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Anti-Inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 3rd...
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Anti-Inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 3rd Edition

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

Deadline for manuscript submissions: 30 January 2027 | Viewed by 4956

Special Issue Editor

Prof. Dr. Ariane Leite Rozza

E-Mail Website
Guest Editor
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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

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.

Prof. Dr. Ariane Leite Rozza
Guest Editor

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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. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

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

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Related Special Issues

Published Papers (4 papers)

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Research

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15 pages, 2365 KB  
Article
Menthol-Based Cream as a Novel Therapy for Diabetic Skin Wounds
by Ana Júlia Vieira, Fernando Pereira Beserra, Gabriel Bacil Prata, Emanuel Ricardo Monteiro Martinez, Rafael Henrique Nóbrega, Luis Fernando Barbisan, Claudia Helena Pellizzon and Ariane Leite Rozza
Pharmaceutics 2026, 18(1), 125; https://doi.org/10.3390/pharmaceutics18010125 - 19 Jan 2026
Viewed by 1042
Abstract
Background/Objectives: Diabetes mellitus impairs skin wound healing by promoting a chronic inflammatory response and increased oxidative stress. This study aimed to investigate the healing potential of menthol in skin wounds of diabetic rats. Methods: A single dose of streptozotocin (50 mg/kg, [...] Read more.
Background/Objectives: Diabetes mellitus impairs skin wound healing by promoting a chronic inflammatory response and increased oxidative stress. This study aimed to investigate the healing potential of menthol in skin wounds of diabetic rats. Methods: A single dose of streptozotocin (50 mg/kg, i.p.) induced type 1 diabetes mellitus in male Wistar rats. After nine days, a skin wound was made on the rats’ back and treated with vehicle, insulin-based cream (0.5 U/g), or menthol-based cream (0.5%) for 14 days. After the euthanasia, the wound area was destined for assays of anti-inflammatory and antioxidant activity, protein expression levels by Western blotting, measurement of MPO activity, and quantitative mRNA expression. Nitrite levels were measured in blood plasma. Results: The group treated with menthol-based cream decreased the wound area by 94%. Also, menthol reduced the levels of TNF-α and IL-6 and increased IL-10 levels, besides stimulating the activity of antioxidant enzymes SOD, GPx, and GR, and enhancement in GSH and nitrite levels. Menthol downregulated the expression of Nfκb and upregulated the Il10 and Ki67 gene expression and the eNOS protein expression. Conclusions: Topically applied menthol accelerated the skin wound healing in diabetic rats through anti-inflammatory and antioxidant activities and increased cell proliferation, supporting its potential as a therapeutic strategy for diabetic wound management. Full article
(This article belongs to the Special Issue Anti-Inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 3rd Edition)
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17 pages, 3619 KB  
Article
Nobiletin Attenuates Inflammation and Modulates Lipid Metabolism in an In Vitro Model of Intestinal Failure-Associated Liver Disease
by Marta Belka, Aleksandra Gostyńska-Stawna, Karina Sommerfeld-Klatta, Maciej Stawny and Violetta Krajka-Kuźniak
Pharmaceutics 2026, 18(1), 87; https://doi.org/10.3390/pharmaceutics18010087 - 9 Jan 2026
Cited by 1 | Viewed by 1070
Abstract
Background: Intestinal failure-associated liver disease (IFALD) is a serious complication in patients receiving parenteral nutrition, often exacerbated by inflammation, lipid overload, and oxidative stress. Nobiletin (NOB), a polymethoxylated flavone, is known for its anti-inflammatory and lipid-regulating properties. Methods: We employed an [...] Read more.
Background: Intestinal failure-associated liver disease (IFALD) is a serious complication in patients receiving parenteral nutrition, often exacerbated by inflammation, lipid overload, and oxidative stress. Nobiletin (NOB), a polymethoxylated flavone, is known for its anti-inflammatory and lipid-regulating properties. Methods: We employed an in vitro model using THLE-2 human hepatocytes and primary human cholangiocytes exposed to Intralipid (INT) and lipopolysaccharide (LPS) to simulate IFALD conditions. NOB was tested at non-toxic concentrations (10 and 25 µM) to assess its protective effects. MTT viability assays, multiplex bead-based immunoassays (MAGPIX), RT-qPCR, and Western blotting were used to evaluate changes in inflammation markers, gene expression, and protein signaling. Moreover, ALT and AST activities were used to assess hepatocellular injury. Results: NOB maintained high cell viability in THLE-2 hepatocytes and cholangiocytes, confirming its low cytotoxicity. NOB normalized ALT and AST activities in both tested cell lines, but the effect reached statistical significance only for ALT in cholangiocytes. Under IFALD-like conditions (LPS+INT), NOB significantly preserved metabolic activity in both cell types. In THLE-2 and cholangiocytes, NOB markedly reduced the phosphorylation of pro-inflammatory proteins JNK, NF-κB, and STAT3, indicating a broad inhibition of inflammatory signaling. Moreover, in THLE-2 cells, NOB upregulated lipid metabolism-related genes (PRKAA2, CYP7A1, and ABCA1) and decreased oxidative stress, thereby enhancing the nuclear translocation of Nrf2 and increasing SOD1 level, which supports the activation of antioxidant defenses. Conclusions: NOB exhibits hepatoprotective properties under IFALD-like conditions in vitro, likely through modulation of inflammation-related signaling and lipid metabolism pathways. Full article
(This article belongs to the Special Issue Anti-Inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 3rd Edition)
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23 pages, 1706 KB  
Article
Polyphenol-Rich Citrullus lanatus Rind Extract Mitigates Doxorubicin-Induced Cardiotoxicity: HPLC Profiling and In Vivo Evaluation
by Bader Alsuwayt
Pharmaceutics 2025, 17(11), 1469; https://doi.org/10.3390/pharmaceutics17111469 - 14 Nov 2025
Cited by 2 | Viewed by 945
Abstract
Background/Objectives: Cardiovascular diseases (CVDs) remain a major cause of mortality globally, driven in part by oxidative stress and inflammation. The present study investigated the polyphenolic composition and cardioprotective potential of polyphenol-rich Citrullus lanatus (PRCL) rind extract against doxorubicin-induced cardiotoxicity in rats; Methods: [...] Read more.
Background/Objectives: Cardiovascular diseases (CVDs) remain a major cause of mortality globally, driven in part by oxidative stress and inflammation. The present study investigated the polyphenolic composition and cardioprotective potential of polyphenol-rich Citrullus lanatus (PRCL) rind extract against doxorubicin-induced cardiotoxicity in rats; Methods: High-performance liquid chromatography (HPLC) was employed to identify and quantify the major bioactive compounds present in the extract. Total 30 healthy male Wistar Kyoto rats were recruited and divided into 6 groups and various cardiovascular markers and antioxidant were measured in vivo and in vitro methods; Results: Ethanolic extraction of Citrullus lanatus rind yielded 19.58 g extract per 100 g of dry plant material. HPLC analysis identified five phenolic acids, i.e., gallic acid, p-hydroxybenzoic acid (PHBA), chlorogenic acid, caffeic acid, and vanillic acid, and two flavonoids, i.e., catechin and hesperetin, with PHBA (163.66 mg/g of extract) being the most abundant. Total phenolic and flavonoid content was determined to be 35.6 mg GAE/g and 12.8 mg CE/g, respectively. In vitro antioxidant assays showed moderate free radical scavenging, reducing power, and 86.9% inhibition of linoleic acid peroxidation. In vivo, Wistar rats were treated with doxorubicin (10 mg/kg) to induce cardiotoxicity, followed by PRCL extract administration (21 days at 250 and 500 mg/kg/day). The extract significantly improved body weight, serum lipid profile, and reduced cardiovascular risk indices. Antioxidant biomarkers (SOD, CAT, GPx, GSH) were restored, while lipid peroxidation (MDA) and inflammatory cytokines (TNF-α, IL-6) were significantly reduced in treated groups. The 500 mg/kg dose demonstrated superior efficacy, comparable to the standard quercetin group. Histopathological examination revealed notable protection of cardiac tissue architecture in the high-dose PRCL-500 group; Conclusions: These findings suggest that PRCL rind extract contains potent compounds having antioxidant and cardioprotective properties and may be used as a natural therapeutic agent against cardiotoxicity. Full article
(This article belongs to the Special Issue Anti-Inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 3rd Edition)
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Review

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33 pages, 1466 KB  
Review
Current Evidence from Animal Models on Molecular Changes Underlying Antidepressant Effects of Psychobiotics
by Nevena Todorović Vukotić, Neda Đorđević, Andrijana Stanisavljević Ilić, Svetlana Soković Bajić and Ivana Perić
Pharmaceutics 2026, 18(1), 140; https://doi.org/10.3390/pharmaceutics18010140 - 22 Jan 2026
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Abstract
The treatment of depression is an uphill battle due to the low efficiency and delayed clinical response of antidepressants and the fact that most of them cause numerous side effects. Psychobiotics, probiotics that affect brain function and confer mental health benefits, emerged as [...] Read more.
The treatment of depression is an uphill battle due to the low efficiency and delayed clinical response of antidepressants and the fact that most of them cause numerous side effects. Psychobiotics, probiotics that affect brain function and confer mental health benefits, emerged as a promising ally showing protective effects against depressive- and anxiety-like behaviors in various animal models of depression. There is rapidly accumulating evidence that psychobiotics show protective effects at the molecular level as well, affecting several pathophysiological processes implicated in depression. This narrative review summarizes preclinical insights into molecular changes related to the hypothalamic-pituitary-adrenal (HPA) axis, peripheral inflammation, neuroinflammation, neurotransmission and tryptophan metabolism underlying psychobiotic-driven mitigation of depressive and anxiety symptoms in stress-based, corticosterone-induced and inflammation-induced animal models of depression. Research evidence indicates that psychobiotics normalize the activity of the HPA axis, decrease levels of inflammatory mediators in the intestine, circulation, and brain, normalize the levels of neurotransmitters and their receptors, and regulate tryptophan metabolism in various animal models of depression. The main setbacks in this field are the extensive diversity of studied probiotic strains, which are often insufficiently characterized, and the lack of mechanistic studies in animal models. However, despite these challenges, further study of psychobiotics in the pursuit of supportive therapies for depressive disorders is firmly grounded. Full article
(This article belongs to the Special Issue Anti-Inflammatory Effects from Natural Bioactive Compounds—from Bench to Bedside, 3rd Edition)
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