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 - Q2 (Pharmacology & 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:
4.6 (2022);
5-Year Impact Factor:
4.9 (2022)
Latest Articles
Influence of Gut Microbiota-Mediated Immune Regulation on Response to Chemotherapy
Pharmaceuticals 2024, 17(5), 604; https://doi.org/10.3390/ph17050604 - 8 May 2024
Abstract
The involvement of the gut microbiota in anti-cancer treatment has gained increasing attention. Alterations to the structure and function of the gut bacteria are important factors in the development of cancer as well as the efficacy of chemotherapy. Recent studies have confirmed that
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The involvement of the gut microbiota in anti-cancer treatment has gained increasing attention. Alterations to the structure and function of the gut bacteria are important factors in the development of cancer as well as the efficacy of chemotherapy. Recent studies have confirmed that the gut microbiota and related metabolites influence the pharmacological activity of chemotherapeutic agents through interactions with the immune system. This review aims to summarize the current knowledge of how malignant tumor and chemotherapy affect the gut microbiota, how the gut microbiota regulates host immune response, and how interactions between the gut microbiota and host immune response influence the efficacy of chemotherapy. Recent advances in strategies for increasing the efficiency of chemotherapy based on the gut microbiota are also described. Deciphering the complex homeostasis maintained by the gut microbiota and host immunity provides a solid scientific basis for bacterial intervention in chemotherapy.
Full article
(This article belongs to the Special Issue Gut Microbiota Modulation: Probiotics, Postbiotics and other Bioactive Compounds)
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Open AccessArticle
Evaluating the Effectiveness of Phellodendron Amurense Ruprecht Extract as a Natural Anti-Caries Material
by
Yu-Rin Kim, Gyoo-Cheon Kim and Seoul-Hee Nam
Pharmaceuticals 2024, 17(5), 603; https://doi.org/10.3390/ph17050603 - 8 May 2024
Abstract
Background: This study aimed to investigate the antibacterial and cytotoxic potential of Phellodendron amurense Ruprecht (PAR) extract against Streptococcus mutans (S. mutans) and explore the possibility of using PAR extract as an anticariogenic agent. Methods: Mixed extracts were prepared at 0,
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Background: This study aimed to investigate the antibacterial and cytotoxic potential of Phellodendron amurense Ruprecht (PAR) extract against Streptococcus mutans (S. mutans) and explore the possibility of using PAR extract as an anticariogenic agent. Methods: Mixed extracts were prepared at 0, 1.25, 2.5, and 5 mg/mL concentrations, and an S. mutans-containing solution of 100 μL was inoculated into the medium. The survival rate of human keratinocyte (HaCaT) cells was assessed to confirm stability. One-way ANOVA was performed to evaluate the antibacterial activity against S. mutans and the proliferation of HaCaT cells. Results: Higher concentrations of the PAR extract showed more growth inhibition of S. mutans over time, with the complete inactivation of S. mutans at 5 mg/mL. HaCaT cell density was reduced at a PAR extract concentration of 1.25 mg/mL, but IC50 was not observed, confirming that the concentration used did not affect the cytotoxicity and proliferation. Conclusions: Results showed that the PAR extract was excellent as a natural substance with anticariogenic effects that inhibited the growth of S. mutans and did not affect the cell viability, thus indicating the potential for clinical application.
Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
Open AccessReview
Mechanistic Sequence of Histone Deacetylase Inhibitors and Radiation Treatment: An Overview
by
Elsie Neo Seane, Shankari Nair, Charlot Vandevoorde and Anna Joubert
Pharmaceuticals 2024, 17(5), 602; https://doi.org/10.3390/ph17050602 - 8 May 2024
Abstract
Histone deacetylases inhibitors (HDACis) have shown promising therapeutic outcomes in haematological malignancies such as leukaemia, multiple myeloma, and lymphoma, with disappointing results in solid tumours when used as monotherapy. As a result, combination therapies either with radiation or other deoxyribonucleic acid (DNA) damaging
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Histone deacetylases inhibitors (HDACis) have shown promising therapeutic outcomes in haematological malignancies such as leukaemia, multiple myeloma, and lymphoma, with disappointing results in solid tumours when used as monotherapy. As a result, combination therapies either with radiation or other deoxyribonucleic acid (DNA) damaging agents have been suggested as ideal strategy to improve their efficacy in solid tumours. Numerous in vitro and in vivo studies have demonstrated that HDACis can sensitise malignant cells to both electromagnetic and particle types of radiation by inhibiting DNA damage repair. Although the radiosensitising ability of HDACis has been reported as early as the 1990s, the mechanisms of radiosensitisation are yet to be fully understood. This review brings forth the various protocols used to sequence the administration of radiation and HDACi treatments in the different studies. The possible contribution of these various protocols to the ambiguity that surrounds the mechanisms of radiosensitisation is also highlighted.
Full article
(This article belongs to the Special Issue 20th Anniversary of Pharmaceuticals—Advances in Radiopharmaceutical Sciences and Nuclear Medicine)
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Open AccessReview
Recent Advances in the Discovery of SIRT1/2 Inhibitors via Computational Methods: A Perspective
by
Naomi Scarano, Chiara Brullo, Francesca Musumeci, Enrico Millo, Santina Bruzzone, Silvia Schenone and Elena Cichero
Pharmaceuticals 2024, 17(5), 601; https://doi.org/10.3390/ph17050601 - 8 May 2024
Abstract
Sirtuins (SIRTs) are classified as class III histone deacetylases (HDACs), a family of enzymes that catalyze the removal of acetyl groups from the ε-N-acetyl lysine residues of histone proteins, thus counteracting the activity performed by histone acetyltransferares (HATs). Based on their involvement in
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Sirtuins (SIRTs) are classified as class III histone deacetylases (HDACs), a family of enzymes that catalyze the removal of acetyl groups from the ε-N-acetyl lysine residues of histone proteins, thus counteracting the activity performed by histone acetyltransferares (HATs). Based on their involvement in different biological pathways, ranging from transcription to metabolism and genome stability, SIRT dysregulation was investigated in many diseases, such as cancer, neurodegenerative disorders, diabetes, and cardiovascular and autoimmune diseases. The elucidation of a consistent number of SIRT–ligand complexes helped to steer the identification of novel and more selective modulators. Due to the high diversity and quantity of the structural data thus far available, we reviewed some of the different ligands and structure-based methods that have recently been used to identify new promising SIRT1/2 modulators. The present review is structured into two sections: the first includes a comprehensive perspective of the successful computational approaches related to the discovery of SIRT1/2 inhibitors (SIRTIs); the second section deals with the most interesting SIRTIs that have recently appeared in the literature (from 2017). The data reported here are collected from different databases (SciFinder, Web of Science, Scopus, Google Scholar, and PubMed) using “SIRT”, “sirtuin”, and “sirtuin inhibitors” as keywords.
Full article
(This article belongs to the Special Issue Computer-Aided Drug Design and Drug Discovery)
Open AccessArticle
Bioactivity Profiling of Daedaleopsis confragosa (Bolton) J. Schröt. 1888: Implications for Its Possible Application in Enhancing Women’s Reproductive Health
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Djordje Ilić, Maja Karaman, Mirjana Bogavac, Jovana Mišković and Milena Rašeta
Pharmaceuticals 2024, 17(5), 600; https://doi.org/10.3390/ph17050600 - 8 May 2024
Abstract
This study investigates the bioactivity profile of wood-rotting fungal species Daedaleopsis confragosa (Bolton) J. Schröt. 1888, focusing on its antioxidant, cytotoxic, and genotoxic activities and enzyme modulation properties with respect to its possible application in terms of enhancing women’s reproductive health. Two types
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This study investigates the bioactivity profile of wood-rotting fungal species Daedaleopsis confragosa (Bolton) J. Schröt. 1888, focusing on its antioxidant, cytotoxic, and genotoxic activities and enzyme modulation properties with respect to its possible application in terms of enhancing women’s reproductive health. Two types of extracts, including those based on EtOH extraction (DC) and hydrodistillation (DCHD), were investigated. The results indicate that the radical scavenging capacity against the DPPH radical and reduction potential were stronger in the DC extracts owing to the higher total phenolic content (TPC) and total flavonoid content (TFC) (25.30 ± 1.05 mg GAE/g d.w. and 2.84 ± 0.85 mg QE/g d.w., respectively). The same trend was observed in the protein phosphatase-1 (PP1) activity and in the genotoxic activity against the δ virus since only the DC extract exhibited DNA disintegration regarding a dilution of 1:100. Conversely, the DCHD extract exhibited increased hemolytic and cytotoxic effects (339.39% and IC50 = 27.76 ± 0.89 μg/mL—72 h incubation, respectively), along with greater inhibition of the AChE enzyme (IC50 = 3.11 ± 0.45 mg/mL) and hemolytic activity. These results suggest that terpenoids and steroids may be responsible for the observed activity in DCHD as these compounds could potentially be extracted following the HD procedure. This comprehensive bioactivity profiling offers valuable insights into the potential therapeutic applications of D. confragosa from Serbia and underscores the importance of further investigations for harnessing its pharmacological potential.
Full article
(This article belongs to the Special Issue Discovery, Metabolism and Potential Bio-Activities of Natural Products in Traditional Medicine 2024)
Open AccessArticle
Insights from Syzygium aromaticum Essential Oil: Encapsulation, Characterization, and Antioxidant Activity
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Naianny L. O. N. Mergulhão, Laisa C. G. Bulhões, Valdemir C. Silva, Ilza F. B. Duarte, Irinaldo D. Basílio-Júnior, Johnnatan D. Freitas, Adeildo J. Oliveira, Marília O. F. Goulart, Círia V. Barbosa and João X. Araújo-Júnior
Pharmaceuticals 2024, 17(5), 599; https://doi.org/10.3390/ph17050599 - 8 May 2024
Abstract
Alginate encapsulates loaded with clove essential oil (CEO) were prepared by ionic gelation, with subsequent freeze-drying. The objective of the present work was to develop a product with the ability to protect CEO against its easy volatility and oxidation. The following techniques were
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Alginate encapsulates loaded with clove essential oil (CEO) were prepared by ionic gelation, with subsequent freeze-drying. The objective of the present work was to develop a product with the ability to protect CEO against its easy volatility and oxidation. The following techniques were used to characterize the formulations: eugenol release, degree of swelling, GC/MS, TGA/DSC, and SEM. The alginate solution (1.0%) containing different concentrations of CEO (LF1: 1.0%; LF2: 0.5%; LF3: 0.1%) was dropped into a 3.0% CaCl2 solution. After lyophilization, the encapsulated samples were wrinkled and rigid, with high encapsulation power (LF3: 76.9% ± 0.5). Three chemical components were identified: eugenol (the major one), caryophyllene, and humulene. The antioxidant power (LF1: DPPH IC50 18.1 µg mL−1) was consistent with the phenol content (LF1: 172.2 mg GAE g−1). The encapsulated ones were thermally stable, as shown by analysis of FTIR peaks, eugenol molecular structure was kept unaltered. The degree of swelling was 19.2% (PBS). The release of eugenol (92.5%) in the PBS solution was faster than in the acidic medium. It was concluded that the low-cost technology used allows the maintenance of the content and characteristics of CEO in the three concentrations tested, offering a basis for further research with essential oil encapsulates.
Full article
(This article belongs to the Special Issue Pharmaceutical Preparations, Challenges in Formulations and Compatibility Studies)
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Exploring Synergistic Interactions between Natural Compounds and Conventional Chemotherapeutic Drugs in Preclinical Models of Lung Cancer
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Mihaela Boța, Lavinia Vlaia, Alex-Robert Jîjie, Iasmina Marcovici, Flavia Crişan, Cristian Oancea, Cristina Adriana Dehelean, Tudor Mateescu and Elena-Alina Moacă
Pharmaceuticals 2024, 17(5), 598; https://doi.org/10.3390/ph17050598 - 8 May 2024
Abstract
In the current work, the synergy between natural compounds and conventional chemotherapeutic drugs is comprehensively reviewed in light of current preclinical research findings. The prognosis for lung cancer patients is poor, with a 5-year survival rate of 18.1%. The use of natural compounds
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In the current work, the synergy between natural compounds and conventional chemotherapeutic drugs is comprehensively reviewed in light of current preclinical research findings. The prognosis for lung cancer patients is poor, with a 5-year survival rate of 18.1%. The use of natural compounds in combination with conventional chemotherapeutic drugs has gained significant attention as a potential novel approach in the treatment of lung cancer. The present work highlights the importance of finding more effective therapies to increase survival rates. Chemotherapy is a primary treatment option for lung cancer but it has limitations such as reduced effectiveness because cancer cells become resistant. Natural compounds isolated from medicinal plants have shown promising anticancer or chemopreventive properties and their synergistic effect has been observed when combined with conventional therapies. The combined use of an anti-cancer drug and a natural compound exhibits synergistic effects, enhancing overall therapeutic actions against cancer cells. In conclusion, this work provides an overview of the latest preclinical research on medicinal plants and plant-derived compounds as alternative or complementary treatment options for lung cancer chemotherapy and discusses the potential of natural compounds in treating lung cancer with minimal side effects.
Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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Open AccessReview
Emerging Vistas for the Nutraceutical Withania somnifera in Inflammaging
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Vivek Basudkar, Gunjan Gujrati, Saiprasad Ajgaonkar, Manav Gandhi, Dilip Mehta and Sujit Nair
Pharmaceuticals 2024, 17(5), 597; https://doi.org/10.3390/ph17050597 - 7 May 2024
Abstract
Inflammaging, a coexistence of inflammation and aging, is a persistent, systemic, low-grade inflammation seen in the geriatric population. Various natural compounds have been greatly explored for their potential role in preventing and treating inflammaging. Withania somnifera has been used for thousands of years
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Inflammaging, a coexistence of inflammation and aging, is a persistent, systemic, low-grade inflammation seen in the geriatric population. Various natural compounds have been greatly explored for their potential role in preventing and treating inflammaging. Withania somnifera has been used for thousands of years in traditional medicine as a nutraceutical for its numerous health benefits including regenerative and adaptogenic effects. Recent preclinical and clinical studies on the role of Withania somnifera and its active compounds in treating aging, inflammation, and oxidative stress have shown promise for its use in healthy aging. We discuss the chemistry of Withania somnifera, the etiology of inflammaging and the protective role(s) of Withania somnifera in inflammaging in key organ systems including brain, lung, kidney, and liver as well as the mechanistic underpinning of these effects. Furthermore, we elucidate the beneficial effects of Withania somnifera in oxidative stress/DNA damage, immunomodulation, COVID-19, and the microbiome. We also delineate a putative protein–protein interaction network of key biomarkers modulated by Withania somnifera in inflammaging. In addition, we review the safety/potential toxicity of Withania somnifera as well as global clinical trials on Withania somnifera. Taken together, this is a synthetic review on the beneficial effects of Withania somnifera in inflammaging and highlights the potential of Withania somnifera in improving the health-related quality of life (HRQoL) in the aging population worldwide.
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(This article belongs to the Section Natural Products)
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Open AccessArticle
Optimizing Encapsulation: Comparative Analysis of Spray-Drying and Freeze-Drying for Sustainable Recovery of Bioactive Compounds from Citrus x paradisi L. Peels
by
Jolita Stabrauskiene, Lauryna Pudziuvelyte and Jurga Bernatoniene
Pharmaceuticals 2024, 17(5), 596; https://doi.org/10.3390/ph17050596 - 7 May 2024
Abstract
Spray-drying and freeze-drying are indispensable techniques for microencapsulating biologically active compounds, crucial for enhancing their bioavailability and stability while protecting them from environmental degradation. This study evaluates the effectiveness of these methods in encapsulating Citrus x paradisi L. (grapefruit) peel extract, focusing on
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Spray-drying and freeze-drying are indispensable techniques for microencapsulating biologically active compounds, crucial for enhancing their bioavailability and stability while protecting them from environmental degradation. This study evaluates the effectiveness of these methods in encapsulating Citrus x paradisi L. (grapefruit) peel extract, focusing on sustainable recovery from waste peels. Key objectives included identifying optimal wall materials and assessing each encapsulation technique’s impact on microencapsulation. The investigation highlighted that the choice of wall material composition significantly affects the microencapsulation’s efficiency and morphological characteristics. A wall material mixture of 17 g maltodextrin, 0.5 g carboxymethylcellulose, and 2.5 g β-cyclodextrin was optimal for spray drying. This combination resulted in a sample with a wettability time of 1170 (s), a high encapsulation efficiency of 91.41%, a solubility of 60.21%, and a low moisture content of 5.1 ± 0.255%. These properties indicate that spray-drying, particularly with this specific wall material composition, offers a durable structure and can be conducive to prolonged release. Conversely, varying the precise compositions used in the freeze-drying process yielded different results: quick wettability at 132.6 (s), a solubility profile of 61.58%, a moisture content of 5.07%, and a high encapsulation efficiency of 78.38%. The use of the lyophilization technique with this latter wall material formula resulted in a more porous structure, which may facilitate a more immediate release of encapsulated compounds and lower encapsulation efficiency.
Full article
(This article belongs to the Special Issue Emerging Freeze Drying and Spray Drying Techniques)
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Open AccessArticle
Pharmacokinetic–Pharmacodynamic Correlation Analysis of Rhodiola crenulata in Rats with Myocardial Ischemia
by
Zhixin Jia, Guoming Zou, Yongyan Xie, Enning Zhang, Mureziya Yimingjiang, Xianlong Cheng, Cong Fang and Feng Wei
Pharmaceuticals 2024, 17(5), 595; https://doi.org/10.3390/ph17050595 - 7 May 2024
Abstract
The pharmacokinetics (PK) of Rhodiola crenulata in rats were studied, and pharmacokinetic–pharmacodynamic (PK-PD) correlation analysis was performed to elucidate their time–concentration–effect relationship. The myocardial ischemia model was made with pituitrin. Rats were divided into sham operation, sham operation administration, model, and model administration
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The pharmacokinetics (PK) of Rhodiola crenulata in rats were studied, and pharmacokinetic–pharmacodynamic (PK-PD) correlation analysis was performed to elucidate their time–concentration–effect relationship. The myocardial ischemia model was made with pituitrin. Rats were divided into sham operation, sham operation administration, model, and model administration groups (SG, SDG, MG, and MDG, respectively; n = 6). Blood was collected from the fundus venous plexus at different time points after oral administration. The HPLC-QQQ-MS/MS method was established for the quantification of five components of Rhodiola crenulata. CK, HBDH, SOD, LDH, and AST at different time points were detected via an automatic biochemical analyzer. DAS software was used to analyze PK parameters and PK-PD correlation. The myocardial ischemia model was established successfully. There were significant differences in the PK parameters (AUC0–, AUC0–∞, Cmax) in MDG when compared with SDG. Two PD indicators, CK and HBDH, conforming to the sigmoid-Emax model, had high correlation with the five components, which indicated a delay in the pharmacological effect relative to the drug concentration in plasma. The difference in the PK parameters between modeled and normal rats was studied, and the time–concentration–effect of composition and effect indicators were investigated. This study can provide reference for the rational clinical application of Rhodiola crenulata and for related studies of other anti-myocardial ischemia drugs.
Full article
(This article belongs to the Section Natural Products)
Open AccessArticle
Transcriptomics Reveals Effect of Pulsatilla Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling
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Hui Wu, Can Li, Yemei Wang, Mengxiang Zhang, Daqiang Wu, Jing Shao, Tianming Wang and Changzhong Wang
Pharmaceuticals 2024, 17(5), 594; https://doi.org/10.3390/ph17050594 - 7 May 2024
Abstract
The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced
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The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced by heparan sulfate (HS), do not successfully engulf Candida albicans (C. albicans). Instead, they release many inflammatory factors that cause damage to the vaginal mucosa. This study aims to understand the molecular mechanism by which the n-butanol extract of Pulsatilla decoction (BEPD) treats VVC through transcriptomics. High-performance liquid chromatography was used to identify the primary active components of BEPD. A VVC mouse model was induced using an estrogen-dependent method and the mice were treated daily with BEPD (20 mg/kg, 40 mg/kg, and 80 mg/kg) for seven days. The vaginal lavage fluid of the mice was analyzed for various experimental indices, including fungal morphology, fungal burden, degree of neutrophil infiltration, and cytokines. Various assessments were then performed on mouse vaginal tissues, including pathological assessment, immunohistochemistry, immunofluorescence, Western blot (WB), quantitative real-time PCR, and transcriptome assays. Our results showed that BEPD reduced vaginal redness and swelling, decreased white discharge, inhibited C. albicans hyphae formation, reduced neutrophil infiltration and fungal burden, and attenuated vaginal tissue damage compared with the VVC model group. The high-dose BEPD group even restored the damaged vaginal tissue to normal levels. The medium- and high-dose groups of BEPD also significantly reduced the levels of IL-1β, IL-6, TNF-α, and LDH. Additionally, transcriptomic results showed that BEPD regulated several chemokine (CXCL1, CXCL3, and CXCL5) and S100 alarmin (S100A8 and S100A9) genes, suggesting that BEPD may treat VVC by affecting chemokine- and alarmin-mediated neutrophil chemotaxis. Finally, we verified that BEPD protects the vaginal mucosa of VVC mice by inhibiting neutrophil recruitment and chemotaxis in an animal model of VVC via the TLR4/MyD88/NF-κB pathway. This study provides further evidence to elucidate the mechanism of BEPD treatment of VVC.
Full article
(This article belongs to the Section Pharmacology)
Open AccessFeature PaperArticle
Cistus, Acacia, and Lemon verbena Valorization through Response Surface Methodology: Optimization Studies and Potential Application in the Pharmaceutical and Nutraceutical Industries
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Filipa A. Fernandes, Márcio Carocho, Tiane C. Finimundy, Miguel A. Prieto, Isabel C. F. R. Ferreira, Lillian Barros and Sandrina A. Heleno
Pharmaceuticals 2024, 17(5), 593; https://doi.org/10.3390/ph17050593 - 7 May 2024
Abstract
Cistus ladanifer L., Acacia dealbata L., and Aloysia citrodora Paláu were subject to an optimization procedure for two extraction techniques (heat-assisted extraction (HAE) and ultrasound-assisted extraction (UAE)). The extracts were then analyzed by HPLC-DAD-ESI/MS for their phenolic profile (cistus—15 compounds, acacia—21 compounds, and
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Cistus ladanifer L., Acacia dealbata L., and Aloysia citrodora Paláu were subject to an optimization procedure for two extraction techniques (heat-assisted extraction (HAE) and ultrasound-assisted extraction (UAE)). The extracts were then analyzed by HPLC-DAD-ESI/MS for their phenolic profile (cistus—15 compounds, acacia—21 compounds, and lemon verbena—9 compounds). The response surface methodology was applied, considering four varying factors: ethanol percentage; extraction time; temperature/power; and S/L ratio, generating two responses (the major phenolic compound, or family of compounds, and the extraction yield). For cistus, both techniques optimized the extraction yield of punicalagins, with UAE proving to be the most efficient extraction method (3.22% ethanol, 22 min, 171 W, and 35 g/L). For acacia, HAE maximized the extraction of procyanidin (74% ethanol, 86 min, 24 °C, and 50 g/L), and UAE maximized the content of myricetin (65% ethanol, 8 min, 50 W, and 50 g/L). For lemon verbena, HAE favored the extraction of martynoside (13% ethanol, 96 min, 49 °C and 17 g/L) and forsythiaside UAE (94% ethanol, 25 min, 399 W, and 29 g/L). The optimal conditions for the extraction of compounds with high added value and potential for use in pharmaceuticals and nutraceuticals were defined.
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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A Hybrid Approach Combining Shape-Based and Docking Methods to Identify Novel Potential P2X7 Antagonists from Natural Product Databases
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Natiele Carla da Silva Ferreira, Lucas Gasparello Viviani, Lauro Miranda Lima, Antonia Tavares do Amaral, João Victor Paiva Romano, Anderson Lage Fortunato, Rafael Ferreira Soares, Anael Viana Pinto Alberto, Jose Aguiar Coelho Neto and Luiz Anastacio Alves
Pharmaceuticals 2024, 17(5), 592; https://doi.org/10.3390/ph17050592 - 7 May 2024
Abstract
P2X7 is an ATP-activated purinergic receptor implicated in pro-inflammatory responses. It is associated with the development of several diseases, including inflammatory and neurodegenerative conditions. Although several P2X7 receptor antagonists have recently been reported in the literature, none of them is approved for clinical
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P2X7 is an ATP-activated purinergic receptor implicated in pro-inflammatory responses. It is associated with the development of several diseases, including inflammatory and neurodegenerative conditions. Although several P2X7 receptor antagonists have recently been reported in the literature, none of them is approved for clinical use. However, the structure of the known antagonists can serve as a scaffold for discovering effective compounds in clinical therapy. This study aimed to propose an improved virtual screening methodology for the identification of novel potential P2X7 receptor antagonists from natural products through the combination of shape-based and docking approaches. First, a shape-based screening was performed based on the structure of JNJ-47965567, a P2X7 antagonist, using two natural product compound databases, MEGx (~5.8 × 103 compounds) and NATx (~32 × 103 compounds). Then, the compounds selected by the proposed shape-based model, with Shape–Tanimoto score values ranging between 0.624 and 0.799, were filtered for drug-like properties. Finally, the compounds that met the drug-like filter criteria were docked into the P2X7 allosteric binding site, using the docking programs GOLD and DockThor. The docking poses with the best score values were submitted to careful visual inspection of the P2X7 allosteric binding site. Based on our established visual inspection criteria, four compounds from the MEGx database and four from the NATx database were finally selected as potential P2X7 receptor antagonists. The selected compounds are structurally different from known P2X7 antagonists, have drug-like properties, and are predicted to interact with key P2X7 allosteric binding pocket residues, including F88, F92, F95, F103, M105, F108, Y295, Y298, and I310. Therefore, the combination of shape-based screening and docking approaches proposed in our study has proven useful in selecting potential novel P2X7 antagonist candidates from natural-product-derived compounds databases. This approach could also be useful for selecting potential inhibitors/antagonists of other receptors and/or biological targets.
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(This article belongs to the Special Issue Structure and Ligand Based Drug Design)
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Open AccessReview
Change in Neurocognitive Function in Patients who Receive CAR-T Cell Therapies: A Steep Hill to Climb
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Evlampia Strongyli, Paschalis Evangelidis, Ioanna Sakellari, Maria Gavriilaki and Eleni Gavriilaki
Pharmaceuticals 2024, 17(5), 591; https://doi.org/10.3390/ph17050591 - 6 May 2024
Abstract
Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B cell neoplasms. However, complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit the therapeutic efficacy of
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Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B cell neoplasms. However, complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit the therapeutic efficacy of this treatment approach. ICANS can have a broad range of clinical manifestations, while various scoring systems have been developed for its grading. Cognitive decline is prevalent in CAR-T therapy recipients including impaired attention, difficulty in item naming, and writing, agraphia, and executive dysfunction. In this review, we aim to present the diagnostic methods and tests that have been used for the recognition of cognitive impairment in these patients. Moreover, up-to-date data about the duration of cognitive impairment symptoms after the infusion are presented. More research on the risk factors, pathogenesis, preventive measures, and therapy of neurocognitive impairment is crucial for better outcomes for our patients.
Full article
(This article belongs to the Section Biopharmaceuticals)
Open AccessReview
Potential Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports
by
Ana C. Gonçalves, Sofia Rodrigues, Rafael Fonseca and Luís R. Silva
Pharmaceuticals 2024, 17(5), 590; https://doi.org/10.3390/ph17050590 - 6 May 2024
Abstract
Rheumatoid arthritis (RA) is a complex illness with both hereditary and environmental components. Globally, in 2019, 18 million people had RA. RA is characterized by persistent inflammation of the synovial membrane that lines the joints, cartilage loss, and bone erosion. Phenolic molecules are
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Rheumatoid arthritis (RA) is a complex illness with both hereditary and environmental components. Globally, in 2019, 18 million people had RA. RA is characterized by persistent inflammation of the synovial membrane that lines the joints, cartilage loss, and bone erosion. Phenolic molecules are the most prevalent secondary metabolites in plants, with a diverse spectrum of biological actions that benefit functional meals and nutraceuticals. These compounds have received a lot of attention recently because they have antioxidant, anti-inflammatory, immunomodulatory, and anti-rheumatoid activity by modulating tumor necrosis factor, mitogen-activated protein kinase, nuclear factor kappa-light-chain-enhancer of activated B cells, and c-Jun N-terminal kinases, as well as other preventative properties. This article discusses dietary polyphenols, their pharmacological properties, and innovative delivery technologies for the treatment of RA, with a focus on their possible biological activities. Nonetheless, commercialization of polyphenols may be achievable only after confirming their safety profile and completing successful clinical trials.
Full article
(This article belongs to the Special Issue The Role of Bioactive Compounds in the Prevention of Rheumatoid Arthritis)
Open AccessArticle
Glycyrrhizic Acid Nanoparticles Subside the Activity of Methicillin-Resistant Staphylococcus aureus by Suppressing PBP2a
by
Patricia Rijo, Tamer M. M. Abuamara, Lashin Saad Ali Lashin, Sherif A. Kamar, Vera M. S. Isca, Tahseen S. Mohammed, Mohamed S. M. Abdrabo, Mohamed A. Amin, Ahmed I. Abd El Maksoud and Amr Hassan
Pharmaceuticals 2024, 17(5), 589; https://doi.org/10.3390/ph17050589 - 6 May 2024
Abstract
Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) are classified as high-risk infections that can lead to death, particularly among older individuals. Nowadays, plant nanoparticles such as glycyrrhizic acid are recognized as efficient bactericides against a wide range of bacterial strains. Recently, scientists have
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Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) are classified as high-risk infections that can lead to death, particularly among older individuals. Nowadays, plant nanoparticles such as glycyrrhizic acid are recognized as efficient bactericides against a wide range of bacterial strains. Recently, scientists have shown interest in plant extract nanoparticles, derived from natural sources, which can be synthesized into nanomaterials. Interestingly, glycyrrhizic acid is rich in antioxidants as well as antibacterial agents, and it exhibits no adverse effects on normal cells. In this study, glycyrrhizic acid nanoparticles (GA-NPs) were synthesized using the hydrothermal method and characterized through physicochemical techniques such as UV–visible spectrometry, DLS, zeta potential, and TEM. The antimicrobial activity of GA-NPs was investigated through various methods, including MIC assays, anti-biofilm activity assays, ATPase activity assays, and kill-time assays. The expression levels of mecA, mecR1, blaR1, and blaZ genes were measured by quantitative RT-qPCR. Additionally, the presence of the penicillin-binding protein 2a (PBP2a) protein of S. aureus and MRSA was evaluated by a Western blot assay. The results emphasized the fabrication of GA nanoparticles in spherical shapes with a diameter in the range of 40–50 nm. The data show that GA nanoparticles exhibit great bactericidal effectiveness against S. aureus and MRSA. The treatment with GA-NPs remarkably reduces the expression levels of the mecA, mecR1, blaR1, and blaZ genes. PBP2a expression in MRSA was significantly reduced after treatment with GA-NPs. Overall, this study demonstrates that glycyrrhizic acid nanoparticles have potent antibacterial activity, particularly against MRSA. This research elucidates the inhibition mechanism of glycyrrhizic acid, which involves the suppressing of PBP2a expression. This work emphasizes the importance of utilizing plant nanoparticles as effective antimicrobial agents against a broad spectrum of bacteria.
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(This article belongs to the Special Issue Interaction between Nanoparticles and Antibiotics:Against Antimicrobial Resistance)
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Open AccessArticle
Ethnomedicinal Study and Evaluation of the Anxiolytic-like and Diuretic Effects of the Orchid Stanhopea tigrina Bateman ex Lindl—(Orchidaceae)
by
Rocío del Carmen Díaz-Torres, Eunice Yáñez-Barrientos, José Ángel Montes-Rocha, David Jeremías Morales-Tirado, Clara Alba-Betancourt, Deisy Gasca-Martínez, Maria L. Gonzalez-Rivera, María del Carmen Juárez-Vázquez, Martha Alicia Deveze-Álvarez, Mario Alberto Isiordia-Espinoza, Candy Carranza-Álvarez and Angel Josabad Alonso-Castro
Pharmaceuticals 2024, 17(5), 588; https://doi.org/10.3390/ph17050588 - 6 May 2024
Abstract
Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as “Calavera” or “calaverita”, in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to
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Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as “Calavera” or “calaverita”, in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α1-adrenergic receptors, and 5-HT2 receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of S. tigrina leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.
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(This article belongs to the Section Natural Products)
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Open AccessReview
Pharmaceutical Nanoparticles Formation and Their Physico-Chemical and Biomedical Properties
by
Tatyana I. Shabatina, Yana A. Gromova, Olga I. Vernaya, Andrei V. Soloviev, Andrei V. Shabatin, Yurii N. Morosov, Irina V. Astashova and Michail Y. Melnikov
Pharmaceuticals 2024, 17(5), 587; https://doi.org/10.3390/ph17050587 - 5 May 2024
Abstract
The use of medicinal substances in nanosized forms (nanoforms, nanoparticles) allows the therapeutic effectiveness of pharmaceutical preparations to be increased due to several factors: (1) the high specific surface area of nanomaterials, and (2) the high concentration of surface-active centers interacting with biological
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The use of medicinal substances in nanosized forms (nanoforms, nanoparticles) allows the therapeutic effectiveness of pharmaceutical preparations to be increased due to several factors: (1) the high specific surface area of nanomaterials, and (2) the high concentration of surface-active centers interacting with biological objects. In the case of drug nanoforms, even low concentrations of a bioactive substance can have a significant therapeutic effect on living organisms. These effects allow pharmacists to use lower doses of active components, consequently lowering the toxic side effects of pharmaceutical nanoform preparations. It is known that many drug substances that are currently in development are poorly soluble in water, so they have insufficient bioavailability. Converting them into nanoforms will increase their rate of dissolution, and the increased saturation solubility of drug nanocrystals also makes a significant contribution to their high therapeutic efficiency. Some physical and chemical methods can contribute to the formation of both pure drug nanoparticles and their ligand or of polymer-covered nanoforms, which are characterized by higher stability. This review describes the most commonly used methods for the preparation of nanoforms (nanoparticles) of different medicinal substances, paying close attention to modern supercritical and cryogenic technologies and the advantages and disadvantages of the described methods and techniques; moreover, the improvements in the physico-chemical and biomedical properties of the obtained medicinal nanoforms are also discussed.
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(This article belongs to the Section Pharmaceutical Technology)
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Open AccessArticle
Amber (Succinite) Extract Enhances Glucose Uptake through the Up-Regulation of ATP and Down-Regulation of ROS in Mouse C2C12 Cells
by
Mahmoud Ben Othman, Reiko Takeda, Marie Sekita, Kazuma Okazaki and Kazuichi Sakamoto
Pharmaceuticals 2024, 17(5), 586; https://doi.org/10.3390/ph17050586 - 3 May 2024
Abstract
Traditionally, amber (Succinite) has been used to alleviate all types of pain, skin allergies, and headaches. However, no studies have been conducted on its antidiabetic and antioxidant effects. In this study, differentiated skeletal muscle C2C12 cells were used to demonstrate the protective effects
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Traditionally, amber (Succinite) has been used to alleviate all types of pain, skin allergies, and headaches. However, no studies have been conducted on its antidiabetic and antioxidant effects. In this study, differentiated skeletal muscle C2C12 cells were used to demonstrate the protective effects of amber (AMB) against H2O2-induced cell death. In addition, the effects of AMB on glucose uptake and ATP production were investigated. Our results showed that AMB at 10, 25, and 50 μg/mL suppressed the elevation of ROS production induced by H2O2 in a dose-dependent manner. Moreover, AMB enhanced glucose utilization in C2C12 cells through the improvement of ATP production and an increase in PGC-1α gene expression resulting in an amelioration of mitochondrial activity. On the other hand, AMB significantly increased the gene expression of glucose transporters GLUT4 and GLUT1. Our finding suggests that AMB can be used as a natural supplement for diabetes treatment and for the promotion of skeletal muscle function.
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(This article belongs to the Section Pharmacology)
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Open AccessArticle
Hydrogen Sulfide Delivery to Enhance Bone Tissue Engineering Cell Survival
by
Soheila Ali Akbari Ghavimi, Trent J. Faulkner, Rama Rao Tata, August J. Hemmerla, Samantha E. Huddleston, Farnoushsadat Rezaei, Ethan S. Lungren, Rui Zhang, Erin E. Bumann and Bret D. Ulery
Pharmaceuticals 2024, 17(5), 585; https://doi.org/10.3390/ph17050585 - 2 May 2024
Abstract
Though crucial for natural bone healing, local calcium ion (Ca2+) and phosphate ion (Pi) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H2S can be
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Though crucial for natural bone healing, local calcium ion (Ca2+) and phosphate ion (Pi) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H2S can be employed as a cytoprotective molecule to enhance mesenchymal stem cell (MSC) tolerance to cytotoxic Ca2+/Pi concentrations. Varied concentrations of sodium hydrogen sulfide (NaSH), a fast-releasing H2S donor, were applied to assess the influence of H2S on MSC proliferation. The results suggested a toxicity limit of 4 mM for NaSH and that 1 mM of NaSH could improve cell proliferation and differentiation in the presence of cytotoxic levels of Ca2+ (32 mM) and/or Pi (16 mM). To controllably deliver H2S over time, a novel donor molecule (thioglutamic acid—GluSH) was synthesized and evaluated for its H2S release profile. Excitingly, GluSH successfully maintained cytoprotective level of H2S over 7 days. Furthermore, MSCs exposed to cytotoxic Ca2+/Pi concentrations in the presence of GluSH were able to thrive and differentiate into osteoblasts. These findings suggest that the incorporation of a sustained H2S donor such as GluSH into CaP-based bone graft substitutes can facilitate considerable cytoprotection, making it an attractive option for complex bone regenerative engineering applications.
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(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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