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The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: closed (10 July 2023) | Viewed by 18992

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Dr. Anca Roxana Petrovici

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Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, Romania
Interests: biopolymers’ biosynthesis by microorganism strains; isolation, purification, characterization and quantification of active compounds from culture media, vegetal materials, biological fluids; methods development and validation; determination of antioxidant properties of active compounds from ex vivo, in vitro and in vivo media

Dr. Mihaela Silion

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Physics of Polymers and Polymeric Materials Department, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, Romania
Interests: development of new separation/identification methods of organic and inorganic, natural or synthetic compounds; drugs and biopolymers using HPLC-ESI-MS; Gas-Chromatography or Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS)

Dr. Natalia Simionescu

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Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, Romania
Interests: cell culture techniques; in vitro biocompatibility/cytotoxicity and intracellular antioxidant activity of active compounds and polymeric materials; biological activity of natural compounds; biochemical assays; ELISA and molecular biology

Special Issue Information

Dear Colleagues,

The study of plant compounds with therapeutic properties dates back to ancient times. However, every research group that studies the extraction, purification, identification, and quantification of these compounds, with each study conducted, discovers new facts, which through existing analysis techniques, always confirm the antioxidant and anticancer properties of these valuable compounds. The most interesting aspect of plant extracts is the study of the existing compounds’ synergistic effects compared to the isolated compounds’ effects. Furthermore, the antioxidant and anticancer activities are different for the individual compounds compared to the extraction mixture. Another important aspect in standard and complementary therapies using plants’ natural compounds is the way of their delivery in the human body, without modifying their therapeutic properties. Furthermore, their controlled release in effective therapeutic concentrations must be achieved in order to provide efficient therapeutic response in different types of cancer.

We are pleased to invite you to contribute with valuable research in the field of plant extracts and the determination of their biologically active properties, as well as efficient delivery systems of natural compounds. This Special Issue aims to highlight recent advances in biologically active properties of plant compounds and their delivery systems suitable for efficient therapeutic effects.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the following: plant compounds extraction, purifications, identifications and quantifications, also in delivery systems that are able to transport the active compounds in the human body with antioxidant and anticancer properties preservation.

We look forward to receiving your contributions.

Dr. Anca Roxana Petrovici
Dr. Mihaela Silion
Dr. Natalia Simionescu
Guest Editors

Manuscript Submission Information

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Keywords

delivery and controlled-release systems for plant compounds
plant compounds used for smart medical devices
anticancer properties of plant compounds
antimicrobial properties of plant compounds
antioxidant properties of plant compounds
nanomedicine
drug targeting using plant compounds
drug design using plant compounds
physiological and biochemical effects of plant compounds on the body
plant compounds–receptor interaction

Published Papers (9 papers)

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Research

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15 pages, 3655 KiB

Open AccessArticle

Doxorubicin Activity Is Modulated by Traditional Herbal Extracts in a 2D and 3D Multicellular Sphere Model of Leukemia

by Laura Corzo Prada, Claudia Urueña, Efraín Leal-García, Alfonso Barreto, Ricardo Ballesteros-Ramírez, Viviana Rodríguez-Pardo and Susana Fiorentino

Pharmaceutics 2023, 15(6), 1690; https://doi.org/10.3390/pharmaceutics15061690 - 09 Jun 2023

Cited by 1 | Viewed by 1412

Abstract

The modulation of the tumor microenvironment by natural products may play a significant role in the response of tumor cells to chemotherapy. In this study, we evaluated the effect of extracts derived from P2Et (Caesalpinia spinosa) and Anamú-SC (Petiveria alliacea) plants, previously studied by our group, on the viability and ROS levels in the K562 cell line (Pgp− and Pgp+), endothelial cells (ECs, Eahy.926 cell line) and mesenchymal stem cells (MSC) cultured in 2D and 3D. The results show that: (a) the two botanical extracts are selective on tumor cells compared to doxorubicin (DX), (b) cytotoxicity is independent of the modulation of intracellular ROS for plant extracts, unlike DX, (c) the interaction with DX can be influenced by chemical complexity and the expression of Pgp, (d) the 3D culture shows a greater sensitivity of the tumor cells to chemotherapy, in co-treatment with the extracts. In conclusion, the effect of the extracts on the viability of leukemia cells was modified in multicellular spheroids with MSC and EC, suggesting that the in vitro evaluation of these interactions can contribute to the comprehension of the pharmacodynamics of the botanical drugs. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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27 pages, 4757 KiB

Open AccessArticle

Pullulan/Poly(vinyl alcohol) Hydrogels Loaded with Calendula officinalis Extract: Design and In Vitro Evaluation for Wound Healing Applications

by Irina Mihaela Pelin, Mihaela Silion, Irina Popescu, Cristina Mihaela Rîmbu, Gheorghe Fundueanu and Marieta Constantin

Pharmaceutics 2023, 15(6), 1674; https://doi.org/10.3390/pharmaceutics15061674 - 07 Jun 2023

Cited by 7 | Viewed by 2200

Abstract

The therapeutic efficiency of plant extracts has been limited by their poor pharmaceutical availability. Hydrogels have promising potential to be applied as wound dressings due to their high capacity to absorb exudates and their enhanced performance in loading and releasing plant extracts. In this work, pullulan/poly (vinyl alcohol) (P/PVA) hydrogels were first prepared using an eco-friendly method based on both a covalent and physical cross-linking approach. Then, the hydrogels were loaded with the hydroalcoholic extract of Calendula officinalis by a simple post-loading immersion method. Different loading capacities were investigated in terms of the physico-chemical properties, chemical composition, mechanical properties, and water absorption. The hydrogels exhibited high loading efficiency due to the hydrogen bonding interactions between polymer and extract. The water retention capacity as well as the mechanical properties decreased with the increase in the extract amount in hydrogel. However, higher amounts of extract in the hydrogel improved the bioadhesiveness. The release of extract from hydrogels was controlled by the Fickian diffusion mechanism. Extract-loaded hydrogels expressed high antioxidant activity, reaching 70% DPPH radical scavenging after 15 min immersion in buffer solution at pH 5.5. Additionally, loaded hydrogels showed a high antibacterial activity against Gram-positive and Gram-negative bacteria and were non-cytotoxic against HDFa cells. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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24 pages, 4059 KiB

Open AccessArticle

Formulation of Phytosomes with Extracts of Ginger Rhizomes and Rosehips with Improved Bioavailability, Antioxidant and Anti-Inflammatory Effects In Vivo

by Mariana Deleanu, Laura Toma, Gabriela Maria Sanda, Teodora Barbălată, Loredan Ştefan Niculescu, Anca Volumnia Sima, Calin Deleanu, Liviu Săcărescu, Alexandru Suciu, Georgeta Alexandru, Iuliana Crişan, Mariana Popescu and Camelia Sorina Stancu

Pharmaceutics 2023, 15(4), 1066; https://doi.org/10.3390/pharmaceutics15041066 - 25 Mar 2023

Cited by 3 | Viewed by 3813

Abstract

The poor water solubility of natural antioxidants restricts their bioavailability and therapeutic use. We aimed to develop a new phytosome formulation with active compounds from extracts of ginger (GINex) and rosehips (ROSAex) designed to increase their bioavailability, antioxidant and anti-inflammatory properties. The phytosomes (PHYTOGINROSA-PGR) were prepared from freeze-dried GINex, ROSAex and phosphatidylcholine (PC) in different mass ratios using the thin-layer hydration method. PGR was characterized for structure, size, zeta potential, and encapsulation efficiency. Results showed that PGR comprises several different populations of particles, their size increasing with ROSAex concentration, having a zeta potential of ~-21mV. The encapsulation efficiency of 6-gingerol and β-carotene was >80%. ³¹P NMR spectra showed that the shielding effect of the phosphorus atom in PC is proportional to the amount of ROSAex in PGR. PGR with a mass ratio GINex:ROSAex:PC-0.5:0.5:1 had the most effective antioxidant and anti-inflammatory effects in cultured human enterocytes. PGR-0.5:0.5:1 bioavailability and biodistribution were assessed in C57Bl/6J mice, and their antioxidant and anti-inflammatory effects were evaluated after administration by gavage to C57Bl/6J mice prior to LPS-induced systemic inflammation. Compared to extracts, PGR induced a 2.6-fold increase in 6-gingerol levels in plasma and over 40% in the liver and kidneys, in parallel with a 65% decrease in the stomach. PGR treatment of mice with systemic inflammation increased the sera antioxidant enzymes paraoxonase-1 and superoxide dismutase-2 and decreased the proinflammatory TNFα and IL-1β levels in the liver and small intestine. No toxicity was induced by PGR either in vitro or in vivo. In conclusion, the phytosome formulation of GINex and ROSAex we developed resulted in stable complexes for oral administration with increased bioavailability, antioxidant and anti-inflammatory potential of their active compounds. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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13 pages, 1683 KiB

Open AccessArticle

Encapsulated Phytomedicines against Cancer: Overcoming the “Valley of Death”

by Ana Brotons-Canto, Claudia P. Urueña, Izaskun Imbuluzqueta, Edurne Luque-Michel, Ana Luisa Martinez-López, Ricardo Ballesteros-Ramírez, Laura Rojas and Susana Fiorentino

Pharmaceutics 2023, 15(4), 1038; https://doi.org/10.3390/pharmaceutics15041038 - 23 Mar 2023

Viewed by 1612

Abstract

P2Et is the standardized extract of Caesalpinia spinosa (C. spinosa), which has shown the ability to reduce primary tumors and metastasis in animal models of cancer, by mechanisms involving the increase in intracellular Ca++, reticulum stress, induction of autophagy, and subsequent activation of the immune system. Although P2Et has been shown to be safe in healthy individuals, the biological activity and bioavailability can be increased by improving the dosage form. This study investigates the potential of a casein nanoparticle for oral administration of P2Et and its impact on treatment efficacy in a mouse model of breast cancer with orthotopically transplanted 4T1 cells. Animals were treated with either free or encapsulated oral P2Et orally or i.p. Tumor growth and macrometastases were evaluated. All P2Et treatments significantly delayed tumor growth. The frequency of macrometastasis was reduced by 1.1 times with P2Et i.p., while oral P2Et reduced it by 3.2 times and nanoencapsulation reduced it by 3.57 times. This suggests that nanoencapsulation led to higher doses of effective P2Et being delivered, slightly improving bioavailability and biological activity. Therefore, the results of this study provide evidence to consider P2Et as a potential adjuvant in the treatment of cancer, while the nanoencapsulation of P2Et provides a novel perspective on the delivery of these functional ingredients. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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17 pages, 9835 KiB

Open AccessArticle

Dermatocosmetic Emulsions Based on Resveratrol, Ferulic Acid and Saffron (Crocus sativus) Extract to Combat Skin Oxidative Stress-Trigger Factor of Some Potential Malignant Effects: Stability Studies and Rheological Properties

by Delia Turcov, Ana Simona Barna, Alexandra Cristina Blaga, Constanta Ibanescu, Maricel Danu, Adriana Trifan, Anca Zbranca and Daniela Suteu

Pharmaceutics 2022, 14(11), 2376; https://doi.org/10.3390/pharmaceutics14112376 - 04 Nov 2022

Cited by 2 | Viewed by 1628

Abstract

The increasing incidence of skin diseases, against the background of increased pollution, urbanism, poor habits in lifestyle, work, rest, diet and general medication, led to the development of products with a protective effect. These new types of dermatocosmetic preparations ensure maximum benefits with minimal formulation. Antioxidants are, nowadays, ingredients that stand out with a proven role in skin protection from oxidative stress and its effects. Thus, research has shown that light-textured formulas, quickly absorbed into the skin, with optimum hydration and protection against excessive free radicals, uphold the skin integrity and appearance. This article aims to evaluate essential criteria for a newly marketed product: stability, rheological properties and microbiological characteristics of oil-in-water emulsions based on a mixture of 3% resveratrol 0.5% ferulic acid and 1mL alcoholic extract of Saffron. The tests led to the conclusion that O / W dermatocosmetic emulsions, based on 3% resveratrol and 0.5% ferulic acid, or also 1mL alcoholic extract of Saffron, show resistance to microbiological contamination, good rheological properties (viscoelastic behavior, structural stability, acceptable shearing behavior) that reveal satisfactory texture and high physical stability during storage. These results encourage the transition to dermatological testing as the final stage in considering a new commercial product. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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13 pages, 1841 KiB

Open AccessArticle

Antioxidant, Antimicrobial, and Kinetic Studies of Β-Cyclodextrin Crosslinked with Lignin for Drug Delivery

by Narcis Anghel, Violeta Melinte, Iuliana Spiridon and Mihaela Pertea

Pharmaceutics 2022, 14(11), 2260; https://doi.org/10.3390/pharmaceutics14112260 - 22 Oct 2022

Cited by 9 | Viewed by 1323

Abstract

β-Cyclodextrin was attached to lignin/lignin crosslinked by epichlorohydrin and served as a drug delivery matrix. Ketoconazole and piroxicam were added into the polymeric matrix as antifungal and anti-inflammatory agents, respectively. The percentage of drug retained ranged from 48.4% to 58.4% for ketoconazole and piroxicam, respectively. It was found that their tensile strengths increased with decreasing particle size, ranging between 59% and 71% for lignin crosslinked with β-cyclodextrin base matrix (LCD). Depending on the polymeric matrix, the drug release kinetics fit well in the Korsmeyer–Peppas model, with or without Fickian diffusion. From the materials based on the mixture of epoxidized lignin and β-cyclodextrin, the medicines were released more slowly (the release rate constant presents lower values ranging between 1.117 and 1.783), as compared with those comprising LCD (2.210–4.824). The materials were also demonstrated to have antimicrobial activity. The antioxidant activity of LCD loaded with piroxicam was found to be 23.9% greater than that of the base matrix (LCD). These findings could be useful towards β-cyclodextrin attached to lignin formulation development of drug carriers with antioxidant activity. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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20 pages, 4336 KiB

Open AccessArticle

Simultaneous Determination of Glibenclamide and Silymarin Released from Chitosan Microparticles by HPLC-ESI-MS Technique: Method Development and Validation

by Mihaela-Iustina Condurache, Anca-Roxana Petrovici, Natalia Simionescu, Bianca-Stefania Profire, Luminita-Georgeta Confederat, Alexandra Bujor, Anca Miron and Lenuta Profire

Pharmaceutics 2022, 14(10), 2164; https://doi.org/10.3390/pharmaceutics14102164 - 11 Oct 2022

Cited by 1 | Viewed by 1335

Abstract

The study aim was to develop and validate a high-performance liquid chromatography–electrospray ionization mass spectrometry (HPLC-ESI-MS) method to simultaneously determine glibenclamide (Gli) and silymarin (Sil) released from chitosan (CS) microparticles in aqueous solutions. The CS microparticles were synthesized using an ionic gelation method, and their morphology, swelling degree, encapsulation efficiency and active substance release were investigated. Gli and Sil were loaded in different concentrations, and their identification and quantification were performed using the HPLC-ESI-MS method, which was further validated. The drugs’ characteristic m/z was found in the higher intensity of retention time (Rt) (Gli, 8.909 min; Sil A, 5.41 min; and Sil B, 5.66 min). The method selectivity and precision are very good, and the blank solution proved no interference. The linearity of the answer function is very good for Sil A (R² = 1), Sil B (R² = 0.9998) and Gli (R² = 0.9991). For Gli, we obtained a limit of detection (LOD) = 0.038 mg/mL and limit of quantification (LOQ) = 1.275 mg/mL; for Sil A, a LOD = 0.285 mg/mL and LOQ = 0.95 mg/mL; and for Sil B, a LOD = 0.045 mg/mL and LOQ = 0.15 mg/mL. A high-resolution HPLC-ESI-MS method was developed and validated, which allowed the simultaneous determination of Gli and Sil loaded in CS microparticles, in a concentration range of 0.025–1 mg/mL. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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34 pages, 15258 KiB

Open AccessArticle

Formulation and Development of Bioadhesive Oral Films Containing Usnea barbata (L.) F.H.Wigg Dry Ethanol Extract (F-UBE-HPC) with Antimicrobial and Anticancer Properties for Potential Use in Oral Cancer Complementary Therapy

by Violeta Popovici, Elena Matei, Georgeta-Camelia Cozaru, Laura Bucur, Cerasela Elena Gîrd, Verginica Schröder, Emma Adriana Ozon, Iulian Sarbu, Adina Magdalena Musuc, Irina Atkinson, Adriana Rusu, Simona Petrescu, Raul-Augustin Mitran, Mihai Anastasescu, Aureliana Caraiane, Dumitru Lupuliasa, Mariana Aschie and Victoria Badea

Pharmaceutics 2022, 14(9), 1808; https://doi.org/10.3390/pharmaceutics14091808 - 28 Aug 2022

Cited by 9 | Viewed by 2973

Abstract

Medical research explores plant extracts’ properties to obtain potential anticancer drugs. The present study aims to formulate, develop, and characterize the bioadhesive oral films containing Usnea barbata (L.) dry ethanol extract (F-UBE-HPC) and to investigate their anticancer potential for possible use in oral cancer therapy. The physicochemical and morphological properties of the bioadhesive oral films were analyzed through Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Atomic Force Microscopy (AFM), thermogravimetric analysis (TG), and X-ray diffraction techniques. Pharmacotechnical evaluation (consisting of the measurement of the specific parameters: weight uniformity, thickness, folding endurance, tensile strength, elongation, moisture content, pH, disintegration time, swelling rate, and ex vivo mucoadhesion time) completed the bioadhesive films’ analysis. Next, oxidative stress, caspase 3/7 activity, nuclear condensation, lysosomal activity, and DNA synthesis induced by F-UBE-HPC in normal blood cell cultures and oral epithelial squamous cell carcinoma (CLS-354) cell line and its influence on both cell types’ division and proliferation was evaluated. The results reveal that each F-UBE-HPC contains 0.330 mg dry extract with a usnic acid (UA) content of 0.036 mg. The bioadhesive oral films are thin (0.093 ± 0.002 mm), reveal a neutral pH (7.10 ± 0.02), a disintegration time of 118 ± 3.16 s, an ex vivo bioadhesion time of 98 ± 3.58 min, and show a swelling ratio after 6 h of 289 ± 5.82%, being suitable for application on the oral mucosa. They displayed in vitro anticancer activity on CLS-354 tumor cells. By considerably increasing cellular oxidative stress and caspase 3/7 activity, they triggered apoptotic processes in oral cancer cells, inducing high levels of nuclear condensation and lysosomal activity, cell cycle arrest in G0/G1, and blocking DNA synthesis. All these properties lead to considering the UBE-loaded bioadhesive oral films suitable for potential application as a complementary therapy in oral cancer. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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Review

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22 pages, 2692 KiB

Open AccessEditor’s ChoiceReview

Exploring the Antioxidant Potential of Gellan and Guar Gums in Wound Healing

by Gianina Dodi, Rosina E. Sabau, Bianca E.-B. Crețu and Ioannis Gardikiotis

Pharmaceutics 2023, 15(8), 2152; https://doi.org/10.3390/pharmaceutics15082152 - 17 Aug 2023

Cited by 1 | Viewed by 1359

Abstract

It is acknowledged that the presence of antioxidants boosts the wound-healing process. Many biopolymers have been explored over the years for their antioxidant potential in wound healing, but limited research has been performed on gum structures and their derivatives. This review aims to evaluate whether the antioxidant properties of gellan and guar gums and wound healing co-exist. PubMed was the primary platform used to explore published reports on the antioxidant wound-healing interconnection, wound dressings based on gellan and guar gum, as well as the latest review papers on guar gum. The literature search disclosed that some wound-healing supports based on gellan gum hold considerable antioxidant properties, as evident from the results obtained using different antioxidant assays. It has emerged that the antioxidant properties of guar gum are overlooked in the wound-healing field, in most cases, even if this feature improves the healing outcome. This review paper is the first that examines guar gum vehicles throughout the wound-healing process. Further research is needed to design and evaluate customized wound dressings that can scavenge excess reactive oxygen species, especially in clinical practice. Full article

(This article belongs to the Special Issue The Study of Plant Compounds in Antioxidant Activity and Anticancer Activity)

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