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The Role of Natural Compounds in Cancer and Inflammation
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The Role of Natural Compounds in Cancer and Inflammation

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

Deadline for manuscript submissions: 20 May 2025 | Viewed by 14690

Special Issue Editor

Dr. Elia Ranzato

E-Mail Website
Guest Editor
DiSIT-Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy
Interests: cell biology; wound repair; calcium signalling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products are treasures given to us by nature. Millions of years of evolution have allowed most natural products to develop specific biological activities. An increasing number of studies have shown that natural products possess anticancer, anti-inflammatory and other beneficial properties. These natural products can inhibit the growth and spread of tumors and tumor cells. They can also improve human immunity to help the body resist cancer. Therefore, the application of natural products in the field of medicine is becoming increasingly important. With further research on natural products, more medicines have been developed, such as aspirin and resveratrol. Many natural products have complex structures and various activities, which play an important role in organic synthesis and biological activity research. This Special Issue aims to collect papers focused on the discovery of new natural products and the elucidation of their role in cancer, autoimmune conditions and other diseases. Both research articles and reviews are welcome.

Dr. Elia Ranzato
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.

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Keywords

  • natural compounds
  • oxidative stress
  • anti-cancer
  • anti-inflammatory
  • natural product synthesis and biological activities

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Published Papers (7 papers)

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Research

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13 pages, 1469 KiB  
Article
Characterization of the Coriolopsis gallica DyP for Its Potential to Biotransform Various Fluoroquinolones
by Karima Staita, Imen Akrout, Julien Lambert, Annick Turbé-Doan, Anne Lomascolo, Craig B. Faulds, Héla Zouari-Mechichi, Giuliano Sciara, Tahar Mechichi and Eric Record
Int. J. Mol. Sci. 2024, 25(21), 11392; https://doi.org/10.3390/ijms252111392 - 23 Oct 2024
Viewed by 708
Abstract
Coriolopsis gallica (Cga) is a white-rot fungus renowned for its ability to secrete ligninolytic enzymes that are capable of oxidizing phenolic compounds. This study aimed to investigate the biochemical characteristics of a dye-decolorizing peroxidase named CgaDyP1 and test its ability to [...] Read more.
Coriolopsis gallica (Cga) is a white-rot fungus renowned for its ability to secrete ligninolytic enzymes that are capable of oxidizing phenolic compounds. This study aimed to investigate the biochemical characteristics of a dye-decolorizing peroxidase named CgaDyP1 and test its ability to biotransform antibiotics. CgaDyP1 was cloned and heterologously expressed in Escherichia coli. We fully characterized the biochemical properties of CgaDyP1 and evaluated its dye-decolorizing potential to confirm that it belongs to the DyP class of enzymes. We also tested its fluoroquinolone antibiotic biotransformation potential for possible biotechnological applications. Alignment of the primary amino acid sequence with DyP homolog sequences showed that CgaDyP1 has high similarity with other fungal DyPs. The recombinant CgaDyP1 exhibited activity on substrates such as ABTS and 2,6-dimethoxyphenol (DMP) with optimal performance at a pH of 3, although activity at pH 2.5, pH 4, and pH5 diminished over time. Thermostability tests indicated that the enzyme remains stable at temperatures between 30 °C and 50 °C and retains 70% of its initial activity after 180 min at 50 °C. Tests on the effect of hydrogen peroxide on CgaDyP1 activity found peak activity at 0.25 mM H2O2. CgaDyP1 decolorized five industrial dyes, and kinetics data confirmed that it belongs to the DyP class of enzymes. CgaDyP1 was shown to biotransform some of the 7 recalcitrant fluoroquinolone antibiotics tested here, including levofloxacin, moxifloxacin, and norfloxacin, and thus holds potential for biotechnological applications. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation)
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23 pages, 5428 KiB  
Article
Encapsulation of Dexamethasone into mRNA–Lipid Nanoparticles Is a Promising Approach for the Development of Liver-Targeted Anti-Inflammatory Therapies
by Ignacio Rivero Berti, Rocío Celeste Gambaro, María José Limeres, Cristián Huck-Iriart, Malin Svensson, Silvia Fraude-El Ghazi, Leah Pretsch, Shutian Si, Ingo Lieberwirth, Katharina Landfester, Maximiliano Luis Cacicedo, Germán Abel Islan and Stephan Gehring
Int. J. Mol. Sci. 2024, 25(20), 11254; https://doi.org/10.3390/ijms252011254 - 19 Oct 2024
Cited by 1 | Viewed by 1610
Abstract
The objective of this study was to develop two lipid nanoparticle (LNP) formulations capable of efficiently expressing a reporter mRNA while co-delivering the anti-inflammatory drug dexamethasone (DX) to reduce inflammatory side effects in protein replacement therapies. Two types of LNPs were developed, in [...] Read more.
The objective of this study was to develop two lipid nanoparticle (LNP) formulations capable of efficiently expressing a reporter mRNA while co-delivering the anti-inflammatory drug dexamethasone (DX) to reduce inflammatory side effects in protein replacement therapies. Two types of LNPs were developed, in which 25% of cholesterol was replaced by DX. These LNPs contained either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as a helper lipid. The resulting LNPs exhibited high stability, homogeneity, and near-neutral Zeta potentials. SAXS experiments confirmed DX incorporation into the LNP core, with slow in vitro DX release observed over 48 h. The LNPs achieved high mRNA encapsulation efficiency (95–100%) and effectively transfected HepG2 cells, dendritic cells, and hPBMCs. While LNPs increased cytokine release (IL-1β, TNF-α, MCP-1), LNPs-DX significantly reduced cytokine levels, demonstrating enhanced anti-inflammatory properties while maintaining mRNA expression levels. In vivo biodistribution showed predominant liver localization post-intramuscular injection, regardless of the DSPC or DOPE composition. LNPs co-loaded with mRNA and DX are promising candidates for continuous protein replacement. Due to their ability to reduce treatment-related inflammation while maintaining significant mRNA expression levels, these LNPs are perfectly suited for the treatment of liver-related metabolic diseases. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation)
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16 pages, 5177 KiB  
Article
Flavonoids-Enriched Vegetal Extract Prevents the Activation of NFκB Downstream Mechanisms in a Bowel Disease In Vitro Model
by Paolo Corbetta, Elena Lonati, Stefania Pagliari, Mario Mauri, Emanuela Cazzaniga, Laura Botto, Luca Campone, Paola Palestini and Alessandra Bulbarelli
Int. J. Mol. Sci. 2024, 25(14), 7869; https://doi.org/10.3390/ijms25147869 - 18 Jul 2024
Cited by 1 | Viewed by 1070
Abstract
Inflammatory bowel disease (IBD) incidence has increased in the last decades due to changes in dietary habits. IBDs are characterized by intestinal epithelial barrier disruption, increased inflammatory mediator production and excessive tissue injury. Since the current treatments are not sufficient to achieve and [...] Read more.
Inflammatory bowel disease (IBD) incidence has increased in the last decades due to changes in dietary habits. IBDs are characterized by intestinal epithelial barrier disruption, increased inflammatory mediator production and excessive tissue injury. Since the current treatments are not sufficient to achieve and maintain remission, complementary and alternative medicine (CAM) becomes a primary practice as a co-adjuvant for the therapy. Thus, the intake of functional food enriched in vegetal extracts represents a promising nutritional strategy. This study evaluates the anti-inflammatory effects of artichoke, caihua and fenugreek vegetal extract original blend (ACFB) in an in vitro model of gut barrier mimicking the early acute phases of the disease. Caco2 cells cultured on transwell supports were treated with digested ACFB before exposure to pro-inflammatory cytokines. The pre-treatment counteracts the increase in barrier permeability induced by the inflammatory stimulus, as demonstrated by the evaluation of TEER and CLDN-2 parameters. In parallel, ACFB reduces p65NF-κB pro-inflammatory pathway activation that results in the decrement of COX-2 expression as PGE2 and IL-8 secretion. ACFB properties might be due to the synergistic effects of different flavonoids, indicating it as a valid candidate for new formulation in the prevention/mitigation of non-communicable diseases. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation)
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12 pages, 2451 KiB  
Article
Pseudolaric Acid B Targets CD147 to Selectively Kill Acute Myeloid Leukemia Cells
by Sheng Zou, Ekaterina Parfenova, Nikolina Vrdoljak, Mark D. Minden and Paul A. Spagnuolo
Int. J. Mol. Sci. 2024, 25(12), 6517; https://doi.org/10.3390/ijms25126517 - 13 Jun 2024
Cited by 1 | Viewed by 1161
Abstract
Acute myeloid leukemia (AML) is an aggressive blood cancer. With low survival rates, new drug targets are needed to improve treatment regimens and patient outcomes. Pseudolaric acid B (PAB) is a plant-derived bioactive compound predicted to interact with cluster of differentiation 147 (CD147/BSG). [...] Read more.
Acute myeloid leukemia (AML) is an aggressive blood cancer. With low survival rates, new drug targets are needed to improve treatment regimens and patient outcomes. Pseudolaric acid B (PAB) is a plant-derived bioactive compound predicted to interact with cluster of differentiation 147 (CD147/BSG). CD147 is a transmembrane glycoprotein overexpressed in various malignancies with suggested roles in regulating cancer cell survival, proliferation, invasion, and apoptosis. However, the detailed function of PAB in AML remains unknown. In this study, AML cell lines and patient-derived cells were used to show that PAB selectively targeted AML (IC50: 1.59 ± 0.47 µM). Moreover, proliferation assays, flow cytometry, and immunoblotting confirmed that PAB targeting of CD147 resulted in AML cell apoptosis. Indeed, the genetic silencing of CD147 significantly suppressed AML cell growth and attenuated PAB activity. Overall, PAB imparts anti-AML activity through transmembrane glycoprotein CD147. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation)
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20 pages, 2962 KiB  
Article
Evaluating the Anti-Osteoarthritis Potential of Standardized Boswellia serrata Gum Resin Extract in Alleviating Knee Joint Pathology and Inflammation in Osteoarthritis-Induced Models
by Yean-Jung Choi, Jae In Jung, Jaewoo Bae, Jae Kyoung Lee and Eun Ji Kim
Int. J. Mol. Sci. 2024, 25(6), 3218; https://doi.org/10.3390/ijms25063218 - 12 Mar 2024
Cited by 6 | Viewed by 3402
Abstract
Osteoarthritis is a widespread chronic degenerative disease marked by the deterioration of articular cartilage, modifications in subchondral bone, and a spectrum of symptoms, including pain, stiffness, and disability. Ultimately, this condition impairs the patient’s quality of life. This study aimed to evaluate the [...] Read more.
Osteoarthritis is a widespread chronic degenerative disease marked by the deterioration of articular cartilage, modifications in subchondral bone, and a spectrum of symptoms, including pain, stiffness, and disability. Ultimately, this condition impairs the patient’s quality of life. This study aimed to evaluate the therapeutic efficacy of standardized Boswellia serrata gum resin extract (BSRE) in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. A total of 60 rats were allocated into six groups: normal control group (NC), osteoarthritis control (injected with MIA, OC), O + B50 (injected with MIA and treated with 50 mg/kg body weight (BW) BSRE), O + B75 (injected with MIA and treated with 75 mg/kg BW BSRE), O + B100 (injected with MIA and treated with 100 mg/kg BW BSRE), and O + M (injected with MIA and treated with 150 mg/kg BW methyl sulfonyl methane). Several parameters, including knee joint swelling, histopathological changes, and the expression of collagen type II alpha 1 (COL2A1) and aggrecan, were comprehensively assessed. Concurrently, the serum levels and mRNA expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) were analyzed in both the serum and knee joint synovium. The results demonstrated that BSRE significantly mitigated knee joint swelling, cartilage destruction, and tissue deformation. Notably, BSRE administration markedly upregulated the expression of COL2A1 and aggrecan while concurrently reducing levels of nitric oxide, prostaglandin E2, leukotriene B4, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Furthermore, a substantial decrease was observed in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-6, TNF-α and MMP-3 and -13, thereby indicating promising therapeutic implications for osteoarthritis. In conclusion, BSRE exhibited anti-inflammatory properties and inhibited cartilage matrix degradation in a rat model of MIA-induced osteoarthritis, with the O + B100 group showing significant reductions in swelling and notable improvements in joint cartilage damage. These findings illuminate the preventive and therapeutic potential of BSRE for osteoarthritis treatment, emphasizing the criticality of exhaustive evaluation of novel compounds. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation)
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Review

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12 pages, 600 KiB  
Review
Understanding the Anticancer Properties of Honey
by Simona Martinotti, Gregorio Bonsignore and Elia Ranzato
Int. J. Mol. Sci. 2024, 25(21), 11724; https://doi.org/10.3390/ijms252111724 - 31 Oct 2024
Cited by 2 | Viewed by 1676
Abstract
Uncontrolled cell growth that possesses the capacity to exhibit malignant behavior is referred to as cancer. The cytotoxic drugs used to fight cancer are associated with several adverse effects and are not always readily available or affordable, especially in developing countries. These issues [...] Read more.
Uncontrolled cell growth that possesses the capacity to exhibit malignant behavior is referred to as cancer. The cytotoxic drugs used to fight cancer are associated with several adverse effects and are not always readily available or affordable, especially in developing countries. These issues are in addition to the shortcomings of the current cancer treatment regimen. According to growing research, honey is not cytotoxic to normal cells but is highly and particularly cytotoxic to tumor cells, suggesting that honey may display anticancer effects. Research has shown that honey affects a number of cell signaling pathways; however, at the moment, the precise method is not completely known. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation)
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45 pages, 1484 KiB  
Review
Blockage of Autophagy for Cancer Therapy: A Comprehensive Review
by Ahmed Mostafa Ibrahim Abdelrahman Hassan, Yuxin Zhao, Xiuping Chen and Chengwei He
Int. J. Mol. Sci. 2024, 25(13), 7459; https://doi.org/10.3390/ijms25137459 - 7 Jul 2024
Cited by 7 | Viewed by 3939
Abstract
The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, [...] Read more.
The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibitors and their mechanisms in cancer therapy. The review includes original articles utilizing in vitro and in vivo experimental methods, literature reviews, and clinical trials. Key terms used were “Autophagy”, “Inhibitors”, “Molecular mechanism”, “Cancer therapy”, and “Clinical trials”. Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation)
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