Pharmaceuticals

25 pages, 6491 KiB

Open AccessArticle

Traditional Processing Can Enhance the Medicinal Effects of Polygonatum cyrtonema by Inducing Significant Chemical Changes in the Functional Components in its Rhizomes

by Jianjun Shen, Weiting Pu, Qiyan Song, Bihuan Ye, Xiaoxiao Shi, Youwu Chen, Yefei Yu and Haibo Li

Pharmaceuticals 2024, 17(8), 1074; https://doi.org/10.3390/ph17081074 (registering DOI) - 15 Aug 2024

Abstract

The aims of this study were to explore the significant chemical changes in functional components induced by the traditional processing method and evaluate whether this method based on nine cycles of steaming and drying can effectively enhance the medicinal effects of Polygonatum cyrtonema [...] Read more.

The aims of this study were to explore the significant chemical changes in functional components induced by the traditional processing method and evaluate whether this method based on nine cycles of steaming and drying can effectively enhance the medicinal effects of Polygonatum cyrtonema rhizome. A global analysis on dynamic changes in secondary metabolites during nine processing cycles was performed, and the significantly differentially accumulated secondary metabolites were initially identified based on the secondary metabolome. Unsupervised principal component analysis (PCA), hierarchical clustering analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLA-DA) on secondary metabolites clearly showed that processing significantly increased the global accumulation of secondary metabolites in processed P. cyrtonema rhizomes compared to unprocessed crude rhizomes. The first six processing cycles induced drastic changes in the accumulation of functional components, while the last three did not induce further changes. The accumulations of most functional components were significantly enhanced after the first three cycles and stabilized after six cycles; meanwhile, the first three cycles also led to numerous new components. However, the enhancing effects were unavoidably reversed or weakened under continued processing lasting 6–9 cycles. Furthermore, continued processing also reduced the contents of a small number of original components to undetectable levels. Processing induced some significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, among which the first three processing cycles enhanced the synthesis of various secondary metabolites and significantly affected the metabolisms of amino acids. In conclusion, this study not only reveals that processing can effectively enhance the medicinal effects, by two main mechanisms including enhancing chemical synthesis and inducing structural transformation of functional components, but also provides theoretical guidance for the optimization of the traditional processing method based on nine cycles of steaming and drying for achieving optimal effects on enhancing the medicinal effects of P. cyrtonema rhizome. Full article

(This article belongs to the Section Pharmacology)

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24 pages, 1688 KiB

Open AccessReview

Unlocking Cholesterol Metabolism in Metabolic-Associated Steatotic Liver Disease: Molecular Targets and Natural Product Interventions

by Xiaoxiao Li and Meng Li

Pharmaceuticals 2024, 17(8), 1073; https://doi.org/10.3390/ph17081073 - 15 Aug 2024

Abstract

Metabolic-associated steatotic liver disease (MASLD), the hepatic manifestation of metabolic syndrome, represents a growing global health concern. The intricate pathogenesis of MASLD, driven by genetic, metabolic, epigenetic, and environmental factors, leads to considerable clinical variability. Dysregulation of hepatic lipid metabolism, particularly cholesterol homeostasis, [...] Read more.

Metabolic-associated steatotic liver disease (MASLD), the hepatic manifestation of metabolic syndrome, represents a growing global health concern. The intricate pathogenesis of MASLD, driven by genetic, metabolic, epigenetic, and environmental factors, leads to considerable clinical variability. Dysregulation of hepatic lipid metabolism, particularly cholesterol homeostasis, is a critical factor in the progression of MASLD and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH). This review elucidates the multifaceted roles of cholesterol metabolism in MASLD, focusing on its absorption, transportation, biosynthesis, efflux, and conversion. We highlight recent advancements in understanding these processes and explore the therapeutic potential of natural products such as curcumin, berberine, and resveratrol in modulating cholesterol metabolism. By targeting key molecular pathways, these natural products offer promising strategies for MASLD management. Finally, this review also covers the clinical studies of natural products in MASLD, providing new insights for future research and clinical applications. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention 2024)

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16 pages, 1729 KiB

Open AccessArticle

Searching for Novel HDAC6/Hsp90 Dual Inhibitors with Anti-Prostate Cancer Activity: In Silico Screening and In Vitro Evaluation

by Luca Pinzi, Silvia Belluti, Isabella Piccinini, Carol Imbriano and Giulio Rastelli

Pharmaceuticals 2024, 17(8), 1072; https://doi.org/10.3390/ph17081072 - 15 Aug 2024

Abstract

Prostate cancer (PCA) is one of the most prevalent types of male cancers. While current treatments for early-stage PCA are available, their efficacy is limited in advanced PCA, mainly due to drug resistance or low efficacy. In this context, novel valuable therapeutic opportunities [...] Read more.

Prostate cancer (PCA) is one of the most prevalent types of male cancers. While current treatments for early-stage PCA are available, their efficacy is limited in advanced PCA, mainly due to drug resistance or low efficacy. In this context, novel valuable therapeutic opportunities may arise from the combined inhibition of histone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90). These targets are mutually involved in the regulation of several processes in cancer cells, and their inhibition is demonstrated to provide synergistic effects against PCA. On these premises, we performed an extensive in silico virtual screening campaign on commercial compounds in search of dual inhibitors of HDAC6 and Hsp90. In vitro tests against recombinant enzymes and PCA cells with different levels of aggressiveness allowed the identification of a subset of compounds with inhibitory activity against HDAC6 and antiproliferative effects towards LNCaP and PC-3 cells. None of the candidates showed appreciable Hsp90 inhibition. However, the discovered compounds have low molecular weight and a chemical structure similar to that of potent Hsp90 blockers. This provides an opportunity for structural and medicinal chemistry optimization in order to obtain HDAC6/Hsp90 dual modulators with antiproliferative effects against prostate cancer. These findings were discussed in detail in the study. Full article

(This article belongs to the Special Issue Selective Histone Deacetylase Isoforms as Potential Therapeutic Targets)

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21 pages, 4607 KiB

Open AccessArticle

Formulation of a Three-Component Essential Oil Mixture from Lavandula dentata, Rosmarinus officinalis, and Myrtus communis for Improved Antioxidant Activity

by Amine Elbouzidi, Mohamed Taibi, Naoufal El Hachlafi, Mounir Haddou, Mohamed Jeddi, Abdellah Baraich, Aya Aouraghe, Reda Bellaouchi, Ramzi A. Mothana, Mohammed F. Hawwal, François Mesnard, Christophe Hano, Abdeslam Asehraou, Khalid Chaabane, Bouchra El Guerrouj and Mohamed Addi

Pharmaceuticals 2024, 17(8), 1071; https://doi.org/10.3390/ph17081071 - 15 Aug 2024

Abstract

The optimization of existing natural antioxidants that are highly effective is crucial for advancements in medicine and the food industry. Due to growing concerns regarding the safety of synthetic antioxidants, researchers are increasingly focusing on natural sources, particularly essential oils (EOs). Combining EOs [...] Read more.

The optimization of existing natural antioxidants that are highly effective is crucial for advancements in medicine and the food industry. Due to growing concerns regarding the safety of synthetic antioxidants, researchers are increasingly focusing on natural sources, particularly essential oils (EOs). Combining EOs might enhance antioxidant activity due to increased chemical diversity. This study investigates, for the first time, the antioxidant properties of EOs from Lavandula dentata, Rosmarinus officinalis, and Myrtus communis, both individually and in combination, using the augmented-simplex design methodology. The in vitro evaluation of the antioxidant activity was performed using DPPH and ABTS radical scavenging assays. Chromatography gas-mass spectrometry (CG-MS) revealed that 1,8-cineol (37.27%) and pinocarveol (12.67%) are the primary components of L. dentata; verbenone (16.90%), camphor (15.00%), and camphene (11.03%) are predominant in R. officinalis; while cineol (43.32%) is the main component of M. communis. The EOs showed varying scavenging activities against ABTS and DPPH radicals, with DPPH assay values ranging from 194.10 ± 3.01 to 541.19 ± 3.72 µg/mL and ABTS assay values ranging from 134.07 ± 1.70 to 663.42 ± 2.99 µg/mL. These activities were enhanced when the EOs were combined. The optimal antioxidant blend for DPPH_IC50 consisted of 20% L. dentata, 50% R. officinalis, and 30% M. communis. For the highest ABTS radical scavenging activity, the best combination was 18% L. dentata, 43% R. officinalis, and 40% M. communis. These results highlight the potential of EO combinations as new natural formulations for use in cosmeceutical, food, and pharmaceutical sectors. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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33 pages, 835 KiB

Open AccessReview

Advances in Intrathecal Nanoparticle Delivery: Targeting the Blood–Cerebrospinal Fluid Barrier for Enhanced CNS Drug Delivery

by Ahmad Khalid Madadi and Moon-Jun Sohn

Pharmaceuticals 2024, 17(8), 1070; https://doi.org/10.3390/ph17081070 - 15 Aug 2024

Abstract

The blood–cerebrospinal fluid barrier (BCSFB) tightly regulates molecular exchanges between the bloodstream and cerebrospinal fluid (CSF), creating challenges for effective central nervous system (CNS) drug delivery. This review assesses intrathecal (IT) nanoparticle (NP) delivery systems that aim to enhance drug delivery by circumventing [...] Read more.

The blood–cerebrospinal fluid barrier (BCSFB) tightly regulates molecular exchanges between the bloodstream and cerebrospinal fluid (CSF), creating challenges for effective central nervous system (CNS) drug delivery. This review assesses intrathecal (IT) nanoparticle (NP) delivery systems that aim to enhance drug delivery by circumventing the BCSFB, complementing approaches that target the blood–brain barrier (BBB). Active pharmaceutical ingredients (APIs) face hurdles like restricted CNS distribution and rapid clearance, which diminish the efficacy of IT therapies. NPs can be engineered to extend drug circulation times, improve CNS penetration, and facilitate sustained release. This review discusses key pharmacokinetic (PK) parameters essential for the effectiveness of these systems. NPs can quickly traverse the subarachnoid space and remain within the leptomeninges for extended periods, often exceeding three weeks. Some designs enable deeper brain parenchyma penetration. Approximately 80% of NPs in the CSF are cleared through the perivascular glymphatic pathway, with microglia-mediated transport significantly contributing to their paravascular clearance. This review synthesizes recent progress in IT-NP delivery across the BCSFB, highlighting critical findings, ongoing challenges, and the therapeutic potential of surface modifications and targeted delivery strategies. Full article

(This article belongs to the Topic Challenges and Opportunities in Drug Delivery Research)

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17 pages, 1918 KiB

Open AccessReview

Novel Treatments in Refractory Recurrent Pericarditis

by Emilia Lazarou, Christos Koutsianas, Panayotis K. Vlachakis, Panagiotis Theofilis, Dimitrios Vassilopoulos, Costas Tsioufis, George Lazaros and Dimitris Tousoulis

Pharmaceuticals 2024, 17(8), 1069; https://doi.org/10.3390/ph17081069 - 15 Aug 2024

Abstract

Refractory recurrent pericarditis is a troublesome condition that severely impairs the quality of life of affected patients and significantly increases healthcare spending. Until recently, therapeutic options included only a few medications and most of the patients resorted to chronic glucocorticoid treatment with steroid [...] Read more.

Refractory recurrent pericarditis is a troublesome condition that severely impairs the quality of life of affected patients and significantly increases healthcare spending. Until recently, therapeutic options included only a few medications and most of the patients resorted to chronic glucocorticoid treatment with steroid dependence. In the most recent decade, the introduction of interleukin-1 blockers in clinical practice has revolutionized the treatment of glucocorticoid-dependent and colchicine-resistant recurrent pericarditis due to their excellent efficacy and good safety profile. The rationale for the introduction of this class of medications in clinical practice is the autoinflammatory nature of recurrent pericarditis in a substantial rate of cases, with interleukin-1 being the main pro-inflammatory cytokine involved in this context. This review aims to discuss the contemporary available evidence from original research and real-world data on interleukin-1 blocker use in refractory recurrent pericarditis, in terms of indications, mechanism of action, efficacy, side effects, and recommended treatment protocols. Moreover, novel treatment proposals, such as hydroxychloroquine, beta blockers, and cannabidiol, which showed encouraging preliminary results, are addressed. Finally, gaps in knowledge, unmet needs, and future perspectives related to recurrent pericarditis are thoroughly discussed. Full article

(This article belongs to the Section Pharmacology)

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19 pages, 4132 KiB

Open AccessReview

In Vitro Resistance-Predicting Studies and In Vitro Resistance-Related Parameters—A Hit-to-Lead Perspective

by Joanna Krajewska, Stefan Tyski and Agnieszka E. Laudy

Pharmaceuticals 2024, 17(8), 1068; https://doi.org/10.3390/ph17081068 - 15 Aug 2024

Abstract

Despite the urgent need for new antibiotics, very few innovative antibiotics have recently entered clinics or clinical trials. To provide a constant supply of new drug candidates optimized in terms of their potential to select for resistance in natural settings, in vitro resistance-predicting [...] Read more.

Despite the urgent need for new antibiotics, very few innovative antibiotics have recently entered clinics or clinical trials. To provide a constant supply of new drug candidates optimized in terms of their potential to select for resistance in natural settings, in vitro resistance-predicting studies need to be improved and scaled up. In this review, the following in vitro parameters are presented: frequency of spontaneous mutant selection (FSMS), mutant prevention concentration (MPC), dominant mutant prevention concentration (MPC-D), inferior-mutant prevention concentration (MPC-F), and minimal selective concentration (MSC). The utility of various adaptive laboratory evolution (ALE) approaches (serial transfer, continuous culture, and evolution in spatiotemporal microenvironments) for comparing hits in terms of the level and time required for multistep resistance to emerge is discussed. We also consider how the hit-to-lead stage can benefit from high-throughput ALE setups based on robotic workstations, do-it-yourself (DIY) continuous cultivation systems, microbial evolution and growth arena (MEGA) plates, soft agar gradient evolution (SAGE) plates, microfluidic chips, or microdroplet technology. Finally, approaches for evaluating the fitness of in vitro-generated resistant mutants are presented. This review aims to draw attention to newly emerged ideas on how to improve the in vitro forecasting of the potential of compounds to select for resistance in natural settings. Full article

(This article belongs to the Special Issue Development of Antibacterial Drugs to Combat Drug-Resistant Bacteria)

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20 pages, 6138 KiB

Open AccessArticle

Employing Machine Learning-Based QSAR for Targeting Zika Virus NS3 Protease: Molecular Insights and Inhibitor Discovery

by Hisham N. Altayb and Hanan Ali Alatawi

Pharmaceuticals 2024, 17(8), 1067; https://doi.org/10.3390/ph17081067 - 15 Aug 2024

Abstract

Zika virus infection is a mosquito-borne viral disease that has become a global health concern recently. Zika virus belongs to the Flavivirus genus and is primarily transmitted by Aedes mosquitoes. Prevention of Zika virus infection involves avoiding mosquito bites by using repellent, wearing [...] Read more.

Zika virus infection is a mosquito-borne viral disease that has become a global health concern recently. Zika virus belongs to the Flavivirus genus and is primarily transmitted by Aedes mosquitoes. Prevention of Zika virus infection involves avoiding mosquito bites by using repellent, wearing protective clothing, and staying in screened areas, especially for pregnant women. Treatment focuses on managing symptoms with rest, fluids, and acetaminophen, with close monitoring for pregnant women. Currently, there is no specific antiviral treatment or vaccine for the Zika virus, highlighting the importance of prevention strategies to control its spread. Therefore, in this study, the Zika virus non-structural protein NS3 was targeted to inhibit Zika infection by identifying the novel inhibitor through an in silico approach. Here, 2864 natural compounds were screened using a machine learning-based QSAR model, and later docking was performed to select the potential target. Subsequently, Tanimoto similarity and clustering were performed to obtain the potential target. The three most potential compounds were obtained: (a) 5297, (b) 432449, and (c) 85137543. The protein–ligand complex’s stability and flexibility were then investigated by dynamic modelling. The 300 ns simulation showed that 5297 exhibited the steadiest deviation and constant creation of hydrogen bonds. Compared to the other compounds, 5297 demonstrated a superior binding free energy (ΔG = −20.81 kcal/mol) with the protein when the MM/GBSA technique was used. The study determined that 5297 showed significant therapeutic potential and justifies further experimental investigation as a possible inhibitor of the NS2B-NS3 protease target implicated in Zika virus infection. Full article

(This article belongs to the Special Issue Application of 2D and 3D-QSAR Models in Drug Design)

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15 pages, 1895 KiB

Open AccessArticle

Fish Oil Containing Pro-Resolving Mediators Enhances the Antioxidant System and Ameliorates LPS-Induced Inflammation in Human Bronchial Epithelial Cells

by Alfio Distefano, Laura Orlando, Sebastiano Giallongo, Emanuela Tropea, Mariarita Spampinato, Annalisa Santisi, Lucia Longhitano, Giuseppe Parisi, Salvatore Leonardi, Arcangelo Russo, Massimo Caruso, Michelino Di Rosa, Daniele Tibullo, Maurizio Salamone, Giovanni Li Volti and Ignazio Alberto Barbagallo

Pharmaceuticals 2024, 17(8), 1066; https://doi.org/10.3390/ph17081066 - 14 Aug 2024

Abstract

Fish oil, renowned for its high content of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has gained considerable attention for its potential health benefits. EPA and DHA exhibit anti-inflammatory effects by promoting the production of specialized pro-resolving mediators (SPMs), [...] Read more.

Fish oil, renowned for its high content of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has gained considerable attention for its potential health benefits. EPA and DHA exhibit anti-inflammatory effects by promoting the production of specialized pro-resolving mediators (SPMs), such as resolvins and protectins. Fish oil has been studied for its potential to reduce bronchial inflammation, a key feature of respiratory conditions like asthma and COPD. This study investigates the cellular mechanisms of fish oil in an in vitro model of lung inflammation using lipopolysaccharide (LPS) on a healthy human bronchial epithelium cell line. LPS exposure for 24 h reduced cell viability, elevated reactive oxygen species (ROS), depleted glutathione (GSH), and induced mitochondrial depolarization, indicating oxidative stress and inflammation. Fish oil administration significantly mitigated ROS production, prevented GSH depletion, and reduced mitochondrial depolarization. This was associated with the upregulation of the endogenous antioxidant system, evidenced by restored GSH levels and the increased gene expression of glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2). Fish oil also suppressed IL-6 and IL-1β expression and increased anti-inflammatory cytokine IL-10 expression. Furthermore, fish oil upregulated the expression of pro-resolving mediator receptors, suggesting a role in inflammation resolution. These findings highlight the potential of fish oil supplementation as a preventive measure against pulmonary diseases characterized by unresolved inflammation such as lung inflammation. Full article

(This article belongs to the Special Issue New Therapeutic Opportunities for Epigenetic Drugs)

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24 pages, 4497 KiB

Open AccessArticle

Establishment of Dissolution Test Method for Multi-Components in Traditional Chinese Medicine Preparations Based on In Vitro–In Vivo Correlation

by Pengcheng Guo, Qizheng Wang, Xiaoqiang Xiang, Yufeng Zhang, Yue Pan, Zhong Zuo and Jianxin Wang

Pharmaceuticals 2024, 17(8), 1065; https://doi.org/10.3390/ph17081065 - 14 Aug 2024

Abstract

In this study, a multi-component integrated dissolution evaluation system of Yuanhu Zhitong tablets (YZTs) was established based on in vitro and in vivo correlation (IVIVC). The dissolution tests of five quality markers (Q-markers), including tetrahydropalmatine, α-allocryptopine, protopine, corydaline, and byakangelicin, in YZTs were [...] Read more.

In this study, a multi-component integrated dissolution evaluation system of Yuanhu Zhitong tablets (YZTs) was established based on in vitro and in vivo correlation (IVIVC). The dissolution tests of five quality markers (Q-markers), including tetrahydropalmatine, α-allocryptopine, protopine, corydaline, and byakangelicin, in YZTs were conducted under different dissolution conditions, and pharmacokinetic studies were performed in beagle dogs to construct a correlation model using numerical deconvolution. The data of the five ingredients were integrated in vitro and in vivo according to the biopharmaceutical classification system (BCS) to establish an IVIVC integrating multiple Q-markers. The dissolution media with the best correlation of components were obtained and validated. The results showed that all five components were classified as BCS I compounds, and α-allocryptopine, byakangelicin, tetrahydropalmatine, and corydaline showed good correlation in the paddle method, 75 rpm, with dissolution media of artificial gastric fluid, acetate buffer, acetate buffer and 0.1 M HCl, respectively. Protopine showed good correlation in the paddle method, 100 rpm, with dissolution media of 0.1 M HCl. The integrated BCS I Q-markers showed the best correlation in the medium of acetate buffer. The multi-component integrated dissolution evaluation system established in this experiment accurately predicted the pharmacokinetic data of YZTs by verifying the media, which can be used for the quality control of YZTs. The present study provides an effective and promising strategy for the dissolution evaluation for traditional Chinese medicine preparations. Full article

(This article belongs to the Section Pharmaceutical Technology)

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25 pages, 7591 KiB

Open AccessArticle

Beta vulgaris Betalains Mitigate Parasitemia and Brain Oxidative Stress Induced by Plasmodium berghei in Mice

by Samar A. Khan, Muslimah N. Alsulami, Atif A. Alsehimi, Majed S. Alzahrani, Dina A. Mosule and Haleema H. Albohiri

Pharmaceuticals 2024, 17(8), 1064; https://doi.org/10.3390/ph17081064 - 13 Aug 2024

Abstract

Although many drugs have been discovered to treat malaria infection, many of them face resistance from the host’s body with long-term use. Therefore, this study aimed to evaluate the activity of betalains (from Beta vulgaris) and chloroquine (a reference drug) against brain [...] Read more.

Although many drugs have been discovered to treat malaria infection, many of them face resistance from the host’s body with long-term use. Therefore, this study aimed to evaluate the activity of betalains (from Beta vulgaris) and chloroquine (a reference drug) against brain oxidative stress induced by Plasmodium berghei in male mice. Two protocols were applied in this study: the therapeutic and prophylactic protocols. The results of the therapeutic protocol revealed a significant decrease in the level of parasitemia caused by P. berghei. Additionally, the histopathological changes in various brain regions were markedly improved after treatment with betalains. Regarding the prophylactic protocol, betalains were able to protect the brain tissues from oxidative stress, inflammation, and disrupted neurotransmitters expected to occur as a result of infection by P. berghei. This was demonstrated by modulating the activities of brain antioxidants (SOD and GSH), inflammatory cytokines (IL-6, IL-10, IL-12, TNF-α, and INF-γ), and neurotransmitters (serotonin, epinephrine, and norepinephrine). This study has proven that using betalains as a treatment or as a preventive has a vital and effective role in confronting the brain histopathological, oxidative stress, and inflammatory changes induced by P. berghei infection. Full article

(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)

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17 pages, 3701 KiB

Open AccessReview

Unearthing the Potential Therapeutic Effects of Oxyresveratrol Based on Intrinsic Links between Pharmacological Effects: Implications for the Gut–Liver–Brain Axis

by Lijuan Zhao, Yan Duan, Zhaoxing Li, Juan Li and Shunxiang Li

Pharmaceuticals 2024, 17(8), 1063; https://doi.org/10.3390/ph17081063 - 13 Aug 2024

Abstract

Oxyresveratrol is a stilbene compound with a simple chemical structure and various therapeutic potentials. This study summarized and analyzed the multiple pharmacological effects and mechanisms of oxyresveratrol, identifying its prominent performance in neuroprotection, hepatoprotection, and anti-inflammatory activities in the intestines. By integrating the [...] Read more.

Oxyresveratrol is a stilbene compound with a simple chemical structure and various therapeutic potentials. This study summarized and analyzed the multiple pharmacological effects and mechanisms of oxyresveratrol, identifying its prominent performance in neuroprotection, hepatoprotection, and anti-inflammatory activities in the intestines. By integrating the pharmacological effects of oxyresveratrol with insights from the network pharmacology and molecular docking of its interactions with targets linked to gut–liver–brain axis disorders, it has been shown that oxyresveratrol may hold promise for the treatment of gut–liver–brain axis-related disorders. The synergistic effect between various mechanisms has inspired further research and the development of oxyresveratrol’s application value. Full article

(This article belongs to the Special Issue Exploring Natural Metabolites to Identify Novel Potential Therapeutic Agents)

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13 pages, 2100 KiB

Open AccessArticle

Lipid-Lowering and Anti-Inflammatory Effects of Campomanesia adamantium Leaves in Adipocytes and Caenorhabditis elegans

by Paola dos Santos da Rocha, Sarah Lam Orué, Isamara Carvalho Ferreira, Priscilla Pereira de Toledo Espindola, Maria Victória Benites Rodrigues, José Tarcísio Giffoni de Carvalho, Debora da Silva Baldivia, Daniel Ferreira Leite, Helder Freitas dos Santos, Alex Santos Oliveira, Jaqueline Ferreira Campos, Edson Lucas dos Santos and Kely de Picoli Souza

Pharmaceuticals 2024, 17(8), 1062; https://doi.org/10.3390/ph17081062 - 13 Aug 2024

Abstract

Obesity is a pandemic disease characterized by lipid accumulation, increased proinflammatory cytokines, and reactive oxygen species. It is associated with the development of comorbidities that lead to death. Additionally, drug treatments developed to control obesity are insufficient and have a variety of adverse [...] Read more.

Obesity is a pandemic disease characterized by lipid accumulation, increased proinflammatory cytokines, and reactive oxygen species. It is associated with the development of comorbidities that lead to death. Additionally, drug treatments developed to control obesity are insufficient and have a variety of adverse effects. Thus, the search for new anti-obesity therapies is necessary. Campomanesia adamantium is a species from the Brazilian Cerrado that has the potential to treat obesity, as described by the antihyperlipidemic activity of its roots. Therefore, this study aimed to investigate the activity of the aqueous extract of C. adamantium leaves (AECa) on the control of reactive species in vitro, on lipid accumulation in adipocytes and Caenorhabditis elegans, and on the production of proinflammatory cytokines in adipocytes. The antioxidant capacity of AECa was observed by its action in scavenging DPPH^• free radical, iron-reducing power, and inhibition of β-carotene bleaching. AECa reduced lipid accumulation in preadipocytes and in C. elegans. Moreover, AECa reduced the production of the proinflammatory cytokines MCP-1, TNF-α, and IL-6 in adipocytes. In summary, the antioxidant activity and the ability of AECa to reduce the accumulation of lipids and proinflammatory cytokines indicate, for the first time, the anti-obesity potential of C. adamantium leaves. Full article

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

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13 pages, 1159 KiB

Open AccessArticle

Neuroprotective Effects of Phenolic Constituents from Drynariae Rhizoma

by Jin Sung Ahn, Chung Hyeon Lee, Xiang-Qian Liu, Kwang Woo Hwang, Mi Hyune Oh, So-Young Park and Wan Kyunn Whang

Pharmaceuticals 2024, 17(8), 1061; https://doi.org/10.3390/ph17081061 - 13 Aug 2024

Abstract

This study aimed to provide scientific data on the anti-Alzheimer’s disease (AD) effects of phenolic compounds from Drynariae Rhizoma (DR) extract using a multi-component approach. Screening of DR extracts, fractions, and the ten phenolic compounds isolated from DR against the key AD-related enzymes [...] Read more.

This study aimed to provide scientific data on the anti-Alzheimer’s disease (AD) effects of phenolic compounds from Drynariae Rhizoma (DR) extract using a multi-component approach. Screening of DR extracts, fractions, and the ten phenolic compounds isolated from DR against the key AD-related enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and monoamine oxidase-B (MAO-B) confirmed their significant inhibitory activities. The DR extract was confirmed to have BACE1-inhibitory activity, and the ethyl acetate and butanol fractions were found to inhibit all AD-related enzymes, including BACE1, AChE, BChE, and MAO-B. Among the isolated phenolic compounds, compounds (2) caffeic acid 4-O-β-D-glucopyranoside, (6) kaempferol 3-O-rhamnoside 7-O-glucoside, (7) kaempferol 3-o-b-d-glucopyranoside-7-o-a-L-arabinofuranoside, (8) neoeriocitrin, (9) naringin, and (10) hesperidin significantly suppressed AD-related enzymes. Notably, compounds 2 and 8 reduced soluble Amyloid Precursor Protein β (sAPPβ) and β-secretase expression by over 45% at a concentration of 1.0 μM. In the thioflavin T assay, compounds 6 and 7 decreased Aβ aggregation by approximately 40% and 80%, respectively, and degraded preformed Aβ aggregates. This study provides robust evidence regarding the potential of DR as a natural therapeutic agent for AD, highlighting specific compounds that may contribute to its efficacy. Full article

(This article belongs to the Section Natural Products)

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11 pages, 1503 KiB

Open AccessReview

Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension

by Rocio Bautista-Pérez and Martha Franco

Pharmaceuticals 2024, 17(8), 1060; https://doi.org/10.3390/ph17081060 - 13 Aug 2024

Abstract

The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as [...] Read more.

The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as chronic renal failure, which is frequently observed in hypertensive patients. Therefore, new approaches that may improve the control of arterial blood pressure should be considered to prevent serious cardiovascular disorders. The contribution of purinergic receptors has been acknowledged in the pathophysiology of hypertension; this review describes the participation of these receptors in the alteration of kidney function in hypertension. Elevated interstitial ATP concentrations are essential for the activation of renal purinergic receptors; this becomes a fundamental pathway that leads to the development and maintenance of hypertension. High ATP levels modify essential mechanisms implicated in the long-term control of blood pressure, such as pressure natriuresis, the autoregulation of the glomerular filtration rate and renal blood flow, and tubuloglomerular feedback responses. Any alteration in these mechanisms decreases sodium excretion. ATP stimulates the release of vasoactive substances, causes renal function to decline, and induces tubulointerstitial damage. At the same time, a deleterious interaction involving angiotensin II and purinergic receptors leads to the deterioration of renal function. Full article

(This article belongs to the Special Issue Pharmacological Advances for Treatment in Hypertension 2.0)

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29 pages, 2155 KiB

Open AccessReview

Nanoparticle-Based Drug Delivery Systems in Inhaled Therapy: Improving Respiratory Medicine

by Elena Cojocaru, Ovidiu Rusalim Petriș and Cristian Cojocaru

Pharmaceuticals 2024, 17(8), 1059; https://doi.org/10.3390/ph17081059 - 12 Aug 2024

Abstract

Inhaled nanoparticle (NP) therapy poses intricate challenges in clinical and pharmacodynamic realms. Recent strides have revolutionized NP technology by enabling the incorporation of diverse molecules, thus circumventing systemic clearance mechanisms and enhancing drug effectiveness while mitigating systemic side effects. Despite the established success [...] Read more.

Inhaled nanoparticle (NP) therapy poses intricate challenges in clinical and pharmacodynamic realms. Recent strides have revolutionized NP technology by enabling the incorporation of diverse molecules, thus circumventing systemic clearance mechanisms and enhancing drug effectiveness while mitigating systemic side effects. Despite the established success of systemic NP delivery in oncology and other disciplines, the exploration of inhaled NP therapies remains relatively nascent. NPs loaded with bronchodilators or anti-inflammatory agents exhibit promising potential for precise distribution throughout the bronchial tree, offering targeted treatment for respiratory diseases. This article conducts a comprehensive review of NP applications in respiratory medicine, highlighting their merits, ranging from heightened stability to exacting lung-specific delivery. It also explores cutting-edge technologies optimizing NP-loaded aerosol systems, complemented by insights gleaned from clinical trials. Furthermore, the review examines the current challenges and future prospects in NP-based therapies. By synthesizing current data and perspectives, the article underscores the transformative promise of NP-mediated drug delivery in addressing chronic conditions such as chronic obstructive pulmonary disease, a pressing global health concern ranked third in mortality rates. This overview illuminates the evolving landscape of NP inhalation therapies, presenting optimistic avenues for advancing respiratory medicine and improving patient outcomes. Full article

(This article belongs to the Special Issue Recent Advances in Inhalation Therapy)

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13 pages, 3371 KiB

Open AccessArticle

Safflower Yellow Injection Alleviates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative and Endoplasmic Reticulum Stress

by Wulin Liang, Mingqian Zhang, Jiahui Gao, Rikang Huang, Lu Cheng, Liyuan Zhang, Zhishan Huang, Zhanhong Jia and Shuofeng Zhang

Pharmaceuticals 2024, 17(8), 1058; https://doi.org/10.3390/ph17081058 - 12 Aug 2024

Abstract

Safflower yellow is an extract of the famous Chinese medicine Carthamus tinctorious L, and safflower yellow injection (SYI) is widely used clinically to treat angina pectoris. However, there are few studies on the anti-myocardial ischemia/reperfusion (I/R) injury effect of SYI, and its mechanisms [...] Read more.

Safflower yellow is an extract of the famous Chinese medicine Carthamus tinctorious L, and safflower yellow injection (SYI) is widely used clinically to treat angina pectoris. However, there are few studies on the anti-myocardial ischemia/reperfusion (I/R) injury effect of SYI, and its mechanisms are unclear. In the present study, we aimed to investigate the protective effect of SYI on myocardial I/R injury and explore its underlying mechanisms. Male Sprague Dawley rats were randomly divided into a control group, sham group, model group, and SYI group (20 mg/kg, femoral vein injection 1 h before modeling). The left anterior descending coronary artery was ligated to establish a myocardial I/R model. H9c2 cells were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) after incubation with 80 μg/mL SYI for 24 h. In vivo, TsTC, HE, and TUNEL staining were performed to evaluate myocardial injury and apoptosis. A kit was used to detect superoxide dismutase (SOD) and malondialdehyde (MDA) to assess oxidative stress. In vitro, flow cytometry was used to detect the reactive oxygen species (ROS) content and apoptosis rate. Protein levels were determined via Western blotting. Pretreatment with SYI significantly reduced infarct size and pathological damage in rat hearts and suppressed cardiomyocyte apoptosis in vivo and in vitro. In addition, SYI inhibited oxidative stress by increasing SOD activity and decreasing MDA content and ROS production. Myocardial I/R and OGD/R activate endoplasmic reticulum (ER) stress, as evidenced by increased expression of activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), cysteinyl aspartate-specific proteinase caspase-12, and C/EBP-homologous protein (CHOP), which were all inhibited by SYI. SYI ameliorated myocardial I/R injury by attenuating apoptosis, oxidative damage, and ER stress, which revealed new mechanistic insights into its application. Full article

(This article belongs to the Section Pharmacology)

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Graphical abstract

18 pages, 357 KiB

Open AccessReview

Hypoxia as a Target for Combination with Transarterial Chemoembolization in Hepatocellular Carcinoma

by Zizhuo Wang, Qing Li and Bin Liang

Pharmaceuticals 2024, 17(8), 1057; https://doi.org/10.3390/ph17081057 - 11 Aug 2024

Abstract

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proven to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable [...] Read more.

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proven to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in the treatment of HCC. This review summarizes the impact of hypoxia on HCC tumor biology and the adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC. Full article

(This article belongs to the Special Issue Novel Therapeutic Target for Hepatocellular Carcinoma)

17 pages, 5189 KiB

Open AccessArticle

The Association between Statin Use and Reduced Migraine Likelihood: A Comprehensive Analysis of Migraine Subtypes and Statin Types in a Nationwide Korean Cohort

by Ho Suk Kang, Joo-Hee Kim, Ji Hee Kim, Woo Jin Bang, Dae Myoung Yoo, Na-Eun Lee, Kyeong Min Han, Nan Young Kim, Hyo Geun Choi, Kyueng-Whan Min and Mi Jung Kwon

Pharmaceuticals 2024, 17(8), 1056; https://doi.org/10.3390/ph17081056 - 10 Aug 2024

Abstract

Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case–control study within the Korean National Health Insurance Service-Health Screening Cohort (2002–2019) investigated [...] Read more.

Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case–control study within the Korean National Health Insurance Service-Health Screening Cohort (2002–2019) investigated this association using 38,957 migraine patients and 155,828 controls, considering migraine subtypes (with/without aura) and statin types (lipophilic vs. hydrophilic). Using propensity score matching and adjusting for confounders, statin use was linked to reduced migraine likelihood overall (odds ratio (OR) 0.93), particularly for migraines with aura (OR 0.75) and without aura (OR 0.94). Lipophilic statins were effective for both subtypes, while hydrophilic statins mainly reduced the likelihood of migraines without aura. Subgroup analyses showed consistent benefits across demographics, but varied effectiveness based on weight, smoking, alcohol use, hemoglobin levels, and dyslipidemia history. In summary, this nationwide cohort study suggests that statin use may reduce migraine likelihood among Korean adults across diverse demographics and clinical profiles, but varied effectiveness based on certain lifestyle and comorbidity factors underscores the importance of considering individual patient profiles when assessing the potential benefits of statin therapy for migraine prevention. Full article

(This article belongs to the Special Issue Pharmacological Modulation of Lipoproteins)

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