Integrative Roles of Natural Products in Cancer Treatment and Chronic Inflammatory Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 3768

Special Issue Editor


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Guest Editor
Department of Pathology, College of Korean Medicine, Dongguk University, Goyang-si 10326, Gyeonggi-do, Republic of Korea
Interests: cancer; hyperthermia; heat shock response; ROS; natural product
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Special Issue Information

Dear Colleagues, 

Cancer is a multifactorial disease characterized by uncontrolled cell proliferation and the acquisition of metastatic potential. Natural products have attracted significant attention as promising anticancer agents due to their ability to selectively target malignant cells while minimizing toxicity in normal tissues. Furthermore, natural compounds can alleviate the side effects of conventional therapies such as chemotherapy, radiotherapy, and hyperthermia, thereby enhancing both treatment efficacy and patient tolerance. 

Beyond oncology, natural products also demonstrate important therapeutic potential in chronic inflammatory diseases, including metabolic, cardiovascular, autoimmune, and neurodegenerative disorders. These conditions frequently coexist with cancer as comorbidities, posing additional challenges to clinical management. Natural products, through regulation of oxidative stress, inflammatory pathways, and metabolic mechanisms, offer opportunities for dual therapeutic models that combine anticancer activity with the modulation of comorbid chronic conditions. 

This Special Issue could serve as a platform to highlight emerging research on the following: 

  • Molecular mechanisms of natural products in cancer therapy and chronic inflammatory diseases;
  • Natural compounds with dual-function activity in enhancing anticancer efficacy while protecting or restoring tissue homeostasis;
  • Therapeutic models addressing cancer with comorbid chronic conditions;
  • Integrative and adjuvant strategies combining natural products with chemotherapy, radiotherapy, or hyperthermia;
  • Mechanistic insights into natural product–mediated regulation of oxidative stress, immunity, and inflammation. 

We kindly invite researchers to submit original research articles as well as review articles on these subject.

Dr. Seungho Baek
Guest Editor

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Keywords

  • natural products
  • cancer
  • chronic inflammatory diseases
  • therapy
  • oxidative stress

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Published Papers (4 papers)

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Research

12 pages, 1402 KB  
Article
Contribution of Phenolic Acid Profiles to the Anti-Adipogenic Activity of Different Mesona procumbens Hemsl. Ethanol Extracts
by Ching-Chang Cho, Gow-Chin Yen, Hsin-Yi Lee, Wei-Tang Chang, Li-You Chen and Chin-Lin Hsu
Biomedicines 2026, 14(4), 824; https://doi.org/10.3390/biomedicines14040824 - 4 Apr 2026
Viewed by 468
Abstract
Background/Objectives: Obesity represents a critical risk factor for various chronic illnesses and metabolic dysfunctions, underscoring the urgency of identifying safe, food-based interventions to curb fat over-accumulation. Mesona procumbens Hemsl. (Hsian-tsao) is a traditional Chinese herb known for its antioxidant and health-promoting properties; [...] Read more.
Background/Objectives: Obesity represents a critical risk factor for various chronic illnesses and metabolic dysfunctions, underscoring the urgency of identifying safe, food-based interventions to curb fat over-accumulation. Mesona procumbens Hemsl. (Hsian-tsao) is a traditional Chinese herb known for its antioxidant and health-promoting properties; however, it remains unclear how its phenolic acid profiles contribute to anti-obesity activity. This research explored the anti-adipogenic potential of various Hsian-tsao ethanol extracts, focusing on how their phenolic profiles influence lipid suppression in 3T3-L1 adipocytes. Methods: Ethanol extracts prepared using different ethanol concentrations were analyzed for total polyphenol content, antioxidant capacity, and phenolic acid profiles. Adipocytes were exposed to 0, 100, and 250 μg/mL of Hsian-tsao ethanol extract for 48 h duration to monitor changes in cell count and intracellular triglyceride levels. Results: Among all fractions, the 40% ethanol extract (40EEHT) possessed the most robust antioxidant capacity and highest polyphenol content, specifically showing enriched levels of caffeic acid, p-coumaric acid, and total phenolic acids. Notably, while 40EEHT influenced cell density at certain concentrations, it significantly and specifically reduced intracellular triglyceride content, indicating a potent inhibitory effect on lipid storage independent of changes in cell number. Comparative analysis using phenolic acid standards revealed that caffeic acid exerted the strongest inhibitory effect on lipid accumulation, suggesting that it is a key contributor to the anti-adipogenic activity of 40EEHT. Conclusions: Collectively, these findings demonstrate that phenolic acid profiles, particularly caffeic acid enrichment, critically contribute to the potential anti-adipogenic effects of specific ethanol extracts of M. procumbens. Therefore, Hsian-tsao ethanol extracts represent a promising natural source for the development of functional ingredients targeting obesity and related metabolic disorders. Full article
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14 pages, 633 KB  
Article
Improving Cytotoxicity of Saporin with Saponin SO1406 Isolated from the Roots of Saponaria Officinalis
by Chaeeun Lim-Paik, Qinghua Zeng, Rebekah Beyea, Rebecca Boohaker and Pengfei Wang
Biomedicines 2026, 14(3), 626; https://doi.org/10.3390/biomedicines14030626 - 11 Mar 2026
Viewed by 837
Abstract
Background/Objectives: Saponins have recently emerged as promising natural products that enhance toxin-based anticancer therapeutics by improving cytosol uptake. This study aimed to identify structurally defined novel natural saponins and evaluate their ability to enhance anticancer cytotoxicity. Methods: The roots of Saponaria [...] Read more.
Background/Objectives: Saponins have recently emerged as promising natural products that enhance toxin-based anticancer therapeutics by improving cytosol uptake. This study aimed to identify structurally defined novel natural saponins and evaluate their ability to enhance anticancer cytotoxicity. Methods: The roots of Saponaria officinalis L. were extracted with aqueous ethanol and purified by silica gel column chromatography and reverse-phase high-performance liquid chromatography (RP HPLC). The structures of new saponins were elucidated by NMR spectroscopy and mass spectrometry. Biological activity was assessed in vitro using multiple cancer cell lines. Results: Two pairs of structurally defined pure saponins were obtained: SO1406 and SO1448, and SO1684 and SO1726. Structural elucidation revealed that SO1684 and SO1726 share the core structure 3-O-β-D-Gal-(1→2)-[β-D-Xyl-(1→3)]-β-D-GlcA-gypsogenin-28-O-β-D-Qui-(1→4)-[β-D-Xyl-(1→3)-β-D-Xyl-(1→4)]-α-L-Rha-(1→2)-β-D-Fuc, with SO1684 acetylated at Qui O-4 and SO1726 bearing additional acetylation at Qui O-3. Deacetylation of either SO1684 or SO1726 afforded a known saponin SA1641 isolated from Saponinum album (Merck). Similarly, SO1406 and SO1448 were identified as 3-O-β-D-Gal-(1→2)-[β-D-Xyl-(1→3)]-β-D-GlcA-gypsogenin-28-O-β-D-Xyl-(1→4)-α-L-Rha-(1→2)-β-D-Fuc derivatives, each acetylated at Fuc O-4, with SO1448 containing an additional acetyl group at Fuc O-3. Among the isolated compounds, SO1684 is a known saponin and SO1406 exhibited the most pronounced biological activity, significantly enhancing the cytotoxicity of the ribosome-inactivating protein saporin (SAP) in the MDA-MB231 (triple-negative breast cancer) cell line. Conclusions: SO1406 demonstrates strong cytotoxicity-enhancing activity, highlighting the significant potential of structurally defined natural saponins to advance intracellular delivery and improve the therapeutic performance of protein-based anticancer agents. Full article
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15 pages, 14619 KB  
Article
Targeting the FTO-ACSL4 Pathway: A Novel Mechanism for Sanguinarine Chloride-Induced Ferroptosis in Endometrial Cancer
by Wenyan Li, Shanhui Liu, Ke Wang, Jianzhong Lu, Shengjun Fu, Lanlan Li and Yan Tao
Biomedicines 2026, 14(3), 608; https://doi.org/10.3390/biomedicines14030608 - 9 Mar 2026
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Abstract
Objective: Endometrial cancer (EC) remains a significant clinical challenge, particularly for patients with advanced or recurrent disease. This study aims to investigate the effects of Sanguinarine Chloride (S.C), a natural benzophenanthridine alkaloid with broad anti-tumor properties, on EC cell growth and invasion, and [...] Read more.
Objective: Endometrial cancer (EC) remains a significant clinical challenge, particularly for patients with advanced or recurrent disease. This study aims to investigate the effects of Sanguinarine Chloride (S.C), a natural benzophenanthridine alkaloid with broad anti-tumor properties, on EC cell growth and invasion, and to elucidate its underlying molecular mechanisms. Methods: S.C’s effects on EC cell viability, proliferation, invasion, and apoptosis were evaluated using CCK-8, EdU, colony formation, 3D matrigel drop assay, FACS and Western blotting (WB). To evaluate its effects on ferroptosis, malondialdehyde (MDA) assay kits, DCFH-DA and the C11 BODIPY581/591 probe, were employed. The molecular mechanisms through which S.C regulates FTO-ACSL4 axis were investigated using plasmid transfection and WB. Additionally, a mouse xenograft model derived from EC cells was established to evaluate the in vivo effects of S.C and its molecular mechanisms, utilizing hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and WB. Results: S.C significantly inhibited EC cell growth and invasion. It induced cell death primarily through ferroptosis, as inhibitors (Ferrostatin-1, Deferoxamine) reversed this effect. S.C downregulated the RNA demethylase FTO, leading to increased ACSL4 expression, enhanced lipid peroxidation, suppression of the NRF2-GPX4 axis, and activated NCOA4-mediated ferritinophagy. Knocking down or pharmacologically inhibiting ACSL4 reduced S.C-induced ferroptosis. Furthermore, in a murine xenograft model, S.C significantly suppressed tumor growth, which was associated with consistent alterations in these ferroptosis-related markers in vivo. Conclusions: Our findings reveal that S.C triggers ferroptosis in EC via the novel FTO-ACSL4 axis, highlighting its potential as a therapeutic agent and identifying the FTO-ACSL4 pathway as a promising target for endometrial cancer treatment. Full article
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20 pages, 1840 KB  
Article
Evaluation of the Antibacterial, Antioxidant, Anticancer, and Antidiabetic Activities of the Leaves and Inflorescences of Crassula capitella
by Sahar Abdulaziz AlSedairy, Manal Abdulaziz Binobead, Fuad Alanazi and Ibrahim M. Aziz
Biomedicines 2026, 14(1), 121; https://doi.org/10.3390/biomedicines14010121 - 7 Jan 2026
Cited by 2 | Viewed by 1007
Abstract
Background/Objectives: Plants of the Crassulaceae family have been utilized in traditional medicine because of their medicinal properties. Crassula capitella, an ornamental succulent plant, has not yet received significant attention from physiochemists or pharmacologists. The objective of this study was to investigate [...] Read more.
Background/Objectives: Plants of the Crassulaceae family have been utilized in traditional medicine because of their medicinal properties. Crassula capitella, an ornamental succulent plant, has not yet received significant attention from physiochemists or pharmacologists. The objective of this study was to investigate the in vitro phytochemical properties and biological activity of methanolic extracts obtained from the leaves (CCLE) and inflorescences (CCIE) of C. capitella. Methods: Phytochemical screening included GC/MS analysis. The in vitro investigation of biological properties includes the assessment of antibacterial activity, utilizing disk diffusion assays and measuring MIC and MBC values for Gram-positive and Gram-negative bacteria. Antioxidant properties were determined through IC50 values in DPPH and ABTS assays. Cytotoxicity properties were evaluated using the MTT assay in MCF-7 and HepG2 cells, along with an analysis of apoptosis gene expression. Additionally, the antidiabetic effects were examined through α-amylase or α-glucosidase inhibition assays. Results: GC/MS analysis revealed distinct differences. CCLE contained more terpenoids such as betulinaldehyde (30.53%) followed by lupeol (19%) and betulin (4.07%), whereas CCIE was rich in fatty acids. The TPC and TFC of CCIE (88.17 mg GAE/g and 57 mg QE/g) were significantly greater than those of CCLE. Compared with CCLE, CCIE exhibited greater antibacterial properties (MIC values of 6.25 µg/mL toward S. aureus), greater antioxidant properties (IC50 values in the DPPH/ABTS assay), antitumor properties (IC50 values of approximately 90–96 µg/mL), and antidiabetic properties (IC50 values of 87–83 µg/mL in the α-amylase/α-glucosidase assay). Both bioactive extracts induced apoptosis in cancer cells by downregulating the expression of the tumorigenesis genes bcl-2 and bcl-xL. Conclusions: The findings provided the first evidence about the evaluated the potential antibacterial, antioxidant, anticancer, and antidiabetic activities of C. capitella, which is attributed to its robust chemical composition and position it as a compelling candidate for further in vivo and sub-clinical applications. Full article
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