Journal Description
Pharmaceuticals
Pharmaceuticals
is a peer-reviewed, open access journal of medicinal chemistry and related drug sciences, published monthly online by MDPI. The Academy of Pharmaceutical Sciences (APS) is partners of Pharmaceuticals and their members receive a discount on the article processing charge.
- Open Access free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology and Pharmacy) / CiteScore - Q2 (Pharmaceutical Science)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 14.6 days after submission; acceptance to publication is undertaken in 3.6 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Testimonials: See what our editors and authors say about Pharmaceuticals.
- International Electronic Conference on Medicinal Chemistry (https://sciforum.net/series/ecmc/latest)
- Companion journals for Pharmaceuticals include: Pharmacoepidemiology, Psychoactives and Drugs and Drug Candidates.
Impact Factor:
4.3 (2023);
5-Year Impact Factor:
4.6 (2023)
Latest Articles
Effectiveness of Duloxetine versus Other Therapeutic Modalities in Patients with Diabetic Neuropathic Pain: A Systematic Review and Meta-Analysis
Pharmaceuticals 2024, 17(7), 856; https://doi.org/10.3390/ph17070856 (registering DOI) - 28 Jun 2024
Abstract
Objectives: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus (DM) with symptoms like intense pain and impaired quality of life. This condition has no treatment; instead, the pain is managed with various antidepressants, including duloxetine. The aim of this study
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Objectives: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus (DM) with symptoms like intense pain and impaired quality of life. This condition has no treatment; instead, the pain is managed with various antidepressants, including duloxetine. The aim of this study is to analyze the evidence on the efficacy of duloxetine in the management of DPN. Methods: A systematic search in different databases was conducted using the keywords “diabetic neuropathy”, “duloxetine therapy”, “neuropathic pain”, and “Diabetes Mellitus”. Finally, eight studies were included in this meta-analysis. Results: All articles comparing duloxetine at different doses vs. a placebo reported significant differences in favor of duloxetine on pain scales like 24 h Average Pain Severity (standardized mean difference [SMD] = −1.06, confidence interval [CI] = −1.09 to −1.03, and p < 0.00001) and BPI Severity (SMD = −0.70, CI = −0.72 to −0.68, and p < 0.00001), among others. A total of 75% of the meta-analyses of studies comparing duloxetine at different doses showed a tendency in favor of the 120 mg/d dose. There were significant differences in favor of duloxetine when compared to routine care on the Euro Quality of Life (SMD = −0.04, CI = −0.04 to −0.03, and p < 0.00001) and SF-36 Survey (SMD = −5.86, CI = −6.28 to −5.44, and p < 0.00001) scales. There were no significant differences on the visual analog scale (VAS) when comparing duloxetine and gabapentin. Conclusions: Duloxetine appears to be effective in the management of DPN in different pain, symptom improvement, and quality of life scales.
Full article
(This article belongs to the Section Pharmacology)
Open AccessArticle
Integrating Natural Deep Eutectic Solvents into Nanostructured Lipid Carriers: An Industrial Look
by
Luísa Schuh, Luane Almeida Salgado, Tathyana Benetis Piau, Ariane Pandolfo Silveira, Caio Leal, Luís Felipe Romera, Marina Arantes Radicchi, Mac-Kedson Medeiros Salviano Santos, Leila Falcao, Cesar Koppe Grisolia, Eliana Fortes Gris, Luis Alexandre Muehlmann, Sônia Nair Báo and Victor Carlos Mello
Pharmaceuticals 2024, 17(7), 855; https://doi.org/10.3390/ph17070855 (registering DOI) - 28 Jun 2024
Abstract
The industries are searching for greener alternatives for their productions due to the rising concern about the environment and creation of waste and by-products without industrial utility for that specific line of products. This investigation describes the development of two stable nanostructured lipid
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The industries are searching for greener alternatives for their productions due to the rising concern about the environment and creation of waste and by-products without industrial utility for that specific line of products. This investigation describes the development of two stable nanostructured lipid carriers (NLCs): one is the formulation of a standard NLC, and the other one is the same NLC formulation associated with a natural deep eutectic solvent (NaDES). The research presents the formulation paths of the NLCs through completeness, which encompass dynamic light scattering (DLS), zeta potential tests, and pH. Transmission electron microscopy (TEM) and confocal microscopy were performed to clarify the morphology. Cytotoxicity tests with zebrafish were realized, and the results are complementary to the in vitro outcomes reached with fibroblast L132 tests by the MTT technique and the zymography test. Infrared spectroscopy and X-ray diffractometry tests elucidated the link between the physicochemical characteristics of the formulation and its behavior and properties. Different cooling techniques were explored to prove the tailorable properties of the NLCs for any industrial applications. In conclusion, the compiled results show the successful formulation of new nanocarriers based on a sustainable, eco-friendly, and highly tailorable technology, which presents low cytotoxic potential.
Full article
(This article belongs to the Section Natural Products)
Open AccessArticle
Prospective Audit and Feedback for Antimicrobial Treatment of Patients Receiving Renal Replacement Therapy in Community-Based University Hospitals: A before-and-after Study
by
Namgi Park, Jiyeon Bae, Soo Yeon Nam, Ji Yun Bae, Kang-Il Jun, Jeong-Han Kim, Chung-Jong Kim, Kyunghee Kim, Sun Ah Kim, Hee Jung Choi and Sandy Jeong Rhie
Pharmaceuticals 2024, 17(7), 854; https://doi.org/10.3390/ph17070854 (registering DOI) - 28 Jun 2024
Abstract
In South Korea, because of manpower and budgetary limitations, antimicrobial stewardship programs have relied on preauthorization. This study analyzed the impact of a prospective audit and feedback (PAF) program targeting inpatients undergoing intermittent hemodialysis or continuous renal replacement therapy, which was implemented at
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In South Korea, because of manpower and budgetary limitations, antimicrobial stewardship programs have relied on preauthorization. This study analyzed the impact of a prospective audit and feedback (PAF) program targeting inpatients undergoing intermittent hemodialysis or continuous renal replacement therapy, which was implemented at two community-based university hospitals. During three years of PAF, 27,906 antimicrobial prescriptions were reviewed, with 622 (2.2%) interventions. The mean incidence density per 1000 patient days of multidrug-resistant organisms, except for carbapenem-resistant Acinetobacter baumannii, decreased in the study population, whereas it increased among inpatients. Multivariable Poisson regression analysis revealed that after PAF, the incidences of vancomycin-resistant Enterococcus and mortality decreased (incidence risk ratio, 95% confidence interval: 0.53, 0.31–0.93 and 0.70, 0.55–0.90, respectively). Notably, after PAF, incorrect antimicrobial dosing rates significantly decreased (tau −0.244; p = 0.02). However, the incidences of other multidrug-resistant organisms, Clostridioides difficile, length of stay, and readmission did not significantly change. This study shows that in patients undergoing intermittent hemodialysis or continuous renal replacement, targeted PAF can significantly reduce multidrug-resistant organism rates and all-cause hospital mortality, despite limited resources. Furthermore, it can improve antimicrobial dosage accuracy.
Full article
(This article belongs to the Section Pharmacology)
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Graphical abstract
Open AccessArticle
Euiin-Tang Attenuates Obesity-Induced Asthma by Resolving Metaflammation
by
Ye-Eul Lee and Dong-Soon Im
Pharmaceuticals 2024, 17(7), 853; https://doi.org/10.3390/ph17070853 (registering DOI) - 28 Jun 2024
Abstract
Euiin-tang reduces obesity and hypertension. Patients with obesity may develop obesity-induced asthma (OIA) owing to phlegm dampness. This study aimed to determine whether euiin-tang alleviates high-fat diet (HFD)-induced OIA in C57BL/6 mice. OIA was developed by HFD feeding for 15 weeks in C57BL/6
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Euiin-tang reduces obesity and hypertension. Patients with obesity may develop obesity-induced asthma (OIA) owing to phlegm dampness. This study aimed to determine whether euiin-tang alleviates high-fat diet (HFD)-induced OIA in C57BL/6 mice. OIA was developed by HFD feeding for 15 weeks in C57BL/6 mice, and euiin-tang (5 mg/10 g/day) was orally administered for the last five weeks. Oral administration of euiin-tang suppressed HFD-induced changes in body weight, liver weight, airway hypersensitivity (AHR), and immune cell infiltration in bronchoalveolar lavage fluid. Histological analysis revealed that euiin-tang treatment suppressed HFD-induced mucosal inflammation, hypersecretion, and fibrosis. The lungs and gonadal white adipose tissue showed increased expression of inflammatory cytokines (IL-1β, IL-17A, TNF-α, IL-6, IL-13, IFN-γ, MPO, and CCL2) following HFD, whereas euiin-tang inhibited this increase. HFD also increased the number of pro-inflammatory CD86+ M1 macrophages and decreased the number of anti-inflammatory CD206+ M2 macrophages in the lungs, whereas euiin-tang treatment reversed these effects. HFD induced a decrease in adiponectin and an increase in leptin, which was reversed by euiin-tang. Therefore, euiin-tang may be a potential therapeutic agent for OIA because it suppresses metaflammation as demonstrated in the present study.
Full article
(This article belongs to the Special Issue The Mode of Action of Herbal Medicines and Natural Products)
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Open AccessArticle
Neuroprotective Effects of Glycyrrhiza glabra Total Extract and Isolated Compounds
by
Ali O. E. Eltahir, Sylvester I. Omoruyi, Tanya N. Augustine, Robert C. Luckay and Ahmed A. Hussein
Pharmaceuticals 2024, 17(7), 852; https://doi.org/10.3390/ph17070852 - 28 Jun 2024
Abstract
Glycyrrhiza glabra L. is a plant commonly utilized in herbal medicine and stands out as one of the more extensively researched medicinal plants globally. It has been documented with respect to several pharmacological activities, notably, neuroprotective effects, among others. However, the neuroprotective activity
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Glycyrrhiza glabra L. is a plant commonly utilized in herbal medicine and stands out as one of the more extensively researched medicinal plants globally. It has been documented with respect to several pharmacological activities, notably, neuroprotective effects, among others. However, the neuroprotective activity of pure phenolic compounds has not been reported yet. The chromatographic of a methanolic extract yielded twenty-two compounds, viz.: naringenin 4′-O-glucoside (1), 3′,4′,7-trihydroxyflavanone (butin) (2), liquiritin (3), liquiritin apioside (4), abyssinone (5), glabrol (6), isoliquiritin (7), neoisoliquiritin (8), isoliquiritin apioside (9), licuraside (10). 3’[O], 4’-(2,2-dimethylpyrano)-3,7-dihydroxyflavanone (11), glabrocoumarin (12), glabrene (13), isomedicarpin (14), 7-hydroxy-4′-methoxyflavone (formononetin) (15), ononin (16), glycyroside (17), (3S)-7,4′-dihydroxy-2′-methoxyisoflavan (18), glabridin (19), neoliquiritin (20), 3,11-dioxooleana-1,12-dien-29-oic acid (21), and 3-oxo-18β-glycyrrhetinic acid (22). The results of the neuroprotection evaluation showed that G. glabra total extract (TE) and compounds 1, 7, 11, 16, and 20 protected SH-SY5Y cells by inhibiting the depletion of ATP and elevated caspase 3/7 activities induced by MPP+. Indeed, this study reports for the first time the structure and activity of compound 11 and the neuroprotective activity of some phenolic constituents from G. glabra.
Full article
(This article belongs to the Special Issue Anti-obesity and Anti-aging Natural Products)
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Open AccessArticle
Electrospun Gelatin Scaffolds with Incorporated Antibiotics for Skin Wound Healing
by
Katarina Virijević, Marko Živanović, Jelena Pavić, Luka Dragačević, Biljana Ljujić, Marina Miletić Kovačević, Miloš Papić, Suzana Živanović, Strahinja Milenković, Ivana Radojević and Nenad Filipović
Pharmaceuticals 2024, 17(7), 851; https://doi.org/10.3390/ph17070851 - 28 Jun 2024
Abstract
Recent advances in regenerative medicine provide encouraging strategies to produce artificial skin substitutes. Gelatin scaffolds are successfully used as wound-dressing materials due to their superior properties, such as biocompatibility and the ability to mimic the extracellular matrix of the surrounding environment. In this
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Recent advances in regenerative medicine provide encouraging strategies to produce artificial skin substitutes. Gelatin scaffolds are successfully used as wound-dressing materials due to their superior properties, such as biocompatibility and the ability to mimic the extracellular matrix of the surrounding environment. In this study, five gelatin combination solutions were prepared and successfully electrospun using an electrospinning technique. After careful screening, the optimal concentration of the most promising combination was selected for further investigation. The obtained scaffolds were crosslinked with 25% glutaraldehyde vapor and characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. The incorporation of antibiotic agents such as ciprofloxacin hydrochloride and gentamicin sulfate into gelatin membranes improved the already existing antibacterial properties of antibiotic-free gelatin scaffolds against Pseudomonas aeruginosa and Staphylococcus aureus. Also, the outcomes from the in vivo model study revealed that skin regeneration was significantly accelerated with gelatin/ciprofloxacin scaffold treatment. Moreover, the gelatin nanofibers were found to strongly promote the neoangiogenic process in the in vivo chick embryo chorioallantoic membrane assay. Finally, the combination of gelatin’s extracellular matrix and antibacterial agents in the scaffold suggests its potential for effective wound-healing treatments, emphasizing the importance of gelatin scaffolds in tissue engineering.
Full article
(This article belongs to the Section Pharmacology)
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Graphical abstract
Open AccessArticle
Evolutionary Trend Analysis of Research on Immunotherapy for Brain Metastasis Based on Machine-Learning Scientometrics
by
Xiaoqian Hu, Xinpei Deng, Jindong Xie, Hanqi Zhang, Huiting Zhang, Beibei Feng, Yutian Zou and Chuhuai Wang
Pharmaceuticals 2024, 17(7), 850; https://doi.org/10.3390/ph17070850 - 28 Jun 2024
Abstract
Brain metastases challenge cancer treatments with poor prognoses, despite ongoing advancements. Immunotherapy effectively alleviates advanced cancer, exhibiting immense potential to revolutionize brain metastasis management. To identify research priorities that optimize immunotherapies for brain metastases, 2164 related publications were analyzed. Scientometric visualization via R
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Brain metastases challenge cancer treatments with poor prognoses, despite ongoing advancements. Immunotherapy effectively alleviates advanced cancer, exhibiting immense potential to revolutionize brain metastasis management. To identify research priorities that optimize immunotherapies for brain metastases, 2164 related publications were analyzed. Scientometric visualization via R software, VOSviewer, and CiteSpace showed the interrelationships among literature, institutions, authors, and topic areas of focus. The publication rate and citations have grown exponentially over the past decade, with the US, China, and Germany as the major contributors. The University of Texas MD Anderson Cancer Center ranked highest in publications, while Memorial Sloan Kettering Cancer Center was most cited. Clusters of keywords revealed six hotspots: ‘Immunology’, ‘Check Point Inhibitors’, ‘Lung Cancer’, ‘Immunotherapy’, ‘Melanoma’, ‘Breast Cancer’, and ‘Microenvironment’. Melanoma, the most studied primary tumor with brain metastases offers promising immunotherapy advancements with generalizability and adaptability to other cancers. Our results outline the holistic overview of immunotherapy research for brain metastases, which pinpoints the forefront in the field, and directs researchers toward critical inquiries for enhanced mechanistic insight and improved clinical outcomes. Moreover, governmental and funding agencies will benefit from assigning financial resources to entities and regions with the greatest potential for combating brain metastases through immunotherapy.
Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—How Artificial Intelligence Is Reshaping Pharmaceuticals Technology)
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Open AccessArticle
Effect of Curcumin Plus Piperine on Redox Imbalance, Fecal Calprotectin and Cytokine Levels in Inflammatory Bowel Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
by
Amylly Sanuelly da Paz Martins, Orlando Roberto Pimentel de Araújo, Amanda da Silva Gomes, Fernanda Lívia Cavalcante Araujo, José Oliveira Junior, Joice Kelly Gomes de Vasconcelos, José Israel Rodrigues Junior, Islany Thaissa Cerqueira, Manoel Álvaro de Freitas Lins Neto, Nassib Bezerra Bueno, Marília Oliveira Fonseca Goulart and Fabiana Andréa Moura
Pharmaceuticals 2024, 17(7), 849; https://doi.org/10.3390/ph17070849 - 28 Jun 2024
Abstract
The development and course of inflammatory bowel disease (IBD) are significantly influenced by inflammation and oxidative stress. Antioxidant therapy is a promising therapeutic option to enhance the clinical results of these individuals in this particular scenario. The purpose of this study is to
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The development and course of inflammatory bowel disease (IBD) are significantly influenced by inflammation and oxidative stress. Antioxidant therapy is a promising therapeutic option to enhance the clinical results of these individuals in this particular scenario. The purpose of this study is to assess the impact of curcumin, with or without piperine, on cytokines, fecal calprotectin (CalF), and oxidative stress enzymatic and non-enzymatic indicators in patients with IBD. Methods: Patients with Crohn’s disease (CD) or ulcerative colitis (UC) who were at least 18 years old and had intact liver and kidney function participated in this randomized, double-blind trial (trial registration: ensaiosclinicos.gov.br as RBR-89q4ydz). For 12 weeks, participants were randomly assigned to one of three groups: placebo, curcumin (1000 mg/day), or curcumin plus piperine (1000 mg + 10 mg/day). In order to examine oxidative stress indicators, CalF, and pro-inflammatory cytokines, blood and fecal samples were obtained, both prior to and following the intervention time. Results: After adjusting for age, sex, and type of IBD, the curcumin plus piperine group had substantially higher serum levels of superoxide dismutase (SOD) than the placebo group (4346.9 ± 879.0 vs. 3614.5 ± 731.5; p = 0.041). There were no discernible variations between the groups in CalF, inflammatory markers, or other indicators of oxidative stress. Conclusions: In patients with inflammatory bowel disease (IBD), our study indicates that a 12-week curcumin plus piperine treatment effectively increases enzymatic antioxidant defense, especially SOD. These results demonstrate the potential therapeutic benefits of managing redox imbalance in individuals with IBD.
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(This article belongs to the Section Natural Products)
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Open AccessReview
Comprehensive Review of Cyclamen: Development, Bioactive Properties, and Therapeutic Applications
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Aya Sharara, Adnan Badran, Akram Hijazi, Ghosoon Albahri, Mikhael Bechelany, Joelle Edward Mesmar and Elias Baydoun
Pharmaceuticals 2024, 17(7), 848; https://doi.org/10.3390/ph17070848 - 27 Jun 2024
Abstract
Plants are being researched as potential sources of novel drugs, which has led to a recent acceleration in the discovery of new bioactive compounds. Research on tissue culture technology for the synthesis and processing of plant compounds has skyrocketed, surpassing all expectations. These
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Plants are being researched as potential sources of novel drugs, which has led to a recent acceleration in the discovery of new bioactive compounds. Research on tissue culture technology for the synthesis and processing of plant compounds has skyrocketed, surpassing all expectations. These plants can be bought either raw or as extracts, where some of the chemicals are extracted by mashing the plant in water, alcohol, or another solvent. The use of herbal medicine may open new chances for reducing the onset of infections and treating different diseases including cancer. A perennial plant that blooms in the winter, Cyclamen, is one of the most widely used potted flowers in many nations. Alkaloids, flavonoids, phenols, tannins, saponins, sterols, and glycosides are the main active components of Cyclamen. Analgesic, cytotoxic, antioxidant, antimicrobial, and anti-inflammatory properties have all been demonstrated as potential effects of various extracts of Cyclamen tubers. However, the use of this medicinal plant in official medicine will require further research in the areas of pharmacology. Furthermore, it is necessary to create standard operating procedures for a crude herbal medication. In this regard, this review aims to highlight the key characteristics of the Cyclamen plant, such as its various parts, species, stages of development, and geographic range; pinpoint its intriguing bioactivities, its antioxidant, anti-inflammatory, and its anti-cancerous effects; and ascertain its potential medicinal uses and the main future perspectives.
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(This article belongs to the Section Natural Products)
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Open AccessReview
Skin-Related Adverse Reactions Induced by Oral Antidiabetic Drugs—A Review of Literature and Case Reports
by
Justyna Kowalska and Dorota Wrześniok
Pharmaceuticals 2024, 17(7), 847; https://doi.org/10.3390/ph17070847 - 27 Jun 2024
Abstract
Type 2 diabetes (T2DM) is a chronic metabolic disease with a steadily increasing prevalence worldwide. Diabetes affects the function of many organs, including the skin. Pharmacotherapy for T2DM is mainly based on oral hypoglycemic drugs. The therapeutic strategy is chosen taking into account
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Type 2 diabetes (T2DM) is a chronic metabolic disease with a steadily increasing prevalence worldwide. Diabetes affects the function of many organs, including the skin. Pharmacotherapy for T2DM is mainly based on oral hypoglycemic drugs. The therapeutic strategy is chosen taking into account the individual patient’s characteristics, among other comorbidities. Antidiabetic drugs can induce cutaneous adverse reactions (CADRs) ranging in severity from mild erythema to serious disorders such as DRESS or Stevens–Johnson syndrome. CADRs can result from hypersensitivity to the drug but can also be related to the mechanism of action of the drug or cross-reactivity with drugs of similar structure. This paper reviews CADRs induced by oral antidiabetic drugs, considering their dermatological manifestations and possible pathomechanisms. Particular attention was paid to specific dermatological conditions such as dipeptidylpeptidase 4 inhibitor-associated bullous pemphigoid or Fournier’s gangrene associated with sodium-glucose cotransporter 2 inhibitor therapy. Knowledge of the dermatological manifestations of CADRs is important in clinical practice. Recognition of a skin lesion resulting from an adverse drug reaction allows for appropriate management, which in this case is primarily related to drug discontinuation. This is particularly important in the treatment of T2DM since this disease has a high prevalence in the elderly, who are at higher risk of adverse drug reactions.
Full article
(This article belongs to the Section Pharmacology)
Open AccessArticle
Examining the Role of Oxytocinergic Signaling and Neuroinflammatory Markers in the Therapeutic Effects of MDMA in a Rat Model for PTSD
by
Haron Avgana, Roni Shira Toledano and Irit Akirav
Pharmaceuticals 2024, 17(7), 846; https://doi.org/10.3390/ph17070846 - 27 Jun 2024
Abstract
MDMA-assisted psychotherapy has shown potential as an effective treatment for post-traumatic stress disorder (PTSD). Preclinical studies involving rodents have demonstrated that MDMA can facilitate the extinction of fear memories. It has been noted that MDMA impacts oxytocin neurons and pro-inflammatory cytokines. Thus, the
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MDMA-assisted psychotherapy has shown potential as an effective treatment for post-traumatic stress disorder (PTSD). Preclinical studies involving rodents have demonstrated that MDMA can facilitate the extinction of fear memories. It has been noted that MDMA impacts oxytocin neurons and pro-inflammatory cytokines. Thus, the aim of this study was to explore the role of oxytocinergic signaling and neuroinflammatory markers in the therapeutic effects of MDMA. To achieve this, male rats were subjected to a model of PTSD involving exposure to shock and situational reminders. MDMA was microinjected into the medial prefrontal cortex (mPFC) before extinction training, followed by behavioral tests assessing activity levels, anxiety, and social function. Our findings indicate that MDMA treatment facilitated fear extinction and mitigated the shock-induced increase in freezing, as well as deficits in social behavior. Shock exposure led to altered expression of the gene coding for OXT-R and neuroinflammation in the mPFC and basolateral amygdala (BLA), which were restored by MDMA treatment. Importantly, the OXT-R antagonist L-368,899 prevented MDMA’s therapeutic effects on extinction and freezing behavior. In conclusion, MDMA’s therapeutic effects in the PTSD model are associated with alterations in OXT-R expression and neuroinflammation, and MDMA’s effects on extinction and anxiety may be mediated by oxytocinergic signaling.
Full article
(This article belongs to the Section Pharmacology)
Open AccessReview
Small Natural Cyclic Peptides from DBAASP Database
by
Evgenia Alimbarashvili, Natia Samsonidze, Maia Grigolava and Malak Pirtskhalava
Pharmaceuticals 2024, 17(7), 845; https://doi.org/10.3390/ph17070845 - 27 Jun 2024
Abstract
Antimicrobial peptides (AMPs) are promising tools for combating microbial resistance. However, their therapeutic potential is hindered by two intrinsic drawbacks—low target affinity and poor in vivo stability. Macrocyclization, a process that improves the pharmacological properties and bioactivity of peptides, can address these limitations.
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Antimicrobial peptides (AMPs) are promising tools for combating microbial resistance. However, their therapeutic potential is hindered by two intrinsic drawbacks—low target affinity and poor in vivo stability. Macrocyclization, a process that improves the pharmacological properties and bioactivity of peptides, can address these limitations. As a result, macrocyclic peptides represent attractive drug candidates. Moreover, many drugs are macrocycles that originated from natural product scaffolds, suggesting that nature offers solutions to the challenges faced by AMPs. In this review, we explore natural cyclic peptides from the DBAASP database. DBAASP is a comprehensive repository of data on antimicrobial/cytotoxic activities and structures of peptides. We analyze the data on small (≤25 AA) ribosomal and non-ribosomal cyclic peptides from DBAASP according to their amino acid composition, bonds used for cyclization, targets they act on, and mechanisms of action. This analysis will enhance our understanding of the small cyclic peptides that nature has provided to defend living organisms.
Full article
(This article belongs to the Special Issue Selected Papers from the 9th International Electronic Conference on Medicinal Chemistry (ECMC2023))
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Open AccessArticle
Inula salicina L.: Insights into Its Polyphenolic Constituents and Biological Activity
by
Viktoria Ivanova, Paraskev Nedialkov, Petya Dimitrova, Tsvetelina Paunova-Krasteva and Antoaneta Trendafilova
Pharmaceuticals 2024, 17(7), 844; https://doi.org/10.3390/ph17070844 - 27 Jun 2024
Abstract
In this study, UHPLC-HRMS analysis of the defatted methanol extract obtained from Inula salicina L. led to the identification of 58 compounds—hydroxycinnamic and hydroxybenzoic acids and their glycosides, acylquinic and caffeoylhexaric acids, and flavonoids and their glycosides. In addition, a new natural compound,
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In this study, UHPLC-HRMS analysis of the defatted methanol extract obtained from Inula salicina L. led to the identification of 58 compounds—hydroxycinnamic and hydroxybenzoic acids and their glycosides, acylquinic and caffeoylhexaric acids, and flavonoids and their glycosides. In addition, a new natural compound, N-(8-methylnepetin)-3-hydroxypiperidin-2-one was isolated and its structure was elucidated by NMR spectroscopy. The presence of a flavoalkaloid in genus Inula is described now for the first time. Chlorogenic acid was the main compound followed by 3,5-, 1,5- and 4,5-dicaffeoylquinic acids. The methanol extract was studied for its antioxidant potential by DPPH, ABTS, and FRAP assays and sun protective properties. In addition, a study was conducted to assess the effectiveness of the tested extract in inhibiting biofilm formation by Gram-positive and Gram-negative strains. Results from crystal violet tests revealed a notable decrease in biofilm mass due to the extract. The anti-biofilm efficacy was confirmed through the observation of the biofilm viability by live/dead staining. The obtained results showed that this plant extract could be used in the development of cosmetic products with antibacterial and sun protection properties.
Full article
(This article belongs to the Special Issue Plant-Derived Natural Compounds as Bioactive Molecules with Beneficial Effects on Human Health)
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Open AccessArticle
Intestinal Metabolism of Crocin and a Pharmacokinetics and Pharmacodynamics Study in the Chronic Social Defeat Stress Mouse Model
by
Fan Xiao, Yulong Song, Guangji Wang and Jiye Aa
Pharmaceuticals 2024, 17(7), 843; https://doi.org/10.3390/ph17070843 - 27 Jun 2024
Abstract
Orally administered crocin rapidly and efficiently rescues depressive-like behaviors in depression models; however, crocin levels in the circulatory and central nervous systems are rather low. The underlying mechanism responsible for the inconsistency between pharmacokinetics and pharmacodynamics is unknown. To identify the active metabolites
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Orally administered crocin rapidly and efficiently rescues depressive-like behaviors in depression models; however, crocin levels in the circulatory and central nervous systems are rather low. The underlying mechanism responsible for the inconsistency between pharmacokinetics and pharmacodynamics is unknown. To identify the active metabolites and clarify the underlying mechanisms, the pharmacokinetics and metabolic effects of the gut flora and hepatic and intestinal microsomes on crocin were examined, and the pharmacodynamics of crocin and its major metabolite, crocetin, were also evaluated in both normal and pseudo germ-free mice subjected to chronic social defeat stress. The results showed that oral administration of 300 mg/kg crocin significantly improved the depression-like behaviors of chronic social defeat stress mice, although the levels of crocin in the circulatory system were rather low (Cmax = 43.5 ± 8.6 μg/L; AUC = 151 ± 20.8 μg·h/L). However, the primary metabolite of crocetin was much more abundant in vivo (Cmax = 4662.5 ± 586.1 μg/L; AUC = 33,451.9 ± 3323.6 μg·h/L). Orally administered crocin was primarily metabolized into crocetin by the gut flora instead of hepatic or intestinal microsomal enzymes, and less than 10% of crocin was transformed into crocetin in the liver or intestinal microsomes. Inhibition of the gut flora dramatically reduced the production of and in vivo exposure to crocetin, and the rapid antidepressant effect of crocin disappeared. Moreover, crocetin showed rapid antidepressant effects similar to those of crocin, and the effects were independent of the gut flora. In conclusion, the metabolic transformation of crocin to crocetin primarily contributes to the rapid antidepressant effects of crocin and is dependent on the gut flora.
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(This article belongs to the Section Pharmacology)
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Open AccessReview
Does Topical Capsaicin Affect the Central Nervous System in Neuropathic Pain? A Narrative Review
by
Kareem Alalami, Jenna Goff, Hannah Grimson, Oliver Martin, Eloise McDonald, Thonima Mirza, Dhruvi Mistry, Adanma Ofodile, Sara Raja, Tooba Shaker, Danah Sleibi and Patrice Forget
Pharmaceuticals 2024, 17(7), 842; https://doi.org/10.3390/ph17070842 - 27 Jun 2024
Abstract
Research has been conducted investigating the neuronal pathways responsible for the generation of chronic neuropathic pain, including the components of it in conditions such as chronic post-surgical pain, phantom limb pain, and cluster headaches. Forming part of the management of such conditions, capsaicin
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Research has been conducted investigating the neuronal pathways responsible for the generation of chronic neuropathic pain, including the components of it in conditions such as chronic post-surgical pain, phantom limb pain, and cluster headaches. Forming part of the management of such conditions, capsaicin as a molecule has proven effective. This review has investigated the central nervous system modifications exhibited in such conditions and the pharmacological mechanisms of capsaicin relevant to this. The current paradigm for explaining topical capsaicin-induced analgesia is that TRPV1-mediated calcium ion influx induces calpain, in turn causing axonal ablation and functional defunctionalisation in the PNS (Peripheral Nervous System). Demonstrated through the analysis of existing data, this review demonstrates the changes seen in the CNS (Central Nervous System) in chronic neuropathic pain, as well as some of the evidence for capsaicin modulation on the CNS. Further supporting this, the specific molecular mechanisms of capsaicin-induced analgesia will also be explored, including the action of TRPV1, as well as discussing the further need for clinical research into this area of uncertainty due to the limited specific data with suitable parameters. Further research this review identified as potentially useful in this field included fMRI (functional Magnetic Resonance Imaging) studies, though more specific observational studies of patients who have already been administered capsaicin as a current treatment may prove helpful in studying the modification of the CNS in the long term.
Full article
(This article belongs to the Special Issue Use of Anesthetic Agents: Management and New Strategy)
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Open AccessPerspective
Use of Extracellular Monomeric Ubiquitin as a Therapeutic Option for Major Depressive Disorder
by
José Luis Maldonado-García, Lissette Haydee García-Mena, Danelia Mendieta-Cabrera, Gilberto Pérez-Sánchez, Enrique Becerril-Villanueva, Samantha Alvarez-Herrera, Toni Homberg, Luis Vallejo-Castillo, Sonia Mayra Pérez-Tapia, Martha C. Moreno-Lafont, Daniel Ortuño-Sahagún and Lenin Pavón
Pharmaceuticals 2024, 17(7), 841; https://doi.org/10.3390/ph17070841 - 27 Jun 2024
Abstract
Major depressive disorder (MDD) is a mood disorder that has become a global health emergency according to the World Health Organization (WHO). It affects 280 million people worldwide and is a leading cause of disability and financial loss. Patients with MDD present immunoendocrine
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Major depressive disorder (MDD) is a mood disorder that has become a global health emergency according to the World Health Organization (WHO). It affects 280 million people worldwide and is a leading cause of disability and financial loss. Patients with MDD present immunoendocrine alterations like cortisol resistance and inflammation, which are associated with alterations in neurotransmitter metabolism. There are currently numerous therapeutic options for patients with MDD; however, some studies suggest a high rate of therapeutic failure. There are multiple hypotheses explaining the pathophysiological mechanisms of MDD, in which several systems are involved, including the neuroendocrine and immune systems. In recent years, inflammation has become an important target for the development of new therapeutic options. Extracellular monomeric ubiquitin (emUb) is a molecule that has been shown to have immunomodulatory properties through several mechanisms including cholinergic modulation and the generation of regulatory T cells. In this perspective article, we highlight the influence of the inflammatory response in MDD. In addition, we review and discuss the evidence for the use of emUb contained in Transferon as a concomitant treatment with selective serotonin reuptake inhibitors (SSRIs).
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(This article belongs to the Section Pharmacology)
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Open AccessArticle
Czech Honeydew Honeys—A Potential Source of Local Medical Honey with Strong Antimicrobial Activity
by
Ludovit Pudelka, Radek Sleha, Sylva Janovska, Vera Radochova and Pavel Bostik
Pharmaceuticals 2024, 17(7), 840; https://doi.org/10.3390/ph17070840 - 27 Jun 2024
Abstract
An increasing resistance of microbes to antibiotics, the emergence of multidrug-resistant and extremely resistant strains, and the long time needed to develop new antibiotics are driving the search for additional sources of antibacterial agents. The aim of the study was to compare the
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An increasing resistance of microbes to antibiotics, the emergence of multidrug-resistant and extremely resistant strains, and the long time needed to develop new antibiotics are driving the search for additional sources of antibacterial agents. The aim of the study was to compare the efficacy of Czech honeys with already available pharmaceutical agents containing medicinal honey, and to perform basic biochemical analysis of Czech samples, including detection of undesirable chemical substances. The results showed strong antibacterial activity of Czech honeydew honeys compared to the control group, especially against G+ pathogens, with an average MIC of 9.44% compared to 17.54%, and comparable activity against G− of 16.48% versus 16.66%. In addition to the strong antibacterial activity, this study confirmed the safety and quality of Czech honeys and helped to select the character of a possible source for in vivo testing and subsequent clinical trials.
Full article
(This article belongs to the Special Issue Natural Products and Their Modifications as Agents Used in the Fight against Pathogens)
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Open AccessArticle
Discovery of 1H-benzo[d]imidazole-(halogenated)Benzylidenebenzohydrazide Hybrids as Potential Multi-Kinase Inhibitors
by
Tebyan O. Mirgany, Hanadi H. Asiri, A. F. M. Motiur Rahman and Mohammed M. Alanazi
Pharmaceuticals 2024, 17(7), 839; https://doi.org/10.3390/ph17070839 - 26 Jun 2024
Abstract
In an effort to develop improved and effective targeted tyrosine kinase inhibitors (TKIs), a series of twelve novel compounds with the structural motif “(E)-4-(((1H-benzo[d]imidazol-2-yl)methyl)amino)-N′-(halogenated)benzylidenebenzohydrazide” were successfully synthesized in three steps, yielding high product yields (53–97%).
[...] Read more.
In an effort to develop improved and effective targeted tyrosine kinase inhibitors (TKIs), a series of twelve novel compounds with the structural motif “(E)-4-(((1H-benzo[d]imidazol-2-yl)methyl)amino)-N′-(halogenated)benzylidenebenzohydrazide” were successfully synthesized in three steps, yielding high product yields (53–97%). Among this new class of compounds, 6c and 6h-j exhibited excellent cytotoxic effects against four different cancer cell lines, with half-maximal inhibitory concentration (IC50) values ranging from 7.82 to 21.48 μM. Notably, compounds 6h and 6i emerged as the most potent inhibitors, demonstrating significant activity against key kinases such as EGFR, HER2, and CDK2. Furthermore, compound 6h displayed potent inhibitory activity against AURKC, while 6i showed potent inhibitory effects against the mTOR enzyme, with excellent IC50 values comparable with well-established TKIs. The mechanistic study of lead compound 6i revealed its ability to induce cell cycle arrest and apoptosis in HepG2 liver cancer cells. This was accompanied by upregulation of pro-apoptotic caspase-3 and Bax and downregulation of anti-apoptotic Bcl-2. Additionally, molecular docking studies indicated that the binding interactions of compounds 6h and 6i with the target enzymes give multiple interactions. These results underscore the ability of compound 6i as a compelling lead candidate warranting further optimization and development as a potent multi-targeted kinase inhibitor, which could have significant implications for the treatment of various cancers. The detailed structural optimization, mechanism of action, and in vivo evaluation of this class of compounds warrant further investigation to assess their therapeutic potential.
Full article
(This article belongs to the Special Issue Heterocyclic Compounds in Medicinal Chemistry)
Open AccessReview
Sex-Gender Differences Are Completely Neglected in Treatments for Neuropathic Pain
by
Francesco Salis, Salvatore Sardo, Gabriele Finco, Gian Luigi Gessa, Flavia Franconi and Roberta Agabio
Pharmaceuticals 2024, 17(7), 838; https://doi.org/10.3390/ph17070838 - 26 Jun 2024
Abstract
As sex-gender differences have been described in the responses of patients to certain medications, we hypothesized that the responses to medications recommended for neuropathic pain may differ between men and women. We conducted a literature review to identify articles reporting potential sex-gender differences
[...] Read more.
As sex-gender differences have been described in the responses of patients to certain medications, we hypothesized that the responses to medications recommended for neuropathic pain may differ between men and women. We conducted a literature review to identify articles reporting potential sex-gender differences in the efficacy and safety of these medications. Only a limited number of studies investigated potential sex-gender differences. Our results show that women seem to achieve higher blood concentrations than men during treatment with amitriptyline, nortriptyline, duloxetine, venlafaxine, and pregabalin. Compared to men, higher rates of women develop side effects during treatment with gabapentin, lidocaine, and tramadol. Globally, the sex-gender differences would suggest initially administering smaller doses of these medications to women with neuropathic pain compared to those administered to men. However, most of these differences have been revealed by studies focused on the treatment of other diseases (e.g., depression). Studies focused on neuropathic pain have overlooked potential sex-gender differences in patient responses to medications. Despite the fact that up to 60% of patients with neuropathic pain fail to achieve an adequate response to medications, the potential role of sex-gender differences in the efficacy and safety of pharmacotherapy has not adequately been investigated. Targeted studies should be implemented to facilitate personalized treatments for neuropathic pain.
Full article
(This article belongs to the Special Issue Sex Differences in Pharmaceutical Practice)
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Open AccessReview
Non-Apoptotic Programmed Cell Death as Targets for Diabetic Retinal Neurodegeneration
by
Yingjia Lin, Shuping Ke, Weiqing Ye, Biyao Xie and Zijing Huang
Pharmaceuticals 2024, 17(7), 837; https://doi.org/10.3390/ph17070837 - 26 Jun 2024
Abstract
Diabetic retinopathy (DR) remains the leading cause of blindness among the global working-age population. Emerging evidence underscores the significance of diabetic retinal neurodegeneration (DRN) as a pivotal biomarker in the progression of vasculopathy. Inflammation, oxidative stress, neural cell death, and the reduction in
[...] Read more.
Diabetic retinopathy (DR) remains the leading cause of blindness among the global working-age population. Emerging evidence underscores the significance of diabetic retinal neurodegeneration (DRN) as a pivotal biomarker in the progression of vasculopathy. Inflammation, oxidative stress, neural cell death, and the reduction in neurotrophic factors are the key determinants in the pathophysiology of DRN. Non-apoptotic programmed cell death (PCD) plays a crucial role in regulating stress response, inflammation, and disease management. Therapeutic modalities targeting PCD have shown promising potential for mitigating DRN. In this review, we highlight recent advances in identifying the role of various PCD types in DRN, with specific emphasis on necroptosis, pyroptosis, ferroptosis, parthanatos, and the more recently characterized PANoptosis. In addition, the therapeutic agents aimed at the regulation of PCD for addressing DRN are discussed.
Full article
(This article belongs to the Special Issue New Insights into Therapy for Alzheimer’s and Other Neurodegenerative Diseases)
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