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Volume 18
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Pharmaceuticals, Volume 18, Issue 9 (September 2025) – 16 articles

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30 pages, 5976 KiB  
Review
Electrochemical Sensors for Chloramphenicol: Advances in Food Safety and Environmental Monitoring
by Matiar M. R. Howlader, Wei-Ting Ting and Md Younus Ali
Pharmaceuticals 2025, 18(9), 1257; https://doi.org/10.3390/ph18091257 (registering DOI) - 24 Aug 2025
Abstract
Excessive use of antibiotics can lead to antibiotic resistance, posing a significant threat to human health and the environment. Chloramphenicol (CAP), once widely used, has been banned in many regions for over 20 years due to its toxicity. Detecting CAP residues in food [...] Read more.
Excessive use of antibiotics can lead to antibiotic resistance, posing a significant threat to human health and the environment. Chloramphenicol (CAP), once widely used, has been banned in many regions for over 20 years due to its toxicity. Detecting CAP residues in food products is crucial for regulating safe use and preventing unnecessary antibiotic exposure. Electrochemical sensors are low-cost, sensitive, and easily detect CAP. This paper reviews recent research on electrochemical sensors for CAP detection, with a focus on the materials and fabrication techniques employed. The sensors are evaluated based on key performance parameters, including limit of detection, sensitivity, linear range, selectivity, and the ability to perform simultaneous detection. Specifically, we highlight the use of metal and carbon-based electrode modifications, including gold nanoparticles (AuNPs), nickel–cobalt (Ni-Co) hollow nano boxes, platinum–palladium (Pt-Pd), graphene (Gr), and covalent organic frameworks (COFs), as well as molecularly imprinted polymers (MIPs) such as polyaniline (PANI) and poly(o-phenylenediamine) (P(o-PD)). The mechanisms by which these modifications enhance CAP detection are discussed, including improved conductivity, increased surface-to-volume ratio, and enhanced binding site availability. The reviewed sensors demonstrated promising results, with some exhibiting high selectivity and sensitivity, and the effective detection of CAP in complex sample matrices. This review aims to support the development of next-generation sensors for antibiotic monitoring and contribute to global efforts to combat antibiotic resistance. Full article
(This article belongs to the Special Issue Application of Biosensors in Pharmaceutical Research)
19 pages, 4308 KiB  
Article
Histology of Pompia Peel and Bioactivity of Its Essential Oil: A New Citrus-Based Approach to Skin Regeneration
by Emma Cocco, Giulia Giorgi, Valeria Marsigliesi, Francesco Mura, Jorge M. Alves-Silva, Mónica Zuzarte, Lígia Salgueiro, Valentina Ghiani, Enrico Sanjust, Danilo Falconieri, Delia Maccioni, Alessio Valletta, Elisa Brasili and Andrea Maxia
Pharmaceuticals 2025, 18(9), 1256; https://doi.org/10.3390/ph18091256 (registering DOI) - 24 Aug 2025
Abstract
Background/Objectives: Pompia is an ancient, endemic citrus ecotype native to Sardinia (Italy), characterized by distinctive morphology and high content of bioactive compounds. Despite increasing interest, several aspects of this fruit, including its histological characteristics, remain poorly understood. This study aims to address [...] Read more.
Background/Objectives: Pompia is an ancient, endemic citrus ecotype native to Sardinia (Italy), characterized by distinctive morphology and high content of bioactive compounds. Despite increasing interest, several aspects of this fruit, including its histological characteristics, remain poorly understood. This study aims to address this gap by investigating the anatomical features and spatial distribution of secretory cavities involved in essential oil (EO) production and accumulation, while also evaluating the EO’s chemical profile and associated biological activity. Methods: Pompia peel (flavedo and albedo) was subjected to histological analysis through fixation, dehydration, resin inclusion and sectioning. Sections were stained with 0.05% toluidine blue and observed under a light microscope to measure different parameters of secretory cavities. Essential oil (EO) was obtained from Pompia peel by hydrodistillation and characterized by gas chromatography–mass spectrometry (GC–MS) analysis. The biological activity of Pompia EO was assessed in vitro using NIH/3T3 fibroblasts, where wound-healing was evaluated by scratch assay and anti-senescence effects by β-galactosidase and γH2AX activity. Results: Microscopic analysis of the peel revealed pronounced variability in depth and size of the secretory cavities, along with the presence of lenticel-like structures in the epidermis. GC–MS analysis showed that Pompia EO is dominated by limonene (89%), with minor compounds including myrcene, geranial and neral. In vitro biological assays demonstrated that the EO promotes cell migration in a wound-healing model at concentrations ≥ 12.5 µg/mL and reduces markers of cellular senescence, including β-galactosidase activity and γH2AX foci, in etoposide-induced senescent fibroblasts. Conclusions: Overall, this study provides the first histological characterization of Pompia peel and confirms the bioactive potential of its EO. These findings support future applications in skin regeneration and anti-aging strategies and contribute to the valorization of this underexplored Citrus ecotype. Full article
(This article belongs to the Special Issue Advances in the Chemical-Biological Knowledge of Essential Oils)
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18 pages, 997 KiB  
Article
Use of TLC and Computational Methods to Determine Lipophilicity Parameters of Selected Neuroleptics: Comparison of Experimental and Theoretical Studies
by Daria Klimoszek, Małgorzata Dołowy, Małgorzata Jeleń and Katarzyna Bober-Majnusz
Pharmaceuticals 2025, 18(9), 1255; https://doi.org/10.3390/ph18091255 (registering DOI) - 24 Aug 2025
Abstract
Background: Compound lipophilicity is a fundamental physicochemical property for determining the pharmacokinetic and pharmacodynamic profiles of therapeutic substances. It is successfully used in the early stages of drug candidates’ design and development. Aim: Taking into account the importance of this parameter, we [...] Read more.
Background: Compound lipophilicity is a fundamental physicochemical property for determining the pharmacokinetic and pharmacodynamic profiles of therapeutic substances. It is successfully used in the early stages of drug candidates’ design and development. Aim: Taking into account the importance of this parameter, we aimed to assess and compare the utility of a hybrid procedure based on calculation methods and an experimental one for rapid and simple estimation of the lipophilicity of selected neuroleptics such as fluphenazine, triflupromazine, trifluoperazine, flupentixol and zuclopenthixol and their potential new derivatives. Methods: Log P values of the studied compounds were predicted by means of different platforms and algorithms: AlogPs, ilogP, XlogP3, WlogP, MlogP, milogP, logPsilicos-it, logPconsensus, logPchemaxon and logPACD/Labs. The experimental determination of lipophilicity was carried out by reverse-phase thin-layer chromatography (RP-TLC) using three types of stationary phases—RP-2F254, RP-8F254 and RP-18F254—and mobile phases consisted of acetone, acetonitrile and 1,4-dioxane as organic modifiers. Results: Our results provide a confident proposal of optimal chromatographic conditions to experimentally determine the lipophilicity of neuroleptic drugs, including new derivatives. Conclusions: Additionally, for the first time, the paper shows the application of selected topological indices in determining lipophilicity factors and other ADMET parameters of neuroleptics and, in the future, the newly synthesized quinoline derivatives of the studied compounds. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—New Insights in Medicinal Chemistry of Nitrogen-Containing Compounds)
21 pages, 2872 KiB  
Article
ε-Viniferin Rejuvenates Senescence via RGS16 Regulation: In Vitro Evidence
by Ji Ho Park, Yun Haeng Lee, Kyeong Seon Lee, Yoo Jin Lee, Jee Hee Yoon, Byeonghyeon So, Duyeol Kim, Minseon Kim, Hyung Wook Kwon, Youngjoo Byun, Ki Yong Lee and Joon Tae Park
Pharmaceuticals 2025, 18(9), 1254; https://doi.org/10.3390/ph18091254 (registering DOI) - 24 Aug 2025
Abstract
Background: Reactive oxygen species (ROS) generated due to mitochondrial dysfunction are one of the primary causes of the initiation and progression of senescence. Although reducing mitochondrial ROS production is known as an effective strategy for the treatment of aging, effective components that [...] Read more.
Background: Reactive oxygen species (ROS) generated due to mitochondrial dysfunction are one of the primary causes of the initiation and progression of senescence. Although reducing mitochondrial ROS production is known as an effective strategy for the treatment of aging, effective components that reduce mitochondrial ROS production or effective treatments that utilize them have not yet been developed. Methods: Screening of plant-generated secondary metabolites to overcome ROS-mediated stress found that ε-viniferin, a dimer of resveratrol, effectively reduces mitochondrial ROS production. Results: ε-viniferin induced efficient electron transport and reduced mitochondrial ROS, a consequence of inefficient electron transport. In addition, ε-viniferin acted as a senolytic that selectively eliminates senescent fibroblasts, thereby restoring mitochondrial function and senescence-associated phenotypes. RNA sequencing analysis revealed that regulator of G protein signaling 16 (RGS16) was an important gene for ε-viniferin-mediated senescence rejuvenation. Upregulation of RGS16 showed similar effects as ε-viniferin in reducing mitochondrial ROS production and restoring mitochondrial function. Conclusions: This study discovered a novel mechanism by which ε-viniferin rejuvenates senescence by lowering ROS production in mitochondria. The novel mechanism will serve as a basis for developing therapeutics that regulate mitochondrial ROS production to treat aging. Full article
(This article belongs to the Special Issue The Role of Phytochemicals in Aging and Aging-Related Diseases)
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16 pages, 1474 KiB  
Article
Development, Validation and Application of the Dried Blood Spot Analysis Method for the Determination of Ustekinumab in Patients with Inflammatory Bowel Disease
by Panagiotis-Dimitrios Mingas, Jurij Aguiar Zdovc, Iztok Grabnar, David Drobne and Tomaž Vovk
Pharmaceuticals 2025, 18(9), 1253; https://doi.org/10.3390/ph18091253 (registering DOI) - 24 Aug 2025
Abstract
Background: Ustekinumab (UST) is a monoclonal antibody (mAb) used in the treatment of inflammatory bowel disease (IBD). Elevated serum concentrations are typically associated with improved therapeutic outcomes, and therapeutic drug monitoring (TDM) is a useful tool for guiding mAbs treatment. This study [...] Read more.
Background: Ustekinumab (UST) is a monoclonal antibody (mAb) used in the treatment of inflammatory bowel disease (IBD). Elevated serum concentrations are typically associated with improved therapeutic outcomes, and therapeutic drug monitoring (TDM) is a useful tool for guiding mAbs treatment. This study aimed to develop a dried blood spot (DBS) method for TDM of UST in patients with IBD. Methods: The commercial enzyme-linked immunosorbent assay for plasma samples was optimized for DBS samples and subsequently validated according to international guidelines for classical and DBS-specific validation parameters. It was then applied to analyze serum and DBS samples obtained from venous and capillary blood of IBD patients undergoing UST therapy. Results: The method was linear (3–12 mg/L) with acceptable inter-day accuracy (90.1–106%) and precision (<12%). We confirmed that there was no hematocrit effect and that DBS samples were stable for one month under room conditions. A linear model was developed between venous DBS and serum UST concentrations, which showed no systemic bias, and 71% of the samples were within ±20% of the mean. In addition, a linear correlation between venous DBS and capillary DBS samples was established, showing no significant bias, with 84% of samples within ±20% of the mean. Finally, a novel strategy was developed to overcome the limitations of poor-quality samples (irregular shapes) based on area image analysis. Conclusions: The newly developed DBS method is the first to enable reliable measurement of UST in capillary blood, appropriate clinical interpretation of the measured concentrations, and remote monitoring of patients in the early phase of therapy. Full article
(This article belongs to the Special Issue Innovative Tools for Drug Analysis and Therapeutic Drug Monitoring (TDM))
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25 pages, 1030 KiB  
Article
Real-World Evidence of Neuropsychiatric Adverse Reactions to Isotretinoin: Insights from EudraVigilance (2005–2025)
by Denisa Viola Szilagyi, Delia Mirela Tit, Claudia Teodora Judea-Pusta, Andrei-Flavius Radu, Gabriela S. Bungau, Ada Radu, Laura Maria Endres and Ruxandra-Cristina Marin
Pharmaceuticals 2025, 18(9), 1252; https://doi.org/10.3390/ph18091252 (registering DOI) - 24 Aug 2025
Abstract
Background/Objectives: Isotretinoin is a highly effective therapy for severe acne, but its potential neuropsychiatric adverse reactions (NPsRs) have been controversial. This study evaluated EudraVigilance data from 2005 to 2025 to better understand the frequency, typology, and predictors of such events. Methods: We conducted [...] Read more.
Background/Objectives: Isotretinoin is a highly effective therapy for severe acne, but its potential neuropsychiatric adverse reactions (NPsRs) have been controversial. This study evaluated EudraVigilance data from 2005 to 2025 to better understand the frequency, typology, and predictors of such events. Methods: We conducted a retrospective analysis of 33,381 individual case safety reports (ICSRs) related to isotretinoin. Using descriptive statistics, chi-square tests, and logistic regression, we assessed associations between NPsRs and variables such as age, sex, geographic region, and reporter type. Results: A total of 9793 cases (29.3%) involved at least one NPsR. Depression (31%) and suicidal ideation (8.6%) were the most frequently reported symptoms. Adolescents (12–17 years) had the highest proportion of NPsR cases, while male patients and reports submitted by non-healthcare professionals were significantly overrepresented. Reports from non-European Economic Area countries also had slightly increased odds of including NPsRs. All predictors were statistically significant in the logistic regression model, though the explained variance was modest (Nagelkerke R2 = 0.065). Conclusions: Neuropsychiatric reactions remain a prominent and persistent signal in isotretinoin pharmacovigilance, particularly among younger patients and non-professional reporters. Although causality cannot be inferred from spontaneous reporting data and confounding factors like acne-related depression cannot be excluded, these findings highlight the clinical value of pre-treatment psychiatric screening, patient-centered education, and proactive mental health monitoring throughout isotretinoin therapy. Full article
(This article belongs to the Special Issue Pharmacovigilance Insights: Addressing Drug Misuse and Enhancing Drug Safety)
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27 pages, 3086 KiB  
Article
Trimetazidine–Profen Hybrid Molecules: Synthesis, Chemical Characterization, and Biological Evaluation of Their Racemates
by Diyana Dimitrova, Stanimir Manolov, Iliyan Ivanov, Dimitar Bojilov, Nikol Dimova, Gabriel Marc, Smaranda Oniga and Ovidiu Oniga
Pharmaceuticals 2025, 18(9), 1251; https://doi.org/10.3390/ph18091251 (registering DOI) - 23 Aug 2025
Abstract
Background: Trimetazidine is a clinically established cardioprotective agent with anti-ischemic and antioxidant properties, widely used in the management of coronary artery disease. Combining its metabolic and cytoprotective effects with the potent anti-inflammatory activity of profens presents a promising therapeutic strategy. Methods: Five novel [...] Read more.
Background: Trimetazidine is a clinically established cardioprotective agent with anti-ischemic and antioxidant properties, widely used in the management of coronary artery disease. Combining its metabolic and cytoprotective effects with the potent anti-inflammatory activity of profens presents a promising therapeutic strategy. Methods: Five novel trimetazidine–profen hybrid compounds were synthesized using N,N′-dicyclohexylcarbodiimide-mediated coupling and structurally characterized by NMR and high-resolution mass spectrometry. Their antioxidant activity was evaluated by hydroxyl radical scavenging assays (HRSA), and the anti-inflammatory potential was assessed via the inhibition of albumin denaturation (IAD). Lipophilicity was determined chromatographically. Molecular docking and 100 ns molecular dynamics simulations were performed to investigate the binding modes and stability in human serum albumin (HSA) binding sites. The acute toxicity of the hybrid molecules was predicted in silico using GUSAR software. Results: All synthesized hybrids demonstrated varying degrees of biological activity, with compound 3c exhibiting the most potent antioxidant (HRSA IC₅₀ = 71.13 µg/mL) and anti-inflammatory (IAD IC₅₀ = 108.58 µg/mL) effects. Lipophilicity assays indicated moderate membrane permeability, with compounds 3c and 3d showing favorable profiles. Docking studies revealed stronger binding affinities of S-enantiomers, particularly 3c and 3d, to Sudlow sites II and III in HSA. Molecular dynamics simulations confirmed stable ligand–protein complexes, highlighting compound 3c as maintaining consistent and robust interactions. The toxicity results indicate that most hybrids, particularly compounds 3b–3d, exhibit a favorable safety profile compared to the parent trimetazidine. Conclusion: The hybrid trimetazidine–profen compounds synthesized herein, especially compound 3c, demonstrate promising dual antioxidant and anti-inflammatory therapeutic potential. Their stable interaction with serum albumin and balanced physicochemical properties support further development as novel agents for managing ischemic heart disease and associated inflammatory conditions. Full article
(This article belongs to the Special Issue Advances in the Medicinal Synthesis of Bioactive Compounds)
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13 pages, 2086 KiB  
Article
Bioactivity-Guided Fractionation and Mechanistic Insights into Aristolochia ringens Root Extract-Induced G1 Phase Arrest and Mitochondria-Mediated Apoptosis in Human Colon Adenocarcinoma Cells
by Saheed O. Anifowose, Abdalrhaman M. Salih, Musa K. Oladejo, Ahmad Rady, Mobarak S. Al Mosallam, Hasan A. Aljohi, Mansour I. Almansour, Saad Hussin Alkahtani, Ibrahim O. Alanazi and Badr A. Al-Dahmash
Pharmaceuticals 2025, 18(9), 1250; https://doi.org/10.3390/ph18091250 (registering DOI) - 23 Aug 2025
Abstract
Background/Objectives: Aristolochia ringens, a medicinal plant widely used in traditional medicine, has shown potential therapeutic applications. This study aimed to investigate the anticancer mechanism of action of its crude extract against human colorectal adenocarcinoma cells (Caco-2 and HT-29). Methods: Cell [...] Read more.
Background/Objectives: Aristolochia ringens, a medicinal plant widely used in traditional medicine, has shown potential therapeutic applications. This study aimed to investigate the anticancer mechanism of action of its crude extract against human colorectal adenocarcinoma cells (Caco-2 and HT-29). Methods: Cell viability was assessed using the MTT assay to determine IC50 values. Immunofluorescence microscopy was used to examine nuclear morphology and microtubule integrity. Flow cytometry with PI staining was used for cell cycle analysis and Annexin V-FITC/PI staining for apoptosis detection. Mitochondrial membrane potential was evaluated using JC-1 dye. Bioactivity-guided fractionation was performed via HPLC, and GC–MS was used to profile active constituents. Results: The extract exhibited dose-dependent cytotoxicity with IC50 values below 30 µg/mL in colon adenocarcinoma cell lines. Treated Caco-2 cells showed nuclear shrinkage and disrupted microtubules. PI-based flow cytometry revealed G1 phase arrest, and Annexin V-FITC/PI staining indicated enhanced late apoptosis. JC-1 staining demonstrated mitochondrial depolarization. HPLC fractionation identified fractions 2 and 3 as active, and preliminary GC–MS analysis tentatively annotated the presence of alkaloids, sesquiterpenes/diterpenes, and steroidal compounds. Conclusions: A. ringens exerts anticancer effects through a mitochondria-mediated apoptotic pathway, involving G1 checkpoint arrest and cytoskeletal disruption. These findings provide the first integrated cellular and mechanistic evidence of its anticancer potential in colorectal cancer, supporting its promise as a source of novel therapeutic lead compounds. Full article
(This article belongs to the Special Issue Natural Compounds as Potential Anticancer, Anti-inflammatory and Antioxidant Agents in Medicine)
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22 pages, 9849 KiB  
Article
Exploring the In Vitro Mechanism of Action of β-Acetoxyisovalerylalkannin on Inflammatory Skin Diseases Using Network-Based Pharmacology and Non-Targeted Metabolomics
by Yinglan Ma, Xuehong Ma, Yue Ma, Liuqian Peng, Zixin Zhang, Jinyan Li, Lu Zhang and Jianguang Li
Pharmaceuticals 2025, 18(9), 1249; https://doi.org/10.3390/ph18091249 (registering DOI) - 22 Aug 2025
Abstract
Objective: Lithospermum erythrorhizon has been extensively used for the clinical treatment of skin diseases, but its material basis and mechanism of action remain unclear. This study integrates network pharmacology, untargeted metabolomics, and in vitro experimental validation to elucidate the anti-inflammatory effects and underlying [...] Read more.
Objective: Lithospermum erythrorhizon has been extensively used for the clinical treatment of skin diseases, but its material basis and mechanism of action remain unclear. This study integrates network pharmacology, untargeted metabolomics, and in vitro experimental validation to elucidate the anti-inflammatory effects and underlying mechanisms of β-acetoxyisovalerylalkannin, a bioactive naphthoquinone compound isolated from Arnebiae Radix, using inflammatory skin disease models. Methods: Core targets for β-Acetoxyisovalerylalkannin and skin inflammation were identified via network pharmacology and validated through molecular docking. In vitro assays assessed β-Acetoxyisovalerylalkannin’s impact on keratinocyte proliferation, migration, apoptosis, and inflammatory factors (CXCL1, CXCL2, CXCL8, CCL20, IFN-γ, MCP-1, TNF-α, NF-κB). Non-targeted metabolomics identified differential metabolites and pathways. Results: Network pharmacology revealed 66 common targets significantly enriched in the MAPK/STAT3 signaling pathway. In vitro, β-Acetoxyisovalerylalkannin suppressed proliferative viability and hypermigration and induced apoptosis in HaCaTs. Moreover, it downregulated the mRNA levels of inflammatory markers (CXCL1, CXCL2, CXCL8, CCL20, IFN-γ, MCP-1, TNF-α, and NF-κB) by inhibiting the activation of the MAPK/STAT3 signaling pathway. Metabolomics identified 177 modified metabolites, associating them with the arginine/proline, glycine/serine/threonine, glutathione, and nitrogen metabolic pathways. Conclusions: β-Acetoxyisovalerylalkannin exerts protective effects against skin inflammation by reducing abnormal cell proliferation and inflammatory responses, promoting apoptosis, and effectively improving the metabolic abnormalities of HaCaTs. β-Acetoxyisovalerylalkannin is, therefore, a potential therapeutic option for mitigating skin inflammation-related damage. Full article
(This article belongs to the Section Pharmacology)
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23 pages, 2178 KiB  
Review
Comparison of the Effectiveness Differences Between Western and Chinese Medicinal Ointments Against Eczema
by Siu Kan Law, Yanping Wang and Xiao Xiao Wu
Pharmaceuticals 2025, 18(9), 1248; https://doi.org/10.3390/ph18091248 - 22 Aug 2025
Abstract
Eczema is the most common skin disease among Hong Kong’s adults and children, affecting an estimated 30% of the total population. Western and Chinese medicinal ointments are the usual treatment for eczema. Conventional Western medicinal ointments are topical corticosteroids and non-steroidal agents. Eczema [...] Read more.
Eczema is the most common skin disease among Hong Kong’s adults and children, affecting an estimated 30% of the total population. Western and Chinese medicinal ointments are the usual treatment for eczema. Conventional Western medicinal ointments are topical corticosteroids and non-steroidal agents. Eczema skin products include “Aveeno Parabens Lotion”, “Cerave Moisturizing Cream”, and “Cetaphil Lotion”. However, these are not a long-term solution for managing significant erythema. Chinese medicinal ointments are based on adjusting the formula, including the ingredients and amount, to address an individual’s skin condition and other factors that may be worsening symptoms. This approach aims to regulate the immune system and make it less reactive to environmental and food allergies. This approach is mainly for local topical use. The ingredients of eczema skin products should include Coptis chinensis Franch, Phellodendron chinense Schneid, Angelica sinensis (Oliv.) Diels, Rehmannia glutinosa Libosch, Curcuma longa L., and sesame oil. Chinese medicinal ointments are natural ingredients, personalized formulas, and concerned with holistic healing, while Western medicinal ointments provide fast-acting relief, targeted action, and a standardized dosage. Methods: Nine electronic databases, such as WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and the China National Knowledge Infrastructure (CNKI), were searched mainly within the past twenty years and without any language restrictions. The inclusion criteria were the keywords “Western medicine and ointment”, “Chinese medicine and ointment”, and “Western and Chinese medicines and ointment”. Differences in effectiveness between Western and Chinese ointments were evaluated to determine if they had functions against eczema. This review included an analysis and summary of all relevant papers. Results: Western medicinal ointments are topical corticosteroids, and they exert their pharmacological activities via many mechanisms, including anti-inflammatory, immunosuppressive, antiproliferative, and vasoconstrictive effects on eczema. Similarly, Chinese medicinal ointments have the same pharmacological functions, but they may focus on the immune system for the treatment of inflammatory and skin conditions, including erythema, edema, dryness, desquamation, and callus exfoliation. Conclusion: Based on the clinical research, the effectiveness rate of integrated Chinese and Western medicines was 88%, which was greater than the 70% rate for using Western medicine alone to treat eczema. Western and Chinese medicinal ointments have different active ingredients with advantages and disadvantages for eczema or when acting as skin care products. The most important thing is knowing “How” to use Western and Chinese medicinal ointments properly, especially for some formulations of Chinese ointments. It may be beneficial to consider the pharmacokinetic studies of herbal ingredients, which offer personalized formulas tailored to individual body constitutions and conditions, as well as to emphasize holistic healing, addressing both symptoms and underlying imbalances in the body. Much more work needs to be carried out, such as safety assessments of these ointments for use as skin care products for eczema. Full article
(This article belongs to the Special Issue Natural Products for Skin Applications)
43 pages, 18411 KiB  
Review
Physiological Conditions, Bioactive Ingredients, and Drugs Stimulating Non-Shivering Thermogenesis as a Promising Treatment Against Diabesity
by Diego Salagre, Ciskey V. Ayala-Mosqueda, Samira Aouichat and Ahmad Agil
Pharmaceuticals 2025, 18(9), 1247; https://doi.org/10.3390/ph18091247 - 22 Aug 2025
Abstract
Obesity (lipotoxicity) results from a chronic imbalance between energy intake and expenditure. It is strongly associated with type 2 diabetes mellitus (T2DM, glucotoxicity) and considered a major risk factor for the development of metabolic complications. Their convergence constitutes “diabesity”, representing a major challenge [...] Read more.
Obesity (lipotoxicity) results from a chronic imbalance between energy intake and expenditure. It is strongly associated with type 2 diabetes mellitus (T2DM, glucotoxicity) and considered a major risk factor for the development of metabolic complications. Their convergence constitutes “diabesity”, representing a major challenge for public health worldwide. Limited treatment efficacy highlights the need for novel, multi-targeted therapies. Non-shivering thermogenesis (NST), mediated by brown and beige adipose tissue and skeletal muscle, has emerged as a promising therapy due to its capacity to increase energy expenditure and improve metabolic health. Also, skeletal muscle plays a central role in glucose uptake and lipid oxidation, further highlighting its relevance in diabesity. This review explores current and emerging knowledge on physiological stimuli, including cold exposure, physical activity, and fasting, as well as bioactive ingredients and drugs that stimulate NST in thermogenic tissues. Special emphasis is placed on melatonin as a potential regulator of mitochondrial function and energy balance. The literature search was conducted using MEDLINE and Web of Science. Studies were selected based on scientific relevance, novelty, and mechanistic insight; prioritizing human and high-quality rodent research published in peer-reviewed journals. Evidence shows that multiple interventions enhance NST, leading to improved glucose metabolism, reduced fat accumulation, and increased energy expenditure in humans and/or rodents. Melatonin, in particular, shows promise in modulating thermogenesis through organelle-molecular pathways and mitochondrial protective effects. In conclusion, a multi-target approach through the activation of NST by physiological, nutritional, and pharmacological agents offers an effective and safe treatment for diabesity. Further research is needed to confirm these effects in clinical practice and support their use as effective therapeutic strategies. Full article
(This article belongs to the Special Issue Potential Therapeutic Targets for the Management of Diabetes Mellitus, Obesity and Cancer)
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16 pages, 1198 KiB  
Article
Leveraging Natural Compounds for Pancreatic Lipase Inhibition via Virtual Screening
by Emanuele Liborio Citriniti, Roberta Rocca, Claudia Sciacca, Nunzio Cardullo, Vera Muccilli, Francesco Ortuso and Stefano Alcaro
Pharmaceuticals 2025, 18(9), 1246; https://doi.org/10.3390/ph18091246 - 22 Aug 2025
Abstract
Background: Pancreatic lipase (PL), the principal enzyme catalyzing the hydrolysis of dietary triacylglycerols in the intestinal lumen, is pivotal for efficient lipid absorption and plays a central role in metabolic homeostasis. Enhanced PL activity promotes excessive lipid assimilation and contributes to positive [...] Read more.
Background: Pancreatic lipase (PL), the principal enzyme catalyzing the hydrolysis of dietary triacylglycerols in the intestinal lumen, is pivotal for efficient lipid absorption and plays a central role in metabolic homeostasis. Enhanced PL activity promotes excessive lipid assimilation and contributes to positive energy balance, key pathophysiological mechanisms underlying the escalating global prevalence of obesity—a complex, multifactorial condition strongly associated with metabolic disorders, including type 2 diabetes mellitus and cardiovascular disease. Inhibition of pancreatic lipase (PL) constitutes a well-established therapeutic approach for attenuating dietary lipid absorption and mitigating obesity. Methods: With the aim to identify putative PL inhibitors, a Structure-Based Virtual Screening (SBVS) of PhytoHub database naturally occurring derivatives was performed. A refined library of 10,404 phytochemicals was virtually screened against a crystal structure of pancreatic lipase. Candidates were filtered out based on binding affinity, Lipinski’s Rule of Five, and structural clustering, resulting in six lead compounds. Results: In vitro, enzymatic assays confirmed theoretical suggestions, highlighting Pinoresinol as the best PL inhibitor. Molecular dynamics simulations, performed to investigate the stability of protein–ligand complexes, revealed key interactions, such as persistent hydrogen bonding to catalytic residues. Conclusions: This integrative computational–experimental workflow highlighted new promising natural PL inhibitors, laying the foundation for future development of safe, plant-derived anti-obesity therapeutics. Full article
(This article belongs to the Special Issue Computer-Aided Drug Design and Drug Discovery, 2nd Edition)
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46 pages, 2116 KiB  
Review
Advances in the Application of Graphene and Its Derivatives in Drug Delivery Systems
by Changzhou Jin, Huishan Zheng and Jianmin Chen
Pharmaceuticals 2025, 18(9), 1245; https://doi.org/10.3390/ph18091245 - 22 Aug 2025
Abstract
Graphene, owing to its exceptionally high specific surface area, abundant surface functional groups, and outstanding biocompatibility, exhibits tremendous potential in the development of nanodrug delivery systems. This review systematically outlines the latest research advancements regarding graphene and its derivatives in drug loading, targeted [...] Read more.
Graphene, owing to its exceptionally high specific surface area, abundant surface functional groups, and outstanding biocompatibility, exhibits tremendous potential in the development of nanodrug delivery systems. This review systematically outlines the latest research advancements regarding graphene and its derivatives in drug loading, targeted delivery, and smart release. It covers delivery strategies and mechanisms for various types of drugs, including small molecules and macromolecules, with a particular emphasis on their applications in major diseases such as cancer, neurological disorders, and infection control. The article also discusses stimulus-responsive release mechanisms, such as pH-responsiveness and photothermal responsiveness, and highlights the critical role of surface functionalization of graphene and its derivatives in enhancing therapeutic efficacy while reducing systemic toxicity. Furthermore, the review evaluates key challenges to the clinical translation of graphene-based materials, including safety, toxicity, and metabolic uncertainties. It points out that future research should focus on integrating structural modulation of materials with biological behavior to construct intelligent nanoplatforms featuring biodegradability, low immunogenicity, and precise therapeutic targeting. The aim of this paper is to provide theoretical insights and technical guidance for the customized design and precision medicine applications of graphene and its derivative-based drug delivery systems. Full article
(This article belongs to the Section Pharmaceutical Technology)
20 pages, 891 KiB  
Review
Phytocannabinoids and Nanotechnology in Lung Cancer: A Review of Therapeutic Strategies with a Focus on Halloysite Nanotubes
by Dorota Bęben, Helena Moreira and Ewa Barg
Pharmaceuticals 2025, 18(9), 1244; https://doi.org/10.3390/ph18091244 - 22 Aug 2025
Abstract
Lung cancer is the leading cause of cancer mortality worldwide, with a poor prognosis driven by late diagnosis, systemic toxicity of existing therapies, and rapid development of multidrug resistance (MDR) to agents such as paclitaxel and cisplatin. MDR arises through multiple mechanisms, including [...] Read more.
Lung cancer is the leading cause of cancer mortality worldwide, with a poor prognosis driven by late diagnosis, systemic toxicity of existing therapies, and rapid development of multidrug resistance (MDR) to agents such as paclitaxel and cisplatin. MDR arises through multiple mechanisms, including overexpression of efflux transporters, alterations in apoptotic pathways, and tumour microenvironment-mediated resistance. The application of nanotechnology offers a potential solution to the aforementioned challenges by facilitating the enhancement of drug solubility, stability, bioavailability, and tumour-specific delivery. Additionally, it facilitates the co-loading of agents, thereby enabling the attainment of synergistic effects. Halloysite nanotubes (HNTs) are naturally occurring aluminosilicate nanocarriers with unique dual-surface chemistry, allowing hydrophobic drug encapsulation in the positively charged lumen and functionalisation of the negatively charged outer surface with targeting ligands or MDR modulators. This architecture supports dual-delivery strategies, enabling simultaneous administration of phytocannabinoids and chemotherapeutics or efflux pump inhibitors to enhance intracellular retention and cytotoxicity in resistant tumour cells. HNTs offer additional advantages over conventional nanocarriers, including mechanical and chemical stability and low production cost. Phytocannabinoids such as cannabidiol (CBD) and cannabigerol (CBG) show multitarget anticancer activity in lung cancer models, including apoptosis induction, proliferation inhibition, and oxidative stress modulation. However, poor solubility, instability, and extensive first-pass metabolism have limited their clinical use. Encapsulation in HNTs can overcome these barriers, protect against degradation, and enable controlled, tumour-targeted release. This review examined the therapeutic potential of HNT-based phytocannabinoid delivery systems in the treatment of lung cancer, with an emphasis on improving therapeutic selectivity, which represents a promising direction for more effective and patient-friendly treatments for lung cancer. Full article
(This article belongs to the Special Issue Combating Drug Resistance in Cancer)
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16 pages, 2209 KiB  
Article
ETAS®, a Standardized Extract of Asparagus officinalis Stem, Alleviates Sarcopenia via Regulating Protein Turnover and Mitochondrial Quality
by Sue-Joan Chang, Yung-Chia Chen, Yun-Ching Chang, Chung-Che Cheng and Yin-Ching Chan
Pharmaceuticals 2025, 18(9), 1243; https://doi.org/10.3390/ph18091243 - 22 Aug 2025
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Abstract
Background: ETAS®, a standardized extract of Asparagus officinalis stem, has been found to alleviate cognitive impairment in senescence-accelerated mice prone 8 (SAMP8) and is now considered a functional food in aging. The present study aimed to investigate the impacts of [...] Read more.
Background: ETAS®, a standardized extract of Asparagus officinalis stem, has been found to alleviate cognitive impairment in senescence-accelerated mice prone 8 (SAMP8) and is now considered a functional food in aging. The present study aimed to investigate the impacts of ETAS® on relieving aging-related muscle atrophy in SAMP8 mice. Methods: The SAMP8 mice were fed a regular diet supplemented with 200 or 1000 mg/kg BW ETAS®50 for 12 weeks. Grip strength, muscle mass, and molecular markers of protein synthesis, degradation, and mitochondrial quality were assessed. Results: We found that ETAS® significantly increased grip strength and muscle mass in SAMP8 mice. At the molecular level, ETAS® significantly upregulated protein synthesis via PI3K/Akt/mTOR/p70S6K and downregulated protein degradation via FoxO1a/atrogin-1 and MuRF-1 and myostatin via NFκB expression. In addition, ETAS® improved mitochondrial quality via promoting mitochondrial biogenesis genes, oxidative respiration genes, fusion/fission genes, PGC1α, and PINK1 proteins and maintained the autophagic flux via reducing ATG13, LC3-II/LC3-I, and p62. Conclusions: ETAS® exerts beneficial effects on sarcopenia by modulating the positive protein turnover and improving mitochondrial quality in aging. Full article
(This article belongs to the Special Issue Discovering Novel Drugs from Plants)
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20 pages, 2004 KiB  
Review
Chaya Leaf: A Promising Approach for Diabetes Management
by Fabiola Curiel Ayala, Francisco Ignacio García Rodríguez, Sandra N. Jimenez-Garcia and Lina Garcia-Mier
Pharmaceuticals 2025, 18(9), 1242; https://doi.org/10.3390/ph18091242 - 22 Aug 2025
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Abstract
Chaya leaf has long been used in folk medicine and is gaining scientific interest for its potential role in diabetes management. Recent research indicates that chaya leaf may help to regulate glucose, enhance insulin secretion, and reduce related complications, primarily due to the [...] Read more.
Chaya leaf has long been used in folk medicine and is gaining scientific interest for its potential role in diabetes management. Recent research indicates that chaya leaf may help to regulate glucose, enhance insulin secretion, and reduce related complications, primarily due to the presence of bioactive compounds such as polyphenols and flavonoids. These compounds are believed to enhance insulin sensitivity and offer protection against oxidative stress, a key contributor to diabetes-related complications. Chaya extracts, particularly methanolic and aqueous forms, have shown anti-diabetic effects in animal models, lowering blood glucose, cholesterol, and triglycerides and reducing inflammation; their bioactive compounds, like quercetin, rutin, and ferulic acid, may enhance the insulin response, reduce inflammation, and improve antioxidant activity. Some studies warn of potential interactions with metformin. This review compiles findings from the past five years, drawing from databases such as PubMed, SciELO, ScienceDirect, Dialnet, Web of Science, and Google Scholar. It highlights chaya’s phytochemical profile, explores proposed anti-diabetic mechanisms, and summarizes evidence from in vivo, in vitro, and clinical studies. The results indicate that adding chaya leaf to the diet may help people with diabetes as a complementary therapy to conventional treatment; nonetheless, further clinical studies are required to comprehend the exact mechanisms and define specific usage instructions. Further investigation into the specific types of compounds present in chaya, their effective dosages, and their safety in human populations is essential to support its integration into medical practice. Full article
(This article belongs to the Special Issue Natural Products in Diabetes Mellitus: 2nd Edition)
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