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Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and...
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Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds

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

Deadline for manuscript submissions: 25 July 2025 | Viewed by 7947

Special Issue Editors

Dr. Normand Garcia-Hernandez

E-Mail Website
Guest Editor
Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría 2° Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, Mexico
Interests: cancer; natural products; proteomics; traditional medicine; bioactive compound; mitochondrial function in disease
Dr. Rosa Ordoñez Razo

E-Mail Website
Guest Editor
Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría 2° Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, Mexico
Interests: cancer; molecular biology; proteomics; new therapies; natural products
Dr. Israel Ramírez-Sánchez

E-Mail Website
Guest Editor
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City CP 07738, Mexico
Interests: aging; sarcopenia; flavonoids; obesity; mitochondrial function in health and disease

Special Issue Information

Dear Colleagues,

The development of new strategies and treatments from natural compounds offers the opportunity to provide benefits such as to reduce incidence, prevalence, or mortality for a wide range of chronic or degenerative diseases. Natural compounds, for example, sesquiterpene lactones, have shown properties such as neurodegeneration preventive, analgesic, antimigraine, sedative, phytotoxic, antiprotozoal, antibacterial and anti-tumor. However, there are still many natural compounds that are currently used only in traditional medicine and that have pharmacological properties, such as antidiabetic, antimicrobial, antioxidant, antiarthritic, cardioprotective, hepatoprotective, nephroprotective, fibrinolytic and healing. These compounds can be studied extensively to develop new treatments for a wide variety of diseases. In this Special Issue, we aim to entice research experts in the field of therapeutic agents and strategies, to publish discoveries, developments and the future implementation of new therapies pertaining to the use of sesquiterpene lactones and of all possible natural compounds.

Dr. Normand Garcia-Hernandez
Dr. Rosa Ma. Ordoñez Razo
Dr. Israel Ramírez-Sánchez
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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • therapeutic potential
  • natural compounds
  • biological activity
  • traditional medicine
  • sesquiterpene lactone
  • pharmacological activities
  • terpenoids
  • flavonoids

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Published Papers (6 papers)

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Research

Jump to: Review

17 pages, 2122 KiB  
Article
Antibacterial Activity and Molecular Docking of Lignans Isolated from Artemisia cina Against Multidrug-Resistant Bacteria
by Leslie Cynthia García Hernández, Rosa Isabel Higuera-Piedrahita, Nallely Rivero-Perez, Ana Lizet Morales-Ubaldo, Benjamín Valladares-Carranza, Héctor Alejandro de la Cruz-Cruz, Jorge Alfredo Cuéllar-Ordaz, Cynthia González-Ruiz, María Inés Nicolás-Vázquez and Adrian Zaragoza-Bastida
Pharmaceuticals 2025, 18(6), 781; https://doi.org/10.3390/ph18060781 - 23 May 2025
Viewed by 194
Abstract
The World Health Organization notes that some bacteria have been demonstrated to possess significant public health risks; they have antibiotic resistance, and there are fewer alternatives for control. The n-hexane extract and cinaguaiacin obtained from Artemisia cina show promising antibacterial activity, including [...] Read more.
The World Health Organization notes that some bacteria have been demonstrated to possess significant public health risks; they have antibiotic resistance, and there are fewer alternatives for control. The n-hexane extract and cinaguaiacin obtained from Artemisia cina show promising antibacterial activity, including against multidrug-resistant bacteria that affect animal and human health. Objective: The aim of this study was to determine the antibacterial activity of the n-hexane extract of A. cina and cinaguaiacin against multidrug-resistant bacteria. Methods:A. cina was collected in the pre-flowering period, the n-hexane extract was obtained, and chromatographic techniques and structure were used to separate the lignans, which were elucidated with nuclear magnetic resonance techniques. Four ATCC strains were used, and four strains were isolated from clinical cases with different resistance profiles. The antibacterial activity was determined by calculating the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), the time-kill kinetics assay, and the cell membrane integrity and DNA release assay. Molecular docking studies of lignans demonstrated the binding mode involved in the active site of DNA gyrase B. Results: The n-hexane extract inhibited growth against 87.5% of the strains tested (MIC 5.31 to 42.5 mg/mL) and showed bactericidal activity against 25% of the strains tested (MBC 0.62 to 85 mg/mL). Cinaguaiacin inhibited growth against 100% of the strains tested (MIC, 0.56 to 2.25 mg/mL) and exhibited bactericidal activity against 25% of the strains tested (MBC, 0.62 to 85 mg/mL). Conclusions: The mechanism of cinaguaiacin’s action may be associated with damage to the plasma membrane, as the protein and DNA levels were higher than those of the positive control. The n-hexane extract and cinaguaiacin obtained from A. cina showed a bacteriostatic or bactericidal effect, depending on the strain evaluated. Full article
(This article belongs to the Special Issue Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds)
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37 pages, 44373 KiB  
Article
Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II
by Normand García-Hernández, Fernando Calzada, Elihú Bautista, José Manuel Sánchez-López, Miguel Valdes, Marta Elena Hernández-Caballero and Rosa María Ordoñez-Razo
Pharmaceuticals 2025, 18(2), 242; https://doi.org/10.3390/ph18020242 - 11 Feb 2025
Viewed by 818
Abstract
Background/Objectives: Incomptine A (IA) has cytotoxic activity in non-Hodgkin lymphoma (NHL) cancer cell lines. Its effects on U-937 cells include induction of apoptosis, production of reactive oxygen species, and inhibition of glycolytic enzymes. We examined the altered protein levels present in the lymph [...] Read more.
Background/Objectives: Incomptine A (IA) has cytotoxic activity in non-Hodgkin lymphoma (NHL) cancer cell lines. Its effects on U-937 cells include induction of apoptosis, production of reactive oxygen species, and inhibition of glycolytic enzymes. We examined the altered protein levels present in the lymph nodes of an in vivo mouse model. Methods: We induced an in vivo model with Balb/c mice with U-937 cells and treated it with IA or methotrexate, as well as healthy mice. We determined expressed proteins by TMT based on the LC-MS/MS method (Data are available via ProteomeXchange with identifier PXD060392) and a molecular docking study targeting 15 deregulated proteins. We developed analyses through the KEGG, Reactome, and Gene Ontology databases. Results: A total of 2717 proteins from the axillary and inguinal lymph nodes were analyzed and compared with healthy mice. Of 412 differentially expressed proteins, 132 were overexpressed (FC ≥ 1.5) and 117 were underexpressed (FC ≤ 0.67). This altered expression was associated with 20 significantly enriched processes, including chromatin remodeling, transcription, translation, metabolic and energetic processes, oxidative phosphorylation, glycolysis/gluconeogenesis, cell proliferation, cytoskeletal organization, and with cell death with necroptosis. Conclusions: We confirmed the previously observed dose-dependent effect of IA as a secondary metabolite with important potential as an anticancer agent for the treatment of NHL, showing that the type of drug or the anatomical location influences the response to treatment. The IA promises to be a likely safer and more effective treatment to improve outcomes, reduce toxicities, and improve survival in patients with NHL, initially targeting histones and transcription factors that will affect cell death proteins. Full article
(This article belongs to the Special Issue Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds)
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11 pages, 904 KiB  
Article
Skin Tear Treatment with Copaifera multijuga Hayne in Polymeric Hydrogel: A Randomized Clinical Trial
by Camila Castanho Cardinelli, Jéssica Teixeira Gâmba Passos, Valdir Florêncio Veiga-Junior, Beatriz Guitton Renaud Baptista de Oliveira, Elisabete Pereira dos Santos, Guilherme Guilhermino Neto, Karina Chamma Di Piero and Zaida Maria Faria de Freitas
Pharmaceuticals 2024, 17(12), 1691; https://doi.org/10.3390/ph17121691 - 15 Dec 2024
Viewed by 788
Abstract
A double-blind, randomized, and controlled clinical trial with therapeutic intervention was performed at a university hospital in Rio de Janeiro to evaluate whether the addition of Copaifera multijuga Hayne oleoresin to a carboxypolymethylene hydrogel is more effective in skin tear healing than standard [...] Read more.
A double-blind, randomized, and controlled clinical trial with therapeutic intervention was performed at a university hospital in Rio de Janeiro to evaluate whether the addition of Copaifera multijuga Hayne oleoresin to a carboxypolymethylene hydrogel is more effective in skin tear healing than standard treatment. The sample consisted of 84 patients, predominantly men, with a mean age of 67.37 years. These participants were divided into three groups (29 in the intervention group, which received 10% Copaifera oleoresin; 28 in the intervention group, which received 2% Copaifera oleoresin; and 27 in the control group, which received carboxypolymethylene hydrogel). Data were tabulated and analyzed according to the relevant protocols and included only patients who had completed the treatment, while losses were excluded. Weekly follow-ups were conducted to monitor progress. The average healing time differed among the three groups (p > 0.05). There was also a significant difference in healing time between the two intervention groups. Ultimately, CopaibaPolyHy-2 led to significantly faster wound healing than CopaibaPolyHy-10 (p < 0.05). A high increase in granulation and epithelial tissue and a decrease in exudate quantity were observed in the CopaibaPolyHy-2 group. It was not possible to infer whether the wound size reduction differed between the treatments (p > 0.05). At the end of the study, 100% of wounds were healed, with 47,6% healing in week 2 (n = 40). No participants experienced local or serious adverse effects throughout the study period. The current study shows that CopaibaPolyHy-2 is effective, offering a statistically significantly faster healing time, better-quality tissue, and safe treatment for skin tears. Full article
(This article belongs to the Special Issue Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds)
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18 pages, 6357 KiB  
Article
Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis
by Dumitriţa Rugină, Mihai Adrian Socaciu, Madalina Nistor, Zorita Diaconeasa, Mihai Cenariu, Flaviu Alexandru Tabaran and Carmen Socaciu
Pharmaceuticals 2024, 17(12), 1630; https://doi.org/10.3390/ph17121630 - 4 Dec 2024
Cited by 2 | Viewed by 938
Abstract
Background/Objectives: Pentacyclic triterpenoids are increasingly studied as anticancer agents with many advantages compared to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of silver birch (Betula pendula) outer bark [...] Read more.
Background/Objectives: Pentacyclic triterpenoids are increasingly studied as anticancer agents with many advantages compared to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of silver birch (Betula pendula) outer bark (TTs) and to evaluate their potential as anticancer agents in vitro, using Melanoma B16-F10 and Walker carcinoma cells. Methods: Appropriate solvents were selected for efficient TTs extraction, and original recipes were used to obtain Pegylated liposomes and nanolipid complexes with entrapped TTs, comparative to pure standards (betulinic acid and doxorubicin) in similar conditions. The composition, morphology, and sizes of all nanoformulations were checked by high-performance liquid chromatography/mass spectrometry, Transmission Electronic Microscopy, and Diffraction Light Scattering. The entrapment efficiency and its impact on cell viability, cell cycle arrest, and apoptosis by flow cytometry was also measured on both cancer cell lines. Conclusions: The standardized TTs, including betulin, lupeol, and betulinic acid, showed good stability and superior activity compared to pure betulinic acid. According to experimental data, TTs showed good entrapment in liposomal and NLC nanoformulations, both delivery systems including natural, biodegradable ingredients and enhanced bioavailability. The apoptosis and necrosis effects were more pronounced for TTs liposomal formulations in both types of cancer cells, with lower cytotoxicity compared to Doxorubicin, and can be correlated with their increased bioavailability. Full article
(This article belongs to the Special Issue Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds)
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24 pages, 3455 KiB  
Article
Biomedical Promise of Aspergillus Flavus-Biosynthesized Selenium Nanoparticles: A Green Synthesis Approach to Antiviral, Anticancer, Anti-Biofilm, and Antibacterial Applications
by Eman Jassim Mohammed, Ahmed E. M. Abdelaziz, Alsayed E. Mekky, Nashaat N. Mahmoud, Mohamed Sharaf, Mahmoud M. Al-Habibi, Nehal M. Khairy, Abdulaziz A. Al-Askar, Fady Sayed Youssef, Mahmoud Ali Gaber, Ebrahim Saied, Gehad AbdElgayed, Shimaa A Metwally and Aly A. Shoun
Pharmaceuticals 2024, 17(7), 915; https://doi.org/10.3390/ph17070915 - 9 Jul 2024
Cited by 12 | Viewed by 2748
Abstract
This study utilized Aspergillus flavus to produce selenium nanoparticles (Se-NPs) in an environmentally friendly and ecologically sustainable manner, targeting several medicinal applications. These biosynthesized Se-NPs were meticulously characterized using X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscope (TEM), and UV–visible spectroscopy [...] Read more.
This study utilized Aspergillus flavus to produce selenium nanoparticles (Se-NPs) in an environmentally friendly and ecologically sustainable manner, targeting several medicinal applications. These biosynthesized Se-NPs were meticulously characterized using X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscope (TEM), and UV–visible spectroscopy (UV), revealing their spherical shape and size ranging between 28 and 78 nm. We conducted further testing of Se-NPs to evaluate their potential for biological applications, including antiviral, anticancer, antibacterial, antioxidant, and antibiofilm activities. The results indicate that biosynthesized Se-NPs could be effective against various pathogens, including Salmonella typhimurium (ATCC 14028), Bacillus pumilus (ATCC 14884), Staphylococcus aureus (ATCC 6538), Clostridium sporogenes (ATCC 19404), Escherichia coli (ATCC 8739), and Bacillus subtilis (ATCC 6633). Additionally, the biosynthesized Se-NPs exhibited anticancer activity against three cell lines: pancreatic carcinoma (PANC1), cervical cancer (Hela), and colorectal adenocarcinoma (Caco-2), with IC50 values of 177, 208, and 216 μg/mL, respectively. The nanoparticles demonstrated antiviral activity against HSV-1 and HAV, achieving inhibition rates of 66.4% and 15.1%, respectively, at the maximum non-toxic concentration, while also displaying antibiofilm and antioxidant properties. In conclusion, the biosynthesized Se-NPs by A. flavus present a promising avenue for various biomedical applications with safe usage. Full article
(This article belongs to the Special Issue Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds)
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Review

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38 pages, 1377 KiB  
Review
Advances in Molecular Function and Recombinant Expression of Human Collagen
by Wenli Sun, Mohamad Hesam Shahrajabian, Kun Ma and Shubin Wang
Pharmaceuticals 2025, 18(3), 430; https://doi.org/10.3390/ph18030430 - 18 Mar 2025
Viewed by 1414
Abstract
Collagen is the main protein found in skin, bone, cartilage, ligaments, tendons and connective tissue, and it can exhibit properties ranging from compliant to rigid or form gradients between these states. The collagen family comprises 28 members, each containing at least one triple-helical [...] Read more.
Collagen is the main protein found in skin, bone, cartilage, ligaments, tendons and connective tissue, and it can exhibit properties ranging from compliant to rigid or form gradients between these states. The collagen family comprises 28 members, each containing at least one triple-helical domain. These proteins play critical roles in maintaining mechanical characteristics, tissue organization, and structural integrity. Collagens regulate cellular processes such as proliferation, migration, and differentiation through interactions with cell surface receptors. Fibrillar collagens, the most abundant extracellular matrix (ECM) proteins, provide organs and tissues with structural stability and connectivity. In the mammalian myocardial interstitium, types I and III collagens are predominant: collagen I is found in organs, tendons, and bones; collagen II is found in cartilage; collagen III is found in reticular fibers; collagen IV is found in basement membranes; and collagen V is found in nails and hair. Recombinant human collagens, particularly in sponge-like porous formats combined with bone morphogenetic proteins, serve as effective scaffolds for bone repair. Due to their biocompatibility and low immunogenicity, collagens are pivotal in tissue engineering applications for skin, bone, and wound regeneration. Recombinant technology enables the production of triple-helical collagens with amino acid sequences identical to human tissue-derived collagens. This review summarizes recent advances in the molecular functions and recombinant expression of human collagens, with a focus on their biomedical applications. Full article
(This article belongs to the Special Issue Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds)
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