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Pharmaceuticals
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Anticancer Compounds in Medicinal Plants—4th Edition
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Anticancer Compounds in Medicinal Plants—4th Edition

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: 15 June 2026 | Viewed by 1692

Special Issue Editors

Dr. Paulo Santos

E-Mail Website1 Website2
Guest Editor
Department of Chemistry and Chemistry Center–Vila Real (CQ-VR), School of Life and Environmental Sciences, University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
Interests: organic synthesis; functional dyes; structural elucidation; natural products chemistry; medicinal plants; natural bioactive compounds
Special Issues, Collections and Topics in MDPI journals
Dr. Lillian Barros

grade E-Mail Website
Guest Editor
CIMO, LA SusTEC, Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Braganza, Portugal
Interests: natural bioactive compounds; medicinal chemistry; bioactivity and toxicology; functional applications
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer, in its multiple forms, is presently one of the leading causes of death in both developing and developed countries, and it has become a major health problem and a burden on most public health care systems worldwide. Although several decades of drug discovery and development have provided a number of useful chemotherapeutic agents, there is a continuous interest in the search for new chemical entities with improved anticancer effectiveness and safety.

Since ancient times, humankind has relied on herbal medicines for the treatment and prevention of a plethora of different ailments, and their beneficial properties have been recognized both in traditional medicines and more contemporary herbalism practices. Medicinal plants, which have contributed to the collection of compounds that are now at our disposal for cancer therapy, constitute a reservoir of natural products that are able to provide new molecules with anticancer activity and new molecular frameworks, inspiring the design of derivatives with improved therapeutic ability.

The attention paid by scientific researchers to natural compounds as a source of anticancer molecules has increased exponentially in the last two decades, highlighting their enormous future potential.

For this Special Issue, “Anticancer Compounds in Medicinal Plants—4th Edition”, we invite researchers to contribute with original research or review articles related to natural compounds with anticancer properties isolated from medicinal plants. Contributions can include the discovery of new compounds, in vitro and in vivo assessments of the anticancer properties of medicinal plant-derived compounds, the elucidation of their mechanisms of action, and the design of derivatives with improved efficacy.

Dr. Paulo Santos
Dr. Lillian Barros
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural products
  • phytochemicals
  • cancer
  • secondary metabolites
  • medicinal plants

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Published Papers (3 papers)

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Research

16 pages, 5689 KB  
Article
Potential Value of a Combination of Polypodium leucotomos and Aspalathus linearis Extracts in Protecting Vitamin D Receptor Levels During Skin Oxidative Stress
by Marta Mascaraque, María Gallego-Rentero, Andrea Barahona-López, Paula Cano, Ángeles Juarranz, Ana López Sánchez and Salvador González
Pharmaceuticals 2026, 19(3), 494; https://doi.org/10.3390/ph19030494 - 17 Mar 2026
Viewed by 115
Abstract
Background/Objectives: Vitamin D (VD), through the interaction with its receptor (VDR), plays essential roles in the skin. VDR-mediated signaling prevents cancer development and improves prognosis, making it an appealing target for therapy. However, VD cutaneous synthesis begins with solar exposure, which is the [...] Read more.
Background/Objectives: Vitamin D (VD), through the interaction with its receptor (VDR), plays essential roles in the skin. VDR-mediated signaling prevents cancer development and improves prognosis, making it an appealing target for therapy. However, VD cutaneous synthesis begins with solar exposure, which is the first etiological factor for cutaneous cancer and increases oxidative stress (OS). This complicates the dermatologist’s perspective when advising photoprotective strategies while aiming to consider the benefits of VD signaling. In this context, and in the absence of cutaneous data to date, this research aims to address VDR dynamics in skin cells and tissue subjected to OS. It also explores the potential of a natural photoprotectant with antioxidant properties (a specific combination of Polypodium leucotomos and Aspalathus linearis extracts) in preventing VDR depletion. Methods: HaCaT cell cultures and skin explants were used as experimental models. OS was induced by treatments with hydrogen peroxide (H2O2). The proteins of interest (VDR and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)) were analyzed by immunostaining. Cell viability, nuclear counterstaining, and Haematoxylin/Eosin staining were used as cyto/histochemical controls. Results: In both experimental models, we observed the reduction of VDR under OS. Pre-treatments with the botanical ingredient preserved VDR levels from that decline, probably through a mechanism involving NRF2. Conclusions: Cutaneous VDR levels are altered under oxidative stress, and certain photoprotectants could preserve them. This opens the door to preserving the benefits of VDR signaling while preventing solar radiation damage, bringing a new viewpoint for designing future strategies in skin cancer prevention and treatment. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants—4th Edition)
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17 pages, 9440 KB  
Article
Gedunin Impacts Pancreatic Cancer Stem Cells Through the Sonic Hedgehog Signaling Pathway
by Karla Perez, Sheryl Rodriguez, Jose Barragan, Poornimadevi Narayanan, Alberto Ruiseco, Preetha Rajkumar, Nallely Ramirez, Victor Vasquez, Rajkumar Lakshmanaswamy and Ramadevi Subramani
Pharmaceuticals 2026, 19(1), 19; https://doi.org/10.3390/ph19010019 - 22 Dec 2025
Viewed by 659
Abstract
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a high rate of recurrence and a dismal prognosis. Studies have shown that pancreatic cancer stem cells (PCSCs) are a subpopulation that contributes to tumor progression, resistance to therapeutics, and metastasis, making [...] Read more.
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a high rate of recurrence and a dismal prognosis. Studies have shown that pancreatic cancer stem cells (PCSCs) are a subpopulation that contributes to tumor progression, resistance to therapeutics, and metastasis, making them a key subpopulation to target for treatment. Gedunin (GD), a natural compound derived from Azadirachta indica (neem), has shown anticancer properties in pancreatic cancer cells, but its effects on PCSCs remains unclear. This study evaluated the effects of GD in pancreatic cancer stem cells, highlighting its impacts on tumor growth and progression and focusing on its impact on the sonic hedgehog (Shh) signaling pathway. Methods: Functional assays were performed to assess the effect of GD on the sphere-forming ability, colony formation, and self-renewal of PCSCs. Athymic mice xenograft models were utilized to evaluate the tumor suppression effect of GD in vivo. Furthermore, the anticancer effect of GD on PCSCs was assessed using both in vitro and in vivo limiting dilution assay. GD-induced changes in Shh signaling and key stem cell marker expressions in PCSCs were evaluated. Results: GD effectively inhibited tumor growth in xenograft models and reduced the percentage of PCSCs. GD was effective in decreasing PCSCs’ proliferative, self-renewal, and colony-forming capacity. GD decreased the protein expression levels of key Shh signaling markers Gli1 and Shh, stem cell markers SOX2, Nanog, and Oct4, metastasis-related proteins MMP-2, MMP-3, and MMP-9, and EMT markers Tgf1, Slug, Snail, and Twist in both PDAC cells and PCSCs. We demonstrated a significant decrease in the spheroid formation and self-renewal capacity of the (ALDH+) PCSC population following GD treatment in HPAC cells, indicating its potential antagonistic effects on PCSCs. GD was highly effective in reducing tumor volume, stemness, and metastasis in both early and late chemotherapy. In vivo limiting dilution assay using CD133+/LGR5+ PCSC xenografts demonstrated that GD reduces tumor growth, metastasis, and stemness associated with PCSCs by downregulating the expression of Shh and Gli1. GD treatment also reduced micrometastatic lesions in the lung, liver, and brain, as identified using H&E staining. Conclusions: The findings highlight GD’s potential as a promising therapeutic candidate for PDAC, with the ability to target both bulk tumor cells and PCSCs. By simultaneously suppressing tumor growth, stemness, and metastatic spread, GD may contribute to more effective treatment strategies and improved patient outcomes. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants—4th Edition)
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20 pages, 2765 KB  
Article
Unveiling the Cytotoxicity Potential of Nanoemulsion of Peltophorum pterocarpum Extract: A Natural Hemocompatible Injection Competing with Doxorubicin
by Al Zahraa G. Al Ashmawy, Afaf E. AbdelGhani, Wafaa H. B. Hassan, Fatma O. El Weshahy, Wael M. Abdelmageed, Shaza M. Al-Massarani, Omer A. Basudan, Aalaa Gamil and May Ahmed El-Sayed
Pharmaceuticals 2025, 18(12), 1818; https://doi.org/10.3390/ph18121818 - 28 Nov 2025
Viewed by 568
Abstract
Background/Objectives: According to the WHO, more than one million deaths of liver cancer patients will occur in 2030. Hepatocellular carcinoma (HCC) is the third leading cause of death among all cancer types. Doxorubicin is commonly used for the treatment of HCC, yet [...] Read more.
Background/Objectives: According to the WHO, more than one million deaths of liver cancer patients will occur in 2030. Hepatocellular carcinoma (HCC) is the third leading cause of death among all cancer types. Doxorubicin is commonly used for the treatment of HCC, yet it possesses major side effects. The aim of this work was to formulate a nanoemulsion of Peltophorum pterocarpum extract containing bergenin intended for intravenous injection as a natural alternative to doxorubicin. Methods: The saturation solubility of the extract in different oils, surfactants, and co-surfactants was determined. Surfactant to co-surfactant mixtures (Smix) were used at six different weight ratios. A pseudoternary phase diagram was constructed, and the ratio with the highest area was chosen. Six formulations were prepared by changing the oil-to-Smix ratio. They were evaluated by percentage transmission, dilution test, self-emulsification, pH, viscosity, drug content, droplet size, PDI, zeta potential, TEM, in vitro drug release, stability, in vitro hemolysis percentage, and cytotoxicity (for the optimized formula). Results: F6 of oil-to-Smix ratio (1:6) was chosen for further investigations, as it possesses the lowest droplet size, the highest zeta potential, drug content, and in vitro drug release. The pH, viscosity, and self-emulsification time of F6 were also acceptable. F6 possesses shelf-life stability and is hemocompatible. It possesses high cytotoxicity against the HepG-2 cell line (IC50 = 14.19 µg/mL). Conclusions: Although the nanoemulsion is less potent than doxorubicin in terms of IC50, it offers a safer profile and natural origin, which may be used for the treatment of HCC. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants—4th Edition)
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