Pharmaceuticals

17 pages, 2265 KiB

Open AccessArticle

Sika Deer Velvet Antler Peptide Exerts Neuroprotective Effect in a Parkinson’s Disease Model via Regulating Oxidative Damage and Gut Microbiota

by Ying Liu, Hongyuan Li, Min Yang, Jia Guo, Zepeng Sun, Shuyue Wang, Ru Li, Xin Pang, Yumi Kim, Xiaohui Wang and Yinghua Peng

Pharmaceuticals 2024, 17(7), 972; https://doi.org/10.3390/ph17070972 - 22 Jul 2024

Viewed by 548

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder globally. Recognizing the potential of velvet antler in the nervous system, as shown in numerous studies, this research was aimed at evaluating the neuroprotective effects of Sika Deer velvet antler peptide (VAP), along [...] Read more.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder globally. Recognizing the potential of velvet antler in the nervous system, as shown in numerous studies, this research was aimed at evaluating the neuroprotective effects of Sika Deer velvet antler peptide (VAP), along with the underlying mechanisms in neurotoxin-induced PD models. Initially, a peptidomic analysis of the VAP, which comprised 189 varieties of peptides, was conducted using LC-MS. Nine sequences were identified as significant using Proteome Discoverer 2.5 software. In a cellular model of PD, where PC12 cells are treated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺), the administration of the VAP reduced the cell damage and apoptosis induced by MPP⁺. This protective effect was associated with a decrease in oxidative stress. This protective mechanism was found to be mediated through the activation of the SIRT1-dependent Akt/Nrf2/HO-1-signaling pathway. In animal models, specifically in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD, the administration of the VAP effectively reduced the dopaminergic neuron damage and reversed the neurobehavioral deficits. They also diminished microglia activation and apoptosis, all without any noticeable adverse effects. Additionally, the VAP was observed to beneficially alter the gut microbiota, as marked by an increase in the abundances of Prevotellaceae, Helicobacteraceae, and Prevotella. These findings suggest that VAP exerts its neuroprotective effect against neurodegeneration by inhibiting oxidative stress and modulating gut microbiota. Full article

(This article belongs to the Section Pharmacology)

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22 pages, 2168 KiB

Open AccessSystematic Review

Strong Early Impact of Letrozole on Ovulation Induction Outperforms Clomiphene Citrate in Polycystic Ovary Syndrome

by Rita Zsuzsanna Vajna, András Mihály Géczi, Fanni Adél Meznerics, Nándor Ács, Péter Hegyi, Emma Zoé Feig, Péter Fehérvári, Szilvia Kiss-Dala, Szabolcs Várbíró, Judit Réka Hetthessy and Levente Sára

Pharmaceuticals 2024, 17(7), 971; https://doi.org/10.3390/ph17070971 - 22 Jul 2024

Viewed by 594

Abstract

Polycystic ovary syndrome is a common endocrine disorder, characterized by hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. The aim of this systematic review and meta-analysis was to explore the efficacy of letrozole compared with clomiphene citrate for ovulation induction in women with [...] Read more.

Polycystic ovary syndrome is a common endocrine disorder, characterized by hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. The aim of this systematic review and meta-analysis was to explore the efficacy of letrozole compared with clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome. The study protocol has been registered with PROSPERO (registration number CRD42022376611). The literature search included randomized clinical trials. We conducted our systematic literature search across three medical databases: MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. The data synthesis employed a random effects model. Out of the 1994 articles screened, 25 studies fulfilled the inclusion criteria. The letrozole group exhibited a significant increase in endometrial thickness (mean difference = 1.70, confidence interval: 0.55–2.86; I² = 97%, p-value = 0.008). The odds of ovulation (odds ratio = 1.8, confidence interval: 1.21–2.69; I² = 51%, p-value = 0.010) and pregnancy (odds ratio = 1.96, confidence interval: 1.37–2.81; I² = 32%, p-value = 0.002) were significantly higher. The resistance index of the subendometrial arteries showed a significant decrease (mean difference = −0.15, confidence interval: −0.27 to −0.04; I² = 92%, p-value = 0.030). Women diagnosed with polycystic ovarian syndrome and treated with letrozole for ovulation induction had increased ovulation and pregnancy rates and increased endometrial thickness. The lower resistance index of subendometrial arteries can enhance intrauterine circulation, creating more favorable conditions for embryo implantation and development. Full article

(This article belongs to the Topic Research in Pharmacological Therapies)

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23 pages, 11722 KiB

Open AccessArticle

A First Metabolite Analysis of Norfolk Island Pine Resin and Its Hepatoprotective Potential to Alleviate Methotrexate (MTX)-Induced Hepatic Injury

by Sherouk Hussein Sweilam, Dalia E. Ali, Ahmed M. Atwa, Ali M. Elgindy, Aya M. Mustafa, Manar M. Esmail, Mahmoud Abdelrahman Alkabbani, Mohamed Magdy Senna and Riham A. El-Shiekh

Pharmaceuticals 2024, 17(7), 970; https://doi.org/10.3390/ph17070970 - 22 Jul 2024

Cited by 1 | Viewed by 669

Abstract

Drug-induced liver injury (DILI) represents a significant clinical challenge characterized by hepatic dysfunction following exposure to diverse medications. Methotrexate (MTX) is a cornerstone in treating various cancers and autoimmune disorders. However, the clinical utility of MTX is overshadowed by its ability to induce [...] Read more.

Drug-induced liver injury (DILI) represents a significant clinical challenge characterized by hepatic dysfunction following exposure to diverse medications. Methotrexate (MTX) is a cornerstone in treating various cancers and autoimmune disorders. However, the clinical utility of MTX is overshadowed by its ability to induce hepatotoxicity. The current study aims to elucidate the hepatoprotective effect of the alcoholic extract of Egyptian Araucaria heterophylla resin (AHR) on MTX-induced liver injury in rats. AHR (100 and 200 mg/kg) significantly decreased hepatic markers (AST, ALT, and ALP), accompanied by an elevation in the antioxidant’s markers (SOD, HO-1, and NQO1). AHR extract also significantly inhibited the TGF-β/NF-κB signaling pathway as well as the downstream cascade (IL-6, JAK, STAT-3, and cyclin D). The extract significantly reduced the expression of VEGF and p38 with an elevation in the BCL2 levels, in addition to a significant decrease in the IL-1β and TNF-α levels, with a prominent effect at a high dose (200 mg/kg). Using LC-HRMS/MS analysis, a total of 43 metabolites were tentatively identified, and diterpenes were the major class. This study presents AHR as a promising hepatoprotective agent through inhibition of the TGF-β/NF-κB and JAK/STAT3 pathways, besides its antioxidant and anti-inflammatory effects. Full article

(This article belongs to the Section Natural Products)

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17 pages, 7242 KiB

Open AccessArticle

Exploring the Mechanism of Asiatic Acid against Atherosclerosis Based on Molecular Docking, Molecular Dynamics, and Experimental Verification

by Zhihao Wu, Luyin Yang, Rong Wang, Jie Yang, Pan Liang, Wei Ren and Hong Yu

Pharmaceuticals 2024, 17(7), 969; https://doi.org/10.3390/ph17070969 - 22 Jul 2024

Viewed by 565

Abstract

Asiatic acid (AA) is a pentacyclic triterpene derived from the traditional medicine Centella asiatica. It is known for its anti-inflammatory, antioxidant, and lipid-regulating properties. Though previous studies have suggested its potential therapeutic benefits for atherosclerosis, its pharmacological mechanism is unclear. The objective [...] Read more.

Asiatic acid (AA) is a pentacyclic triterpene derived from the traditional medicine Centella asiatica. It is known for its anti-inflammatory, antioxidant, and lipid-regulating properties. Though previous studies have suggested its potential therapeutic benefits for atherosclerosis, its pharmacological mechanism is unclear. The objective of this study was to investigate the molecular mechanism of AA in the treatment of atherosclerosis. Therefore, network pharmacology was employed to uncover the mechanism by which AA acts as an anti-atherosclerotic agent. Furthermore, molecular docking, molecular dynamics (MD) simulation, and in vitro experiments were performed to elucidate the mechanism of AA’s anti-atherosclerotic effects. Molecular docking analysis demonstrated a strong affinity between AA and PPARγ. Further MD simulations demonstrated the favorable stability of AA-PPARγ protein complexes. In vitro experiments demonstrated that AA can dose-dependently inhibit the expression of inflammatory factors induced by lipopolysaccharide (LPS) in RAW264.7 cells. This effect may be mediated through the PPARγ/NF-κB signaling pathway. This research underscores anti-inflammation as a crucial biological process in AA treatments for atherosclerosis, with PPARγ potentially serving as a key target. Full article

(This article belongs to the Special Issue The Mode of Action of Herbal Medicines and Natural Products)

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23 pages, 5969 KiB

Open AccessArticle

Parkia javanica Edible Pods Reveal Potential as an Anti-Diabetic Agent: UHPLC-QTOF-MS/MS-Based Chemical Profiling, In Silico, In Vitro, In Vivo, and Oxidative Stress Studies

by Alekhya Sarkar, Arjita Chakrabarti, Samhita Bhaumik, Bimal Debnath, Shiv Shankar Singh, Rajat Ghosh, Magdi E. A. Zaki, Sami A. Al-Hussain and Sudhan Debnath

Pharmaceuticals 2024, 17(7), 968; https://doi.org/10.3390/ph17070968 - 21 Jul 2024

Viewed by 832

Abstract

According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last [...] Read more.

According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last few decades. This study aims to determine the phytochemicals in the edible part of Perkia javanica, predict their α-glucosidase inhibitory potential, one of the promising targets for diabetes, and then carry out in vitro and in vivo studies. The phytochemicals present in the n-butanol fraction of the methanol extract of P. javanica pods were analyzed using UHPLC-QTOF-MS/MS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry). The UHPLC-QTOF analysis revealed the presence of 79 different compounds in the n-butanol fraction. Among these, six compounds demonstrated excellent binding affinities with α-glucosidase, surpassing the performance of two standard inhibitors, Miglitol and Voglibose. In vitro α-glucosidase inhibitory activities were assessed by the n-butanol fraction, followed by in vivo studies. According to the in vitro study, the inhibitory efficiency against α-glucosidase was determined to have an IC₅₀ value of 261.9 µg/mL. The in vivo findings revealed a significant reduction in blood glucose levels in Swiss albino mice treated with the same extract, decreasing from 462.66 mg/dL to 228.66 mg/dL. Additionally, the extract significantly increased the activity of the enzymes catalase and superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) in the liver and kidney tissue. The predicted physicochemical parameters indicated that most of the compounds would be excreted from the body after inhibition in the small intestine without being absorbed. Considering the low cost and wide availability of raw materials, P. javanica pods can serve as a good food supplement that may help prevent type 2 diabetes management. Full article

(This article belongs to the Section Natural Products)

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54 pages, 2198 KiB

Open AccessReview

Medicinal Plant Extracts against Cardiometabolic Risk Factors Associated with Obesity: Molecular Mechanisms and Therapeutic Targets

by Jorge Gutiérrez-Cuevas, Daniel López-Cifuentes, Ana Sandoval-Rodriguez, Jesús García-Bañuelos and Juan Armendariz-Borunda

Pharmaceuticals 2024, 17(7), 967; https://doi.org/10.3390/ph17070967 - 21 Jul 2024

Viewed by 949

Abstract

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to the development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease, hypertension, heart failure, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and [...] Read more.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to the development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease, hypertension, heart failure, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen and C-reactive protein, and others, all of which increase the risk of CVD events. The mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokine dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left-ventricular remodeling and diastolic dysfunction. Natural products of plants provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discuss the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herb and plant extracts for the prevention and treatment of CRFs are also reviewed. Full article

(This article belongs to the Special Issue Anti-obesity and Anti-aging Natural Products)

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23 pages, 6892 KiB

Open AccessArticle

Enhancement of Cognitive Function by Andrographolide-Loaded Lactose β-Cyclodextrin Nanoparticles: Synthesis, Optimization, and Behavioural Assessment

by Debashish Paramanick, Kagithala Naga Rani, Vijay Kumar Singh, Parakh Basist, Rahmuddin Khan, Jameel H. Al-Tamimi, Omar M. Noman, Mansour N. Ibrahim and Abdulsalam Alhalmi

Pharmaceuticals 2024, 17(7), 966; https://doi.org/10.3390/ph17070966 - 21 Jul 2024

Viewed by 649

Abstract

This study investigates whether Andrographolide-loaded Lactose β-Cyclodextrin (ALN-βCD) nanoparticles enhance cognitive function, particularly spatial learning and memory. The successful conjugation of lactose to β-cyclodextrin was confirmed via 1H NMR spectroscopy, facilitating neuronal cell entry. The solvent evaporation method was used to create the [...] Read more.

This study investigates whether Andrographolide-loaded Lactose β-Cyclodextrin (ALN-βCD) nanoparticles enhance cognitive function, particularly spatial learning and memory. The successful conjugation of lactose to β-cyclodextrin was confirmed via 1H NMR spectroscopy, facilitating neuronal cell entry. The solvent evaporation method was used to create the nanoparticles, which were characterised for particle size, PDI, zeta potential, and drug release. The nanoparticles exhibited a size of 247.9 ± 3.2 nm, a PDI of 0.5 ± 0.02, and a zeta potential of 26.8 ± 2.5 mV. FTIR and TEM analyses, along with in vitro drug release and BBB permeability studies, confirmed their stability and efficacy. Behavioural tests, including the Elevated Plus Maze, Y-Maze, Object Recognition, and Locomotor Activity tests, demonstrated significant improvements in memory, motor coordination, and exploration time in the nanoparticle-treated groups. The group treated with ALN-βCD at a dose of 100 mg/kg/p.o. showed superior cognitive performance compared to the group receiving free andrographolides (AG). Biochemical assays indicated a significant reduction in acetylcholinesterase activity and lipid peroxidation, suggesting increased acetylcholine levels and reduced oxidative stress. Histopathological examination showed improved neuronal function without toxicity. The results showed significant improvements (p < 0.001) in memory and cognitive abilities in experimental animals, highlighting the potential of ALN-βCD nanoparticles as a non-invasive treatment for memory loss. These promising findings warrant further exploration through clinical trials. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Drug Delivery System and Its Pharmaceutical and Biomedical Application 2024)

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12 pages, 599 KiB

Open AccessArticle

Close Cardiovascular Monitoring during the Early Stages of Treatment for Patients Receiving Immune Checkpoint Inhibitors

by Danielle Delombaerde, Christof Vulsteke, Nico Van de Veire, Delphine Vervloet, Veronique Moerman, Lynn Van Calster, Anne-Marie Willems, Lieselot Croes, Félix Gremonprez, Astrid De Meulenaere, Ximena Elzo Kraemer, Kristien Wouters, Marc Peeters, Hans Prenen and Johan De Sutter

Pharmaceuticals 2024, 17(7), 965; https://doi.org/10.3390/ph17070965 - 21 Jul 2024

Viewed by 535

Abstract

Background: There is an unmet medical need for the early detection of immune checkpoint inhibitor (ICI)-induced cardiovascular (CV) adverse events due to a lack of adequate biomarkers. This study aimed to provide insights on the incidence of troponin elevations and echocardiographic dynamics during [...] Read more.

Background: There is an unmet medical need for the early detection of immune checkpoint inhibitor (ICI)-induced cardiovascular (CV) adverse events due to a lack of adequate biomarkers. This study aimed to provide insights on the incidence of troponin elevations and echocardiographic dynamics during ICI treatment in cancer patients and their role as potential biomarkers for submyocardial damage. In addition, it is the first study to compare hs-TnT and hs-TnI in ICI-treated patients and to evaluate their interchangeability in the context of screening. Results: Among 59 patients, the mean patient age was 68 years, and 76% were men. Overall, 25% of patients received combination therapy. Although 10.6% [95% CI: 5.0–22.5] of the patients developed troponin elevations, none experienced a CV event. No significant changes were found in 3D left ventricular (LV) ejection fraction nor in global longitudinal strain f (56 ± 6% vs. 56 ± 6%, p = 0.903 and −17.8% [−18.5; −14.2] vs. −17.0% [−18.8; −15.1], p = 0.663) at 3 months. There were also no significant changes in diastolic function and right ventricular function. In addition, there was poor agreement between hs-TnT and hs-TnI. Methods: Here, we present a preliminary analysis of the first 59 patients included in our ongoing prospective clinical trial (NCT05699915) during the first three months of treatment. All patients underwent electrocardiography and echocardiography along with blood sampling at standardized time intervals. This study aimed to investigate the incidence of elevated hs-TnT levels within the first three months of ICI treatment. Elevations were defined as hs-TnT above the upper limit of normal (ULN) if the baseline value was normal, or 1.5 ≥ times baseline if the baseline value was above the ULN. Conclusions: Hs-TnT elevations occurred in 10.6% of the patients. However, no significant changes were found on 3D echocardiography, nor did any of the patients develop a CV event. There were also no changes found in NT-proBNP. The study is still ongoing, but these preliminary findings do not show a promising role for cardiac troponins nor for echocardiographic dynamics in the prediction of CV events during the early stages of ICI treatment. Full article

(This article belongs to the Special Issue Immune-Related Adverse Effects of Checkpoint Inhibitors in Cancer Patients)

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33 pages, 1718 KiB

Open AccessReview

Insights into Immune Exhaustion in Chronic Hepatitis B: A Review of Checkpoint Receptor Expression

by João Panão Costa, Armando de Carvalho, Artur Paiva and Olga Borges

Pharmaceuticals 2024, 17(7), 964; https://doi.org/10.3390/ph17070964 - 21 Jul 2024

Viewed by 946

Abstract

Hepatitis B, caused by the hepatitis B virus (HBV), often progresses to chronic infection, leading to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HBV infection is characterized by a complex interplay between the virus and the host immune system, [...] Read more.

Hepatitis B, caused by the hepatitis B virus (HBV), often progresses to chronic infection, leading to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HBV infection is characterized by a complex interplay between the virus and the host immune system, resulting in immune cell exhaustion, a phenomenon commonly observed in chronic viral infections and cancer. This state of exhaustion involves elevated levels of inhibitory molecules, cells, and cell surface receptors, as opposed to stimulatory counterparts. This review aims to elucidate the expression patterns of various co-inhibitory and co-stimulatory receptors on immune cells isolated from chronic hepatitis B (CHB) patients. By analyzing existing data, the review conducts comparisons between CHB patients and healthy adults, explores the differences between HBV-specific and total T cells in CHB patients, and examines variations between intrahepatic and peripheral immune cells in CHB patients. Understanding the mechanisms underlying immune exhaustion in CHB is crucial for developing novel immunotherapeutic approaches. This detailed analysis sheds light on the immune exhaustion observed in CHB and lays the groundwork for future combined immunotherapy strategies aimed at leveraging checkpoint receptors to restore immune function and improve clinical outcomes. Full article

(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)

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HBV replication cycle after entering the hepatocyte. Image created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>. Full article ">Figure 2
Mechanism and key factors leading to immune cell exhaustion in a CHB scenario. The increased HBV viral load and antigen level overwhelm the immune system, while cytokine imbalance, increased inhibitory receptors and ligands, decreased stimulatory receptors and ligands, increased regulatory T cells, decreased T helper activity, and decreased T-bet expression all contribute to T-cell exhaustion. Image created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>. Full article ">Figure 3
Outcomes of immune cell exhaustion in CHB patients. Immune cell exhaustion in CHB patients leads to decreased T cell proliferation, survival, and differentiation, as well as impaired cytokine responses and decreased cytotoxic activity. This exhaustion results in a lack of effective T cell responses against the virus, making it challenging for the immune system to effectively clear the infection. Full article ">Figure 4
Depiction of co-stimulatory and co-inhibitory ligand–receptor interactions between APCs and T cells studied in CHB patients. The regulatory molecules and their ligands are depicted, highlighting the key interactions that influence T cell function. Image created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>. Full article ">

26 pages, 1820 KiB

Open AccessReview

Galangin: A Promising Flavonoid for the Treatment of Rheumatoid Arthritis—Mechanisms, Evidence, and Therapeutic Potential

by Ghada Khawaja, Youmna El-Orfali, Aya Shoujaa and Sonia Abou Najem

Pharmaceuticals 2024, 17(7), 963; https://doi.org/10.3390/ph17070963 - 19 Jul 2024

Viewed by 766

Abstract

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation and damage. Oxidative stress plays a critical role in the onset and progression of RA, significantly contributing to the disease’s symptoms. The complex nature of RA and the role of [...] Read more.

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation and damage. Oxidative stress plays a critical role in the onset and progression of RA, significantly contributing to the disease’s symptoms. The complex nature of RA and the role of oxidative stress make it particularly challenging to treat effectively. This article presents a comprehensive review of RA’s development, progression, and the emergence of novel treatments, introducing Galangin (GAL), a natural flavonoid compound sourced from various plants, as a promising candidate. The bioactive properties of GAL, including its anti-inflammatory, antioxidant, and immunomodulatory effects, are discussed in detail. The review elucidates GAL’s mechanisms of action, focusing on its interactions with key targets such as inflammatory cytokines (e.g., TNF-α, IL-6), enzymes (e.g., SOD, MMPs), and signaling pathways (e.g., NF-κB, MAPK), which impact inflammatory responses, immune cell activation, and joint damage. The review also addresses the lack of comprehensive understanding of potential treatment options for RA, particularly in relation to the role of GAL as a therapeutic candidate. It highlights the need for further research and clinical studies to ascertain the effectiveness of GAL in RA treatment and to elucidate its mechanisms of action. Overall, this review provides valuable insights into the potential of GAL as a therapeutic option for RA, shedding light on its multifaceted pharmacological properties and mechanisms of action, while suggesting avenues for future research and clinical applications. Full article

(This article belongs to the Special Issue Bioactive Substances, Oxidative Stress, and Inflammation)

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39 pages, 7143 KiB

Open AccessReview

Transmission-Blocking Strategies for Malaria Eradication: Recent Advances in Small-Molecule Drug Development

by Federico Appetecchia, Emanuele Fabbrizi, Francesco Fiorentino, Sara Consalvi, Mariangela Biava, Giovanna Poce and Dante Rotili

Pharmaceuticals 2024, 17(7), 962; https://doi.org/10.3390/ph17070962 - 19 Jul 2024

Viewed by 702

Abstract

Malaria drug research and development efforts have resurged in the last decade following the decelerating rate of mortality and malaria cases in endemic regions. The inefficiency of malaria interventions is largely driven by the spreading resistance of the Plasmodium falciparum parasite to current [...] Read more.

Malaria drug research and development efforts have resurged in the last decade following the decelerating rate of mortality and malaria cases in endemic regions. The inefficiency of malaria interventions is largely driven by the spreading resistance of the Plasmodium falciparum parasite to current drug regimens and that of the malaria vector, the Anopheles mosquito, to insecticides. In response to the new eradication agenda, drugs that act by breaking the malaria transmission cycle (transmission-blocking drugs), which has been recognized as an important and additional target for intervention, are being developed. These drugs take advantage of the susceptibility of Plasmodium during population bottlenecks before transmission (gametocytes) and in the mosquito vector (gametes, zygotes, ookinetes, oocysts, sporozoites). To date, compounds targeting stage V gametocytes predominate in the chemical library of transmission-blocking drugs, and some of them have entered clinical trials. The targeting of Plasmodium mosquito stages has recently renewed interest in the development of innovative malaria control tools, which hold promise for the application of compounds effective at these stages. In this review, we highlight the major achievements and provide an update on the research of transmission-blocking drugs, with a particular focus on their chemical scaffolds, antiplasmodial activity, and transmission-blocking potential. Full article

(This article belongs to the Special Issue Small Molecules as Antimicrobials 2022)

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10 pages, 1425 KiB

Open AccessReview

Trackins (Trk-Targeting Drugs): A Novel Therapy for Different Diseases

by George N. Chaldakov, Luigi Aloe, Stanislav G. Yanev, Marco Fiore, Anton B. Tonchev, Manlio Vinciguerra, Nikolai T. Evtimov, Peter Ghenev and Krikor Dikranian

Pharmaceuticals 2024, 17(7), 961; https://doi.org/10.3390/ph17070961 - 19 Jul 2024

Viewed by 722

Abstract

Many routes may lead to the transition from a healthy to a diseased phenotype. However, there are not so many routes to travel in the opposite direction; that is, therapy for different diseases. The following pressing question thus remains: what are the pathogenic [...] Read more.

Many routes may lead to the transition from a healthy to a diseased phenotype. However, there are not so many routes to travel in the opposite direction; that is, therapy for different diseases. The following pressing question thus remains: what are the pathogenic routes and how can be they counteracted for therapeutic purposes? Human cells contain >500 protein kinases and nearly 200 protein phosphatases, acting on thousands of proteins, including cell growth factors. We herein discuss neurotrophins with pathogenic or metabotrophic abilities, particularly brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), pro-NGF, neurotrophin-3 (NT-3), and their receptor Trk (tyrosine receptor kinase; pronounced “track”). Indeed, we introduced the word trackins, standing for Trk-targeting drugs, that play an agonistic or antagonistic role in the function of TrkB^BDNF, TrkC^NT−3, TrkA^NGF, and TrkA^pro-NGF receptors. Based on our own published results, supported by those of other authors, we aim to update and enlarge our trackins concept, focusing on (1) agonistic trackins as possible drugs for (1a) neurotrophin-deficiency cardiometabolic disorders (hypertension, atherosclerosis, type 2 diabetes mellitus, metabolic syndrome, obesity, diabetic erectile dysfunction and atrial fibrillation) and (1b) neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis), and (2) antagonistic trackins, particularly TrkA^NGF inhibitors for prostate and breast cancer, pain, and arrhythmogenic right-ventricular dysplasia. Altogether, the druggability of TrkA^NGF, TrkA^pro-NGF, TrkB^BDNF, and TrkC^NT−3 receptors via trackins requires a further translational pursuit. This could provide rewards for our patients. Full article

(This article belongs to the Special Issue Synthetic Inhibitors of Nucleoside Monophosphate-Kinases)

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24 pages, 2676 KiB

Open AccessReview

Unlocking the Green Gold: Exploring the Cancer Treatment and the Other Therapeutic Potential of Fucoxanthin Derivatives from Microalgae

by Fatouma Mohamed Abdoul-Latif, Ayoub Ainane, Ibrahim Houmed Aboubaker, Ali Merito Ali, Houda Mohamed, Pannaga Pavan Jutur and Tarik Ainane

Pharmaceuticals 2024, 17(7), 960; https://doi.org/10.3390/ph17070960 - 18 Jul 2024

Cited by 1 | Viewed by 1015

Abstract

Fucoxanthin, a carotenoid widely studied in marine microalgae, is at the heart of scientific research because of its promising bioactive properties for human health. Its unique chemical structure and specific biosynthesis, characterized by complex enzymatic conversion in marine organisms, have been examined in [...] Read more.

Fucoxanthin, a carotenoid widely studied in marine microalgae, is at the heart of scientific research because of its promising bioactive properties for human health. Its unique chemical structure and specific biosynthesis, characterized by complex enzymatic conversion in marine organisms, have been examined in depth in this review. The antioxidant, anti-inflammatory, and anti-cancer activities of fucoxanthin have been rigorously supported by data from in vitro and in vivo experiments and early clinical trials. Additionally, this review explores emerging strategies to optimize the stability and efficacy of fucoxanthin, aiming to increase its solubility and bioavailability to enhance its therapeutic applications. However, despite these potential benefits, challenges persist, such as limited bioavailability and technological obstacles hindering its large-scale production. The medical exploitation of fucoxanthin thus requires an innovative approach and continuous optimization to overcome these barriers. Although further research is needed to refine its clinical use, fucoxanthin offers promising potential in the development of natural therapies aimed at improving human health. By integrating knowledge about its biosynthesis, mechanisms of action, and potential beneficial effects, future studies could open new perspectives in the treatment of cancer and other chronic diseases. Full article

(This article belongs to the Special Issue Network Pharmacology of Natural Products)

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3 pages, 186 KiB

Open AccessEditorial

Vascular Endothelial Growth Factor (VEGF) and VEGF Receptor Inhibitors in Health and Disease

by Sylvain Broussy

Pharmaceuticals 2024, 17(7), 959; https://doi.org/10.3390/ph17070959 - 18 Jul 2024

Viewed by 383

Abstract

In this Special Issue of Pharmaceuticals, we present four reviews and seven original articles addressing recent aspects of research on Vascular Endothelial Growth Factors (VEGFs) and their receptors, from clinical practice to fundamental studies in new drug development [...] Full article

(This article belongs to the Special Issue Vascular Endothelial Growth Factor (VEGF) and VEGF Receptor Inhibitors in Health and Disease)

21 pages, 6336 KiB

Open AccessArticle

Anti-Oxidative and Anti-Apoptotic Oligosaccharides from Pichia pastoris-Fermented Cress Polysaccharides Ameliorate Chromium-Induced Liver Toxicity

by Imdad Ullah Khan, Aqsa Aqsa, Yusra Jamil, Naveed Khan, Amjad Iqbal, Sajid Ali, Muhammad Hamayun, Abdulwahed Fahad Alrefaei, Turki Kh. Faraj, Bokyung Lee and Ayaz Ahmad

Pharmaceuticals 2024, 17(7), 958; https://doi.org/10.3390/ph17070958 - 18 Jul 2024

Viewed by 499

Abstract

Oxidative stress impairs the structure and function of the cell, leading to serious chronic diseases. Antioxidant-based therapeutic and nutritional interventions are usually employed for combating oxidative stress-related disorders, including apoptosis. Here, we investigated the hepatoprotective effect of oligosaccharides, produced through Pichia pastoris-mediated [...] Read more.

Oxidative stress impairs the structure and function of the cell, leading to serious chronic diseases. Antioxidant-based therapeutic and nutritional interventions are usually employed for combating oxidative stress-related disorders, including apoptosis. Here, we investigated the hepatoprotective effect of oligosaccharides, produced through Pichia pastoris-mediated fermentation of water-soluble polysaccharides isolated from Lepidium sativum (cress) seed mucilage, on chromium(VI)-induced oxidative stress and apoptosis in mice. Gel permeation chromatography (GPC), using Bio-Gel P-10 column, of the oligosaccharides product of fermentation revealed that P. pastoris effectively fermented polysaccharides as no long chain polysaccharides were observed. At 200 µg/mL, fractions DF73, DF53, DF72, and DF62 exhibited DPPH radical scavenging activity of 92.22 ± 2.69%, 90.35 ± 0.43%, 88.83 ± 3.36%, and 88.83 ± 3.36%, respectively. The antioxidant potential of the fermentation product was further confirmed through in vitro H₂O₂ radical scavenging assay. Among the screened samples, the highest H₂O₂ radical scavenging activity was displayed by DF73, which stabilized the free radicals by 88.83 ± 0.38%, followed by DF53 (86.48 ± 0.83%), DF62 (85.21 ± 6.66%), DF72 (79.9 4± 1.21%), and EPP (77.76 ± 0.53%). The oligosaccharide treatment significantly alleviated chromium-induced liver damage, as evident from the increase in weight gain, improved liver functions, and reduced histopathological alterations in the albino mice. A distinctly increased level of lipid peroxide (LPO) free radicals along with the endogenous hepatic enzymes were evident in chromium induced hepatotoxicity in mice. However, oligosaccharides treatment mitigated these effects by reducing the LPO production and increasing ALT, ALP, and AST levels, probably due to relieving the oxidative stress. DNA fragmentation assays illustrated that Cr(VI) exposure induced massive apoptosis in liver by damaging the DNA which was then remediated by oligosaccharides supplementation. Histopathological observations confirmed that the oligosaccharide treatment reverses the architectural changes in liver induced by chromium. These results suggest that oligosaccharides obtained from cress seed mucilage polysaccharides through P. pastoris fermentation ameliorate the oxidative stress and apoptosis and act as hepatoprotective agent against chromium-induced liver injury. Full article

(This article belongs to the Section Medicinal Chemistry)

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Growth phases of P. pastoris using cress seed mucilage polysaccharides as carbon source, where Y-axis shows P. pastoris count in logCFU/mL, X-axis shows time, and Z-axis shows temprature of the fermentation media. Full article ">Figure 2
Total carbohydrate contents quantified in different oligosaccharide fractions were obtained through microbial bioprocessing of cress seed mucilage polysaccharides. Full article ">Figure 3
Biochemical composition of different oligosaccharide fractions obtained through microbial bioprocessing of cress seed mucilage polysaccharides. Full article ">Figure 4
FT-IR spectroscopic analysis of Df53, DF62, DF72 and DF73 fractions. Full article ">Figure 5
Percent radical scavenging of the DPPH free radical at different concentrations, where EPP; ethanol precipitated polysaccharides, DF53–DF73; oligosaccharides fractions and AA: ascorbic acid as reference compound. Means denoted by different letters (a, b, c…) are significant from each other at p value of 0.05. Full article ">Figure 6
Percent radical scavenging of the H2O2 free radical at different concentrations, where EPP; ethanol precipitated polysaccharides, DF53–DF73; oligosaccharide fractions and Gallic acid: reference compound. Means denoted by different letters (a, b, c…) are significant from each other at p value of 0.05. Full article ">Figure 7
Initial and final body weight along with absolute and relative liver weight of the mice exposed to 100 mg/kg of Cr(IV) and co-treated with 200 mg/kg of oligosaccharides fractions. Means denoted by different letters (a, b, c…) are significant from each other at p value of 0.05. Full article ">Figure 8
Effect of oligosaccharides on liver ALT, MDA, ALP and AST level of chromium exposed mice. Where (A) is ALT level in U/L, (B) is MDA level in µM, (C) is ALP level in units/100 mL and (D) is AST level in U/L. Means denoted by different letters (a, b, c…) are significant from each other at P value of 0.05. Full article ">Figure 9
Oligosaccharides protect the DNA damage in mice liver induced by Cr (VI) exposure, where M; DNA marker (1 Kb), C: Normal mice, Cr: mice received 100 mg/kg of Cr (VI) alone, 1–4: mice received 100 mg/kg of Cr (VI) along with 200 mg/kg of DF53-73 oligosaccharides and 5; mice received Cr (VI) along with ascorbic acid. Full article ">Figure 10
Histology of the mice liver stained with H&E stain, where (A); received 100 mg/kg of Cr(VI) only, (B,C); normal control, (D); received 100 mg/kg of Cr(VI) + 200 mg/kg of DF53, (E); received 100 mg/kg of Cr(VI) + 200 mg/kg of DF62, (F); received 100 mg/kg of Cr(VI) + 200 mg/kg of DF72, (G); received 100 mg/kg of Cr(VI) + 200 mg/kg of DF73 and (H); received 100 mg/kg of Cr(VI) + 100 mg/kg of ascorbic acid. Full article ">

23 pages, 1610 KiB

Open AccessProject Report

Introducing the NUATEI Consortium: A Mexican Research Program for the Identification of Natural and Synthetic Antimicrobial Compounds for Prevalent Infectious Diseases

by Julio César Carrero, Bertha Espinoza, Leonor Huerta, Mayra Silva-Miranda, Silvia-Laura Guzmán-Gutierrez, Alejandro Dorazco-González, Ricardo Reyes-Chilpa, Clara Espitia and Sergio Sánchez

Pharmaceuticals 2024, 17(7), 957; https://doi.org/10.3390/ph17070957 - 18 Jul 2024

Viewed by 697

Abstract

The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search [...] Read more.

The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases. Full article

(This article belongs to the Special Issue Recent Advancements in the Development of Antiprotozoal Agents)

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18 pages, 2438 KiB

Open AccessArticle

Novel Coumarin–Nucleobase Hybrids with Potential Anticancer Activity: Synthesis, In Vitro Cell-Based Evaluation, and Molecular Docking

by Maiara Correa de Moraes, Rafaele Frassini, Mariana Roesch-Ely, Favero Reisdorfer de Paula and Thiago Barcellos

Pharmaceuticals 2024, 17(7), 956; https://doi.org/10.3390/ph17070956 - 17 Jul 2024

Viewed by 451

Abstract

A new series of compounds planned by molecular hybridization of the nucleobases uracil and thymine, or the xanthine theobromine, with coumarins, and linked through 1,2,3-triazole heterocycles were evaluated for their in vitro anticancer activity against the human tumor cell lines: colon carcinoma (HCT116), [...] Read more.

A new series of compounds planned by molecular hybridization of the nucleobases uracil and thymine, or the xanthine theobromine, with coumarins, and linked through 1,2,3-triazole heterocycles were evaluated for their in vitro anticancer activity against the human tumor cell lines: colon carcinoma (HCT116), laryngeal tumor cells (Hep-2), and lung carcinoma cells (A549). The hybrid compound 9a exhibited better activity in the series, showing an IC50 of 24.19 ± 1.39 μM against the HCT116 cells, with a selectivity index (SI) of 6, when compared to the cytotoxicity against the non-tumor cell line HaCat. The in silico search for pharmacological targets was achieved through molecular docking studies on all active compounds, which suggested that the synthesized compounds possess a high affinity to the Topoisomerase 1–DNA complex, supporting their antitumor activity. The in silico toxicity prediction studies suggest that the compounds present a low risk of causing theoretical mutagenic and tumorigenic effects. These findings indicate that molecular hybridization from natural derivative molecules is an interesting approach to seek new antitumor candidates. Full article

(This article belongs to the Special Issue Natural Coumarins as Lead Compounds and Their Synthetic Analogues with Biological Activities)

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Representative examples of biologically active coumarin (A) and uracil-containing compounds (B) hybridized through the 1,2,3-triazole heterocycle. Full article ">Figure 2
Synthesis of 4-(azidomethyl)coumarins 4a and 4b. Full article ">Figure 3
Synthetic methodologies employed to prepare the N1-propargylated uracil 6a, the N1-propargylated thymine 6b, the N1,N2-dipropargylated uracil 6c, and the propargylated theobromine 6d. Full article ">Figure 4
A Cu(I)-catalyzed [3+2]-cycloaddition reaction between the 4-(azidomethyl)coumarins 4a,b, and the N1-propargylated uracil 6a, N1-propargylated thymine 6b (Scheme A), N1,N2-dipropargylated uracil 6c (Scheme B), and the propargylated theobromine 6d (Scheme C), leading to the corresponding target hybrid molecules. Full article ">Figure 5
Predicted binding of most active in vitro compounds 9a,b and 10a,b poses (A) and 9a pose (B) in active site of Topo 1-DNA complex (PDB code: 1K4S). Graphic visualization obtained using UCSF Chimera (v.1.10.1) [<a href="#B51-pharmaceuticals-17-00956" class="html-bibr">51</a>]. Full article ">

14 pages, 681 KiB

Open AccessArticle

Coffee with Cordyceps militaris and Hericium erinaceus Fruiting Bodies as a Source of Essential Bioactive Substances

by Katarzyna Kała, Małgorzata Cicha-Jeleń, Kamil Hnatyk, Agata Krakowska, Katarzyna Sułkowska-Ziaja, Agnieszka Szewczyk, Jan Lazur and Bożena Muszyńska

Pharmaceuticals 2024, 17(7), 955; https://doi.org/10.3390/ph17070955 - 17 Jul 2024

Viewed by 846

Abstract

Drinking coffee is a daily routine for many people. Supplement manufacturers have proposed adding powdered Cordyceps militaris, known for its ergogenic and immunostimulating properties, and Hericium erinaceus, known for its nerve growth factor (NGF)-stimulating properties, to coffee. The aim of this [...] Read more.

Drinking coffee is a daily routine for many people. Supplement manufacturers have proposed adding powdered Cordyceps militaris, known for its ergogenic and immunostimulating properties, and Hericium erinaceus, known for its nerve growth factor (NGF)-stimulating properties, to coffee. The aim of this work was to compare the bioactive substances in three types of coffee: machine-brewed, instant, and traditionally brewed, prepared with the addition of H. erinaceus and C. militaris fruiting bodies. The analysis of bioactive substances was performed using AAS and RP-HPLC methods. Among the control samples of coffee, traditionally brewed coffee was the best source of bioelements. Considering the mushroom species tested, the best additional source of Mg, Zn, Cu, Na, K, and Ca was C. militaris. A slightly higher Fe content was determined for H. erinaceus. With the addition of C. militaris, the amounts of 4-feruloylquinic acid (18.6 mg/200 mL) and 3,5-di-caffeoylquinic acid (3.76 mg/200 mL) also increased. In conclusion, the C. militaris species has been proven to be a better source of bioactive substances as a coffee additive in the daily diet. The combination of brewed coffee and the tested mushrooms seems to be the most beneficial in terms of health-promoting effects. Full article

(This article belongs to the Special Issue Natural Products Derived from Fungi and Their Biological Activities)

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1 pages, 144 KiB

Open AccessCorrection

Correction: Singh et al. Nanotechnology-Aided Advancement in Combating the Cancer Metastasis. Pharmaceuticals 2023, 16, 899

by Arun Kumar Singh, Rishabha Malviya, Bhupendra Prajapati, Sudarshan Singh, Deepika Yadav and Arvind Kumar

Pharmaceuticals 2024, 17(7), 954; https://doi.org/10.3390/ph17070954 - 17 Jul 2024

Viewed by 325

Abstract

In the original publication [...] Full article

32 pages, 1631 KiB

Open AccessReview

Dilemmas in Elderly Diabetes and Clinical Practice Involving Traditional Chinese Medicine

by Chongxiang Xue, Ying Chen, Yuntian Bi, Xiaofei Yang, Keyu Chen, Cheng Tang, Xiaolin Tong, Linhua Zhao and Han Wang

Pharmaceuticals 2024, 17(7), 953; https://doi.org/10.3390/ph17070953 - 16 Jul 2024

Viewed by 662

Abstract

Diabetes is a widespread chronic disease that occurs mainly in the elderly population. Due to the difference in pathophysiology between elderly and young patients, the current clinical practice to treat elderly patients with anti-diabetes medications still faces some challenges and dilemmas, such as [...] Read more.

Diabetes is a widespread chronic disease that occurs mainly in the elderly population. Due to the difference in pathophysiology between elderly and young patients, the current clinical practice to treat elderly patients with anti-diabetes medications still faces some challenges and dilemmas, such as the urgent need for early diagnosis and prevention, and an imbalance between restricted dietary intake and the risk of undernutrition. Traditional Chinese medicine (TCM) offers various treatment regimens that are actively utilized in the field of diabetes management. Through multiple targets and multiple pathways, TCM formulas, medicinal herbs, and active natural products enhance the efficacy of diabetes prevention and diabetes control measures, simplify complex medication management, and improve common symptoms and common diabetic complications in elderly people. Historically, natural products have played a key role in material composition analysis of TCM and mechanism interpretation to enable drug discovery. However, there have been few conclusions on this topic. This review summarizes the development of TCM for the prevention and management of diabetes in elderly people, existing evidence-based clinical practices, and prospects for future development. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products and Their Clinical Research)

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21 pages, 5275 KiB

Open AccessArticle

Computational Design of Novel Tau-Tubulin Kinase 1 Inhibitors for Neurodegenerative Diseases

by Shahzaib Ahamad, Iqbal Taliy Junaid and Dinesh Gupta

Pharmaceuticals 2024, 17(7), 952; https://doi.org/10.3390/ph17070952 - 16 Jul 2024

Viewed by 603

Abstract

The tau-tubulin kinase 1 (TTBK1) protein is a casein kinase 1 superfamily member located at chromosome 6p21.1. It is expressed explicitly in the brain, particularly in the cytoplasm of cortical and hippocampal neurons. TTBK1 has been implicated in the phosphorylation and aggregation of [...] Read more.

The tau-tubulin kinase 1 (TTBK1) protein is a casein kinase 1 superfamily member located at chromosome 6p21.1. It is expressed explicitly in the brain, particularly in the cytoplasm of cortical and hippocampal neurons. TTBK1 has been implicated in the phosphorylation and aggregation of tau in Alzheimer’s disease (AD). Considering its significance in AD, TTBK1 has emerged as a promising target for AD treatment. In the present study, we identified novel TTBK1 inhibitors using various computational techniques. We performed a virtual screening-based docking study followed by E-pharmacophore modeling, cavity-based pharmacophore, and ligand design techniques and found ZINC000095101333, LD7, LD55, and LD75 to be potential novel TTBK1 lead inhibitors. The docking results were complemented by Molecular Mechanics/Generalized Born Surface Area (MMGBSA) calculations. The molecular dynamics (MD) simulation studies at a 500 ns scale were carried out to monitor the behavior of the protein toward the identified ligands. Pharmacological and ADME/T studies were carried out to check the drug-likeness of the compounds. In summary, we identified a new series of compounds that could effectively bind the TTBK1 receptor. The newly designed compounds are promising candidates for developing therapeutics targeting TTBK1 for AD. Full article

(This article belongs to the Special Issue Structural and Other Proteomics Approaches in Drug Discovery)

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13 pages, 4416 KiB

Open AccessArticle

Cancer Cell Secreted Legumain Promotes Gastric Cancer Resistance to Anti-PD-1 Immunotherapy by Enhancing Macrophage M2 Polarization

by Xu Pei, Shi-Long Zhang, Bai-Quan Qiu, Peng-Fei Zhang, Tian-Shu Liu and Yan Wang

Pharmaceuticals 2024, 17(7), 951; https://doi.org/10.3390/ph17070951 - 16 Jul 2024

Viewed by 525

Abstract

The interaction between cancer cells and immune cells plays critical roles in gastric cancer (GC) progression and immune evasion. Forced legumain (LGMN) is one of the characteristics correlated with poor prognosis in gastric cancer patients. However, the role of gastric-cancer-secreted LGMN (sLGMN) in [...] Read more.

The interaction between cancer cells and immune cells plays critical roles in gastric cancer (GC) progression and immune evasion. Forced legumain (LGMN) is one of the characteristics correlated with poor prognosis in gastric cancer patients. However, the role of gastric-cancer-secreted LGMN (sLGMN) in modulating the tumor immune microenvironment and the biological effect on the immune evasion of gastric cancer remains unclear. In this study, we found that forced expression of sLGMN in gastric cancer serum correlates with increased M2 macrophage infiltration in GC tissues and predicted resistance to anti-PD-1 immunotherapy. Mechanistically, gastric cancer cells secrete LGMN via binding to cell surface Integrin αvβ3, then activate Integrin αvβ3/PI3K (Phosphatidylinositol-4,5-bisphosphate3-kinase)/AKT (serine/threonine kinase)/mTORC2 (mammalian target of rapamycin complex 2) signaling, promote metabolic reprogramming, and polarize macrophages from the M1 to the M2 phenotype. Either blocking LGMN, Integrin αv, or knocking out Integrin αv expression and abolishing the LGMN/Integrin αvβ3 interaction significantly inhibits metabolic reprogramming and polarizes macrophages from the M1 to the M2 phenotype. This study reveals a critical molecular crosstalk between gastric cancer cells and macrophages through the sLGMN/Integrinαvβ3/PI3K/AKT/mTORC2 axis in promoting gastric cancer immune evasion and resistance to anti-PD-1 immunotherapy, indicating that the sLGMN/Integrinαvβ3/PI3K/AKT/mTORC2 axis may act as a promising therapeutic target. Full article

(This article belongs to the Special Issue Small Molecules in Cancer Immunotherapy)

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Relationship between LGMN expression levels and M2 macrophage infiltration in gastric cancer. (A) Analysis of TCGA database suggests a correlation between LGMN expression levels in gastric cancer and M2 macrophage polarization. (B) Differential serum LGMN expression in patients sensitive and resistant to anti-PD-1 therapy. (C,D) Immunohistochemical detection of M1 or M2 macrophage infiltration in gastric cancer tissues, and their correlation with serum LGMN expression levels in gastric cancer patients (bar 100 μm). * p < 0.05; ** p < 0.01. Full article ">Figure 2
LGMN induces polarization of macrophages from M1 to M2 phenotype. (A) Co-culture of THP-1-derived M1 macrophages with ASG-L and BGC823-L cells followed by flow cytometry to detect expression of M2 macrophage markers CD163 and CD206, and the polarization of M1 macrophages towards M2 macrophages can be blocked by LGMN-neutralizing antibodies. (B) Incubation of THP-1-derived M1 macrophages with rh-LGMN protein for 5 days followed by flow cytometry to detect expression of M2 macrophage markers CD163 and CD206. (C) Stimulation of healthy human PBMCs with IFN-γ followed by flow cytometry to detect expression of CD80 and CD86. (D) Induction of M1 macrophages from PBMCs by culture with rh-LGMN, followed by flow cytometry to detect expression of CD206 and CD163. Full article ">Figure 3
LGMN induces polarization of macrophages from M1 to M2 phenotype by forming a complex with Integrin αvβ3. (A) Western blot analysis of the effect of rh-LGMN, rh-LGMN + Integrin αv antibody, and rh-LGMN + Integrin β3 antibody on mTORC2 activity in M1 macrophages. (B) Flow cytometry analysis of the effect of rh-LGMN, rh-LGMN + Integrin αv antibody, and rh-LGMN + Integrin β3 antibody on the polarization of macrophages from M1 to M2 phenotype. (C) Establishment of M1 macrophage cells derived from THP-1 cells with knockdown of Integrin β3 using lentivirus. (D) Flow cytometry analysis of the effect of knocking down Integrin β3 expression on LGMN-mediated polarize macrophages from M1 to M2 phenotype. (E) Stimulation of M1 macrophages derived from PBMCs with rh-LGMN protein for 48 h followed by Western blot analysis to detect changes in mTORC2 signaling pathway activity. (F) Stimulation of M1 macrophages derived from healthy human PBMCs with rh-LGMN for 48 h followed by flow cytometry to detect changes in CD36 expression. Full article ">Figure 4
mTOR inhibitor blocks LGMN-induced polarization of macrophages from M1 to M2 phenotype. (A) Flow cytometry analysis of the effect of AZD2014 on LGMN-mediated polarization of macrophages from M1 to M2 phenotype. (B) Western blot analysis of the effect of AZD2014 on upregulation of mTORC2 signaling pathway activity by rh-LGMN in M1 macrophages. (C) Western blot analysis of the effect of rh-LGMN on mTORC1 signaling pathway activity in M1 macrophages. Full article ">Figure 5
rh-LGMN protein promotes glycolysis and fatty acid oxidation in M1 macrophages derived from healthy human PBMCs. (A) ECAR assay. (B) Fatty acid oxidation assay. (C) Oxygen consumption assay. (D) Fatty acid uptake assay. (E,F) Low-dose mTOR inhibitor AZD2014 inhibits rh-LGMN-induced glycolysis and oxidative phosphorylation in M1 macrophages. (G,H) Blocking antibodies against Integrin αv but not Integrin β3 inhibits rh-LGMN protein-induced glycolysis (G) and oxygen consumption (H) in M1 macrophages derived from healthy human PBMCs. * p < 0.05; ** p < 0.01; *** p < 0.001 ((G,H): LGMN vs. LGMN + Integrin αv). Full article ">Figure 6
sLGMN induces resistance of gastric cancer to anti-PD-1 therapy. (A) Relationship between serum LGMN levels and PFS of gastric cancer to anti-PD-1 therapy. (B) Establishment of 615 mouse gastric cancer model using MCF cells, followed by different therapies to observe the relationship between sLGMN and sensitivity of gastric cancer to PD-1 mAb. (C) Statistical analysis of tumor volume after different treatments in 615 mouse MFC cell gastric cancer model. ** p < 0.01; *** p < 0.001; NS, not significant. Full article ">

17 pages, 2901 KiB

Open AccessReview

Roles of Two-Dimensional Materials in Antibiofilm Applications: Recent Developments and Prospects

by Lei Xin, Hongkun Zhao, Min Peng and Yuanjie Zhu

Pharmaceuticals 2024, 17(7), 950; https://doi.org/10.3390/ph17070950 - 16 Jul 2024

Viewed by 497

Abstract

Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such [...] Read more.

Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such as those from the graphene family, boron nitride, molybdenum disulfide (MoS₂), MXene, and black phosphorus, hold immense potential for combating biofilms. These nanomaterial-based antimicrobial strategies are novel tools that show promise in overcoming resistant bacteria and stubborn biofilms, with the ability to circumvent existing drug resistance mechanisms. This review comprehensively summarizes recent developments in two-dimensional nanomaterials, as both therapeutics and nanocarriers for precision antibiotic delivery, with a specific focus on nanoplatforms coupled with photothermal/photodynamic therapy in the elimination of bacteria and penetrating and/or ablating biofilm. This review offers important insight into recent advances and current limitations of current antibacterial nanotherapeutic approaches, together with a discussion on future developments in the field, for the overall benefit of public health. Full article

(This article belongs to the Section Biopharmaceuticals)

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Schematic illustration for the preparation of multifunctional MoS2/ICG/Ag nanocomposites for the photothermally activated triple-mode synergistic antibacterial therapy. Copyright 2022, Elsevier. Full article ">Figure 2
Schematic illustration of the preparation and application of multiple stimuli-responsive nanozyme-based cryogel. (A) The preparation of CMCSG, MSPA and C/N/MPA; (B) Mechanism of multiple stimuli-responsive antibacterial and self-adaptive wound management. Copyright 2023, Wiley-VCH. Full article ">Figure 3
Schematic describing (a) the design and synthetic process of DNase-I@V2C and (b) the neutrophil immune function conversion (NIFC) mechanism of DNase-I@V2C in combating diabetic-related biofilm infections. IRBJIs, implant-related biofilm joint infections; BWIs, biofilm wound infections. Copyright 2023, Wiley-VCH. Full article ">Figure 4
Schematic illustration of (A) the preparation of monolayer V2N and (B) 1064 nm laser irradiation enhanced dual-enzyme-like catalytic activities of V2N for promoting the healing of S. aureus-infected abscesses in vivo. Copyright 2023, Elsevier. Full article ">Figure 5
Synthesis and targeting of Ce6@Man-BPN to macrophages and demonstration of the inactivation of intracellular bacteria by combined photothermal and photodynamic therapy. Copyright 2023, Elsevier. Full article ">Figure 6
Preparation of the hydrogels: (a) schematic illustration of OCS, APBA-G-OCS and NPs@gel-2; (b) injectable and sprayable process of NPs@gel-2; (c) schematic diagram of the hydrogel that promotes healing of infected diabetic wounds by combined chemo-photothermal antimicrobial and cytokines modulation. Copyright 2023, Elsevier. Full article ">Scheme 1
Two-dimensional nanomaterials for antibiofilm. Full article ">

38 pages, 7933 KiB

Open AccessReview

Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?

by Auriane de Pellegars-Malhortie, Laurence Picque Lasorsa, Thibault Mazard, Fabien Granier and Corinne Prévostel

Pharmaceuticals 2024, 17(7), 949; https://doi.org/10.3390/ph17070949 - 16 Jul 2024

Viewed by 952

Abstract

Despite significant progress in cancer prevention, screening, and treatment, the still limited number of therapeutic options is an obstacle towards increasing the cancer cure rate. In recent years, many efforts were put forth to develop therapeutics that selectively target different components of the [...] Read more.

Despite significant progress in cancer prevention, screening, and treatment, the still limited number of therapeutic options is an obstacle towards increasing the cancer cure rate. In recent years, many efforts were put forth to develop therapeutics that selectively target different components of the oncogenic Wnt/β-catenin signaling pathway. These include small molecule inhibitors, antibodies, and more recently, gene-based approaches. Although some of them showed promising outcomes in clinical trials, the Wnt/β-catenin pathway is still not targeted in routine clinical practice for cancer management. As for most anticancer treatments, a critical limitation to the use of Wnt/β-catenin inhibitors is their therapeutic index, i.e., the difficulty of combining effective anticancer activity with acceptable toxicity. Protecting healthy tissues from the effects of Wnt/β-catenin inhibitors is a major issue due to the vital role of the Wnt/β-catenin signaling pathway in adult tissue homeostasis and regeneration. In this review, we provide an up-to-date summary of clinical trials on Wnt/β-catenin pathway inhibitors, examine their anti-tumor activity and associated adverse events, and explore strategies under development to improve the benefit/risk profile of this therapeutic approach. Full article

(This article belongs to the Special Issue Wnt Signaling in Cancer: New Advances)

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43 pages, 3516 KiB

Open AccessSystematic Review

Ethnomedicinal Usage, Phytochemistry and Pharmacological Potential of Solanum surattense Burm. f.

by Kamrul Hasan, Shabnam Sabiha, Nurul Islam, João F. Pinto and Olga Silva

Pharmaceuticals 2024, 17(7), 948; https://doi.org/10.3390/ph17070948 - 15 Jul 2024

Viewed by 708

Abstract

Solanum surattense Burm. f. is a significant member of the Solanaceae family, and the Solanum genus is renowned for its traditional medicinal uses and bioactive potential. This systematic review adheres to PRISMA methodology, analyzing scientific publications between 1753 and 2023 from B-on, Google [...] Read more.

Solanum surattense Burm. f. is a significant member of the Solanaceae family, and the Solanum genus is renowned for its traditional medicinal uses and bioactive potential. This systematic review adheres to PRISMA methodology, analyzing scientific publications between 1753 and 2023 from B-on, Google Scholar, PubMed, Science Direct, and Web of Science, aiming to provide comprehensive and updated information on the distribution, ethnomedicinal uses, chemical constituents, and pharmacological activities of S. surattense, highlighting its potential as a source of herbal drugs. Ethnomedicinally, this species is important to treat skin diseases, piles complications, and toothache. The fruit was found to be the most used part of this plant (25%), together with the whole plant (22%) used to treat different ailments, and its decoction was found to be the most preferable mode of herbal drug preparation. A total of 338 metabolites of various chemical classes were isolated from S. surattense, including 137 (40.53%) terpenoids, 56 (16.56%) phenol derivatives, and 52 (15.38%) lipids. Mixtures of different parts of this plant in water–ethanol have shown in vitro and/or in vivo antioxidant, anti-inflammatory, antimicrobial, anti-tumoral, hepatoprotective, and larvicidal activities. Among the metabolites, 51 were identified and biologically tested, presenting antioxidant, anti-inflammatory, and antitumoral as the most reported activities. Clinical trials in humans made with the whole plant extract showed its efficacy as an anti-asthmatic agent. Mostly steroidal alkaloids and triterpenoids, such as solamargine, solanidine, solasodine, solasonine, tomatidine, xanthosaponin A–B, dioscin, lupeol, and stigmasterol are biologically the most active metabolites with high potency that reflects the new and high potential of this species as a novel source of herbal medicines. More experimental studies and a deeper understanding of this plant must be conducted to ensure its use as a source of raw materials for pharmaceutical use. Full article

(This article belongs to the Special Issue Feature Reviews in Natural Products)

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1 pages, 144 KiB

Open AccessCorrection

Correction: Heruye et al. Current Trends in the Pharmacotherapy of Cataracts. Pharmaceuticals 2020, 13, 15

by Segewkal H. Heruye, Leonce N. Maffofou Nkenyi, Neetu U. Singh, Dariush Yalzadeh, Kalu K. Ngele, Ya-Fatou Njie-Mbye, Sunny E. Ohia and Catherine A. Opere

Pharmaceuticals 2024, 17(7), 947; https://doi.org/10.3390/ph17070947 - 15 Jul 2024

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Abstract

In the original publication [...] Full article

23 pages, 2166 KiB

Open AccessArticle

Unraveling the Bioactive Potential of Camellia japonica Edible Flowers: Profiling Antioxidant Substances and In Vitro Bioactivity Assessment

by Antia G. Pereira, Maria Fraga-Corral, Aurora Silva, Maria Fatima Barroso, Clara Grosso, Maria Carpena, Pascual Garcia-Perez, Rosa Perez-Gregorio, Lucia Cassani, Jesus Simal-Gandara and Miguel A. Prieto

Pharmaceuticals 2024, 17(7), 946; https://doi.org/10.3390/ph17070946 - 15 Jul 2024

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Abstract

In recent years, the search for novel natural-based ingredients by food and related industries has sparked extensive research aimed at discovering new sources of functional molecules. Camellia japonica, traditionally known as an ornamental plant, has gained attention due to its diverse array [...] Read more.

In recent years, the search for novel natural-based ingredients by food and related industries has sparked extensive research aimed at discovering new sources of functional molecules. Camellia japonica, traditionally known as an ornamental plant, has gained attention due to its diverse array of bioactive compounds with potential industrial applications. Although C. japonica flowers are edible, their phytochemical profile has not been thoroughly investigated. In this study, a phenolic profile screening through an HPLC–ESI-QQQ-MS/MS approach was applied to C. japonica flower extracts, revealing a total of 36 compounds, including anthocyanins, curcuminoids, dihydrochalcones, dihydroflavonols, flavonols, flavones, hydroxybenzoic acids, hydroxycinnamic acids, isoflavonoids, stilbenes, and tyrosols. Following extract profiling, their bioactivity was assessed by means of in vitro antioxidant, antimicrobial, cytotoxic, and neuroprotective activities. The results showed a multifaceted high correlation of phenolic compounds with all the tested bioactivities according to Pearson’s correlation analysis, unraveling the potential of C. japonica flowers as promising sources of nutraceuticals. Overall, these findings provide insight into the valorization of C. japonica flowers from different unexplored cultivars thus diversifying their industrial outcome. Full article

(This article belongs to the Special Issue Advances in Mass Spectrometry Metrology in Pharmaceutical Sciences)

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Figure 1
Results of crocin assay. (A) Raw experimental signal for the Elegans Variegated cultivarcultivar, with the experimental data fitted to Equation (2) to determine IC50 values. (B) Compilation of IC50 values for all cultivars, providing a comparative view of crocin assay outcomes across the different C. japonica flower cultivars. Full article ">Figure 2
Graphs of in vitro antioxidant studies. Column 1 illustrates hydroxyl radical scavenging activity, column 2 showcases H2O2 scavenging activity, column 3 demonstrates superoxide radical scavenging activity, and column 4 displays nitric oxide scavenging activity. Symbols represent experimental data, while lines depict model values. The bar graphs in the final row present the IC50 values (mg/mL) for each assay across all the cultivars examined in this study. Full article ">Figure 3
Pearson’s correlation heatmap between the different biological activities of C. japonica L. flower extracts (antioxidant activity, by means of DPPH, ABTS, CBA, SRSA, OHSA, NOSA, H2O2 methods; cytotoxic activity towards Vero, AGS, HepG2, A549 cell lines; anti-microbial activity against E. coli, S. epidermidis, S. aureus, P. aeruginosa, S. enteritidis, and B. cereus; and neuroprotective activity). Full article ">

27 pages, 4126 KiB

Open AccessReview

Advances in Nanomedicine for Precision Insulin Delivery

by Alfredo Caturano, Roberto Nilo, Davide Nilo, Vincenzo Russo, Erica Santonastaso, Raffaele Galiero, Luca Rinaldi, Marcellino Monda, Celestino Sardu, Raffaele Marfella and Ferdinando Carlo Sasso

Pharmaceuticals 2024, 17(7), 945; https://doi.org/10.3390/ph17070945 - 15 Jul 2024

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Abstract

Diabetes mellitus, which comprises a group of metabolic disorders affecting carbohydrate metabolism, is characterized by improper glucose utilization and excessive production, leading to hyperglycemia. The global prevalence of diabetes is rising, with projections indicating it will affect 783.2 million people by 2045. Insulin [...] Read more.

Diabetes mellitus, which comprises a group of metabolic disorders affecting carbohydrate metabolism, is characterized by improper glucose utilization and excessive production, leading to hyperglycemia. The global prevalence of diabetes is rising, with projections indicating it will affect 783.2 million people by 2045. Insulin treatment is crucial, especially for type 1 diabetes, due to the lack of β-cell function. Intensive insulin therapy, involving multiple daily injections or continuous subcutaneous insulin infusion, has proven effective in reducing microvascular complications but poses a higher risk of severe hypoglycemia. Recent advancements in insulin formulations and delivery methods, such as ultra-rapid-acting analogs and inhaled insulin, offer potential benefits in terms of reducing hypoglycemia and improving glycemic control. However, the traditional subcutaneous injection method has drawbacks, including patient compliance issues and associated complications. Nanomedicine presents innovative solutions to these challenges, offering promising avenues for overcoming current drug limitations, enhancing cellular uptake, and improving pharmacokinetics and pharmacodynamics. Various nanocarriers, including liposomes, chitosan, and PLGA, provide protection against enzymatic degradation, improving drug stability and controlled release. These nanocarriers offer unique advantages, ranging from enhanced bioavailability and sustained release to specific targeting capabilities. While oral insulin delivery is being explored for better patient adherence and cost-effectiveness, other nanomedicine-based methods also show promise in improving delivery efficiency and patient outcomes. Safety concerns, including potential toxicity and immunogenicity issues, must be addressed, with the FDA providing guidance for the safe development of nanotechnology-based products. Future directions in nanomedicine will focus on creating next-generation nanocarriers with precise targeting, real-time monitoring, and stimuli-responsive features to optimize diabetes treatment outcomes and patient safety. This review delves into the current state of nanomedicine for insulin delivery, examining various types of nanocarriers and their mechanisms of action, and discussing the challenges and future directions in developing safe and effective nanomedicine-based therapies for diabetes management. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy)

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20 pages, 933 KiB

Open AccessSystematic Review

Impact of Anti-CD38 Monoclonal Antibody Therapy on CD34+ Hematopoietic Stem Cell Mobilization, Collection, and Engraftment in Multiple Myeloma Patients—A Systematic Review

by Flavia Bigi, Enrica Manzato, Simona Barbato, Marco Talarico, Michele Puppi, Simone Masci, Ilaria Sacchetti, Roberta Restuccia, Miriam Iezza, Ilaria Rizzello, Chiara Sartor, Katia Mancuso, Lucia Pantani, Paola Tacchetti, Michele Cavo and Elena Zamagni

Pharmaceuticals 2024, 17(7), 944; https://doi.org/10.3390/ph17070944 - 15 Jul 2024

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Abstract

This systematic review examines the available clinical data on CD34+ cell mobilization, collection, and engraftment in multiple myeloma patients treated with the anti-CD38 monoclonal antibodies daratumumab and isatuximab in clinical trials and in real life. Twenty-six clinical reports were published between 2019 and [...] Read more.

This systematic review examines the available clinical data on CD34+ cell mobilization, collection, and engraftment in multiple myeloma patients treated with the anti-CD38 monoclonal antibodies daratumumab and isatuximab in clinical trials and in real life. Twenty-six clinical reports were published between 2019 and February 2024. Most studies documented lower circulating CD34+ cells after mobilization compared to controls, leading to higher plerixafor requirements. Although collection yields were significantly lower in approximately half of the studies, the collection target was achieved in similar proportions of daratumumab- and isatuximab-treated and nontreated patients, and access to autologous stem cell transplant (ASCT) was comparable. This could be explained by the retained efficacy of plerixafor in anti-CD38 monoclonal antibody-treated patients, while no chemotherapy-based or sparing mobilization protocol proved superior. Half of the studies reported slower hematopoietic reconstitution after ASCT in daratumumab- and isatuximab-treated patients, without an excess of infectious complications. While no direct effect on stem cells was observed in vitro, emerging evidence suggests possible dysregulation of CD34+ cell adhesion after daratumumab treatment. Overall, anti-CD38 monoclonal antibodies appear to interfere with CD34+ cell mobilization, without consistently leading to significant clinical consequences. Further research is needed to elucidate the underlying mechanisms and define optimal mobilization strategies in this patient population. Full article

(This article belongs to the Special Issue Multidrug Therapies Containing Monoclonal Antibodies for Multiple Myeloma 2024)

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19 pages, 11576 KiB

Open AccessArticle

In Vitro Biological Evaluation of an Alginate-Based Hydrogel Loaded with Rifampicin for Wound Care

by Tudor Bibire, Radu Dănilă, Cătălina Natalia Yilmaz, Liliana Verestiuc, Isabella Nacu, Ramona Gabriela Ursu and Cristina Mihaela Ghiciuc

Pharmaceuticals 2024, 17(7), 943; https://doi.org/10.3390/ph17070943 - 14 Jul 2024

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Abstract

We report a biocompatible hydrogel dressing based on sodium alginate-grafted poly(N-vinylcaprolactam) prepared by encapsulation of Rifampicin as an antimicrobial drug and stabilizing the matrix through the repeated freeze–thawing method. The hydrogel structure and polymer-drug compatibility were confirmed by FTIR, and a series of [...] Read more.

We report a biocompatible hydrogel dressing based on sodium alginate-grafted poly(N-vinylcaprolactam) prepared by encapsulation of Rifampicin as an antimicrobial drug and stabilizing the matrix through the repeated freeze–thawing method. The hydrogel structure and polymer-drug compatibility were confirmed by FTIR, and a series of hydrogen-bond-based interactions between alginate and Rifampicin were identified. A concentration of 0.69% Rifampicin was found in the polymeric matrix using HPLC analysis and spectrophotometric UV–Vis methods. The hydrogel’s morphology was evaluated by scanning electron microscopy, and various sizes and shapes of pores, ranging from almost spherical geometries to irregular ones, with a smooth surface of the pore walls and high interconnectivity in the presence of the drug, were identified. The hydrogels are bioadhesive, and the adhesion strength increased after Rifampicin was encapsulated into the polymeric matrix, which suggests that these compositions are suitable for wound dressings. Antimicrobial activity against S. aureus and MRSA, with an increased effect in the presence of the drug, was also found in the newly prepared hydrogels. In vitro biological evaluation demonstrated the cytocompatibility of the hydrogels and their ability to stimulate cell multiplication and mutual cell communication. The in vitro scratch assay demonstrated the drug-loaded alginate-grafted poly(N-vinylcaprolactam) hydrogel’s ability to stimulate cell migration and wound closure. All of these results suggest that the prepared hydrogels can be used as antimicrobial materials for wound healing and care applications. Full article

(This article belongs to the Section Pharmaceutical Technology)

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