniques. Thus, FCN may exhibit potent anti-neoplastic effects by affecting diverse oncogenic pathways and may be employed as pro-apoptotic agent against various malignancies. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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14 pages, 4526 KiB  
Article
The Anti-Inflammatory Role of Mannich Curcuminoids; Special Focus on Colitis
by Gábor J. Szebeni, Lajos I. Nagy, Anikó Berkó, Alexandra Hoffmann, Liliána Z. Fehér, Mária Bagyánszki, Beáta Kari, József A. Balog, László Hackler, Jr., Iván Kanizsai, Anikó Pósa, Csaba Varga and László G. Puskás
Molecules 2019, 24(8), 1546; https://doi.org/10.3390/molecules24081546 - 19 Apr 2019
Cited by 16 | Viewed by 3569
Abstract
The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced [...] Read more.
The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis. Treatment with C142 or C150 reduced leukocyte infiltration to the submucosa and muscular propria of the inflamed gut. C142 or C150 rescued the loss of body weight and C150 decreased the weight of standard colon preparations proportional with 20% less tissue oedema. Both C142 and C150 curcumin analogues caused 25% decrease in the severity of colonic inflammation and haemorrhagic lesion size. Colonic MPO (myeloperoxidase) enzyme activity as an indicator of intense neutrophil infiltration was 50% decreased either by C142 or C150 Mannich curcuminoids. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited NF-κB (nuclear factor kappa B) activity on a concentration-dependent manner in an NF-κB-driven luciferase expressing reporter cell line. Co-treatment with LPS and curcuminoids, C142 or C150, resulted in NF-κB inhibition with 3.57 μM or 1.6 μM half maximal effective concentration (EC50) values, respectively. C150 exerted a profound inhibition of the expression of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-4 (IL-4) in human PBMCs (peripheral blood mononuclear cells) upon LPS stimulus. Mannich curcuminoids reported herein possess a powerful anti-inflammatory activity. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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14 pages, 2382 KiB  
Article
Target Proteins of Phloretin for Its Anti-Inflammatory and Antibacterial Activities Against Propionibacterium acnes-Induced Skin Infection
by Dasom Cheon, Jieun Kim, Dasom Jeon, Hang-Cheol Shin and Yangmee Kim
Molecules 2019, 24(7), 1319; https://doi.org/10.3390/molecules24071319 - 03 Apr 2019
Cited by 35 | Viewed by 6455
Abstract
Phloretin is a natural chalcone with antibacterial and anti-inflammatory effects. This study investigated the anti-acne activity of phloretin against Propionibacterium acnes-induced skin infection and the potential target proteins of its anti-inflammatory and antibacterial effects. Phloretin potently inhibited the growth of P. acnes [...] Read more.
Phloretin is a natural chalcone with antibacterial and anti-inflammatory effects. This study investigated the anti-acne activity of phloretin against Propionibacterium acnes-induced skin infection and the potential target proteins of its anti-inflammatory and antibacterial effects. Phloretin potently inhibited the growth of P. acnes and P. acnes-induced Toll-like receptor (TLR) 2-mediated inflammatory signaling in human keratinocytes. Secreted embryonic alkaline phosphatase assay confirmed that the anti-inflammatory activity of phloretin is associated with the P. acnes-stimulated TLR2-mediated NF-κB signaling pathway. Phloretin significantly decreased the level of phosphorylated c-Jun N-terminal kinase (JNK), showing a binding affinity of 1.184 × 10−5 M−1. We also found that phloretin binds with micromolar affinity to P. acnes β-ketoacyl acyl carrier protein (ACP) synthase III (KAS III), an enzyme involved in fatty acid synthesis. Conformation-sensitive native polyacrylamide gel electrophoresis showed that phloretin reduced KAS III-mediated 3-ketoacyl ACP production by over 66%. A docking study revealed that phloretin interacts with the active sites of JNK1 and KAS III, suggesting their involvement in P. acnes-induced inflammation and their potential as targets for the antibacterial activity of phloretin. These results demonstrate that phloretin may be useful in the prevention or treatment of P. acnes infection. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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17 pages, 2808 KiB  
Article
In Vitro and In Vivo Anti-Inflammatory Effects of Polyphyllin VII through Downregulating MAPK and NF-κB Pathways
by Chao Zhang, Chaoying Li, Xuejing Jia, Kai Wang, Yanbei Tu, Rongchun Wang, Kechun Liu, Tao Lu and Chengwei He
Molecules 2019, 24(5), 875; https://doi.org/10.3390/molecules24050875 - 01 Mar 2019
Cited by 61 | Viewed by 5169
Abstract
Background: Polyphyllin VII (PP7), a steroidal saponin from Paris polyphylla, has been found to exert strong anticancer activity. Little is known about the anti-inflammatory property of PP7. In this study, the anti-inflammatory activity and its underlying mechanisms of PP7 were evaluated [...] Read more.
Background: Polyphyllin VII (PP7), a steroidal saponin from Paris polyphylla, has been found to exert strong anticancer activity. Little is known about the anti-inflammatory property of PP7. In this study, the anti-inflammatory activity and its underlying mechanisms of PP7 were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in multiple animal models. Methods: The content of nitric oxide (NO) was determined by spectrophotometry. The levels of prostaglandin E2 (PGE2) and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) assay. The mRNA expression of pro-inflammatory genes was determined by qPCR. The total and phosphorylated protein levels were examined by Western blotting. The in vivo anti-inflammatory activities were evaluated by using mouse and zebrafish models. Results: PP7 reduced the production of NO and PGE2 and the protein and mRNA expressions of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enzymes (inducible NO synthase [iNOS], cyclooxygenase-2 [COX-2], and Matrix metalloproteinase-9 [MMP-9]) in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPKs pathways. Notably, PP7 markedly inhibited xylene-induced ear edema and cotton pellet-induced granuloma formation in mice and suppressed LPS and CuSO4-induced inflammation and toxicity in zebrafish embryos. Conclusion: This study demonstrates that PP7 exerts strong anti-inflammatory activities in multiple in vitro and in vivo models and suggests that PP7 is a potential novel therapeutic agent for inflammatory diseases. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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12 pages, 4048 KiB  
Article
Protective Effects of Astragaloside IV against LPS-Induced Endometritis in Mice through Inhibiting Activation of the NF-κB, p38 and JNK Signaling Pathways
by Fengge Wang, Shuxiong Chen, Liang Deng, Lu Chen, Yuwen Huang, Meng Tian, Chunjin Li and Xu Zhou
Molecules 2019, 24(2), 373; https://doi.org/10.3390/molecules24020373 - 21 Jan 2019
Cited by 30 | Viewed by 4064
Abstract
Endometritis, inflammation of the endometrium, is a common reproductive obstacle disease that can lead to infertility in female animals. Astragaloside IV (AS IV), one of the major and active components of the Astragalus membranaceus (Fisch.) Bunge, is known for its anti-inflammatory effects. In [...] Read more.
Endometritis, inflammation of the endometrium, is a common reproductive obstacle disease that can lead to infertility in female animals. Astragaloside IV (AS IV), one of the major and active components of the Astragalus membranaceus (Fisch.) Bunge, is known for its anti-inflammatory effects. In the present study, the effects and mechanisms of AS IV on lipopolysaccharide (LPS)-induced endometritis were investigated using a mouse model. Female mice were prepared with AS IV (0.01 mg/g) by gavage for six days before being stimulated with LPS. The results showed that the histopathological changes, levels of inflammatory cytokines (IL-1β and TNF-α), concentration of NO, and myeloperoxidase (MPO) activity in LPS-induced uteri were attenuated significantly by pretreatment with AS IV. Furthermore, LPS-induced activations of NF-κB, p38, and JNK signal pathways were suppressed by pretreatment with AS IV. In conclusion, the data provided new evidence that AS IV effectively attenuates LPS-induced endometritis through inhibition of TLR4-mediated NF-κB, p38, and JNK signaling pathways, implying that AS IV might become a promising potential anti-inflammatory agent for endometritis and other inflammatory diseases. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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16 pages, 3290 KiB  
Article
5-Hydroxymethylfurfural Mitigates Lipopolysaccharide-Stimulated Inflammation via Suppression of MAPK, NF-κB and mTOR Activation in RAW 264.7 Cells
by Fanhui Kong, Bae Hoon Lee and Kun Wei
Molecules 2019, 24(2), 275; https://doi.org/10.3390/molecules24020275 - 13 Jan 2019
Cited by 58 | Viewed by 7214
Abstract
5-Hydroxymethylfurfural (5-HMF) is found in many food products including honey, dried fruits, coffee and black garlic extracts. Here, we investigated the anti-inflammatory activity of 5-HMF and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. 5-HMF pretreatment ranging from 31.5 to 126.0 μg/mL [...] Read more.
5-Hydroxymethylfurfural (5-HMF) is found in many food products including honey, dried fruits, coffee and black garlic extracts. Here, we investigated the anti-inflammatory activity of 5-HMF and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. 5-HMF pretreatment ranging from 31.5 to 126.0 μg/mL reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in a concentration-dependent manner in LPS-stimulated cells. Moreover, 5-HMF-pretreated cells significantly down-regulated the mRNA expression of two major inflammatory mediators, nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and suppressed the production of pro-inflammatory cytokines, as compared with the only LPS-stimulated cells. 5-HMF suppressed the phosphorylation of extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK), IκBα, NF-κB p65, the mammalian target of rapamycin (mTOR) and protein kinase B (Akt). Besides, 5-HMF was proved to inhibit NF-κB p65 translocation into nucleus to activate inflammatory gene transcription. These results suggest that 5-HMF could exert the anti-inflammatory activity in the LPS-induced inflammatory response by inhibiting the MAPK, NF-κB and Akt/mTOR pathways. Thus, 5-HMF could be considered as a therapeutic ingredient in functional foods. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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11 pages, 1932 KiB  
Article
IL-6 in Osteoarthritis: Effects of Pine Stilbenoids
by Mirka Laavola, Tiina Leppänen, Mari Hämäläinen, Katriina Vuolteenaho, Teemu Moilanen, Riina Nieminen and Eeva Moilanen
Molecules 2019, 24(1), 109; https://doi.org/10.3390/molecules24010109 - 29 Dec 2018
Cited by 39 | Viewed by 4008
Abstract
Interleukin-6 (IL-6) is involved in the pathogenesis of various inflammatory diseases, like rheumatoid arthritis (RA). In the present study, we investigated the role of IL-6 in osteoarthritis (OA) patients and the effects of the stilbenoids monomethyl pinosylvin and pinosylvin on the expression of [...] Read more.
Interleukin-6 (IL-6) is involved in the pathogenesis of various inflammatory diseases, like rheumatoid arthritis (RA). In the present study, we investigated the role of IL-6 in osteoarthritis (OA) patients and the effects of the stilbenoids monomethyl pinosylvin and pinosylvin on the expression of the cartilage matrix components aggrecan and collagen II and the inflammatory cytokine IL-6 in human OA chondrocytes. Synovial fluid and plasma samples were obtained from 100 patients with severe OA [BMI 29.7 (8.3) kg/m2, age 72 (14) years, median (IQR); 62/38 females/males] undergoing total knee replacement surgery. IL-6 and matrix metalloproteinase (MMP) concentrations in synovial fluid and plasma were measured by immunoassay. The effects of pinosylvin on the expression of IL-6, aggrecan, and collagen II were studied in primary cultures of human OA chondrocytes. IL-6 levels in synovial fluid from OA patients [119.8 (193.5) pg/mL, median (IQR)] were significantly increased as compared to the plasma levels [3.1 (2.7) pg/mL, median (IQR)] and IL-6 levels in synovial fluid were associated with MMPs and radiographic disease severity. Natural stilbenoids monomethyl pinosylvin and pinosylvin increased aggrecan expression and suppressed IL-6 production in OA chondrocytes. The results propose that IL-6 is produced within OA joints and has an important role in the pathogenesis of OA. Stilbenoid compounds monomethyl pinosylvin and pinosylvin appeared to have disease-modifying potential in OA chondrocytes. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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19 pages, 10093 KiB  
Article
Cardioprotective Effects of Puerarin-V on Isoproterenol-Induced Myocardial Infarction Mice Is Associated with Regulation of PPAR-Υ/NF-κB Pathway
by Xuguang Li, Tianyi Yuan, Di Chen, Yucai Chen, Shuchan Sun, Danshu Wang, Lianhua Fang, Yang Lu and Guanhua Du
Molecules 2018, 23(12), 3322; https://doi.org/10.3390/molecules23123322 - 14 Dec 2018
Cited by 42 | Viewed by 5489
Abstract
Puerarin is a well-known traditional Chinese medicine which has been used for the treatment of cardiovascular diseases. Recently, a new advantageous crystal form of puerarin, puerarin-V, has been developed. However, the cardioprotective effects of puerarin-V on myocardial infarction (MI) heart failure are still [...] Read more.
Puerarin is a well-known traditional Chinese medicine which has been used for the treatment of cardiovascular diseases. Recently, a new advantageous crystal form of puerarin, puerarin-V, has been developed. However, the cardioprotective effects of puerarin-V on myocardial infarction (MI) heart failure are still unclear. In this research, we aim to evaluate the cardioprotective effects of puerarin-V on the isoproterenol (ISO)-induced MI mice and elucidate the underlying mechanisms. To induce MI in C57BL/6 mice, ISO was administered at 40 mg/kg subcutaneously every 12 h for three times in total. The mice were randomly divided into nine groups: (1) control; (2) ISO; (3) ISO + puerarin injection; (4–9) ISO + puerarin-V at different doses and timings. After treatment, cardiac function was evaluated by electrocardiogram (ECG), biochemical and histochemical analysis. In vitro inflammatory responses and apoptosis were evaluated in human coronary artery endothelial cells (HCAECs) challenged by lipopolysaccharide (LPS). LPS-induced PPAR-Υ/NF-κB and subsequently activation of cytokines were assessed by the western blot and real-time polymerase chain reaction (PCR). Administration of puerarin-V significantly inhibits the typical ST segment depression compared with that in MI mice. Further, puerarin-V treatment significantly improves ventricular wall infarction, decreases the incidence of mortality, and inhibits the levels of myocardial injury markers. Moreover, puerarin-V treatment reduces the inflammatory milieu in the heart of MI mice, thereby blocking the upregulation of proinflammatory cytokines (TNF-α, IL-1β and IL-6). The beneficial effects of puerarin-V might be associated with the normalization in gene expression of PPAR-Υ and PPAR-Υ/NF-κB /ΙκB-α/ΙΚΚα/β phosphorylation. In the in vitro experiment, treatment with puerarin-V (0.3, 1 and 3 μM) significantly reduces cell death and suppresses the inflammation cytokines expression. Likewise, puerarin-V exhibits similar mechanisms. The cardioprotective effects of puerarin-V treatment on MI mice in the pre + post-ISO group seem to be more prominent compared to those in the post-ISO group. Puerarin-V exerts cardioprotective effects against ISO-induced MI in mice, which may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling in vivo and in vitro. Taken together, our research provides a new therapeutic option for the treatment of MI in clinic. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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13 pages, 4794 KiB  
Article
Pilloin, A Flavonoid Isolated from Aquilaria sinensis, Exhibits Anti-Inflammatory Activity In Vitro and In Vivo
by Yun-Chen Tsai, Sin-Ling Wang, Mei-Yao Wu, Chia-Huei Liao, Chao-Hsiung Lin, Jih-Jung Chen and Shu-Ling Fu
Molecules 2018, 23(12), 3177; https://doi.org/10.3390/molecules23123177 - 02 Dec 2018
Cited by 26 | Viewed by 4084
Abstract
Flavonoids, widely present in medicinal plants and fruits, are known to exhibit multiple pharmacological activities. In this study, we isolated a flavonoid compound, pilloin, from Aquilaria sinensis and investigated its anti-inflammatory activity in bacterial lipopolysaccharide-induced RAW 264.7 macrophages and septic mice. Pilloin inhibited [...] Read more.
Flavonoids, widely present in medicinal plants and fruits, are known to exhibit multiple pharmacological activities. In this study, we isolated a flavonoid compound, pilloin, from Aquilaria sinensis and investigated its anti-inflammatory activity in bacterial lipopolysaccharide-induced RAW 264.7 macrophages and septic mice. Pilloin inhibited NF-κB activation and reduced the phosphorylation of IκB in LPS-stimulated macrophages. Moreover, pilloin significantly suppressed the production of pro-inflammatory molecules, such as TNF-α, IL-6, COX-2 and iNOS, in LPS-treated RAW 264.7 macrophages. Additionally, pilloin suppressed LPS-induced morphological alterations, phagocytic activity and ROS elevation in RAW 264.7 macrophages. The mitogen-activated protein kinase-mediated signalling pathways (including JNK, ERK, p38) were also inhibited by pilloin. Furthermore, pilloin reduced serum levels of TNF-α (from 123.3 ± 7 to 46.6 ± 5.4 ng/mL) and IL-6 levels (from 1.4 ± 0.1 to 0.7 ± 0.1 ng/mL) in multiple organs of LPS-induced septic mice (liver: from 71.8 ± 3.2 to 36.7 ± 4.3; lung: from 118.6 ± 10.6 to 75.8 ± 11.9; spleen: from 185.9 ± 23.4 to 109.6 ± 18.4; kidney: from 160.3 ± 11.8 to 75 ± 10.8 pg/mL). In summary, our results demonstrate the anti-inflammatory potential of pilloin and reveal its underlying molecular mechanism of action. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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18 pages, 3418 KiB  
Article
Anti-Inflammatory Activities of Pentaherbs formula and Its Influence on Gut Microbiota in Allergic Asthma
by Miranda Sin-Man Tsang, Sau-Wan Cheng, Jing Zhu, Karam Atli, Ben Chung-Lap Chan, Dehua Liu, Helen Yau-Tsz Chan, Xiaoyu Sun, Ida Miu-Ting Chu, Kam-Lun Hon, Christopher Wai-Kei Lam, Pang-Chui Shaw, Ping-Chung Leung and Chun-Kwok Wong
Molecules 2018, 23(11), 2776; https://doi.org/10.3390/molecules23112776 - 26 Oct 2018
Cited by 34 | Viewed by 5395
Abstract
Allergic asthma is a highly prevalent airway inflammatory disease, which involves the interaction between the immune system, environmental and genetic factors. Co-relation between allergic asthma and gut microbiota upon the change of diet have been widely reported, implicating that oral intake of alternative [...] Read more.
Allergic asthma is a highly prevalent airway inflammatory disease, which involves the interaction between the immune system, environmental and genetic factors. Co-relation between allergic asthma and gut microbiota upon the change of diet have been widely reported, implicating that oral intake of alternative medicines possess a potential in the management of allergic asthma. Previous clinical, in vivo, and in vitro studies have shown that the Pentaherbs formula (PHF) comprising five traditional Chinese herbal medicines Lonicerae Flos, Menthae Herba, Phellodendri Cortex, Moutan Cortex, and Atractylodis Rhizoma possesses an anti-allergic and anti-inflammatory potential through suppressing various immune effector cells. In the present study, to further investigate the anti-inflammatory activities of PHF in allergic asthma, intragastrical administration of PHF was found to reduce airway hyperresponsiveness, airway wall remodeling and goblet cells hyperplasia in an ovalbumin (OVA)-induced allergic asthma mice model. PHF also significantly suppressed pulmonary eosinophilia and asthma-related cytokines IL-4 and IL-33 in bronchoalveolar lavage (BAL) fluid. In addition, PHF modulated the splenic regulatory T cells population, up-regulated regulatory interleukin (IL)-10 in serum, altered the microbial community structure and the short chain fatty acids content in the gut of the asthmatic mice. This study sheds light on the anti-inflammatory activities of PHF on allergic asthma. It also provides novel in vivo evidence that herbal medicines can ameliorate symptoms of allergic diseases may potentially prevent the development of subsequent atopic disorder such as allergic asthma through the influence of the gut microbiota. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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13 pages, 2988 KiB  
Article
Anti-Inflammatory and Skin-Moisturizing Effects of a Flavonoid Glycoside Extracted from the Aquatic Plant Nymphoides indica in Human Keratinocytes
by You Ah Kim, Dong Hee Kim, Chae Bin Park, Tae Soon Park and Byoung Jun Park
Molecules 2018, 23(9), 2342; https://doi.org/10.3390/molecules23092342 - 13 Sep 2018
Cited by 16 | Viewed by 4942
Abstract
Nymphoides indica, an aquatic plant, is used as folk medicine in some countries. Our previous study demonstrated that the methanol extract of N. indica inhibited the activity of tyrosinases, tyrosine related protein (TRP)1 and TRP2, and microphthalmia-associated transcription factor, as well as [...] Read more.
Nymphoides indica, an aquatic plant, is used as folk medicine in some countries. Our previous study demonstrated that the methanol extract of N. indica inhibited the activity of tyrosinases, tyrosine related protein (TRP)1 and TRP2, and microphthalmia-associated transcription factor, as well as the activity of protein kinase A, by effectively inhibiting cyclic adenosine monophosphate. Although the biological activities of N. indica extract have been reported, there are no reports on the skin bioactivity of the main compound(s) on human keratinocytes. This study investigated the anti-inflammatory and moisturizing effects of quercetin 3,7-dimethyl ether 4′-glucoside (QDG) isolated from N. indica. In brief, ultraviolet B irradiated keratinocytes were pretreated with different concentrations of QDG, and the effects of QDG on various inflammatory markers were determined. QDG significantly inhibited inflammation-related cytokines and chemokines and enhanced the activation of skin barrier factors. Additionally, QDG also attenuated phosphorylation inhibition of the upstream cytokines and nuclear factor-κB expression. These results suggest that QDG isolated from N. indica may serve as a potential source of bioactive substances for chronic inflammatory skin diseases. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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14 pages, 2659 KiB  
Article
Beneficial Effect of Herbal Formulation KM1608 on Inflammatory Bowl Diseases: A Preliminary Experimental Study
by Myoung-Sook Shin, Sang-Back Kim, Jaemin Lee, Han-Seok Choi, Jimin Park, Jun Yeon Park, Sullim Lee, Gwi Seo Hwang, Bon Am Koo and Ki Sung Kang
Molecules 2018, 23(8), 2068; https://doi.org/10.3390/molecules23082068 - 17 Aug 2018
Cited by 13 | Viewed by 4789
Abstract
Aucklandia lappa DC., Terminalia chebula Retz and Zingiber officinale Roscoe have been traditionally used in east Asia to treat chronic diarrhea and abdominal pain. This study aimed to evaluated the anti-inflammatory activity of KM1608, which is composed of three natural herbs in a [...] Read more.
Aucklandia lappa DC., Terminalia chebula Retz and Zingiber officinale Roscoe have been traditionally used in east Asia to treat chronic diarrhea and abdominal pain. This study aimed to evaluated the anti-inflammatory activity of KM1608, which is composed of three natural herbs in a mouse model of dextran sodium sulfate (DSS)-induced ulcerative colitis. The anti-inflammatory activity and underlying mechanism were assessed in vitro using LPS-treated RAW264.7 cells. The in vivo effect of KM1608 on DSS-induced colitis was examined after oral administration in mice. KM1608 significantly inhibited the inflammatory mediators such as nitric oxide, interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor (TNF)-α in LPS-treated RAW264.7 cells. The inhibitory effect of KM1608 was attributed to the reduction of Akt phosphorylation in the LPS-treated cells. In the mouse model, oral administration of KM1608 significantly improved DSS-induced colitis symptoms, such as disease activity index (DAI), colon length, and colon weight, as well as suppressed the expression of IL-6, TNF-α, and myeloperoxidase (MPO) in the DSS-induced colitis tissues. Taken together, KM1608 improved colitis through the regulation of inflammatory responses, suggesting that KM1608 has potential therapeutic use in the treatment of inflammatory diseases. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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14 pages, 1432 KiB  
Article
Decursinol Angelate Inhibits LPS-Induced Macrophage Polarization through Modulation of the NFκB and MAPK Signaling Pathways
by Salman Ul Islam, Jung Ho Lee, Adeeb Shehzad, Eun-Mi Ahn, You Mie Lee and Young Sup Lee
Molecules 2018, 23(8), 1880; https://doi.org/10.3390/molecules23081880 - 27 Jul 2018
Cited by 60 | Viewed by 6631
Abstract
Inflammation is considered the root cause of various inflammatory diseases, including cancers. Decursinol angelate (DA), a pyranocoumarin compound obtained from the roots of Angelica gigas, has been reported to exhibit potent anti-inflammatory effects. In this study, the anti-inflammatory effects of DA on [...] Read more.
Inflammation is considered the root cause of various inflammatory diseases, including cancers. Decursinol angelate (DA), a pyranocoumarin compound obtained from the roots of Angelica gigas, has been reported to exhibit potent anti-inflammatory effects. In this study, the anti-inflammatory effects of DA on the MAP kinase and NFκB signaling pathways and the expression of pro-inflammatory cytokines were investigated in phorbol 12-myristate 13-acetate (PMA)-activated human promyelocytic leukemia (HL-60) and lipopolysaccharide (LPS)-stimulated macrophage (Raw 264.7) cell lines. PMA induced the activation of the MAP kinase-NFκB pathway and the production of pro-inflammatory cytokines in differentiated monocytes. Treatment with DA inhibited the activation of MAP kinases and the translocation of NFκB, and decreased the expression and exogenous secretion of IL-1β and IL-6. Furthermore, LPS-stimulated Raw 264.7 cells were found to have increased expression of M1 macrophage-associated markers, such as NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS), and the M2 macrophage-associated marker CD11b. LPS also activated pro-inflammatory cytokines and Erk-NFκB. Treatment with DA suppressed LPS-induced macrophage polarization and the inflammatory response by blocking Raf-ERK and the translocation of NFκB in Raw 264.7 cells. Treatment with DA also inhibited the expression of pro-inflammatory cytokines, such as IL-1β and IL-6, NOX, and iNOS in Raw 264.7 cells. These results suggest that DA has the potential to inhibit macrophage polarization and inflammation by blocking the activation of pro-inflammatory signals. These anti-inflammatory effects of DA may contribute to its potential use as a therapeutic strategy against various inflammation-induced cancers. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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12 pages, 1928 KiB  
Article
Oregano Essential Oil Attenuates RAW264.7 Cells from Lipopolysaccharide-Induced Inflammatory Response through Regulating NADPH Oxidase Activation-Driven Oxidative Stress
by Chuanshang Cheng, Yi Zou and Jian Peng
Molecules 2018, 23(8), 1857; https://doi.org/10.3390/molecules23081857 - 26 Jul 2018
Cited by 38 | Viewed by 5526
Abstract
Oregano is an aromatic plant widely distributed throughout the Mediterranean area and in Asia. Recent studies have revealed that the anti-inflammatory effect of essential oil in this plant. However, the mechanisms underlying the therapeutic potential have not been well elucidated. This study determined [...] Read more.
Oregano is an aromatic plant widely distributed throughout the Mediterranean area and in Asia. Recent studies have revealed that the anti-inflammatory effect of essential oil in this plant. However, the mechanisms underlying the therapeutic potential have not been well elucidated. This study determined whether oregano essential oil (OEO) exerts an anti-inflammatory effect on lipopolysaccharide (LPS)-treated murine macrophage cells (RAW264.7 cells) in vitro and elucidated the possible underlying molecular mechanisms. The results showed that OEO (2.5–10 μg/mL) inhibited the expression and secretion of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in RAW264.7 cells treated with LPS (1 μg/mL). Consistent with the pro-inflammatory gene expression, the OEO treatment efficiently reduced the LPS-induced activation of mitogen-activated protein kinase, protein kinase B, and nuclear factor κB in RAW264.7 cells. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition in Nox2 protein-silenced cells attenuated the mRNA expression of IL-1β, IL-6, and TNF-α in the LPS-induced RAW264.7 cells. The OEO inhibited the LPS-induced elevation of NADPH oxidase and oxidative stress. This result suggests that LPS induces RAW264.7 cell inflammation through the NADPH oxidase-mediated production of reactive oxygen species (ROS). In conclusion, OEO protects against the LPS-induced RAW264.7 cell inflammatory response through the NADPH oxidase/ROS pathway. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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Review

Jump to: Editorial, Research

27 pages, 1243 KiB  
Review
Lactoferrin in Aseptic and Septic Inflammation
by Maria Stefania Lepanto, Luigi Rosa, Rosalba Paesano, Piera Valenti and Antimo Cutone
Molecules 2019, 24(7), 1323; https://doi.org/10.3390/molecules24071323 - 03 Apr 2019
Cited by 96 | Viewed by 9542
Abstract
Lactoferrin (Lf), a cationic glycoprotein able to chelate two ferric irons per molecule, is synthesized by exocrine glands and neutrophils. Since the first anti-microbial function attributed to Lf, several activities have been discovered, including the relevant anti-inflammatory one, especially associated to the down-regulation [...] Read more.
Lactoferrin (Lf), a cationic glycoprotein able to chelate two ferric irons per molecule, is synthesized by exocrine glands and neutrophils. Since the first anti-microbial function attributed to Lf, several activities have been discovered, including the relevant anti-inflammatory one, especially associated to the down-regulation of pro-inflammatory cytokines, as IL-6. As high levels of IL-6 are involved in iron homeostasis disorders, Lf is emerging as a potent regulator of iron and inflammatory homeostasis. Here, the role of Lf against aseptic and septic inflammation has been reviewed. In particular, in the context of aseptic inflammation, as anemia of inflammation, preterm delivery, Alzheimer’s disease and type 2 diabetes, Lf administration reduces local and/or systemic inflammation. Moreover, Lf oral administration, by decreasing serum IL-6, reverts iron homeostasis disorders. Regarding septic inflammation occurring in Chlamydia trachomatis infection, cystic fibrosis and inflammatory bowel disease, Lf, besides the anti-inflammatory activity, exerts a significant activity against bacterial adhesion, invasion and colonization. Lastly, a critical analysis of literature in vitro data reporting contradictory results on the Lf role in inflammatory processes, ranging from pro- to anti-inflammatory activity, highlighted that they depend on cell models, cell metabolic status, stimulatory or infecting agents as well as on Lf iron saturation degree, integrity and purity. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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