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Pharmaceuticals, Volume 17, Issue 6 (June 2024) – 140 articles

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12 pages, 1252 KiB  
Article
Oral Administration of Efavirenz Dysregulates the Tph2 Gene in Brain Serotonergic Areas and Alters Weight and Mood in Mice
by Sandra Angélica Rojas-Osornio, Minerva Crespo-Ramírez, Vladimir Paredes-Cervantes, Antonio Mata-Marín, Ricardo Martínez-Lara, Miguel Pérez de la Mora and Emiliano Tesoro-Cruz
Pharmaceuticals 2024, 17(6), 801; https://doi.org/10.3390/ph17060801 (registering DOI) - 18 Jun 2024
Viewed by 138
Abstract
Most HIV-antiretroviral drugs have adverse effects. Efavirenz (EFV) is an example of a drug with neuropsychiatric effects, such as anxiety, depression, and suicidal thoughts, in people living with HIV (PLWH). The mechanisms by which EFV causes neuropsychiatric alterations in PLWH are complex, multifactorial, [...] Read more.
Most HIV-antiretroviral drugs have adverse effects. Efavirenz (EFV) is an example of a drug with neuropsychiatric effects, such as anxiety, depression, and suicidal thoughts, in people living with HIV (PLWH). The mechanisms by which EFV causes neuropsychiatric alterations in PLWH are complex, multifactorial, and not fully understood, although several studies in animals have reported changes in brain energy metabolism, alterations in monoamine turnover, GABA, and glutamate levels, and changes in 5-HT receptors. In this report, we studied the effects of EFV on the serotonergic system in healthy mice, specifically, whether EFV results in alterations in the levels of the tryptophan hydroxylase 2 (Tph2) gene in the brain. EFV (10 mg/kg) and distilled water (1.5 µL/kg) (control group) were orally administered to the mice for 36 days. At the end of the treatment, Tph2 expression levels in mouse brains were measured, and mood was evaluated by three trials: the forced swim test, elevated plus maze, and open field test. Our results revealed dysregulation of Tph2 expression in the brainstem, amygdala, and hypothalamus in the EFV group, and 5-HT levels increased in the amygdala in the EFV group. In the behavioral tests, mice given EFV exhibited a passive avoidance response in the forced swim test and anxiety-like behavior in the elevated plus maze, and they lost weight. Herein, for the first time, we showed that EFV triggered dysregulation of the Tph2 gene in the three serotonergic areas studied; and 5-HT levels increased in the amygdala using the ELISA method. However, further studies will be necessary to clarify the increase of 5-HT in the amygdala as well as understand the paradoxical decrease in body weight with the simultaneous increase in food consumption. It will also be necessary to measure 5-HT by other techniques different from ELISA, such as HPLC. Full article
(This article belongs to the Special Issue Recent Advances in the Pharmacology of Serotonin and Its Receptors)
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29 pages, 4012 KiB  
Review
A Comprehensive Research Review of Herbal Textual Research, Phytochemistry, Pharmacology, Traditional Uses, Clinical Application, Safety Evaluation, and Quality Control of Trollius chinensis Bunge
by Keke Yang, Zhen Wang, Panpan Wang, Lai Wang, Yuanjie Li, Lianqing He, Xiubo Liu, Jiao Xu, Yijin Duan and Wei Ma
Pharmaceuticals 2024, 17(6), 800; https://doi.org/10.3390/ph17060800 - 18 Jun 2024
Viewed by 117
Abstract
Trollius chinensis Bunge (TCB) is a perennial plant of the Ranunculaceae family with medicinal and edible values. It is widely distributed and commonly used in various regions, including Asia, Europe, and North America. The main chemical components of TCB include alkaloids, flavonoids, phenolic [...] Read more.
Trollius chinensis Bunge (TCB) is a perennial plant of the Ranunculaceae family with medicinal and edible values. It is widely distributed and commonly used in various regions, including Asia, Europe, and North America. The main chemical components of TCB include alkaloids, flavonoids, phenolic acids, and volatile oil compounds. TCB is renowned for its anti-inflammatory, heat-clearing, detoxifying, and eyesight-improving properties. Its dried flowers are commonly used as a traditional Chinese medicine indicated for the treatment of upper respiratory tract infections, chronic tonsillitis, pharyngitis, influenza, and bronchitis. Modern pharmacology has demonstrated the anti-cancer, anti-inflammatory, antihypertensive, and antioxidant effects of TCB. This study presents a comprehensive overview of various aspects of TCB, including herbal textual research, botany, phytochemistry, pharmacology, traditional uses, clinical application, and quality control, aiming to provide new ideas on the scientific application of TCB as well as the integration of modern research with traditional medicinal uses. Full article
(This article belongs to the Section Natural Products)
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11 pages, 2563 KiB  
Article
Identification of Benzodiazepine Use Based on Dried Blood Stains Analysis
by Lucía Fernández-López, Sandra Rodríguez, Alberto Cánovas-Cabanes, Francisco-Javier Teruel-Fernández, Pilar Almela, Juan-Pedro Hernández del Rincón, Javier Navarro-Zaragoza and María Falcón
Pharmaceuticals 2024, 17(6), 799; https://doi.org/10.3390/ph17060799 - 18 Jun 2024
Viewed by 148
Abstract
Biological matrices are typically used in forensic toxicological or pharmacological analysis: mainly blood, vitreous humor or urine. However, there are many cases in which crimes are a consequence of drug intoxication or drug abuse and they are not closed because over the months [...] Read more.
Biological matrices are typically used in forensic toxicological or pharmacological analysis: mainly blood, vitreous humor or urine. However, there are many cases in which crimes are a consequence of drug intoxication or drug abuse and they are not closed because over the months or years the samples become altered or decomposed. A dried blood stains test (DBS-MS) has recently been proposed to be used in drug toxicology when blood is found at a crime scene. This test could help an investigator to reveal what a person had consumed before the perpetration of the crime. In order to check the possibilities of this test, we analyzed several dried blood stains located on a cotton fabric. Therefore, the aim of this study was to determine if the analysis of a dried blood spot located on a cotton fabric could be an alternate source of obtaining toxicological results, particularly regarding benzodiazepines. We splashed blood stains on cotton fabric with different concentrations of the following benzodiazepines: alprazolam, bromazepam, clonazepam, diazepam and lorazepam, which were dried for 96 h and subsequently quantified by high-performance liquid chromatography coupled mass spectrometry (HPLC-MS). Our results show that it is possible to identify several benzodiazepines contained in a cotton fabric blood stain; consequently, this method may add another sample option to the toxicological analysis of biological vestiges found at a crime scene. Full article
(This article belongs to the Special Issue Psychiatric Drug Treatment and Drug Addiction)
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12 pages, 4374 KiB  
Article
Assessment of Brain-Derived Neurotrophic Factor on Retinal Structure and Visual Function in Rodent Models of Optic Nerve Crush
by Takazumi Taniguchi, Najam A. Sharif, Takashi Ota, Rafal A. Farjo and Rebecca Rausch
Pharmaceuticals 2024, 17(6), 798; https://doi.org/10.3390/ph17060798 - 18 Jun 2024
Viewed by 131
Abstract
The effects of brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival and visual function were assessed in rat and mouse models of optic nerve (ON) crush. ONs were crushed on Day 1, followed by intravitreal injections of a vehicle or BDNF [...] Read more.
The effects of brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival and visual function were assessed in rat and mouse models of optic nerve (ON) crush. ONs were crushed on Day 1, followed by intravitreal injections of a vehicle or BDNF on Days 1 and 8. The spatial frequency threshold was measured using optokinetic tracking on Days 7 and 14. On Day 15, ganglion cell complex (GCC) thickness was quantified using optical coherence tomography. Furthermore, all eyes were enucleated for immunohistochemical analysis of the surviving RGC somas and axons. BDNF significantly reduced the RGC soma in mice and increased GCC thickness in intact eyes, with apparent axonal swelling in both species. It displayed significantly greater RGC soma survival in eyes with ON injury, with moderately thicker axonal bundles in both species and a thicker GCC in rats. Visual function was significantly reduced in all ON-crushed animals, regardless of BDNF treatment. Thus, we obtained a comprehensive analysis of the structural and functional impact of BDNF in intact and ON-crushed eyes in two rodent models. Our results provide a foundation for further BDNF evaluation and the design of preclinical studies on neuroprotectants using BDNF as a reference positive control. Full article
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22 pages, 722 KiB  
Systematic Review
(3D) Bioprinting—Next Dimension of the Pharmaceutical Sector
by Anna Mihaylova, Dobromira Shopova, Nikoleta Parahuleva, Antoniya Yaneva and Desislava Bakova
Pharmaceuticals 2024, 17(6), 797; https://doi.org/10.3390/ph17060797 - 17 Jun 2024
Viewed by 178
Abstract
To create a review of the published scientific literature on the benefits and potential perspectives of the use of 3D bio-nitrification in the field of pharmaceutics. This work was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [...] Read more.
To create a review of the published scientific literature on the benefits and potential perspectives of the use of 3D bio-nitrification in the field of pharmaceutics. This work was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting meta-analyses and systematic reviews. The scientific databases PubMed, Scopus, Google Scholar, and ScienceDirect were used to search and extract data using the following keywords: 3D bioprinting, drug research and development, personalized medicine, pharmaceutical companies, clinical trials, drug testing. The data points to several aspects of the application of bioprinting in pharmaceutics were reviewed. The main applications of bioprinting are in the development of new drug molecules as well as in the preparation of personalized drugs, but the greatest benefits are in terms of drug screening and testing. Growth in the field of 3D printing has facilitated pharmaceutical applications, enabling the development of personalized drug screening and drug delivery systems for individual patients. Bioprinting presents the opportunity to print drugs on demand according to the individual needs of the patient, making the shape, structure, and dosage suitable for each of the patient’s physical conditions, i.e., print specific drugs for controlled release rates; print porous tablets to reduce swallowing difficulties; make transdermal microneedle patches to reduce patient pain; and so on. On the other hand, bioprinting can precisely control the distribution of cells and biomaterials to build organoids, or an Organ-on-a-Chip, for the testing of drugs on printed organs mimicking specified disease characteristics instead of animal testing and clinical trials. The development of bioprinting has the potential to offer customized drug screening platforms and drug delivery systems meeting a range of individualized needs, as well as prospects at different stages of drug development and patient therapy. The role of bioprinting in preclinical and clinical testing of drugs is also of significant importance in terms of shortening the time to launch a medicinal product on the market. Full article
(This article belongs to the Section Pharmaceutical Technology)
21 pages, 2142 KiB  
Article
Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity
by Cristiana Soares-Cardoso, Sandra Leal, Susana I. Sá, Rita Dantas-Barros, Ricardo Jorge Dinis-Oliveira, Juliana Faria and Joana Barbosa
Pharmaceuticals 2024, 17(6), 796; https://doi.org/10.3390/ph17060796 - 17 Jun 2024
Viewed by 229
Abstract
Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. [...] Read more.
Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. The hippocampal formation is known to participate in memory and learning processes and has been documented to contribute to opioid dependence. Accordingly, the present study assessed molecular and cellular alterations in the hippocampal formation of Wistar rats intraperitoneally administered with 50 mg/kg tramadol or tapentadol for eight alternate days. Alterations were found in serum hydrogen peroxide, cysteine, homocysteine, and dopamine concentrations upon exposure to one or both opioids, as well as in hippocampal 8-hydroxydeoxyguanosine and gene expression levels of a panel of neurotoxicity, neuroinflammation, and neuromodulation biomarkers, assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of hippocampal formation sections showed increased glial fibrillary acidic protein (GFAP) and decreased cluster of differentiation 11b (CD11b) protein expression, suggesting opioid-induced astrogliosis and microgliosis. Collectively, the results emphasize the hippocampal neuromodulator effects of tramadol and tapentadol, with potential behavioral implications, underlining the need to prescribe and use both opioids cautiously. Full article
(This article belongs to the Special Issue Pharmacology and Toxicology of Opioids)
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22 pages, 537 KiB  
Systematic Review
Machine Learning Techniques for Predicting Drug-Related Side Effects: A Scoping Review
by Esmaeel Toni, Haleh Ayatollahi, Reza Abbaszadeh and Alireza Fotuhi Siahpirani
Pharmaceuticals 2024, 17(6), 795; https://doi.org/10.3390/ph17060795 - 17 Jun 2024
Viewed by 232
Abstract
Background: Drug safety relies on advanced methods for timely and accurate prediction of side effects. To tackle this requirement, this scoping review examines machine-learning approaches for predicting drug-related side effects with a particular focus on chemical, biological, and phenotypical features. Methods: This was [...] Read more.
Background: Drug safety relies on advanced methods for timely and accurate prediction of side effects. To tackle this requirement, this scoping review examines machine-learning approaches for predicting drug-related side effects with a particular focus on chemical, biological, and phenotypical features. Methods: This was a scoping review in which a comprehensive search was conducted in various databases from 1 January 2013 to 31 December 2023. Results: The results showed the widespread use of Random Forest, k-nearest neighbor, and support vector machine algorithms. Ensemble methods, particularly random forest, emphasized the significance of integrating chemical and biological features in predicting drug-related side effects. Conclusions: This review article emphasized the significance of considering a variety of features, datasets, and machine learning algorithms for predicting drug-related side effects. Ensemble methods and Random Forest showed the best performance and combining chemical and biological features improved prediction. The results suggested that machine learning techniques have some potential to improve drug development and trials. Future work should focus on specific feature types, selection techniques, and graph-based methods for even better prediction. Full article
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18 pages, 3308 KiB  
Article
Chlorogenic Acid as a Potential Therapeutic Agent for Cholangiocarcinoma
by Jiabao Liang, Tong Wen, Xiaojian Zhang and Xiaoling Luo
Pharmaceuticals 2024, 17(6), 794; https://doi.org/10.3390/ph17060794 - 17 Jun 2024
Viewed by 149
Abstract
Chlorogenic acid (CGA) has demonstrated anti-tumor effects across various cancers, but its role in cholangiocarcinoma (CCA) remains unclear. Our study revealed CGA’s potent anti-tumor effects on CCA, significantly suppressing cell proliferation, migration, colony formation, and invasion while inhibiting the epithelial–mesenchymal transition. CGA induced [...] Read more.
Chlorogenic acid (CGA) has demonstrated anti-tumor effects across various cancers, but its role in cholangiocarcinoma (CCA) remains unclear. Our study revealed CGA’s potent anti-tumor effects on CCA, significantly suppressing cell proliferation, migration, colony formation, and invasion while inhibiting the epithelial–mesenchymal transition. CGA induced apoptosis, modulated cell cycle progression, and exhibited a stable binding affinity to AKR1B10 in CCA. AKR1B10 was highly expressed in RBE cells, and CGA treatment reduced AKR1B10 expression. Knocking out AKR1B10 inhibited the proliferation of RBE cells, whereas the overexpression of AKR1B10 promoted their proliferation. Additionally, CGA suppressed the proliferation of RBE cells with AKR1B10 overexpression. Mechanistically, AKR1B10 activated AKT, and CGA exerted its inhibitory effect by reducing AKR1B10 levels, thereby suppressing AKT activation. Furthermore, CGA facilitated the polarization of tumor-associated macrophages towards an anti-tumor phenotype and enhanced T-cell cytotoxicity. These findings underscore CGA’s potential as a promising therapeutic agent for CCA treatment. Full article
(This article belongs to the Section Natural Products)
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21 pages, 4713 KiB  
Article
Approved and Commercialized Antidiabetic Medicines (Excluding Insulin) in Seven European Countries—A Cross-Sectional Comparison
by Ana-Maria Atănăsoie, Robert Viorel Ancuceanu, Dušanka Krajnović, Magdalena Waszyk-Nowaczyk, Marcin Skotnicki, Dorota Tondowska, Guenka Petrova, Andrei Marian Niculae and Adriana-Elena Tăerel
Pharmaceuticals 2024, 17(6), 793; https://doi.org/10.3390/ph17060793 - 17 Jun 2024
Viewed by 257
Abstract
Diabetes mellitus is a complex, multifactorial, progressive condition with a variety of approved therapeutic options. The purpose of this study was to offer an overview of the authorized antidiabetic medicines (excluding insulin) compared with marketed products in seven European countries. Data were obtained [...] Read more.
Diabetes mellitus is a complex, multifactorial, progressive condition with a variety of approved therapeutic options. The purpose of this study was to offer an overview of the authorized antidiabetic medicines (excluding insulin) compared with marketed products in seven European countries. Data were obtained from primary sources, including the websites of national authorities and directly from specialists in the countries of interest. The range of marketed medicines compared with the authorized group was assessed in terms of active pharmaceutical ingredients (>60% in Bulgaria, France, Serbia), brand names (>70% in Bulgaria, the Czech Republic, Romania, Serbia, Spain), pharmaceutical forms (>60% in all countries), strengths (>60% in Bulgaria, the Czech Republic, Romania, Serbia, Spain), marketing authorization holder (≥50% in all countries) and the status of medicine. Spain was found to have the highest number of products based on most of these attributes. Over 90% of authorized medicines had a pharmacy price in Serbia. Regarding the newer class of GLP-1 receptor agonists, a retail price for all approved substances was available in Bulgaria, Romania, Serbia, and Spain. Only one brand name with one concentration was found available for some agents, being susceptible to drug shortages: glibenclamide (Romania, Serbia, Spain), glipizide (the Czech Republic, Poland, Romania, Spain), glisentide (Spain), acarbose (the Czech Republic), sitagliptin (Bulgaria, Poland), vildagliptin (the Czech Republic, Poland) and saxagliptin (the Czech Republic, France, Romania, Serbia). An overview of the national and international therapeutic options may allow competent authorities and health professionals to take rapid measures in case of supply problems or health crises. Full article
(This article belongs to the Section Pharmacology)
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13 pages, 1874 KiB  
Article
Effects of the DL76 Antagonist/Inverse Agonist of Histamine H3 Receptors on Experimental Periodontitis in Rats: Morphological Studies
by Mariusz Geremek, Bogna Drozdzowska, Dorota Łażewska, Katarzyna Kieć-Kononowicz and Jerzy Jochem
Pharmaceuticals 2024, 17(6), 792; https://doi.org/10.3390/ph17060792 - 17 Jun 2024
Viewed by 266
Abstract
Background: Periodontitis preceded by gingivitis is the most common form of periodontal disease and occurs due to the interaction of microorganisms present in the complex bacterial aggregates of dental plaque biofilm and their metabolism products with periodontal tissues. Histamine is a heterocyclic biogenic [...] Read more.
Background: Periodontitis preceded by gingivitis is the most common form of periodontal disease and occurs due to the interaction of microorganisms present in the complex bacterial aggregates of dental plaque biofilm and their metabolism products with periodontal tissues. Histamine is a heterocyclic biogenic amine acting via four types of receptors. Histamine H3 receptors act as presynaptic auto/heteroreceptors to regulate the release of histamine and other neurotransmitters. Aim: Since the nervous system is able to regulate the progression of the inflammatory process and bone metabolism, the aim of this study was to investigate the effects of DL76, which acts as an antagonist/inverse agonist of H3 receptors, on the course of experimental periodontitis. Materials and methods: This study was conducted in 24 mature male Wistar rats weighing 245–360 g, aged 6–8 weeks. A silk ligature was placed on the second maxillary molar of the right maxilla under general anesthesia. From the day of ligating, DL76 and 0.9% NaCl solutions were administered subcutaneously for 28 days in the experimental and control groups, respectively. After the experiment, histopathological, immunohistochemical and radiological examinations were performed. Results: Ligation led to the development of the inflammatory process with lymphocytic infiltration, increased epithelial RANKL and OPG expression as well as bone resorption. DL76 evoked a reduction in (1) lymphocytic infiltration, (2) RANKL and OPG expression as well as (3) bone resorption since the medians of the mesial and distal interdental spaces in the molars with induced periodontitis were 3.56-fold and 10-fold lower compared to the corresponding values in saline-treated animals with periodontitis. Conclusion: DL76 is able to inhibit the progression of experimental periodontitis in rats, as demonstrated by a reduction in the inflammatory cell infiltration, a decrease in the RANKL/RANK OPG pathway expression and a reduction in the alveolar bone resorption. Full article
(This article belongs to the Special Issue Histamine Receptor Ligands in Medicinal Chemistry)
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32 pages, 5347 KiB  
Review
Swellable Microneedles in Drug Delivery and Diagnostics
by Hossein Omidian and Sumana Dey Chowdhury
Pharmaceuticals 2024, 17(6), 791; https://doi.org/10.3390/ph17060791 - 16 Jun 2024
Viewed by 333
Abstract
This manuscript explores the transformative potential of swellable microneedles (MNs) in drug delivery and diagnostics, addressing critical needs in medical treatment and monitoring. Innovations in hydrogel-integrated MN arrays facilitate controlled drug release, thereby expanding treatment options for chronic diseases and conditions that require [...] Read more.
This manuscript explores the transformative potential of swellable microneedles (MNs) in drug delivery and diagnostics, addressing critical needs in medical treatment and monitoring. Innovations in hydrogel-integrated MN arrays facilitate controlled drug release, thereby expanding treatment options for chronic diseases and conditions that require precise dosage control. The review covers challenges, such as scalability, patient compliance, and manufacturing processes, as well as achievements in advanced manufacturing, biocompatibility, and versatile applications. Nonetheless, limitations in physiological responsiveness and long-term stability remain, necessitating further research in material innovation and integration with digital technologies. Future directions focus on expanding biomedical applications, material advancements, and regulatory considerations for widespread clinical adoption. Full article
(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications 2024)
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35 pages, 1938 KiB  
Review
White-to-Beige and Back: Adipocyte Conversion and Transcriptional Reprogramming
by Stanislav Boychenko, Vera S. Egorova, Andrew Brovin and Alexander D. Egorov
Pharmaceuticals 2024, 17(6), 790; https://doi.org/10.3390/ph17060790 - 16 Jun 2024
Viewed by 523
Abstract
Obesity has become a pandemic, as currently more than half a billion people worldwide are obese. The etiology of obesity is multifactorial, and combines a contribution of hereditary and behavioral factors, such as nutritional inadequacy, along with the influences of environment and reduced [...] Read more.
Obesity has become a pandemic, as currently more than half a billion people worldwide are obese. The etiology of obesity is multifactorial, and combines a contribution of hereditary and behavioral factors, such as nutritional inadequacy, along with the influences of environment and reduced physical activity. Two types of adipose tissue widely known are white and brown. While white adipose tissue functions predominantly as a key energy storage, brown adipose tissue has a greater mass of mitochondria and expresses the uncoupling protein 1 (UCP1) gene, which allows thermogenesis and rapid catabolism. Even though white and brown adipocytes are of different origin, activation of the brown adipocyte differentiation program in white adipose tissue cells forces them to transdifferentiate into “beige” adipocytes, characterized by thermogenesis and intensive lipolysis. Nowadays, researchers in the field of small molecule medicinal chemistry and gene therapy are making efforts to develop new drugs that effectively overcome insulin resistance and counteract obesity. Here, we discuss various aspects of white-to-beige conversion, adipose tissue catabolic re-activation, and non-shivering thermogenesis. Full article
(This article belongs to the Special Issue Anti-obesity and Anti-aging Natural Products)
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20 pages, 15838 KiB  
Article
Daphnetin Ameliorates Neuropathic Pain via Regulation of Microglial Responses and Glycerophospholipid Metabolism in the Spinal Cord
by Wulin Liang, Tianrui Zhang, Mingqian Zhang, Jiahui Gao, Rikang Huang, Xiyan Huang, Jianhua Chen, Lu Cheng, Liyuan Zhang, Zhishan Huang, Qiling Tan, Zhanhong Jia and Shuofeng Zhang
Pharmaceuticals 2024, 17(6), 789; https://doi.org/10.3390/ph17060789 - 16 Jun 2024
Viewed by 192
Abstract
Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal [...] Read more.
Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP’s anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1β, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X4, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP. Full article
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27 pages, 6753 KiB  
Review
Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer’s Disease
by Nikita Navolokin, Viktoria Adushkina, Daria Zlatogorskaya, Valeria Telnova, Arina Evsiukova, Elena Vodovozova, Anna Eroshova, Elina Dosadina, Sergey Diduk and Oxana Semyachkina-Glushkovskaya
Pharmaceuticals 2024, 17(6), 788; https://doi.org/10.3390/ph17060788 - 16 Jun 2024
Viewed by 525
Abstract
The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer’s disease (AD) progression. Once it enters the brain, the SARS-CoV-2 virus stimulates accumulation of amyloids in the brain that are highly toxic to neural cells. These [...] Read more.
The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer’s disease (AD) progression. Once it enters the brain, the SARS-CoV-2 virus stimulates accumulation of amyloids in the brain that are highly toxic to neural cells. These amyloids may trigger neurological symptoms in COVID-19. The meningeal lymphatic vessels (MLVs) play an important role in removal of toxins and mediate viral drainage from the brain. MLVs are considered a promising target to prevent COVID-19-exacerbated dementia. However, there are limited methods for augmentation of MLV function. This review highlights new discoveries in the field of COVID-19-mediated amyloid accumulation in the brain associated with the neurological symptoms and the development of promising strategies to stimulate clearance of amyloids from the brain through lymphatic and other pathways. These strategies are based on innovative methods of treating brain dysfunction induced by COVID-19 infection, including the use of photobiomodulation, plasmalogens, and medicinal herbs, which offer hope for addressing the challenges posed by the SARS-CoV-2 virus. Full article
(This article belongs to the Special Issue Multi-target Drug Treatments for Neurodegenerative Disease)
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16 pages, 1968 KiB  
Article
In Vitro/In Vivo Correlation of Two Extended-Release Cilostazol Formulations
by Kyoung Ah Min, Na Young Kim, Min Jeong Jin, Doyeon Kim, Yoonseo Ma, Sandeep Karna and Young-Joon Park
Pharmaceuticals 2024, 17(6), 787; https://doi.org/10.3390/ph17060787 - 16 Jun 2024
Viewed by 183
Abstract
This study aims to evaluate and determine the correlation between in vitro release and in vivo pharmacokinetics of two extended-release dosage forms of Cilostazol. In vitro release profiles for two dosage forms, tablet and capsule, were analyzed under physiologically mimicked medium conditions using [...] Read more.
This study aims to evaluate and determine the correlation between in vitro release and in vivo pharmacokinetics of two extended-release dosage forms of Cilostazol. In vitro release profiles for two dosage forms, tablet and capsule, were analyzed under physiologically mimicked medium conditions using the paddle and basket USP release apparatus. A single-dose, two-period crossover study design in beagle dogs was applied for the pharmacokinetic study. The fed and fast effects were considered for evaluation. Pseudo gastric release medium transfer setup study from pH 1.2 to pH 6.8 (+0.5% SLS) and pH 1.2 to pH 6.8 (+1.0% SLS) demonstrated that Pletaal® SR 200 mg capsules have higher drug release rates than Cilostan® CR 200 mg tablets. Similarly, in vivo study showed Cilostazol concentration in plasma and AUC was lower under the fast state than the fed state. The ratio of least squared geometric mean values, Cmax, AUC0-t, and AUC0-inf of Cilostazol were 2.53-fold, 2.89-fold, and 2.87-fold higher for Pletaal® SR 200 mg capsules compared with Cilostan® CR 200 mg tablets, respectively. Correlation of in vitro/in vivo data indicated that Pletal® SR 200 mg capsules have better release and pharmacodynamic effect than Cilostan® CR 200 mg tablets. Full article
(This article belongs to the Section Pharmaceutical Technology)
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17 pages, 1844 KiB  
Article
Phenolic Composition of Crataegus monogyna Jacq. Extract and Its Anti-Inflammatory, Hepatoprotective, and Antileukemia Effects
by Fatima Ez-Zahra Amrati, Ibrahim Mssillou, Smahane Boukhira, Mehdi Djiddi Bichara, Youness El Abdali, Renata Galvão de Azevedo, Chebaibi Mohamed, Meryem Slighoua, Raffaele Conte, Sotirios Kiokias, Gemilson Soares Pontes and Dalila Bousta
Pharmaceuticals 2024, 17(6), 786; https://doi.org/10.3390/ph17060786 - 15 Jun 2024
Viewed by 230
Abstract
Crataegus monogyna (C. monogyna) is a prominent plant used in Moroccan traditional medicine. This study investigated the phenolic composition and the anti-inflammatory, the hepatoprotective, and the anticancer activities of a hydroethanolic extract of C. monogyna leaves and stems. Ultra-high-performance liquid chromatography [...] Read more.
Crataegus monogyna (C. monogyna) is a prominent plant used in Moroccan traditional medicine. This study investigated the phenolic composition and the anti-inflammatory, the hepatoprotective, and the anticancer activities of a hydroethanolic extract of C. monogyna leaves and stems. Ultra-high-performance liquid chromatography identified the phenolic profile. The in vitro anticancer activity was evaluated using the MTT assay on HL-60 and K-562 myeloleukemia cells and liver (Huh-7) cell lines. The anti-inflammatory effect was assessed in vivo using carrageenan-induced paw edema in rats. The hepatoprotective effect at 300 and 1000 mg/kg doses against the acetaminophen-induced hepatotoxicity on rats was studied for seven days. Additionally, molecular docking simulations were performed to evaluate the extract’s inhibitory potential against key targets: lipoxygenase, cytochrome P450, tyrosine kinase, and TRADD. The extract exhibited significant cytotoxic activity against K-562 and HL-60 cells, but not against lung cancer cells (Huh-7 line). The 1000 mg/kg dose demonstrated the most potent anti-inflammatory effect, inhibiting edema by 99.10% after 6 h. C. monogyna extract displayed promising hepatoprotective properties. Procyanidin (−7.27 kcal/mol), quercetin (−8.102 kcal/mol), and catechin (−9.037 kcal/mol) were identified as the most active molecules against lipoxygenase, cytochrome P450, and tyrosine kinase, respectively. These findings highlight the untapped potential of C. monogyna for further exploration in treating liver damage, inflammation, and leukemia. Full article
15 pages, 2055 KiB  
Article
Novel Anti-Enterovirus A71 Compounds Discovered by Repositioning Antivirals from the Open-Source MMV Pandemic Response Box
by Nattinee Lochaiyakun, Potjanee Srimanote, Onruedee Khantisitthiporn and Jeeraphong Thanongsaksrikul
Pharmaceuticals 2024, 17(6), 785; https://doi.org/10.3390/ph17060785 - 14 Jun 2024
Viewed by 392
Abstract
The open-source drug library, namely, MMV Pandemic Response Box, contains 153 antiviral agents, a chemically and pharmacologically diverse mixture of early-stage, emerging anti-infective scaffolds, and mature compounds currently undergoing clinical development. Hence, the Pandemic Response Box might contain compounds that bind and interfere [...] Read more.
The open-source drug library, namely, MMV Pandemic Response Box, contains 153 antiviral agents, a chemically and pharmacologically diverse mixture of early-stage, emerging anti-infective scaffolds, and mature compounds currently undergoing clinical development. Hence, the Pandemic Response Box might contain compounds that bind and interfere with target molecules or cellular pathways that are conserved or shared among the closely related viruses with enterovirus A71 (EV-A71). This study aimed to screen antiviral agents included in the Pandemic Response Box for repurposing to anti-EV-A71 activity and investigate the inhibitory effects of the compounds on viral replication. The compounds’ cytotoxicity and ability to rescue infected cells were determined by % cell survival using an SRB assay. The hit compounds were verified for anti-EV-A71 activity by virus reduction assays for viral RNA copy numbers, viral protein synthesis, and mature particle production using qRT-PCR, Western blot analysis, and CCID50 assay, respectively. It was found that some of the hit compounds could reduce EV-A71 genome replication and protein synthesis. D-D7 (2-pyridone-containing human rhinovirus 3C protease inhibitor) exhibited the highest anti-EV-A71 activity. Even though D-D7 has been originally indicated as a polyprotein processing inhibitor of human rhinovirus 3C protease, it could be repurposed as an anti-EV-A71 agent. Full article
(This article belongs to the Section Pharmacology)
21 pages, 5137 KiB  
Article
Jingzhi Guanxin Oral Liquids Attenuate Atherosclerotic Coronary Heart Disease via Modulating Lipid Metabolism and PPAR-Related Targets
by Xinning Wang, Tao Hu, Yuliang Jiang, Yan He, Peibo Li, Wei Peng, Yonggang Wang and Weiwei Su
Pharmaceuticals 2024, 17(6), 784; https://doi.org/10.3390/ph17060784 - 14 Jun 2024
Viewed by 189
Abstract
Jingzhi Guanxin Oral Liquids (JZGX), a traditional Chinese medicine formulation prepared from the decoction of five herbs, has been utilized to relieve chest pain with coronary artery disease (CAD). However, the chemical composition and therapeutic mechanisms of JZGX remain obscured. In this research, [...] Read more.
Jingzhi Guanxin Oral Liquids (JZGX), a traditional Chinese medicine formulation prepared from the decoction of five herbs, has been utilized to relieve chest pain with coronary artery disease (CAD). However, the chemical composition and therapeutic mechanisms of JZGX remain obscured. In this research, the potential targets and pathways of JZGX against CAD were anticipated through network pharmacology based on analyzing its chemical constituents using UPLC-Q-TOF-MS/MS. One hundred seven ingredients in JZGX were identified. The 39 active chemicals and 37 key targets were screened, and CAD-related signaling pathways were clustered, mainly associated with lipid metabolism. Subsequently, the atherosclerotic CAD animal model employing 24 weeks of high-fat diet (HFD) ApoE/ mice was constructed to investigate the JZGX efficacy and underlying mechanisms validating network forecasts. The histological staining examination and cardiovascular biomarker tests confirmed that JZGX reduced plaque formation in the aorta and decreased blood lipids in vivo. It featured anti-inflammatory, anti-thrombotic, and myocardial protective effects. JZGX prevented excessive lipid deposits and inflammation within the liver and exhibited hepatoprotective properties. Serum untargeted metabolomics analysis indicated that JZGX ameliorated metabolic abnormalities in atherosclerotic CAD mice and prompted lipid metabolism, especially linoleic acid. The PPARs and attached critical targets (SREBP1, FASN, PTGS2, and CYP3A), filtered from the networks and connected with lipid metabolism, were dramatically modulated through JZGX administration, as revealed by western blotting. The molecular docking outcomes showed that all 39 active ingredients in JZGX had good binding activity with PPARα and PPARγ. These findings illustrate that JZGX alleviates atherosclerotic CAD progression by remodeling the lipid metabolism and regulating PPAR-related proteins. Full article
(This article belongs to the Section Pharmacology)
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17 pages, 1502 KiB  
Article
Evaluating the Antihyperalgesic Potential of Sildenafil–Metformin Combination and Its Impact on Biochemical Markers in Alloxan-Induced Diabetic Neuropathy in Rats
by Ciprian Pușcașu, Simona Negreș, Cristina Elena Zbârcea, Anca Ungurianu, Emil Ștefănescu, Nicoleta Mirela Blebea and Cornel Chiriță
Pharmaceuticals 2024, 17(6), 783; https://doi.org/10.3390/ph17060783 - 14 Jun 2024
Viewed by 242
Abstract
(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic [...] Read more.
(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)–metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats. (2) Methods: This study involved a cohort of 70 diabetic rats and 10 non-diabetic rats. Diabetic neuropathy was induced by a single dose of 130 mg/kg alloxan. The rats were submitted to thermal stimulus test using a hot–cold plate and to tactile stimulus test using von Frey filaments. Moreover, at the end of the experiment, the animals were sacrificed and their brains and livers were collected to investigate the impact of this combination on TNF-α, IL-6, nitrites and thiols levels. (3) Results: The results demonstrated that all sildenafil–metformin combinations decreased the pain sensitivity in the von Frey test, hot plate test and cold plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil–metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect on alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion. Full article
(This article belongs to the Special Issue Advances in Pharmacotherapy of Neuropathic Pain)
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33 pages, 7616 KiB  
Review
Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson’s Disease
by Yiting Zhao, Man Lin, Fengguang Zhai, Jun Chen and Xiaofeng Jin
Pharmaceuticals 2024, 17(6), 782; https://doi.org/10.3390/ph17060782 - 14 Jun 2024
Viewed by 321
Abstract
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder among the elderly population. The pathogenesis of PD encompasses genetic alterations, environmental factors, and age-related neurodegenerative processes. Numerous studies have demonstrated that aberrant functioning of the ubiquitin–proteasome system (UPS) plays a crucial role in the [...] Read more.
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder among the elderly population. The pathogenesis of PD encompasses genetic alterations, environmental factors, and age-related neurodegenerative processes. Numerous studies have demonstrated that aberrant functioning of the ubiquitin–proteasome system (UPS) plays a crucial role in the initiation and progression of PD. Notably, E3 ubiquitin ligases serve as pivotal components determining substrate specificity within UPS and are intimately associated with the regulation of various proteins implicated in PD pathology. This review comprehensively summarizes the mechanisms by which E3 ubiquitin ligases and deubiquitinating enzymes modulate PD-associated proteins and signaling pathways, while exploring the intricate relationship between UPS dysfunctions and PD etiology. Furthermore, this article discusses recent research advancements regarding inhibitors targeting PD-related E3 ubiquitin ligases. Full article
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15 pages, 3671 KiB  
Article
One-Step Synthesis, Crystallography, and Acute Toxicity of Two Boron–Carbohydrate Adducts That Induce Sedation in Mice
by Ricardo Ivan Cordova-Chávez, José G. Trujillo-Ferrara, Itzia I. Padilla-Martínez, Héctor González-Espinosa, Antonio Abad-García, Eunice D. Farfán-García, Clara Ortega-Camarillo, Alejandra Contreras-Ramos and Marvin A. Soriano-Ursúa
Pharmaceuticals 2024, 17(6), 781; https://doi.org/10.3390/ph17060781 - 14 Jun 2024
Viewed by 650
Abstract
Boronic acids form diester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of precursors, even their biological activity. Two carbohydrate derivatives from d-fructose and d-arabinose and phenylboronic acid were synthesized in [...] Read more.
Boronic acids form diester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of precursors, even their biological activity. Two carbohydrate derivatives from d-fructose and d-arabinose and phenylboronic acid were synthesized in a straightforward one-step procedure and chemically characterized via spectroscopy and X-ray diffraction crystallography. Additionally, an acute toxicity test was performed to determine their lethal dose 50 (LD50) values by using Lorke’s method. Analytical chemistry assays confirmed the formation of adducts by the generation of diester bonds with the β-d-pyranose of carbohydrates, including signals corresponding to the formation of new bonds, such as the stretching of B–O bonds. NMR spectra yielded information about the stereoselectivity in the synthesis reaction: Just one signal was found in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests showed that the LD50 value for both compounds was 1265 mg/kg, while the effective dose 50 (ED50) for sedation was 531 mg/kg. However, differences were found in the onset and lapse of sedation. For example, the arabinose derivative induced sedation for more than 48 h at 600 mg/kg, while the fructose derivative induced sedation for less than 6 h at the same dose without the death of the mice. Thus, we report for the first time two boron-containing carbohydrate derivatives inducing sedation after intraperitoneal administration. They are bioactive and highly safe agents. Further biological evaluation is desirable to explore their medical applications. Full article
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19 pages, 3351 KiB  
Article
Biological Activity of Horehound (Marrubium vulgare L.) Herb Grown in Poland and Its Phytochemical Composition
by Monika Michalak, Małgorzata Stryjecka, Martyna Zagórska-Dziok and Paulina Żarnowiec
Pharmaceuticals 2024, 17(6), 780; https://doi.org/10.3390/ph17060780 - 14 Jun 2024
Viewed by 241
Abstract
Marrubium vulgare (Lamiaceae) is a plant which has long been known and used in traditional medicine for various purposes. However, few recent studies have documented its chemical composition and biological properties. The present study investigated the phytochemical composition of horehound, as well as [...] Read more.
Marrubium vulgare (Lamiaceae) is a plant which has long been known and used in traditional medicine for various purposes. However, few recent studies have documented its chemical composition and biological properties. The present study investigated the phytochemical composition of horehound, as well as its protective, antioxidant, and antimicrobial potential. GC-MS analysis revealed that the major components of horehound essential oil are E-caryophyllene (35.7%), germacrene D (25.2%), and bicyclogermacrene (10.6%). The biological activity of horehound hydroethanolic herb extract derives from multiple chemical compounds, including polyphenols (55.72 mg/mL), flavonoids (11.01 mg/mL), phenolic acids (4.33 mg/mL), and tannins (4.46 mg/mL). Chromatographic analyses of the extract identified 12 phenolic compounds, of which ferulic acid, catechin, quercetin, protocatechuic acid, rutin, and syringic acid (35.42, 24.69, 20.65, 18.70, 14.46, and 12.69 mg/mL, respectively) were the main constituents. Its DPPH radical scavenging ability was 68.29%, while its antioxidant properties, determined by the FRAP method, were at the level of 1.22 mmol/L. Moreover, M. vulgare extract decreased the level of intracellular reactive oxygen species in the fibroblasts and keratinocytes in vitro, achieving the strongest antioxidant effect at a concentration of 2.5% in the case of both types of skin cells. Extracts from the horehound herb showed significant antimicrobial and anti-biofilm activity, confirming the plant’s potential in therapeutic applications against various microbial pathogens (gram-positive and gram-negative bacteria and fungi). The research results demonstrate the protective effect of horehound extract on the viability of both fibroblasts and keratinocytes in vitro. To sum up, M. vulgare, as a valuable natural material with high preventive and therapeutic effectiveness, is a potential candidate for new applications in the pharmaceutical and cosmetics industries. Full article
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11 pages, 947 KiB  
Article
Effects of a Dietary Supplement Composed of Baicalin, Bromelain and Escin for Venous Chronic Insufficiency Treatment: Insights from a Retrospective Observational Study
by Selene Francesca Anna Drago, Michelangelo Rottura, Antonino Molonia, Viviana Maria Gianguzzo, Giovanni Pallio, Natasha Irrera, Luana Orlando, Marianna Gigliotti De Fazio, Marilena Isgrò, Natalia Zirilli, Vincenzo Arcoraci and Egidio Imbalzano
Pharmaceuticals 2024, 17(6), 779; https://doi.org/10.3390/ph17060779 - 14 Jun 2024
Viewed by 253
Abstract
Chronic venous insufficiency (CVI) represents a risk factor for cardiovascular events. The first-line treatment includes the use of compression stockings and lifestyle changes. Natural products, such as flavonoids, could be used to improve the effects of compression therapy due to their anti-inflammatory and [...] Read more.
Chronic venous insufficiency (CVI) represents a risk factor for cardiovascular events. The first-line treatment includes the use of compression stockings and lifestyle changes. Natural products, such as flavonoids, could be used to improve the effects of compression therapy due to their anti-inflammatory and anti-oxidant properties. This study aims to evaluate the effects of a dietary supplement containing baicalin, bromeline and escin in CVI patients. A retrospective cohort study was performed by using the medical records of CVI affected outpatients. Patients treated with the dietary supplement were defined as “users”. A modified Venous Clinical Severity Score (VCSS) was calculated, including pain, inflammation, vessels induration and skin pigmentation. All clinical variables were evaluated at baseline (T0), after 30 (T1) and 90(T2) days in “users” and “non-users”. Out of 62 patients, 30 (48.4%) were “users”. No difference was observed between groups at baseline. A lower VCSS value was recorded in “users” than that observed in “non-users” at T2 (7.0 (4.0–9.0) vs. 9.0 (5.0–10.0); p = 0.025). Vessels’ induration and pain significantly reduced in 53.3% and 43.3% of “users” and in 18.8% and 9.4% of “non-users”. Only “users” (33.3%) showed a reduction of the inflammatory signs as well as a decrease in malleolar circumference, from 29.0 (26.5–30.0) to 27.5 (26.0–28.5) (p < 000.1). A reduction of C-reactive Protein levels was found in “users” compared to “non-users” at T2 (1.0 (0.9–1.2) vs. 1.3 (1.0–1.5); p = 0.006). These findings suggest that implementation of a dietary supplement could improve the clinical outcomes of CVI patients. Full article
(This article belongs to the Special Issue Therapeutic Effects of Natural Products and Their Clinical Research)
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12 pages, 253 KiB  
Review
Tailored Treatment Strategies in First Line Therapy for Ovarian Cancer Patients: A Critical Review of the Literature
by Daniela Luvero, Roberto Angioli, Federica Celoro, Francesco Plotti, Corrado Terranova, Federica Guzzo, Gianna Barbara Cundari, Federico Liparulo, Camilla Verdone and Roberto Montera
Pharmaceuticals 2024, 17(6), 778; https://doi.org/10.3390/ph17060778 - 14 Jun 2024
Viewed by 234
Abstract
Background: Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular [...] Read more.
Background: Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular agents like bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi). Materials and Methods: This review systematically searched PubMed from January 2018 to December 2023 for studies on PARPi in OC. Emphasis was on identifying relevant Phase III trials, extracting data on study design, patient demographics, and outcomes. Special focus was on assessing PARPi efficacy, safety, impact on quality of life, and ongoing trials, including those on Clinicaltrials.gov. Results: The efficacy of PARPi in first-line therapy for OC has been extensively studied. Trials like SOLO-1, PRIMA, and ATHENA-MONO have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in patients with BRCA mutations. Additionally, the combination of PARPi with other agents like bevacizumab has shown promising results in extending PFS. However, PARPi treatment is associated with various adverse effects, including hematologic toxicities like anemia, thrombocytopenia, and neutropenia. While most adverse events are manageable, some patients may require dose adjustments or discontinuation of treatment. Importantly, PARPi maintenance therapy has not adversely affected health-related quality of life (HRQoL), with studies reporting similar HRQoL scores between PARPi-treated and placebo-treated patients. Conclusions: PARPi offer effective treatment with manageable side effects, suitable even for medically fragile patients. Individualized dosing can optimize benefits while minimizing adverse events. Exploring diverse treatment approaches, particularly in patients with limited life expectancy or high disease burden, could improve outcomes. Ongoing research is investigating alternative therapies and combinations to broaden treatment options. Combining bevacizumab with PARPi may be justified for first-line and recurrent maintenance therapy. Regardless of mutational status, PARPi should be considered for maintenance therapy in newly diagnosed advanced OC. Platinum sensitivity remains crucial for treatment decisions and predicting survival outcomes. Full article
(This article belongs to the Section Pharmacology)
12 pages, 5178 KiB  
Article
Novel Ultrasound-Responsive Amyloid Formulation
by Maytham Ismail and Mathumai Kanapathipillai
Pharmaceuticals 2024, 17(6), 777; https://doi.org/10.3390/ph17060777 - 13 Jun 2024
Viewed by 226
Abstract
Amyloid aggregates have attracted significant interest in regard to diverse biomedical applications, particularly in the field of drug delivery. Here, we report novel amyloid aggregates based on a 12-amino-acid peptide from the amyloidogenic region of the receptor-interacting kinase 3 (RIP3) protein and a [...] Read more.
Amyloid aggregates have attracted significant interest in regard to diverse biomedical applications, particularly in the field of drug delivery. Here, we report novel amyloid aggregates based on a 12-amino-acid peptide from the amyloidogenic region of the receptor-interacting kinase 3 (RIP3) protein and a thermoresponsive triblock copolymer, namely, Pluronic F127 (RIP3/F127). Physicochemical characterization was performed to determine the aggregation size, morphology, and stimuli-responsive properties. The potential of the aggregates as a drug depot was assessed in lung cancer cells, using Doxorubicin (Dox) as a model drug. The results show that RIP3 and RIP3/F127 exhibit amyloidogenic properties. Further, the RIP3/F127 amyloids exhibited significant ultrasound-responsive properties compared to amyloid aggregates without Pluronic F127. Moreover, the RIP3/F127/Dox amyloid formulations that were subjected to ultrasound treatment exhibited greater toxicity to lung cancer cells compared to that of Dox alone at equal concentrations. Overall, the results from this proof-of-concept study show that amyloidogenic peptide aggregates with stimuli-responsive properties can be utilized as efficient drug delivery depots. Full article
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12 pages, 1893 KiB  
Article
Solubility, pH-Solubility Profile, pH-Rate Profile, and Kinetic Stability of the Tyrosine Kinase Inhibitor, Alectinib
by Dheyaa Tohma Madlool, Israa Al-Ani, Tha’er Ata and Wael Abu Dayyih
Pharmaceuticals 2024, 17(6), 776; https://doi.org/10.3390/ph17060776 - 13 Jun 2024
Viewed by 293
Abstract
Alectinib HCl (ALBHCl) is a tyrosine kinase inhibitor used for non-small cell lung carcinoma (NSCLC). The aim of this study is to unlock some of the physicochemical properties of ALBHCL that serve as a database for any future studies. A solubility study of [...] Read more.
Alectinib HCl (ALBHCl) is a tyrosine kinase inhibitor used for non-small cell lung carcinoma (NSCLC). The aim of this study is to unlock some of the physicochemical properties of ALBHCL that serve as a database for any future studies. A solubility study of ALBHCL was performed in different solvents. Also, photostability was tested in the solution and solid states, and the order of reaction and rate constant were calculated. In addition to the pH solubility relation, the pH-rate relation at different temperatures was also studied, and the profiles were constructed. A solubility study was also performed in different media for the purpose of optimizing suitable sink conditions for the in vitro dissolution testing of solid dosage forms. Solubility tests in multiple solvents and pH conditions revealed that the highest solubility was in DMSO, methanol, and chloroform, with acidic media yielding the maximum solubility but degrading at rather low pH levels. ALBHCL proved unstable at high temperatures and under light exposure, with varying stability across different pH levels. The optimal dissolution media for in vitro oral dosage form evaluation were determined, achieving sink conditions at pH levels of 6.8 and 4.5 with specific additives. This study enhances the existing database on ALBHCL’s physicochemical properties, emphasizing the importance of pH optimization in pharmaceutical processes and providing valuable insights into its pharmaceutical application. Full article
(This article belongs to the Section Pharmaceutical Technology)
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25 pages, 709 KiB  
Review
Polyphenols: Natural Food-Grade Biomolecules for the Treatment of Nervous System Diseases from a Multi-Target Perspective
by Xinchen Wu, Yang Zhou, Yujiang Xi, Haimei Zhou, Zhengxiu Tang, Lei Xiong and Dongdong Qin
Pharmaceuticals 2024, 17(6), 775; https://doi.org/10.3390/ph17060775 - 13 Jun 2024
Viewed by 198
Abstract
Polyphenols are the most prevalent naturally occurring phytochemicals in the human diet and range in complexity from simple molecules to high-molecular-weight polymers. They have a broad range of chemical structures and are generally categorized as “neuroprotective”, “anti-inflammatory”, and “antioxidant” given their main function [...] Read more.
Polyphenols are the most prevalent naturally occurring phytochemicals in the human diet and range in complexity from simple molecules to high-molecular-weight polymers. They have a broad range of chemical structures and are generally categorized as “neuroprotective”, “anti-inflammatory”, and “antioxidant” given their main function of halting disease onset and promoting health. Research has shown that some polyphenols and their metabolites can penetrate the blood–brain barrier and hence increase neuroprotective signaling and neurohormonal effects to provide anti-inflammatory and antioxidant effects. Therefore, multi-targeted modulation of polyphenols may prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for difficult-to-treat neuropsychiatric disorders. Therefore, multi-target modulation of polyphenols has the potential to prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for such nervous system diseases. Herein, we review the therapeutic benefits of polyphenols on autism-spectrum disorders, anxiety disorders, depression, and sleep disorders, along with in vitro and ex vivo experimental and clinical trials. Although their methods of action are still under investigation, polyphenols are still seldom employed directly as therapeutic agents for nervous system disorders. Comprehensive mechanistic investigations and large-scale multicenter randomized controlled trials are required to properly evaluate the safety, effectiveness, and side effects of polyphenols. Full article
(This article belongs to the Special Issue Unraveling the Multifaceted Role of Polyphenols in Health Issues)
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18 pages, 3484 KiB  
Article
Phytochemical Study of the Anthelminthic Potential of Guadeloupean Plant Biodiversity
by Tressy Cabald, Carine Marie-Magdeleine, Lucien Philibert, Cédric Caradeuc, Gildas Bertho, Nicolas Giraud, Gerardo Cebrián-Torrejón and Muriel Sylvestre
Pharmaceuticals 2024, 17(6), 774; https://doi.org/10.3390/ph17060774 - 13 Jun 2024
Viewed by 348
Abstract
Gastrointestinal parasitism is a major health and welfare problem in ruminants. Synthetic chemical anthelmintic drugs have led to the emergence of resistance in gastrointestinal strongyles, inducing the search for alternatives to control the infections that affect ruminants. The objective of this work was [...] Read more.
Gastrointestinal parasitism is a major health and welfare problem in ruminants. Synthetic chemical anthelmintic drugs have led to the emergence of resistance in gastrointestinal strongyles, inducing the search for alternatives to control the infections that affect ruminants. The objective of this work was to evaluate the anthelmintic potential of plant extracts against Haemonchus contortus Rudolphi. Three plants of the Guadeloupean biodiversity, Momordica charantia L., Carica papaya L. and Sargassum spp., were selected based on their high polyphenolic content and natural abundance. The phytochemistry of plants was explored, a biological assay against the parasite H. contortus was carried out, and several hypotheses about the way of action were proposed by an innovative electrochemical screening method. Full article
(This article belongs to the Collection Drug Discovery and Development for Tropical Diseases (TDs))
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34 pages, 834 KiB  
Review
Evaluating Thromboprophylaxis Strategies for High-Risk Pregnancy: A Current Perspective
by Lucia Stančiaková, Kristína Brisudová, Ingrid Škorňová, Tomáš Bolek, Matej Samoš, Kamil Biringer, Ján Staško and Juraj Sokol
Pharmaceuticals 2024, 17(6), 773; https://doi.org/10.3390/ph17060773 (registering DOI) - 13 Jun 2024
Viewed by 169
Abstract
Venous thromboembolism (VTE) represents one of the leading causes of death during pregnancy. The greatest risk for it is the presence of medical or family history of VTE, stillbirth, cesarean section and selected thrombophilia. Appropriate thromboprophylaxis has the potential to decrease the risk [...] Read more.
Venous thromboembolism (VTE) represents one of the leading causes of death during pregnancy. The greatest risk for it is the presence of medical or family history of VTE, stillbirth, cesarean section and selected thrombophilia. Appropriate thromboprophylaxis has the potential to decrease the risk of VTE in at-risk pregnant patients by 60–70%. Based on this, the authors reviewed the PubMed, Web of Science and Scopus databases to identify the possibilities of thromboprophylaxis in pregnant patients with a high risk of VTE. Moreover, they summarized its management in specific situations, such as cesarean delivery or neuraxial blockade. Currently, low-molecular-weight heparins (LMWH) are the preferred drugs for anticoagulant thromboprophylaxis in the course of pregnancy and postpartum due to easy administration and a lower rate of adverse events. Full article
(This article belongs to the Special Issue Pharmacotherapy of Thromboembolism)
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17 pages, 11935 KiB  
Article
Green-Synthesized Characterization, Antioxidant and Antibacterial Applications of CtAC/MNPs-Ag Nanocomposites
by Ayşe Baran, Erdal Ertaş, Mehmet Fırat Baran, Aziz Eftekhari, Zübeyir Gunes, Cumali Keskin, Sergey A. Usanov and Rovshan Khalilov
Pharmaceuticals 2024, 17(6), 772; https://doi.org/10.3390/ph17060772 - 13 Jun 2024
Viewed by 333
Abstract
The emergence of antibiotic resistance, caused by the improper use of antibiotics, is a significant challenge in combating infectious diseases, leading to millions of annual fatalities. The occurrence of antimicrobial side effects catalyzes the investigation of novel antimicrobial compounds and sources of drugs. [...] Read more.
The emergence of antibiotic resistance, caused by the improper use of antibiotics, is a significant challenge in combating infectious diseases, leading to millions of annual fatalities. The occurrence of antimicrobial side effects catalyzes the investigation of novel antimicrobial compounds and sources of drugs. Consequently, the research on biological activity that is conducted on plants, plant extracts, and compounds that are produced from plant components is of utmost significance. In this study, CtAC/MNPs were obtained by the reaction of activated carbon (AC) obtained from the fruits of the Celtis tournefortii (Ct) plant and magnetic nanoparticles (MNPs), and a CtAC/MNPs-Ag nanocomposite was synthesized by the reduction in silver ions added to the reaction. The synthesized CtAC/MNPs and CtAC/MNPs-Ag nanocomposites were analyzed spectroscopically (FTIR, XRD), microscopically (SEM, EDX), optically (DLS), electrochemically (zeta potential) and magnetically (VSM). The antibacterial activities of CtAC/MNPs and CtAC/MNPs-Ag nanocomposites against S. aureus and E. coli were investigated by microdilution method using minimal inhibitory concentration (MIC) and disk diffusion methods. Antioxidant activity study, including total phenolic content and DPPH and cuprac assays, revealed the remarkable effect of the CtAC/MNPs-Ag nanocomposite. This study has the advantages of obtaining CtAC/MNPs and CtAC/MNPs-Ag nanocomposites in a short time without requiring energy, and most importantly, the reaction takes place without using any toxic substances. In addition, according to the data obtained in the study, the CtAC/MNPs-Ag nanocomposite is thought to shed light on biomedical research. Full article
(This article belongs to the Special Issue Therapeutic Potential of Silver Nanoparticles (AgNPs))
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