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Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (20 July 2024) | Viewed by 17271

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Dr. Ariane Leite Rozza

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Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, Brazil
Interests: biopharmaceutics; inflammation; morphophysiology; drug design; natural products; antioxidants; gastrointestinal diseases; diabetes; wound healing
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Dear Colleagues,

Inflammation is a response of organisms to the breakdown of tissue homeostasis. Infection, injury, autoimmune diseases, and chemicals can cause inflammation. The acute inflammatory response begins with increased vascular permeability and leukocyte migration, which will try to eliminate pathogenic organisms through the release of reactive oxygen species, reactive nitrogen species, and proteases. Additionally, neutrophils release inflammatory mediators, including chemokines, attracting macrophages to the site of inflammation and increasing the inflammatory response. These macrophages produce a whole cascade of inflammatory mediators, such as prostaglandins, leukotrienes, and cytokines. The chronic inflammatory response starts with the persistence of the inflammatory agent in a process that could be harmful not only to the inflammatory agent, but also to healthy tissues.

Although conventional anti-inflammatory treatments demonstrate effectiveness in treating inflammation, their use could trigger low, mild, and severe adverse effects. The use of biopharmaceutics and natural products of animal or vegetal origin to treat inflammation is increasing worldwide and encouraging researchers to investigate the anti-inflammatory mechanisms of isolated compounds from natural sources.

Thus, this Special Issue will highlight current research exploring the anti-inflammatory mechanisms of bioproducts of natural origin (including but not limited to vegetal and animal sources), which could be investigated in several diseases using in vivo models or described using in vitro assays. Clinical assays are also welcome.

Dr. Ariane Rozza
Guest Editor

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Keywords

inflammation
bioproducts
isolated compounds
cytokines
macrophages
autoimmune diseases
in vivo assay
in vitro assay

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Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside in Pharmaceutics (20 articles)

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Research

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15 pages, 4769 KiB

Open AccessArticle

Effect of E. cava and C. indicum Complex Extract on Phorbol 12-Myristate 13-Acetate (PMA)-Stimulated Inflammatory Response in Human Pulmonary Epithelial Cells and Particulate Matter (PM)_2.5-Induced Pulmonary Inflammation in Mice

by Sung-Gyu Lee, Chan-Hwi Park and Hyun Kang

Pharmaceutics 2023, 15(11), 2621; https://doi.org/10.3390/pharmaceutics15112621 - 13 Nov 2023

Cited by 1 | Viewed by 1502

Abstract

This study explores the potential of a natural composite formulation known as ED, consisting of Ecklonia cava (E. cava, family: Lessoniaceae) and Chrysanthemum indicum Linne (C. indicum, family: Asteraceae), in alleviating lung inflammation induced by fine particulate matter (PM_2.5). Initial assessments confirmed that neither ED nor one of its components, dieckol, exhibited cytotoxic effects on A549 cells. Subsequently, the impact of ED and dieckol on MUC5AC gene expression in A549 cells stimulated by phorbol 12-myristate 13-acetate (PMA) was investigated, revealing promising results that demonstrated a dose-dependent inhibition of MUC5AC gene expression. The study also delves into the underlying mechanisms, demonstrating that ED and dieckol effectively suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including JNK, ERK, and p38, which are known to be involved in the regulation of MUC5AC gene expression. In in vivo experiments using a PM_2.5-induced pulmonary inflammation mouse model, the research findings showed that ED mitigated cellular accumulation in the airways, leading to a significant reduction in the total cell count in bronchoalveolar lavage fluid (BALF). Moreover, ED exhibited protective effects against PM_2.5-induced pulmonary damage, characterized by reduced inflammatory cell infiltration and decreased mucus secretion in pulmonary tissues. Additionally, ED’s anti-inflammatory properties were evident in its ability to decrease the levels of key inflammatory cytokines, TNF-α and IL-6, both in the serum and lung tissue of the PM_2.5-induced pulmonary inflammation mouse model. These findings suggest the potential of ED as a therapeutic agent for inflammatory respiratory diseases. Full article

(This article belongs to the Special Issue Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition)

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30 pages, 4300 KiB

Open AccessArticle

Punicalagin’s Protective Effects on Parkinson’s Progression in Socially Isolated and Socialized Rats: Insights into Multifaceted Pathway

by Hoda A. Salem, Karema Abu-Elfotuh, Sharifa Alzahrani, Nermin I. Rizk, Howaida S. Ali, Nehal Elsherbiny, Alhanouf Aljohani, Ahmed M. E. Hamdan, Panneerselvam Chellasamy, Nada S. Abdou, Ayah M. H. Gowifel, Alshaymaa Darwish, Osama Mohamed Ibrahim and Zakaria Y. Abd Elmageed

Pharmaceutics 2023, 15(10), 2420; https://doi.org/10.3390/pharmaceutics15102420 - 4 Oct 2023

Cited by 3 | Viewed by 1923

Abstract

Parkinson’s disease (PD) is a gradual deterioration of dopaminergic neurons, leading to motor impairments. Social isolation (SI), a recognized stressor, has recently gained attention as a potential influencing factor in the progress of neurodegenerative illnesses. We aimed to investigate the intricate relationship between SI and PD progression, both independently and in the presence of manganese chloride (MnCl₂), while evaluating the punicalagin (PUN) therapeutic effects, a natural compound established for its cytoprotective, anti-inflammatory, and anti-apoptotic activities. In this five-week experiment, seven groups of male albino rats were organized: G1 (normal control), G2 (SI), G3 (MnCl₂), G4 (SI + MnCl₂), G5 (SI + PUN), G6 (MnCl₂ + PUN), and G7 (SI + PUN + MnCl₂). The results revealed significant changes in behavior, biochemistry, and histopathology in rats exposed to SI and/or MnCl₂, with the most pronounced effects detected in the SI rats concurrently exposed to MnCl₂. These effects were associated with augmented oxidative stress biomarkers and reduced antioxidant activity of the Nrf2/HO-1 pathway. Additionally, inflammatory pathways (HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1 and JAK-2/STAT-3) were upregulated, while dysregulation of signaling pathways (PI3K/AKT/GSK-3β/CREB), sustained endoplasmic reticulum stress by activation PERK/CHOP/Bcl-2, and impaired autophagy (AMPK/SIRT-1/Beclin-1 axis) were observed. Apoptosis induction and a decrease in monoamine levels were also noted. Remarkably, treatment with PUN effectively alleviated behaviour, histopathological changes, and biochemical alterations induced by SI and/or MnCl₂. These findings emphasize the role of SI in PD progress and propose PUN as a potential therapeutic intervention to mitigate PD. PUN’s mechanisms of action involve modulation of pathways such as HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1, JAK-2/STAT-3, PI3K/AKT/GSK-3β/CREB, AMPK/SIRT-1, Nrf2/HO-1, and PERK/CHOP/Bcl-2. Full article

(This article belongs to the Special Issue Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition)

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16 pages, 8999 KiB

Open AccessEditor’s ChoiceArticle

Protopanaxadiol-Enriched Rice Exerted Antiadipogenic Activity during 3T3-L1 Differentiation and Anti-Inflammatory Activity in 3T3-L1 Adipocytes

by Chaiwat Monmai, Jin-Suk Kim, Hyun Bo Sim, Doh-Won Yun, Sung-Dug Oh, Eui-Shik Rha, Jong-Jin Kim and So-Hyeon Baek

Pharmaceutics 2023, 15(8), 2123; https://doi.org/10.3390/pharmaceutics15082123 - 11 Aug 2023

Viewed by 1362

Abstract

Ginseng is a traditional medicine with health benefits for humans. Protopanaxadiol (PPD) is an important bioactive compound found in ginseng. Transgenic rice containing PPD has been generated previously. In the present study, extracts of this transgenic rice were evaluated to assess their antiadipogenic and anti-inflammatory activities. During adipogenesis, cells were treated with transgenic rice seed extracts. The results revealed that the concentrations of the rice seed extracts tested in this study did not affect cell viability at 3 days post-treatment. However, the rice seed extracts significantly reduced the accumulation of lipids in cells and suppressed the activation of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which in turn inhibited the expression of adipogenesis-related mRNAs, such as adiponectin, PPARγ, C/EBPα, sterol regulatory element-binding protein 1, glucose transport member 4, and fatty acid synthase. In adipocytes, the extracts significantly reduced the mRNA expression of inflammation-related factors following LPS treatment. The activation of NF-κB p65 and ERK 1/2 was inhibited in extract-treated adipocytes. Moreover, treatment with extract #8 markedly reduced the cell population of the G2/M phase. Collectively, these results indicate that transgenic rice containing PPD may act as an obesity-reducing and/or -preventing agent. Full article

(This article belongs to the Special Issue Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition)

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18 pages, 12588 KiB

Open AccessArticle

Postbiotic Metabolite of Lactiplantibacillus plantarum PD18 against Periodontal Pathogens and Their Virulence Markers in Biofilm Formation

by Widawal Butrungrod, Chaiyavat Chaiyasut, Netnapa Makhamrueang, Sartjin Peerajan, Wantida Chaiyana and Sasithorn Sirilun

Pharmaceutics 2023, 15(5), 1419; https://doi.org/10.3390/pharmaceutics15051419 - 6 May 2023

Cited by 4 | Viewed by 2093

Abstract

Alternative methods to reduce infectious diseases caused by bacterial pathogens and their virulence factors, biofilm formations, have arisen to reduce the pressure on existing or currently developed disinfectants and antimicrobial agents. The current strategies for reducing the severity of periodontal pathogen-caused disease by using beneficial bacteria and their metabolites are highly desirable. Probiotic strains of lactobacilli related to foods from Thai-fermented foods were selected and their postbiotic metabolites (PM) were isolated with inhibitory activity on periodontal pathogens and their biofilm formation. The PM from Lactiplantibacillus plantarum PD18 (PD18 PM) with the highest antagonistic effect against Streptococcus mutans, Porphyromonas gingivalis, Tannerella forsythia and Prevotella loescheii was selected from 139 Lactobacillus isolates. The minimal inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) values of PD18 PM against the pathogens ranged from 1:2 to 1:4. The PD18 PM demonstrated the ability to prevent the biofilm formation of S. mutans and P. gingivalis by showing a significant reduction in viable cells, high percentages of biofilm inhibition at 92.95 and 89.68%, and the highest effective contact times at 5 and 0.5 min, respectively. L. plantarum PD18 PM showed potential as a promising natural adjunctive agent to inhibit periodontal pathogens and their biofilms. Full article

(This article belongs to the Special Issue Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition)

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25 pages, 6239 KiB

Open AccessArticle

The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome

by Balbino Lino dos Santos, Cleonice Creusa dos Santos, Janaina R. P. Soares, Karina C. da Silva, Juciele Valeria R. de Oliveira, Gabriele S. Pereira, Fillipe M. de Araújo, Maria de Fátima D. Costa, Jorge Mauricio David, Victor Diogenes A. da Silva, Arthur Morgan Butt and Silvia Lima Costa

Pharmaceutics 2023, 15(5), 1410; https://doi.org/10.3390/pharmaceutics15051410 - 5 May 2023

Cited by 4 | Viewed by 2301

Abstract

Agathisflavone, purified from Cenostigma pyramidale (Tul.) has been shown to be neuroprotective in in vitro models of glutamate-induced excitotoxicity and inflammatory damage. However, the potential role of microglial regulation by agathisflavone in these neuroprotective effects is unclear. Here we investigated the effects of agathisflavone in microglia submitted to inflammatory stimulus in view of elucidating mechanisms of neuroprotection. Microglia isolated from cortices of newborn Wistar rats were exposed to Escherichia coli lipopolysaccharide (LPS, 1 µg/mL) and treated or not with agathisflavone (1 µM). Neuronal PC12 cells were exposed to a conditioned medium from microglia (MCM) treated or not with agathisflavone. We observed that LPS induced microglia to assume an activated inflammatory state (increased CD68, more rounded/amoeboid phenotype). However, most microglia exposed to LPS and agathisflavone, presented an anti-inflammatory profile (increased CD206 and branched-phenotype), associated with the reduction in NO, GSH mRNA for NRLP3 inflammasome, IL1-β, IL-6, IL-18, TNF, CCL5, and CCL2. Molecular docking also showed that agathisflavone bound at the NLRP3 NACTH inhibitory domain. Moreover, in PC12 cell cultures exposed to the MCM previously treated with the flavonoid most cells preserved neurites and increased expression of β-tubulin III. Thus, these data reinforce the anti-inflammatory activity and the neuroprotective effect of agathisflavone, effects associated with the control of NLRP3 inflammasome, standing out it as a promising molecule for the treatment or prevention of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition)

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26 pages, 2659 KiB

Open AccessArticle

Therapeutic Efficacy of a Formulation Prepared with Linum usitatissimum L., Plantago ovata Forssk., and Honey on Uncomplicated Pelvic Inflammatory Disease Analyzed with Machine Learning Techniques

by Sana Qayyum, Arshiya Sultana, Md Belal Bin Heyat, Khaleequr Rahman, Faijan Akhtar, Amin ul Haq, Batool Abdulelah Alkhamis, Mohammed Aedh Alqahtani and Reem M. Gahtani

Pharmaceutics 2023, 15(2), 643; https://doi.org/10.3390/pharmaceutics15020643 - 14 Feb 2023

Cited by 11 | Viewed by 2906

Abstract

A single-blind double-dummy randomized study was conducted in diagnosed patients (n = 66) to compare the efficacy of Linseeds (Linum usitatissimum L.), Psyllium (Plantago ovata Forssk.), and honey in uncomplicated pelvic inflammatory disease (uPID) with standard drugs using experimental and computational analysis. The pessary group received placebo capsules orally twice daily plus a per vaginum cotton pessary of powder from linseeds and psyllium seeds, each weighing 3 gm, with honey (5 mL) at bedtime. The standard group received 100 mg of doxycycline twice daily and 400 mg of metronidazole TID orally plus a placebo cotton pessary per vaginum at bedtime for 14 days. The primary outcomes were clinical features of uPID (vaginal discharge, lower abdominal pain (LAP), low backache (LBA), and pelvic tenderness. The secondary outcomes included leucocytes (WBCs) in vaginal discharge on saline microscopy and the SF-12 health questionnaire. In addition, we also classified both (pessary and standard) groups using machine learning models such as Decision Tree (DT), Random Forest (RF), Logistic Regression (LR), and AdaBoost (AB). The pessary group showed a higher percentage reduction than the standard group in abnormal vaginal discharge (87.05% vs. 77.94%), Visual Analogue Scale (VAS)-LAP (80.57% vs. 77.09%), VAS-LBA (74.19% vs. 68.54%), McCormack pain scale (McPS) score for pelvic tenderness (75.39% vs. 67.81%), WBC count of vaginal discharge (87.09% vs. 83.41%) and improvement in SF-12 HRQoL score (94.25% vs. 86.81%). Additionally, our DT 5-fold model achieved the maximum accuracy (61.80%) in the classification. We propose that the pessary group is cost-effective, safer, and more effective as standard drugs for treating uPID and improving the HRQoL of women. Aucubin, Plantamajoside, Herbacetin, secoisolariciresinol diglucoside, Secoisolariciresinol Monoglucoside, and other various natural bioactive molecules of psyllium and linseeds have beneficial effects as they possess anti-inflammatory, antioxidant, antimicrobial, and immunomodulatory properties. The anticipated research work is be a better alternative treatment for genital infections. Full article

(This article belongs to the Special Issue Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition)

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20 pages, 4462 KiB

Open AccessArticle

Alpinetin Suppresses Zika Virus-Induced Interleukin-1β Production and Secretion in Human Macrophages

by Nitwara Wikan, Saranyapin Potikanond, Phateep Hankittichai, Phatarawat Thaklaewphan, Sathit Monkaew, Duncan R. Smith and Wutigri Nimlamool

Pharmaceutics 2022, 14(12), 2800; https://doi.org/10.3390/pharmaceutics14122800 - 14 Dec 2022

Cited by 3 | Viewed by 1973

Abstract

Zika virus (ZIKV) infection has been recognized to cause adverse sequelae in the developing fetus. Specially, this virus activates the excessive release of IL-1β causing inflammation and altered physiological functions in multiple organs. Although many attempts have been invested to develop vaccine, antiviral, and antibody therapies, development of agents focusing on limiting ZIKV-induced IL-1β release have not gained much attention. We aimed to study the effects of alpinetin (AP) on IL-1β production in human macrophage upon exposure to ZIKV. Our study demonstrated that ZIKV stimulated IL-1β release in the culture supernatant of ZIKV-infected cells, and AP could effectively reduce the level of this cytokine. AP exhibited no virucidal activities against ZIKV nor caused alteration in viral production. Instead, AP greatly inhibited intracellular IL-1β synthesis. Surprisingly, this compound did not inhibit ZIKV-induced activation of NF-κB and its nuclear translocation. However, AP could significantly inhibit ZIKV-induced p38 MAPK activation without affecting the phosphorylation status of ERK1/2 and JNK. These observations suggest the possibility that AP may reduce IL-1β production, in part, through suppressing p38 MAPK signaling. Our current study sheds light on the possibility of using AP as an alternative agent for treating complications caused by ZIKV infection-induced IL-1β secretion. Full article

(This article belongs to the Special Issue Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition)

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Review

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37 pages, 4023 KiB

Open AccessReview

Emerging Trends in the Treatment of Skin Disorders by Herbal Drugs: Traditional and Nanotechnological Approach

by Rutvi Agrawal, Priyanka Jurel, Rohitas Deshmukh, Ranjit Kumar Harwansh, Akash Garg, Ashwini Kumar, Sudarshan Singh, Ajay Guru, Arun Kumar and Vinoth Kumarasamy

Pharmaceutics 2024, 16(7), 869; https://doi.org/10.3390/pharmaceutics16070869 - 28 Jun 2024

Cited by 1 | Viewed by 1861

Abstract

Since the earliest days, people have been employing herbal treatments extensively around the world. The development of phytochemical and phytopharmacological sciences has made it possible to understand the chemical composition and biological properties of a number of medicinal plant products. Due to certain challenges like large molecular weight and low bioavailability, some components of herbal extracts are not utilized for therapeutic purposes. It has been suggested that herbal medicine and nanotechnology can be combined to enhance the benefits of plant extracts by lowering dosage requirements and adverse effects and increasing therapeutic activity. Using nanotechnology, the active ingredient can be delivered in an adequate concentration and transported to the targeted site of action. Conventional therapy does not fulfill these requirements. This review focuses on different skin diseases and nanotechnology-based herbal medicines that have been utilized to treat them. Full article

(This article belongs to the Special Issue Anti-inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 2nd Edition)

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