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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 9559

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Dr. Nurettin Sahiner

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1. Department of Ophthalmology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
2. Department of Chemistry, Faculty of Sciences, Canakkale Onsekiz Mart University, Terzioglu Campus, 17100 Canakkale, Turkey
Interests: natural polymers; glycosaminoglycans; sugar alcohols; carbohydrates; polyphenolics; amino acids; peptides; nano/microparticles; antioxidant; anti-inflammatory; antimicrobial activity; ROS-scavenging effect; antiviral; antifungal; biocidal; anticancer; controlled release; drug delivery; biocompatible; blood compatible; surface; (bio)interfaces; smart surfaces; surface modification; superhydrophobic; super hydrophilic; (bio)sensor; theragnostic, biopolymeric MRI agents; injectables biopolymeric materials; hydrogel; cryogel; microgel; nanogels; super porous materials; pharmacology; wound healing; wound dressing; medical device; tissue engineering; stimuli-responsive structures; wearables; artificial skin; shape memory polymers; injectable materials; biodegradable active agent carriers; carbon particle; quantum dots, carbon dots, graphene dots, g-C3N4; lubricant, intra-articular and joints injection materials; cosmetics
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Special Issue Information

Dear Colleagues,

This Special Issue will mainly focus on the role of natural compounds and biomolecules derived from plants, animals, and microorganisms in the application of health-related fields such as the prevention and treatment of infections, diseases, chronic diseases, and so on. Examples of diseases include skin problems, neurodegenerative, cardiovascular, and rheumatic diseases, asthma, diabetes, obesity, and cancers that require a continuous and exhausting treatment process and are posing a serious problem with their increasing occurrence. In addition to certain genetic factors, many environmental factors such as oxidative stress, aging, lifestyle, and diet play a crucial role in health-related problems and diseases. In the treatment of these maladies, the use of active pharmaceutical ingredients may be limited due to inadequate results, the high toxicity of some drugs, high costs, and difficulty in accessing drugs. Natural compounds such as amino acids, carbohydrates, polyphenolics, peptides, and their polymeric derivatives can have additional activities and contribute to deferring, preventing, and treating the emergence of various diseases.

We invite authors in this exciting field to submit their manuscripts (original research, commentaries, short reports, or reviews) to discuss the potential therapeutic effects and mechanisms of action of natural compounds and their derivatives in chronic diseases.

Dr. Nurettin Sahiner
Guest Editor

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

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Keywords

natural therapeutic agents
multifunctional biomaterials based on proteins, enzymes, peptides, amino acids, glucosamines, polyphenolics, and carbohydrates
micro-/nano-/bulk materials
drug delivery systems
targeted therapies
metabolism regulation
ROS-scavenging activity
antibacterial, antifungal, and antiviral
antioxidant, anticancer
biocidal
natural remedy
control release
targeted delivery
natural therapeutics

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Published Papers (7 papers)

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Research

14 pages, 1802 KiB

Open AccessArticle

Iota-Carrageenan from Marine Alga Solieria filiformis Prevents Naproxen-Induced Gastrointestinal Injury via Its Antioxidant and Anti-Inflammatory Activities

by João L. S. Pinheiro, Willer M. Sousa, Lucas H. M. Rodrigues, Francisco F. Bezerra, Cecília L. O. A. Cunha, Victória M. R. Santos, Samara R. B. D. Oliveira, Rudy D. Bingana, André Luiz. R. Barbosa, Marcellus H. L. P. Souza, Ana Lúcia P. Freitas and Renan O. S. Damasceno

Biomedicines 2024, 12(11), 2574; https://doi.org/10.3390/biomedicines12112574 - 10 Nov 2024

Viewed by 648

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in therapy due to their anti-inflammatory and analgesic properties. However, their clinical use is often associated with gastrointestinal complications. Thus, this study aimed to investigate the protective effect of a sulfated iota-carrageenan isolated from the marine alga Solieria filiformis (IC-Sf) against naproxen-induced gastrointestinal injury. Methods: Parameters of gastrointestinal injury, secretory and motor functions, and toxicity were evaluated. Results: The results demonstrated that IC-Sf significantly reduced naproxen-induced gastrointestinal macroscopic injury, with a maximum effect observed at 30 mg/kg. IC-Sf also preserved gastrointestinal antioxidant defense and prevented lipid peroxidation, with a reduction in the non-protein sulfhydryl group (NP-SH) and malondialdehyde (MDA) concentrations induced by naproxen. Additionally, IC-Sf mitigated naproxen-induced gastrointestinal inflammation, as evidenced by reduced myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). IC-Sf did not alter gastric secretion or gastrointestinal motility. In addition, the animals treated with IC-Sf did not present toxic effects. Conclusions: In conclusion, IC-Sf protected the gastrointestinal tract against the harmful effects of naproxen by inhibiting the inflammatory response and lipid peroxidation, suggesting its potential as a new therapeutic agent or food additive. Full article

(This article belongs to the Special Issue Health-Related Applications of Natural Molecule Derived Structures)

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22 pages, 4031 KiB

Open AccessArticle

N-Pep-Zn Improves Cognitive Functions and Acute Stress Response Affected by Chronic Social Isolation in Aged Spontaneously Hypertensive Rats (SHRs)

by Mikhail Y. Stepanichev, Mikhail V. Onufriev, Yulia V. Moiseeva, Olga A. Nedogreeva, Margarita R. Novikova, Pavel A. Kostryukov, Natalia A. Lazareva, Anna O. Manolova, Diana I. Mamedova, Victoria O. Ovchinnikova, Birgit Kastberger, Stefan Winter and Natalia V. Gulyaeva

Biomedicines 2024, 12(10), 2261; https://doi.org/10.3390/biomedicines12102261 - 4 Oct 2024

Viewed by 756

Abstract

Background/Objectives: Aging and chronic stress are regarded as the most important risk factors of cognitive decline. Aged spontaneously hypertensive rats (SHRs) represent a suitable model of age-related vascular brain diseases. The aim of this study was to explore the effects of chronic isolation stress in aging SHRs on their cognitive functions and response to acute stress, as well as the influence of the chronic oral intake of N-Pep-Zn, the Zn derivative of N-PEP-12. Methods: Nine-month-old SHRs were subjected to social isolation for 3 months (SHRiso group), and one group received N-pep-Zn orally (SHRisoP, 1.5 mg/100 g BW). SHRs housed in groups served as the control (SHRsoc). The behavioral study included the following tests: sucrose preference, open field, elevated plus maze, three-chamber sociability and social novelty and spatial learning and memory in a Barnes maze. Levels of corticosterone, glucose and proinflammatory cytokines in blood plasma as well as salivary amylase activity were measured. Restraint (60 min) was used to test acute stress response. Results: Isolation negatively affected the SHRs learning and memory in the Barnes maze, while the treatment of isolated rats with N-Pep-Zn improved their long-term memory and working memory impairments, making the SHRisoP comparable to the SHRsoc group. Acute stress induced a decrease in the relative thymus weight in the SHRiso group (but not SHRsoc), whereas treatment with N-Pep-Zn prevented thymus involution. N-pep-Zn mitigated the increment in blood cortisol and glucose levels induced by acute stress. Conclusions: N-pep-Zn enhanced the adaptive capabilities towards chronic (isolation) and acute (immobilization) stress in aged SHRs and prevented cognitive disturbances induced by chronic isolation, probably affecting the hypothalamo–pituitary–adrenal, sympathetic, and immune systems. Full article

(This article belongs to the Special Issue Health-Related Applications of Natural Molecule Derived Structures)

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17 pages, 1002 KiB

Open AccessArticle

Polydopamine Coating of Graphitic Carbon Nitride, g-C₃N₄, Improves Biomedical Application

by Mehtap Sahiner, Sahin Demirci and Nurettin Sahiner

Biomedicines 2024, 12(6), 1151; https://doi.org/10.3390/biomedicines12061151 - 23 May 2024

Viewed by 1194

Abstract

Graphitic carbon nitride (g-C₃N₄) is an intriguing nanomaterial that exhibits photoconductive fluorescence properties under UV–visible light. Dopamine (DA) coating of g-C₃N₄ prepared from melamine was accomplished via self-polymerization of DA as polydopamine (PDA). The g-C₃N₄ was coated with PDA 1, 3, and 5 times repeatedly as (PDA@g-C₃N₄) in tris buffer at pH 8.5. As the number of PDA coatings was increased on g-C₃N₄, the peak intensity at 1512 cm⁻¹ for N–H bending increased. In addition, the increased weight loss values of PDA@g-C₃N₄ structures at 600 °C from TGA thermograms confirmed that the coating was accomplished. The band gap of g-C₃N₄, 2.72 eV, was reduced to 0.87 eV after five coatings with PDA. A pristine g-C₃N₄ was found to have an isoelectric point (IEP) of 4.0, whereas the isoelectric points of 1PDA@g-C₃N₄ and 3PDA@g-C₃N₄ are close to each other at 3.94 and 3.91, respectively. On the other hand, the IEP of 5PDA@g-C₃N₄ was determined at pH 5.75 assuming complete coating with g-C₃N₄. The biocompatibility of g-C₃N₄ and PDA@g-C₃N₄ against L929 fibroblast cell lines revealed that all PDA@g-C₃N₄ coatings were found to be biocompatible up to a 1000 mg/mL concentration, establishing that PDA coatings did not adversely affect the biocompatibility of the composite materials. In addition, PDA@g-C₃N₄ was screened for antioxidant potential via total phenol content (TPC) and total flavonoid content assays and it was found that PDA@g-C₃N₄ has recognizable TPC values and increased linearly with an increased number of PDA coatings. Furthermore, blood compatibility of pristine g-C₃N₄ is enhanced considerably upon PDA coating, affirmed by hemolysis and the blood clotting index%. Additionally, α-glucosidase inhibitory properties of PDA@g-C₃N₄ structures revealed that 67.6 + 9.8% of this enzyme was evenly inhibited by 3PDA@g-C₃N₄ structure. Full article

(This article belongs to the Special Issue Health-Related Applications of Natural Molecule Derived Structures)

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20 pages, 5933 KiB

Open AccessArticle

Curcumin Co-Encapsulation Potentiates Anti-Arthritic Efficacy of Meloxicam Biodegradable Nanoparticles in Adjuvant-Induced Arthritis Animal Model

by Bilal Aslam, Asif Hussain, Muhammad Naeem Faisal, Zia-ud-Din Sindhu, Rifat Ullah Khan, Ibrahim A. Alhidary, Shabana Naz and Vincenzo Tufarelli

Biomedicines 2023, 11(10), 2662; https://doi.org/10.3390/biomedicines11102662 - 28 Sep 2023

Cited by 4 | Viewed by 2081

Abstract

This study aimed to evaluate the anti-arthritic activity of curcumin and meloxicam co-loaded PLGA nanoparticles in adjuvant-induced arthritic rats. PLGA nanoparticles encapsulating curcumin (nCur) and meloxicam (nMlx) alone and in combination (nCur/Mlx) were used to characterize zeta size and potential, polydispersity index, encapsulation efficiency (%), compound–polymer interactions (FT-IR analysis), and surface morphology (SEM imaging). In vivo, Complete Freund’s adjuvant-induced arthritic rats were intraperitoneally (i.p.) administered with curcumin, meloxicam, curcumin plus meloxicam, nCur, nMlx, and nCur/Mlx for 28 consecutive days. Results showed that nCur, nMlx, and nCur/Mlx significantly (p ≤ 0.05) reduced paw swelling and arthritic score, restored body weight and the immune organ index (thymus and spleen), as well as attenuated serum inflammatory markers (RF, CRP, and PGE2) and oxidative stress parameters (MDA, SOD, and CAT) in adjuvant-induced arthritic rats compared to free compounds. In addition, mono- and dual-compound-loaded nanoparticles significantly (p ≤ 0.05) down-regulated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), up-regulated anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ), and modulated OPG and RANKL expressions in paw tissue. The aforementioned results were further confirmed through radiological and histopathological examinations. Furthermore, the anti-arthritic effect of nCur/Mlx was notably (p ≤ 0.05) enhanced compared to nCur or nMlx alone. In conclusion, the co-nanoencapsulation of curcumin could potentiate the anti-arthritic activity of meloxicam and could provide a novel therapeutic approach for the formulation of nanocarrier pharmaceutical products for the management of arthritis. Full article

(This article belongs to the Special Issue Health-Related Applications of Natural Molecule Derived Structures)

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17 pages, 2432 KiB

Open AccessArticle

Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides

by José Guedes da Silva, Júnior, André de Lima Aires, Rebeca Xavier da Cunha, Talyta Valéria Siqueira do Monte, Shalom Pôrto de Oliveira Assis, Ronaldo Nascimento de Oliveira, Talita Giselly dos Santos Souza, Cristiano Aparecido Chagas, Jacinto da Costa Silva Neto, Hallysson Douglas Andrade de Araújo and Vera Lúcia de Menezes Lima

Biomedicines 2023, 11(9), 2537; https://doi.org/10.3390/biomedicines11092537 - 14 Sep 2023

Viewed by 1444

Abstract

Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman’s capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy. Full article

(This article belongs to the Special Issue Health-Related Applications of Natural Molecule Derived Structures)

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13 pages, 1778 KiB

Open AccessArticle

Fucoidan from Ericaria crinita Alleviates Inflammation in Rat Paw Edema, Downregulates Pro-Inflammatory Cytokine Levels, and Shows Antioxidant Activity

by Paolina Lukova, Elisaveta Apostolova, Alexandra Baldzhieva, Marianna Murdjeva and Vesela Kokova

Biomedicines 2023, 11(9), 2511; https://doi.org/10.3390/biomedicines11092511 - 11 Sep 2023

Cited by 5 | Viewed by 1165

Abstract

Fucoidans are sulfated polysaccharides detected mainly in the cell walls of brown seaweeds. Here, we examined the effects of single doses of fucoidan derived from Ericaria crinita (formerly Cystoseira crinita) on carrageenan-induced paw inflammation in rats. The serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment were also evaluated. Subchronic treatment with fucoidan from E. crinita attenuated the inflammation during the late phase of the degraded carrageenan-induced paw edema (3rd to 5th hour after carrageenan injection) with peak activity at the 3rd hour after the application. Both doses of fucoidan from E. crinita (25 and 50 mg/kg bw) significantly decreased the levels of all tested pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) in the serum of rats with a model of system inflammation but had no effect on the anti-inflammatory cytokine IL-10. The results showed that the repeated application of fucoidan has a more prominent effect on the levels of some pro-inflammatory cytokines in serum in comparison to a single dose of the sulfated polysaccharide. This reveals the potential of E. crinita fucoidan as an anti-inflammatory agent. Furthermore, E. crinita fucoidan exhibited in vitro antioxidant capacity, determined by 2,2-diphenyl-1-picryl-hydrazyl radical scavenging and ferric reducing antioxidant power assays as follows: IC₅₀ = 412 µg/mL and 118.72 μM Trolox equivalent/g, respectively. Full article

(This article belongs to the Special Issue Health-Related Applications of Natural Molecule Derived Structures)

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19 pages, 2770 KiB

Open AccessArticle

Plumbagin: A Promising In Vivo Antiparasitic Candidate against Schistosoma mansoni and In Silico Pharmacokinetic Properties (ADMET)

by Lucas M. N. Silva, Wilza W. M. França, Victor H. B. Santos, Renan A. F. Souza, Adriana M. Silva, Emily G. M. Diniz, Thierry W. A. Aguiar, João V. R. Rocha, Mary A. A. Souza, Wheverton R. C. Nascimento, Reginaldo G. Lima Neto, Iranildo J. Cruz Filho, Eulália C. P. A. Ximenes, Hallysson D. A. Araújo, André L. Aires and Mônica C. P. A. Albuquerque

Biomedicines 2023, 11(9), 2340; https://doi.org/10.3390/biomedicines11092340 - 22 Aug 2023

Cited by 2 | Viewed by 1551

Abstract

Schistosomiasis, a potentially fatal chronic disease whose etiological agents are blood trematode worms of the genus Schistosoma spp., is one of the most prevalent and debilitating neglected diseases. The treatment of schistosomiasis depends exclusively on praziquantel (PZQ), a drug that has been used since the 1970s and that already has reports of reduced therapeutic efficacy, related with the development of Schistosoma-resistant or -tolerant strains. Therefore, the search for new therapeutic alternatives is an urgent need. Plumbagin (PLUM), a naphthoquinone isolated from the roots of plants of the genus Plumbago, has aroused interest in research due to its antiparasitic properties against protozoa and helminths. Here, we evaluated the in vivo schistosomicidal potential of PLUM against Schistosoma mansoni and the in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The study was carried out with five groups of infected mice and divided as follows: an untreated control group, a control group treated with PZQ, and three groups treated orally with 8, 16, or 32 mg/kg of PLUM. After treatment, the Kato–Katz technique was performed to evaluate a quantity of eggs in the feces (EPG). The animals were euthanized for worm recovery, intestine samples were collected to evaluate the oviposition pattern, the load of eggs was determined on the hepatic and intestinal tissues and for the histopathological and histomorphometric evaluation of tissue and hepatic granulomas. PLUM reduced EPG by 65.27, 70.52, and 82.49%, reduced the total worm load by 46.7, 55.25, and 72.4%, and the female worm load by 44.01, 52.76, and 71.16%, for doses of 8, 16, and 32 mg/kg, respectively. PLUM also significantly reduced the number of immature eggs and increased the number of dead eggs in the oogram. A reduction of 36.11, 46.46, and 64.14% in eggs in the hepatic tissue, and 57.22, 65.18, and 80.5% in the intestinal tissue were also observed at doses of 8, 16, and 32 mg/kg, respectively. At all doses, PLUM demonstrated an effect on the histopathological and histomorphometric parameters of the hepatic granuloma, with a reduction of 41.11, 48.47, and 70.55% in the numerical density of the granulomas and 49.56, 57.63, and 71.21% in the volume, respectively. PLUM presented itself as a promising in vivo antiparasitic candidate against S. mansoni, acting not only on parasitological parameters but also on hepatic granuloma. Furthermore, in silico, PLUM showed good predictive pharmacokinetic profiles by ADMET. Full article

(This article belongs to the Special Issue Health-Related Applications of Natural Molecule Derived Structures)

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