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Anticancer, Antioxidant, and Anti-Inflammatory Properties of Natural Products

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

Deadline for manuscript submissions: 20 November 2025 | Viewed by 3079

Special Issue Editors


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Guest Editor
LAQV/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Interests: coffee; coffee by-products; sustainability; circular economy; upcycling; quality; authenticicity; chromatography; green chemistry
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Guest Editor
LAQV/REQUIMTE, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 280, 4050-313 Porto, Portugal
Interests: bioactive compounds; obesity; diabetes

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Guest Editor
LAQV/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
Interests: cancer; glucose; glutamine transport; polyphenols; obesity; type 2 diabetes; microbiota

Special Issue Information

Dear Colleagues,

Natural products have emerged as valuable sources of bioactive compounds, demonstrating significant potential in improving health and preventing diseases.

This Special Issue invites submissions that explore the diverse roles of natural products, particularly their abilities to combat oxidative stress, modulate inflammatory pathways, and exhibit anticancer and antitumoral effects.

We welcome original research and comprehensive review articles exploring recent advances in how plant extracts, medicinal herbs, foods, by-products, and other naturally derived products can provide alternative and complementary therapeutic approaches.

Studies on the bioactivity of these compounds—especially those examining their impact on cellular mechanisms in vitro and in vivo models—are particularly encouraged, as they offer essential insights into the preventive and therapeutic potential of natural products.

Dr. Rita Carneiro Alves
Dr. Nelson Andrade
Dr. Cláudia Silva
Guest Editors

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Keywords

  • bioactive compounds
  • natural extracts
  • health promotion/disease prevention
  • oxidative stress modulation
  • inflammatory pathway regulation
  • anticancer and antitumoral effects
  • cellular mechanisms
  • in vitro and in vivo bioactivity studies

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Published Papers (3 papers)

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Research

14 pages, 1645 KB  
Article
Blockade of PAR2 Signaling by Punicalagin as a Therapeutic Strategy for Atopic Dermatitis
by Hyejin Jeon, Yohan Seo, Wook-Joo Lee, Yunkyung Heo, Won-Sik Shim and Wan Namkung
Int. J. Mol. Sci. 2025, 26(18), 8920; https://doi.org/10.3390/ijms26188920 - 13 Sep 2025
Viewed by 642
Abstract
Atopic dermatitis is a chronic inflammatory skin disorder characterized by persistent inflammation and severe pruritus. Current anti-inflammatory agents carry risks of long-term adverse effects, while antihistamines provide limited relief of pruritus. Protease-activated receptor 2 (PAR2) has emerged as a critical mediator of both [...] Read more.
Atopic dermatitis is a chronic inflammatory skin disorder characterized by persistent inflammation and severe pruritus. Current anti-inflammatory agents carry risks of long-term adverse effects, while antihistamines provide limited relief of pruritus. Protease-activated receptor 2 (PAR2) has emerged as a critical mediator of both inflammation and pruritus, representing a promising therapeutic target. In this study, we investigated the therapeutic potential of punicalagin (PCG), a potent PAR2 antagonist, in atopic dermatitis. PCG fully and potently inhibited trypsin-induced PAR2 activation in HaCaT cells with an IC50 of 1.30 µM, exhibiting over 40-fold greater selectivity over PAR1. PCG significantly inhibited PAR2-induced phosphorylation of ERK1/2 and NF-κB in both HaCaT and human dermal fibroblast cells and reduced IL-8 secretion in HaCaT cells. In addition, PCG did not significantly affect other pruritus-related GPCRs including H1R, H4R, TGR5, 5HT2A, 5HT2B, and MRGPRX2 at 30 µM. Notably, PCG strongly blocked PAR2-AP-induced scratching in mice. In addition, PCG improved skin lesions, reduced dermatitis severity scores, and alleviated scratching behavior in a DNFB-induced atopic dermatitis model. These effects were associated with reduced epidermal thickness, decreased serum TSLP levels, and inhibition of PAR2-dependent calcium signaling in dorsal root ganglion neurons. These findings demonstrate that PCG is a selective PAR2 antagonist that effectively alleviates both inflammatory and pruritic symptoms of atopic dermatitis, suggesting its potential as a novel therapeutic agent. Full article
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17 pages, 692 KB  
Article
Unveiling Synergistic Antioxidant Effects of Green Tea and Peppermint: Role of Polyphenol Interactions and Blend Preparation
by Elena Kurin, Marianna Hajská, Ema Kostovčíková, Kamila Dokupilová, Pavel Mučaji, Milan Nagy, Branislav Novotný and Silvia Bittner Fialová
Int. J. Mol. Sci. 2025, 26(13), 6257; https://doi.org/10.3390/ijms26136257 - 28 Jun 2025
Viewed by 1350
Abstract
This study explores the antioxidant activity of green tea (Camellia sinensis, GT) and peppermint (Mentha × piperita, PM) infusions, individually and in combination, focusing on how preparation methods affect their efficacy. Antiradical and intracellular antioxidant activity was assessed using [...] Read more.
This study explores the antioxidant activity of green tea (Camellia sinensis, GT) and peppermint (Mentha × piperita, PM) infusions, individually and in combination, focusing on how preparation methods affect their efficacy. Antiradical and intracellular antioxidant activity was assessed using DPPH, ABTS, and DCF assays, alongside interaction analysis via combination index (CI) and dose reduction index (DRI). HPLC analysis determined the polyphenolic profiles of GT and PM. GT showed the strongest antioxidant activity, with the lowest IC50 values (4.81 µg/mL in DPPH, 2.70 µg/mL in ABTS, 3.71 µg/mL in DCF), indicating potent radical-scavenging potential. PM exhibited moderate antiradical capacity but similar intracellular activity (IC50 = 3.80 µg/mL). Co-maceration followed by lyophilization of GT:PM extracts led to nearly additive interactions (CI~1.0) and allowed significant dose reduction (DRI up to 4.44). In contrast, post-mixed extracts showed assay-dependent effects, including antagonism in intracellular ROS inhibition (CI = 1.83). Equimolar mixtures of model polyphenols: EGCG, quercetin, and rosmarinic acid demonstrated enhanced effects, with the strongest synergy in ternary mixtures (CI = 0.67–0.86), potentially achievable in GT:PM combinations. These findings highlight that extract preparation critically influences antioxidant efficacy, supporting co-maceration as a promising strategy for developing effective functional formulations based on plant extract combinations. Full article
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22 pages, 8061 KB  
Article
Synthesis and Biological Evaluation of Quercetagetin Derivatives as the Inhibitors of Mcl-1 and Bcl-2 Against Leukemia
by Kang Li, Xiaomei Ge, Wei Liu, Lei Huang, Xinye Lv, Yuhui Tang, Zhehao He, Yingxue Yang, Miaofen Chen, Jianguo Zeng and Pi Cheng
Int. J. Mol. Sci. 2025, 26(6), 2727; https://doi.org/10.3390/ijms26062727 - 18 Mar 2025
Viewed by 788
Abstract
B-cell lymphoma-2 (Bcl-2) family proteins are fundamental regulators of intrinsic cell apoptosis, and overexpression of apoptotic proteins (Bcl-2 and Mcl-1) is a characteristic of many haematological malignancies. Thus, it is necessary to discover novel inhibitors to treat leukemia. In the current study, we [...] Read more.
B-cell lymphoma-2 (Bcl-2) family proteins are fundamental regulators of intrinsic cell apoptosis, and overexpression of apoptotic proteins (Bcl-2 and Mcl-1) is a characteristic of many haematological malignancies. Thus, it is necessary to discover novel inhibitors to treat leukemia. In the current study, we synthesized a series of quercetagetin derivatives (compounds 2a2t, 3a3j and 4a4g) and evaluated their anticancer activities on four leukemia cells (U937, K562, K562R and KG-1). Among those synthesized derivatives, compounds 2a exhibited the best antiproliferative activity (IC50 = 0.276, 0.159, 0.312 and 0.271 µM to U937, K562, K562R and KG-1, respectively). In addition, 2a induced apoptosis in K562 and markedly arrested the cell cycle G2/M phase of K562. The Western blot assay showed that 2a is a potential inhibitor that can effectively suppress the expression of Bcl-2 and Mcl-1. The molecular docking study predicted that 2a had firm interactions with the active pockets of Bcl-2 and Mcl-1. Finally, in silico pharmacokinetic evaluation of 2a indicated its potential as an anti-leukemia drug lead in the future. Full article
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